Bridging the gap between modules in isolation and as part of networks: A systems framework for elucidating interaction and regulation of signalling modules

NASA Astrophysics Data System (ADS)

Menon, Govind; Krishnan, J.

2016-07-01

While signalling and biochemical modules have been the focus of numerous studies, they are typically studied in isolation, with no examination of the effects of the ambient network. In this paper we formulate and develop a systems framework, rooted in dynamical systems, to understand such effects, by studying the interaction of signalling modules. The modules we consider are (i) basic covalent modification, (ii) monostable switches, (iii) bistable switches, (iv) adaptive modules, and (v) oscillatory modules. We systematically examine the interaction of these modules by analyzing (a) sequential interaction without shared components, (b) sequential interaction with shared components, and (c) oblique interactions. Our studies reveal that the behaviour of a module in isolation may be substantially different from that in a network, and explicitly demonstrate how the behaviour of a given module, the characteristics of the ambient network, and the possibility of shared components can result in new effects. Our global approach illuminates different aspects of the structure and functioning of modules, revealing the importance of dynamical characteristics as well as biochemical features; this provides a methodological platform for investigating the complexity of natural modules shaped by evolution, elucidating the effects of ambient networks on a module in multiple cellular contexts, and highlighting the capabilities and constraints for engineering robust synthetic modules. Overall, such a systems framework provides a platform for bridging the gap between non-linear information processing modules, in isolation and as parts of networks, and a basis for understanding new aspects of natural and engineered cellular networks.

Bridging the gap between modules in isolation and as part of networks: A systems framework for elucidating interaction and regulation of signalling modules.

PubMed

Menon, Govind; Krishnan, J

2016-07-21

While signalling and biochemical modules have been the focus of numerous studies, they are typically studied in isolation, with no examination of the effects of the ambient network. In this paper we formulate and develop a systems framework, rooted in dynamical systems, to understand such effects, by studying the interaction of signalling modules. The modules we consider are (i) basic covalent modification, (ii) monostable switches, (iii) bistable switches, (iv) adaptive modules, and (v) oscillatory modules. We systematically examine the interaction of these modules by analyzing (a) sequential interaction without shared components, (b) sequential interaction with shared components, and (c) oblique interactions. Our studies reveal that the behaviour of a module in isolation may be substantially different from that in a network, and explicitly demonstrate how the behaviour of a given module, the characteristics of the ambient network, and the possibility of shared components can result in new effects. Our global approach illuminates different aspects of the structure and functioning of modules, revealing the importance of dynamical characteristics as well as biochemical features; this provides a methodological platform for investigating the complexity of natural modules shaped by evolution, elucidating the effects of ambient networks on a module in multiple cellular contexts, and highlighting the capabilities and constraints for engineering robust synthetic modules. Overall, such a systems framework provides a platform for bridging the gap between non-linear information processing modules, in isolation and as parts of networks, and a basis for understanding new aspects of natural and engineered cellular networks.

A Matlab/Simulink-Based Interactive Module for Servo Systems Learning

ERIC Educational Resources Information Center

Aliane, N.

2010-01-01

This paper presents an interactive module for learning both the fundamental and practical issues of servo systems. This module, developed using Simulink in conjunction with the Matlab graphical user interface (Matlab-GUI) tool, is used to supplement conventional lectures in control engineering and robotics subjects. First, the paper introduces the…

Molecular tweezers modulate 14-3-3 protein-protein interactions

NASA Astrophysics Data System (ADS)

Bier, David; Rose, Rolf; Bravo-Rodriguez, Kenny; Bartel, Maria; Ramirez-Anguita, Juan Manuel; Dutt, Som; Wilch, Constanze; Klärner, Frank-Gerrit; Sanchez-Garcia, Elsa; Schrader, Thomas; Ottmann, Christian

2013-03-01

Supramolecular chemistry has recently emerged as a promising way to modulate protein functions, but devising molecules that will interact with a protein in the desired manner is difficult as many competing interactions exist in a biological environment (with solvents, salts or different sites for the target biomolecule). We now show that lysine-specific molecular tweezers bind to a 14-3-3 adapter protein and modulate its interaction with partner proteins. The tweezers inhibit binding between the 14-3-3 protein and two partner proteins—a phosphorylated (C-Raf) protein and an unphosphorylated one (ExoS)—in a concentration-dependent manner. Protein crystallography shows that this effect arises from the binding of the tweezers to a single surface-exposed lysine (Lys214) of the 14-3-3 protein in the proximity of its central channel, which normally binds the partner proteins. A combination of structural analysis and computer simulations provides rules for the tweezers' binding preferences, thus allowing us to predict their influence on this type of protein-protein interactions.

Online Chemistry Modules: Interaction and Effective Faculty Facilitation

ERIC Educational Resources Information Center

Slocum, Laura E.; Towns Marcy Hamby; Zielinski, Theresa Julia

2004-01-01

Computer supported collaborative learning, cooperative learning combined with electronic communication, physical chemistry online modules, use of discussion boards, its advantages and limitations are experimented and discussed. The most important finding is the example of effective online faculty facilitation and interaction.

Infant Smiling during Social Interaction: Arousal Modulation or Activation Indicator?

ERIC Educational Resources Information Center

Ewy, Richard

In a study of infant smiling, 20 mother-infant dyads were videotaped in normal face-to-face interaction when the infants were 9 and 14 weeks of age. Videotapes were used to determine which of two classes of smiling behavior models, either arousal modulation or activation indicator, was most supported by empirical data. Arousal modulation models…

Development and Evaluation of an Interactive Internet-Based Pharmacokinetic Teaching Module.

ERIC Educational Resources Information Center

Hedaya, Mohsen A.

1998-01-01

Describes an Internet-based, interactive, learner-centered, asynchronous instructional module for pharmacokinetics that requires minimal computer knowledge to operate. Main components are concept presentation, a simulation exercise, and self-assessment questions. The module has been found effective in teaching the steady state concept at the…

The Interaction between Sytactic and Semantic Modules in Chinese Learners' English Spotaneous Speech

ERIC Educational Resources Information Center

Gang, Xu

2014-01-01

According to modular theory, there are interactive effects between the central modules and language modules. The central cognition may deploy and redeploy resources from language modules. Moreover, the language modules can activate the cognitive ability. So this paper studies the spontaneous speech of students who learn English as a foreign…

Functional modules by relating protein interaction networks and gene expression.

PubMed

Tornow, Sabine; Mewes, H W

2003-11-01

Genes and proteins are organized on the basis of their particular mutual relations or according to their interactions in cellular and genetic networks. These include metabolic or signaling pathways and protein interaction, regulatory or co-expression networks. Integrating the information from the different types of networks may lead to the notion of a functional network and functional modules. To find these modules, we propose a new technique which is based on collective, multi-body correlations in a genetic network. We calculated the correlation strength of a group of genes (e.g. in the co-expression network) which were identified as members of a module in a different network (e.g. in the protein interaction network) and estimated the probability that this correlation strength was found by chance. Groups of genes with a significant correlation strength in different networks have a high probability that they perform the same function. Here, we propose evaluating the multi-body correlations by applying the superparamagnetic approach. We compare our method to the presently applied mean Pearson correlations and show that our method is more sensitive in revealing functional relationships.

Functional modules by relating protein interaction networks and gene expression

PubMed Central

Tornow, Sabine; Mewes, H. W.

2003-01-01

Genes and proteins are organized on the basis of their particular mutual relations or according to their interactions in cellular and genetic networks. These include metabolic or signaling pathways and protein interaction, regulatory or co-expression networks. Integrating the information from the different types of networks may lead to the notion of a functional network and functional modules. To find these modules, we propose a new technique which is based on collective, multi-body correlations in a genetic network. We calculated the correlation strength of a group of genes (e.g. in the co-expression network) which were identified as members of a module in a different network (e.g. in the protein interaction network) and estimated the probability that this correlation strength was found by chance. Groups of genes with a significant correlation strength in different networks have a high probability that they perform the same function. Here, we propose evaluating the multi-body correlations by applying the superparamagnetic approach. We compare our method to the presently applied mean Pearson correlations and show that our method is more sensitive in revealing functional relationships. PMID:14576317

Identification of Modules in Protein-Protein Interaction Networks

NASA Astrophysics Data System (ADS)

Erten, Sinan; Koyutürk, Mehmet

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

Task modulated brain connectivity of the amygdala: a meta-analysis of psychophysiological interactions.

PubMed

Di, Xin; Huang, Jia; Biswal, Bharat B

2017-01-01

Understanding functional connectivity of the amygdala with other brain regions, especially task modulated connectivity, is a critical step toward understanding the role of the amygdala in emotional processes and the interactions between emotion and cognition. The present study performed coordinate-based meta-analysis on studies of task modulated connectivity of the amygdala which used psychophysiological interaction (PPI) analysis. We first analyzed 49 PPI studies on different types of tasks using activation likelihood estimation (ALE) meta-analysis. Widespread cortical and subcortical regions showed consistent task modulated connectivity with the amygdala, including the medial frontal cortex, bilateral insula, anterior cingulate, fusiform gyrus, parahippocampal gyrus, thalamus, and basal ganglia. These regions were in general overlapped with those showed coactivations with the amygdala, suggesting that these regions and amygdala are not only activated together, but also show different levels of interactions during tasks. Further analyses with subsets of PPI studies revealed task specific functional connectivities with the amygdala that were modulated by fear processing, face processing, and emotion regulation. These results suggest a dynamic modulation of connectivity upon task demands, and provide new insights on the functions of the amygdala in different affective and cognitive processes. The meta-analytic approach on PPI studies may offer a framework toward systematical examinations of task modulated connectivity.

Accurate formulas for interaction force and energy in frequency modulation force spectroscopy

NASA Astrophysics Data System (ADS)

Sader, John E.; Jarvis, Suzanne P.

2004-03-01

Frequency modulation atomic force microscopy utilizes the change in resonant frequency of a cantilever to detect variations in the interaction force between cantilever tip and sample. While a simple relation exists enabling the frequency shift to be determined for a given force law, the required complementary inverse relation does not exist for arbitrary oscillation amplitudes of the cantilever. In this letter we address this problem and present simple yet accurate formulas that enable the interaction force and energy to be determined directly from the measured frequency shift. These formulas are valid for any oscillation amplitude and interaction force, and are therefore of widespread applicability in frequency modulation dynamic force spectroscopy.

Interactive web-based learning modules prior to general medicine advanced pharmacy practice experiences.

PubMed

Isaacs, Alex N; Walton, Alison M; Nisly, Sarah A

2015-04-25

To implement and evaluate interactive web-based learning modules prior to advanced pharmacy practice experiences (APPEs) on inpatient general medicine. Three clinical web-based learning modules were developed for use prior to APPEs in 4 health care systems. The aim of the interactive modules was to strengthen baseline clinical knowledge before the APPE to enable the application of learned material through the delivery of patient care. For the primary endpoint, postassessment scores increased overall and for each individual module compared to preassessment scores. Postassessment scores were similar among the health care systems. The survey demonstrated positive student perceptions of this learning experience. Prior to inpatient general medicine APPEs, web-based learning enabled the standardization and assessment of baseline student knowledge across 4 health care systems.

Lysine methylation modulates the protein-protein interactions of yeast cytochrome C Cyc1p.

PubMed

Winter, Daniel L; Abeygunawardena, Dhanushi; Hart-Smith, Gene; Erce, Melissa A; Wilkins, Marc R

2015-07-01

In recent years, protein methylation has been established as a major intracellular PTM. It has also been proposed to modulate protein-protein interactions (PPIs) in the interactome. To investigate the effect of PTMs on PPIs, we recently developed the conditional two-hybrid (C2H) system. With this, we demonstrated that arginine methylation can modulate PPIs in the yeast interactome. Here, we used the C2H system to investigate the effect of lysine methylation. Specifically, we asked whether Ctm1p-mediated trimethylation of yeast cytochrome c Cyc1p, on lysine 78, modulates its interactions with Erv1p, Ccp1p, Cyc2p and Cyc3p. We show that the interactions between Cyc1p and Erv1p, and between Cyc1p and Cyc3p, are significantly increased upon trimethylation of lysine 78. This increase of interaction helps explain the reported facilitation of Cyc1p import into the mitochondrial intermembrane space upon methylation. This first application of the C2H system to the study of methyllysine-modulated interactions further confirms its robustness and flexibility. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Finding Correlation between Protein Protein Interaction Modules Using Semantic Web Techniques

NASA Astrophysics Data System (ADS)

Kargar, Mehdi; Moaven, Shahrouz; Abolhassani, Hassan

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

Intranasal oxytocin modulates neural functional connectivity during human social interaction.

PubMed

Rilling, James K; Chen, Xiangchuan; Chen, Xu; Haroon, Ebrahim

2018-02-10

Oxytocin (OT) modulates social behavior in primates and many other vertebrate species. Studies in non-primate animals have demonstrated that, in addition to influencing activity within individual brain areas, OT influences functional connectivity across networks of areas involved in social behavior. Previously, we used fMRI to image brain function in human subjects during a dyadic social interaction task following administration of either intranasal oxytocin (INOT) or placebo, and analyzed the data with a standard general linear model. Here, we conduct an extensive re-analysis of these data to explore how OT modulates functional connectivity across a neural network that animal studies implicate in social behavior. OT induced widespread increases in functional connectivity in response to positive social interactions among men and widespread decreases in functional connectivity in response to negative social interactions among women. Nucleus basalis of Meynert, an important regulator of selective attention and motivation with a particularly high density of OT receptors, had the largest number of OT-modulated connections. Regions known to receive mesolimbic dopamine projections such as the nucleus accumbens and lateral septum were also hubs for OT effects on functional connectivity. Our results suggest that the neural mechanism by which OT influences primate social cognition may include changes in patterns of activity across neural networks that regulate social behavior in other animals. © 2018 Wiley Periodicals, Inc.

Tunable interactions between paramagnetic colloidal particles driven in a modulated ratchet potential.

PubMed

Straube, Arthur V; Tierno, Pietro

2014-06-14

We study experimentally and theoretically the interactions between paramagnetic particles dispersed in water and driven above the surface of a stripe patterned magnetic garnet film. An external rotating magnetic field modulates the stray field of the garnet film and generates a translating potential landscape which induces directed particle motion. By varying the ellipticity of the rotating field, we tune the inter-particle interactions from net repulsive to net attractive. For attractive interactions, we show that pairs of particles can approach each other and form stable doublets which afterwards travel along the modulated landscape at a constant mean speed. We measure the strength of the attractive force between the moving particles and propose an analytically tractable model that explains the observations and is in quantitative agreement with experiment.

Modulated phases in a three-dimensional Maier-Saupe model with competing interactions

NASA Astrophysics Data System (ADS)

Bienzobaz, P. F.; Xu, Na; Sandvik, Anders W.

2017-07-01

This work is dedicated to the study of the discrete version of the Maier-Saupe model in the presence of competing interactions. The competition between interactions favoring different orientational ordering produces a rich phase diagram including modulated phases. Using a mean-field approach and Monte Carlo simulations, we show that the proposed model exhibits isotropic and nematic phases and also a series of modulated phases that meet at a multicritical point, a Lifshitz point. Though the Monte Carlo and mean-field phase diagrams show some quantitative disagreements, the Monte Carlo simulations corroborate the general behavior found within the mean-field approximation.

Ocean-Atmosphere Interactions Modulate Irrigation's Climate Impacts

NASA Technical Reports Server (NTRS)

Krakauer, Nir Y.; Puma, Michael J.; Cook, Benjamin I.; Gentine, Pierre; Nazarenko, Larissa

2016-01-01

Numerous studies have focused on the local and regional climate effects of irrigated agriculture and other land cover and land use change (LCLUC) phenomena, but there are few studies on the role of ocean- atmosphere interaction in modulating irrigation climate impacts. Here, we compare simulations with and without interactive sea surface temperatures of the equilibrium effect on climate of contemporary (year 2000) irrigation geographic extent and intensity. We find that ocean-atmosphere interaction does impact the magnitude of global-mean and spatially varying climate impacts, greatly increasing their global reach. Local climate effects in the irrigated regions remain broadly similar, while non-local effects, particularly over the oceans, tend to be larger. The interaction amplifies irrigation-driven standing wave patterns in the tropics and mid-latitudes in our simulations, approximately doubling the global-mean amplitude of surface temperature changes due to irrigation. The fractions of global area experiencing significant annual-mean surface air temperature and precipitation change also approximately double with ocean-atmosphere interaction. Subject to confirmation with other models, these findings imply that LCLUC is an important contributor to climate change even in remote areas such as the Southern Ocean, and that attribution studies should include interactive oceans and need to consider LCLUC, including irrigation, as a truly global forcing that affects climate and the water cycle over ocean as well as land areas.

Nonlinear modulation of interacting between COMT and depression on brain function.

PubMed

Gong, L; He, C; Yin, Y; Ye, Q; Bai, F; Yuan, Y; Zhang, H; Lv, L; Zhang, H; Zhang, Z; Xie, C

2017-09-01

The catechol-O-methyltransferase (COMT) gene is related to dopamine degradation and has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). However, how this gene affects brain function properties in MDD is still unclear. Fifty patients with MDD and 35 cognitively normal participants underwent a resting-state functional magnetic resonance imaging scan. A voxelwise and data-drive global functional connectivity density (gFCD) analysis was used to investigate the main effects and the interactions of disease states and COMT rs4680 gene polymorphism on brain function. We found significant group differences of the gFCD in bilateral fusiform area (FFA), post-central and pre-central cortex, left superior temporal gyrus (STG), rectal and superior temporal gyrus and right ventrolateral prefrontal cortex (vlPFC); abnormal gFCDs in left STG were positively correlated with severity of depression in MDD group. Significant disease×COMT interaction effects were found in the bilateral calcarine gyrus, right vlPFC, hippocampus and thalamus, and left SFG and FFA. Further post-hoc tests showed a nonlinear modulation effect of COMT on gFCD in the development of MDD. Interestingly, an inverted U-shaped modulation was found in the prefrontal cortex (control system) but U-shaped modulations were found in the hippocampus, thalamus and occipital cortex (processing system). Our study demonstrated nonlinear modulation of the interaction between COMT and depression on brain function. These findings expand our understanding of the COMT effect underlying the pathophysiology of MDD. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Working with interpreters: an interactive Web-based learning module.

PubMed

Kalet, Adina; Gany, Francesca; Senter, Lindsay

2002-09-01

Medical students are presented with unique challenges when they care for patients with limited English proficiency. Students must learn a complex set of skills needed to care for patients across cultural and language barriers and to understand the impact of their own attitudes and beliefs about caring for these patients. We developed and piloted a multimedia interactive Web-based module aimed at teaching students effective strategies for working with interpreters and diverse patient populations, and at raising their awareness of important legal, ethical, and cultural issues. First the learner completes a 37-multiple-choice-question (MCQ) pre-test that assesses attitudes, factual knowledge, and ability to analyze written clinical scenarios relevant to the module's content. Learners are then shown a series of professionally produced video vignettes, which reflect diverse patient populations, interpreters, and effectiveness of interpretation strategies (e.g., a Russian-speaking woman with chest pain whose daughter interprets, a medical student interpreting for a Chinese-speaking man using herbal medication, a Haitian woman told of an abnormal mammogram through a trained simultaneous interpreter). In each case, learners submit short answers to on-screen questions analyzing the effectiveness of the interpretation strategies demonstrated. Immediate feedback is given comparing student responses with those of experts. At any time during the module, the learners may view video commentary by legal, ethics, and cultural experts, or access a glossary and Web site links. Students conclude the module by again taking the MCQ test. A final screen compares their pre- and post-MCQ test responses and shows best answers, allowing them to assess their learning. The learners also complete a survey, providing personal cultural information and feedback on the module. All 160 first-year medical students completed the module and evaluated its effectiveness this year. On average, students

Class II HLA interactions modulate genetic risk for multiple sclerosis

PubMed Central

Dilthey, Alexander T; Xifara, Dionysia K; Ban, Maria; Shah, Tejas S; Patsopoulos, Nikolaos A; Alfredsson, Lars; Anderson, Carl A; Attfield, Katherine E; Baranzini, Sergio E; Barrett, Jeffrey; Binder, Thomas M C; Booth, David; Buck, Dorothea; Celius, Elisabeth G; Cotsapas, Chris; D’Alfonso, Sandra; Dendrou, Calliope A; Donnelly, Peter; Dubois, Bénédicte; Fontaine, Bertrand; Fugger, Lars; Goris, An; Gourraud, Pierre-Antoine; Graetz, Christiane; Hemmer, Bernhard; Hillert, Jan; Kockum, Ingrid; Leslie, Stephen; Lill, Christina M; Martinelli-Boneschi, Filippo; Oksenberg, Jorge R; Olsson, Tomas; Oturai, Annette; Saarela, Janna; Søndergaard, Helle Bach; Spurkland, Anne; Taylor, Bruce; Winkelmann, Juliane; Zipp, Frauke; Haines, Jonathan L; Pericak-Vance, Margaret A; Spencer, Chris C A; Stewart, Graeme; Hafler, David A; Ivinson, Adrian J; Harbo, Hanne F; Hauser, Stephen L; De Jager, Philip L; Compston, Alastair; McCauley, Jacob L; Sawcer, Stephen; McVean, Gil

2016-01-01

Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01–HLA-DRB1*15:01 and HLA-DQB1*03:01–HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles. PMID:26343388

Calcium accelerates SNARE-mediated lipid mixing through modulating α-synuclein membrane interaction.

PubMed

Zhang, Zeting; Jiang, Xin; Xu, Danrui; Zheng, Wenwen; Liu, Maili; Li, Conggang

2018-04-04

α-Synuclein is involved in Parkinson's disease, and its interaction with cell membrane is vital to its pathological and physiological functions. We have shown that Ca 2+ can regulate α-synuclein membrane interaction, but the physiological role of Ca 2+ in modulating α-synuclein membrane interaction is still unexplored. Based on the previous findings that α-synuclein inhibits membrane fusion and its inhibitory effect is highly related to its membrane binding, here we employed solution state Nuclear Magnetic Resonance (NMR) spectroscopy and the ensemble fluorescence fusion assay to show that Ca 2+ can modulate the inhibitory effect of α-synuclein on SNARE-mediated membrane fusion through disrupting α-synuclein membrane interaction, resulting in acceleration of SNARE-mediated membrane fusion. These results suggest a modulatory effect of Ca 2+ on membrane mediated normal function of α-synuclein, which of importance for the study of the Parkinson's disease. Copyright © 2018 Elsevier B.V. All rights reserved.

Cell Adhesions: Actin-Based Modules that Mediate Cell-Extracellular Matrix and Cell-Cell Interactions

PubMed Central

Bachir, Alexia; Horwitz, Alan Rick; Nelson, W. James; Bianchini, Julie M.

2018-01-01

Cell adhesions link cells to the extracellular matrix (ECM) and to each other, and depend on interactions with the actin cytoskeleton. Both cell-ECM and cell-cell adhesion sites contain discrete, yet overlapping functional modules. These modules establish physical association with the actin cytoskeleton, locally modulate actin organization and dynamics, and trigger intracellular signaling pathways. Interplay between these modules generates distinct actin architectures that underlie different stages, types, and functions of cell-ECM and cell-cell adhesions. Actomyosin contractility is required to generate mature, stable adhesions, as well as sense and translate the mechanical properties of the cellular environment to changes in cell organization and behavior. In this chapter we discuss the organization and function of different adhesion modules and how they interact with the actin cytoskeleton. We highlight the molecular mechanisms of mechanotransduction in adhesions, and how adhesion molecules mediate crosstalk between cell-ECM and cell-cell adhesion sites. PMID:28679638

Actin-Based Adhesion Modules Mediate Cell Interactions with the Extracellular Matrix and Neighboring Cells.

PubMed

Bachir, Alexia I; Horwitz, Alan Rick; Nelson, W James; Bianchini, Julie M

2017-07-05

Cell adhesions link cells to the extracellular matrix (ECM) and to each other and depend on interactions with the actin cytoskeleton. Both cell-ECM and cell-cell adhesion sites contain discrete, yet overlapping, functional modules. These modules establish physical associations with the actin cytoskeleton, locally modulate actin organization and dynamics, and trigger intracellular signaling pathways. Interplay between these modules generates distinct actin architectures that underlie different stages, types, and functions of cell-ECM and cell-cell adhesions. Actomyosin contractility is required to generate mature, stable adhesions, as well as to sense and translate the mechanical properties of the cellular environment into changes in cell organization and behavior. Here, we review the organization and function of different adhesion modules and how they interact with the actin cytoskeleton. We highlight the molecular mechanisms of mechanotransduction in adhesions and how adhesion molecules mediate cross talk between cell-ECM and cell-cell adhesion sites. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

A conserved Mediator–CDK8 kinase module association regulates Mediator–RNA polymerase II interaction

PubMed Central

Tsai, Kuang-Lei; Sato, Shigeo; Tomomori-Sato, Chieri; Conaway, Ronald C.; Conaway, Joan W.; Asturias, Francisco J.

2013-01-01

The CDK8 kinase module (CKM) is a conserved, dissociable Mediator subcomplex whose component subunits were genetically linked to the RNA polymerase II (RNAPII) carboxy-terminal domain (CTD) and individually recognized as transcriptional repressors before Mediator was identified as a preeminent complex in eukaryotic transcription regulation. We used macromolecular electron microscopy and biochemistry to investigate the subunit organization, structure, and Mediator interaction of the Saccharomyces cerevisiae CKM. We found that interaction of the CKM with Mediator’s Middle module interferes with CTD-dependent RNAPII binding to a previously unknown Middle module CTD-binding site targeted early on in a multi-step holoenzyme formation process. Taken together, our results reveal the basis for CKM repression, clarify the origin of the connection between CKM subunits and the CTD, and suggest that a combination of competitive interactions and conformational changes that facilitate holoenzyme formation underlie the Mediator mechanism. PMID:23563140

Module discovery by exhaustive search for densely connected, co-expressed regions in biomolecular interaction networks.

PubMed

Colak, Recep; Moser, Flavia; Chu, Jeffrey Shih-Chieh; Schönhuth, Alexander; Chen, Nansheng; Ester, Martin

2010-10-25

Computational prediction of functionally related groups of genes (functional modules) from large-scale data is an important issue in computational biology. Gene expression experiments and interaction networks are well studied large-scale data sources, available for many not yet exhaustively annotated organisms. It has been well established, when analyzing these two data sources jointly, modules are often reflected by highly interconnected (dense) regions in the interaction networks whose participating genes are co-expressed. However, the tractability of the problem had remained unclear and methods by which to exhaustively search for such constellations had not been presented. We provide an algorithmic framework, referred to as Densely Connected Biclustering (DECOB), by which the aforementioned search problem becomes tractable. To benchmark the predictive power inherent to the approach, we computed all co-expressed, dense regions in physical protein and genetic interaction networks from human and yeast. An automatized filtering procedure reduces our output which results in smaller collections of modules, comparable to state-of-the-art approaches. Our results performed favorably in a fair benchmarking competition which adheres to standard criteria. We demonstrate the usefulness of an exhaustive module search, by using the unreduced output to more quickly perform GO term related function prediction tasks. We point out the advantages of our exhaustive output by predicting functional relationships using two examples. We demonstrate that the computation of all densely connected and co-expressed regions in interaction networks is an approach to module discovery of considerable value. Beyond confirming the well settled hypothesis that such co-expressed, densely connected interaction network regions reflect functional modules, we open up novel computational ways to comprehensively analyze the modular organization of an organism based on prevalent and largely available large

Novel cholinesterase modulators and their ability to interact with DNA

NASA Astrophysics Data System (ADS)

Janockova, Jana; Gulasova, Zuzana; Musilek, Kamil; Kuca, Kamil; Kozurkova, Maria

2013-11-01

In the present work, an interaction of four cholinesterase modulators (1-4) with calf thymus DNA was studied via spectroscopic techniques (UV-Vis, fluorescent spectroscopy and circular dichroism). From UV-Vis spectroscopic analysis, the binding constants for DNA-pyridinium oximes complexes were calculated (K = 3.5 × 104 to 1.4 × 105 M-1). All these measurements indicated that the compounds behave as effective DNA-interacting agents. Electrophoretic techniques proved that ligand 2 inhibited topoisomerase I at a concentration 5 μM.

Modulation of additive and interactive effects in lexical decision by trial history.

PubMed

Masson, Michael E J; Kliegl, Reinhold

2013-05-01

Additive and interactive effects of word frequency, stimulus quality, and semantic priming have been used to test theoretical claims about the cognitive architecture of word-reading processes. Additive effects among these factors have been taken as evidence for discrete-stage models of word reading. We present evidence from linear mixed-model analyses applied to 2 lexical decision experiments indicating that apparent additive effects can be the product of aggregating over- and underadditive interaction effects that are modulated by recent trial history, particularly the lexical status and stimulus quality of the previous trial's target. Even a simple practice effect expressed as improved response speed across trials was powerfully modulated by the nature of the previous target item. These results suggest that additivity and interaction between factors may reflect trial-to-trial variation in stimulus representations and decision processes rather than fundamental differences in processing architecture.

Molecular imaging of drug-modulated protein-protein interactions in living subjects.

PubMed

Paulmurugan, Ramasamy; Massoud, Tarik F; Huang, Jing; Gambhir, Sanjiv S

2004-03-15

Networks of protein interactions mediate cellular responses to environmental stimuli and direct the execution of many different cellular functional pathways. Small molecules synthesized within cells or recruited from the external environment mediate many protein interactions. The study of small molecule-mediated interactions of proteins is important to understand abnormal signal transduction pathways in cancer and in drug development and validation. In this study, we used split synthetic renilla luciferase (hRLUC) protein fragment-assisted complementation to evaluate heterodimerization of the human proteins FRB and FKBP12 mediated by the small molecule rapamycin. The concentration of rapamycin required for efficient dimerization and that of its competitive binder ascomycin required for dimerization inhibition were studied in cell lines. The system was dually modulated in cell culture at the transcription level, by controlling nuclear factor kappaB promoter/enhancer elements using tumor necrosis factor alpha, and at the interaction level, by controlling the concentration of the dimerizer rapamycin. The rapamycin-mediated dimerization of FRB and FKBP12 also was studied in living mice by locating, quantifying, and timing the hRLUC complementation-based bioluminescence imaging signal using a cooled charged coupled device camera. This split reporter system can be used to efficiently screen small molecule drugs that modulate protein-protein interactions and also to assess drugs in living animals. Both are essential steps in the preclinical evaluation of candidate pharmaceutical agents targeting protein-protein interactions, including signaling pathways in cancer cells.

Mimosa: Mixture Model of Co-expression to Detect Modulators of Regulatory Interaction

NASA Astrophysics Data System (ADS)

Hansen, Matthew; Everett, Logan; Singh, Larry; Hannenhalli, Sridhar

Functionally related genes tend to be correlated in their expression patterns across multiple conditions and/or tissue-types. Thus co-expression networks are often used to investigate functional groups of genes. In particular, when one of the genes is a transcription factor (TF), the co-expression-based interaction is interpreted, with caution, as a direct regulatory interaction. However, any particular TF, and more importantly, any particular regulatory interaction, is likely to be active only in a subset of experimental conditions. Moreover, the subset of expression samples where the regulatory interaction holds may be marked by presence or absence of a modifier gene, such as an enzyme that post-translationally modifies the TF. Such subtlety of regulatory interactions is overlooked when one computes an overall expression correlation. Here we present a novel mixture modeling approach where a TF-Gene pair is presumed to be significantly correlated (with unknown coefficient) in a (unknown) subset of expression samples. The parameters of the model are estimated using a Maximum Likelihood approach. The estimated mixture of expression samples is then mined to identify genes potentially modulating the TF-Gene interaction. We have validated our approach using synthetic data and on three biological cases in cow and in yeast. While limited in some ways, as discussed, the work represents a novel approach to mine expression data and detect potential modulators of regulatory interactions.

O-GlcNAcylation is a key modulator of skeletal muscle sarcomeric morphometry associated to modulation of protein-protein interactions.

PubMed

Lambert, Matthias; Richard, Elodie; Duban-Deweer, Sophie; Krzewinski, Frederic; Deracinois, Barbara; Dupont, Erwan; Bastide, Bruno; Cieniewski-Bernard, Caroline

2016-09-01

The sarcomere structure of skeletal muscle is determined through multiple protein-protein interactions within an intricate sarcomeric cytoskeleton network. The molecular mechanisms involved in the regulation of this sarcomeric organization, essential to muscle function, remain unclear. O-GlcNAcylation, a post-translational modification modifying several key structural proteins and previously described as a modulator of the contractile activity, was never considered to date in the sarcomeric organization. C2C12 skeletal myotubes were treated with Thiamet-G (OGA inhibitor) in order to increase the global O-GlcNAcylation level. Our data clearly showed a modulation of the O-GlcNAc level more sensitive and dynamic in the myofilament-enriched fraction than total proteome. This fine O-GlcNAc level modulation was closely related to changes of the sarcomeric morphometry. Indeed, the dark-band and M-line widths increased, while the I-band width and the sarcomere length decreased according to the myofilament O-GlcNAc level. Some structural proteins of the sarcomere such as desmin, αB-crystallin, α-actinin, moesin and filamin-C have been identified within modulated protein complexes through O-GlcNAc level variations. Their interactions seemed to be changed, especially for desmin and αB-crystallin. For the first time, our findings clearly demonstrate that O-GlcNAcylation, through dynamic regulations of the structural interactome, could be an important modulator of the sarcomeric structure and may provide new insights in the understanding of molecular mechanisms of neuromuscular diseases characterized by a disorganization of the sarcomeric structure. In the present study, we demonstrated a role of O-GlcNAcylation in the sarcomeric structure modulation. Copyright © 2016 Elsevier B.V. All rights reserved.

BioSIGHT: Interactive Visualization Modules for Science Education

NASA Technical Reports Server (NTRS)

Wong, Wee Ling

1998-01-01

Redefining science education to harness emerging integrated media technologies with innovative pedagogical goals represents a unique challenge. The Integrated Media Systems Center (IMSC) is the only engineering research center in the area of multimedia and creative technologies sponsored by the National Science Foundation. The research program at IMSC is focused on developing advanced technologies that address human-computer interfaces, database management, and high-speed network capabilities. The BioSIGHT project at is a demonstration technology project in the area of education that seeks to address how such emerging multimedia technologies can make an impact on science education. The scope of this project will help solidify NASA's commitment for the development of innovative educational resources that promotes science literacy for our students and the general population as well. These issues must be addressed as NASA marches toward the goal of enabling human space exploration that requires an understanding of life sciences in space. The IMSC BioSIGHT lab was established with the purpose of developing a novel methodology that will map a high school biology curriculum into a series of interactive visualization modules that can be easily incorporated into a space biology curriculum. Fundamental concepts in general biology must be mastered in order to allow a better understanding and application for space biology. Interactive visualization is a powerful component that can capture the students' imagination, facilitate their assimilation of complex ideas, and help them develop integrated views of biology. These modules will augment the role of the teacher and will establish the value of student-centered interactivity, both in an individual setting as well as in a collaborative learning environment. Students will be able to interact with the content material, explore new challenges, and perform virtual laboratory simulations. The BioSIGHT effort is truly cross

Metal-graphene heterojunction modulation via H{sub 2} interaction

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

Cadore, A. R., E-mail: alissoncadore@gmail.com, E-mail: lccampos@fisica.ufmg.br; Mania, E.; Lacerda, R. G.

2016-07-18

Combining experiment and theory, we investigate how a naturally created heterojunction (pn junction) at a graphene and metallic contact interface is modulated via interaction with molecular hydrogen (H{sub 2}). Due to an electrostatic interaction, metallic electrodes induce pn junctions in graphene, leading to an asymmetrical resistance in electronic transport for electrons and holes. We report that the asymmetry in the resistance can be tuned in a reversible manner by exposing graphene devices to H{sub 2}. The interaction between the H{sub 2} and graphene occurs solely at the graphene-contact pn junction and induces a modification on the electrostatic interaction between graphenemore » and metallic contacts. We explain the experimental data with theory providing information concerning the length of the heterojunction and how it changes as a function of H{sub 2} adsorption. Our results are valuable for understanding the nature of the metal-graphene interfaces and have potential application for selective sensors of molecular hydrogen.« less

A New Approach to Developing Interactive Software Modules Through Graduate Education

NASA Astrophysics Data System (ADS)

Sanders, Nathan E.; Faesi, Chris; Goodman, Alyssa A.

2014-06-01

Educational technology has attained significant importance as a mechanism for supporting experiential learning of science concepts. However, the growth of this mechanism is limited by the significant time and technical expertise needed to develop such products, particularly in specialized fields of science. We sought to test whether interactive, educational, online software modules can be developed effectively by students as a curriculum component of an advanced science course. We discuss a set of 15 such modules developed by Harvard University graduate students to demonstrate various concepts related to astronomy and physics. Their successful development of these modules demonstrates that online software tools for education and outreach on specialized topics can be produced while simultaneously fulfilling project-based learning objectives. We describe a set of technologies suitable for module development and present in detail four examples of modules developed by the students. We offer recommendations for incorporating educational software development within a graduate curriculum and conclude by discussing the relevance of this novel approach to new online learning environments like edX.

Modulating bacterial and gut mucosal interactions with engineered biofilm matrix proteins.

PubMed

Duraj-Thatte, Anna M; Praveschotinunt, Pichet; Nash, Trevor R; Ward, Frederick R; Joshi, Neel S

2018-02-22

Extracellular appendages play a significant role in mediating communication between bacteria and their host. Curli fibers are a class of bacterial fimbria that is highly amenable to engineering. We demonstrate the use of engineered curli fibers to rationally program interactions between bacteria and components of the mucosal epithelium. Commensal E. coli strains were engineered to produce recombinant curli fibers fused to the trefoil family of human cytokines. Biofilms formed from these strains bound more mucins than those producing wild-type curli fibers, and modulated mucin rheology as well. When treated with bacteria producing the curli-trefoil fusions mammalian cells behaved identically in terms of their migration behavior as when they were treated with the corresponding soluble trefoil factors. Overall, this demonstrates the potential utility of curli fibers as a scaffold for the display of bioactive domains and an untapped approach to rationally modulating host-microbe interactions using bacterial matrix proteins.

Propagation of modulated electron and X-ray beams through matter and interactions with radio-frequency structures

NASA Astrophysics Data System (ADS)

Harris, J. R.; Miller, R. B.

2018-02-01

The generation and evolution of modulated particle beams and their interactions with resonant radiofrequency (RF) structures are of fundamental interest for both particle accelerator and vacuum electronic systems. When the constraint of propagation in a vacuum is removed, the evolution of such beams can be greatly affected by interactions with matter including scattering, absorption, generation of atmospheric plasma, and the production of multiple generations of secondary particles. Here, we study the propagation of 21 MeV and 25 MeV electron beams produced in S-band and L-band linear accelerators, and their interaction with resonant RF structures, under a number of combinations of geometry, including transmission through both air and metal. Both resonant and nonresonant interactions were observed, with the resonant interactions indicating that the RF modulation on the electron beam is at least partially preserved as the beam propagates through air and metal. When significant thicknesses of metal are placed upstream of a resonant structure, preventing any primary beam electrons from reaching the structure, RF signals could still be induced in the structures. This indicated that the RF modulation present on the electron beam was also impressed onto the x-rays generated when the primary electrons were stopped in the metal, and that this RF modulation was also present on the secondary electrons generated when the x-rays struck the resonant structures. The nature of these interactions and their sensitivities to changes in system configurations will be discussed.

Virtual Reality Simulations and Animations in a Web-Based Interactive Manufacturing Engineering Module

ERIC Educational Resources Information Center

Ong, S. K.; Mannan, M. A.

2004-01-01

This paper presents a web-based interactive teaching package that provides a comprehensive and conducive yet dynamic and interactive environment for a module on automated machine tools in the Manufacturing Division at the National University of Singapore. The use of Internet technologies in this teaching tool makes it possible to conjure…

Designing high-quality interactive multimedia learning modules.

PubMed

Huang, Camillan

2005-01-01

Modern research has broadened scientific knowledge and revealed the interdisciplinary nature of the sciences. For today's students, this advance translates to learning a more diverse range of concepts, usually in less time, and without supporting resources. Students can benefit from technology-enhanced learning supplements that unify concepts and are delivered on-demand over the Internet. Such supplements, like imaging informatics databases, serve as innovative references for biomedical information, but could improve their interaction interfaces to support learning. With information from these digital datasets, multimedia learning tools can be designed to transform learning into an active process where students can visualize relationships over time, interact with dynamic content, and immediately test their knowledge. This approach bridges knowledge gaps, fosters conceptual understanding, and builds problem-solving and critical thinking skills-all essential components to informatics training for science and medicine. Additional benefits include cost-free access and ease of dissemination over the Internet or CD-ROM. However, current methods for the design of multimedia learning modules are not standardized and lack strong instructional design. Pressure from administrators at the top and students from the bottom are pushing faculty to use modern technology to address the learning needs and expectations of contemporary students. Yet, faculty lack adequate support and training to adopt this new approach. So how can faculty learn to create educational multimedia materials for their students? This paper provides guidelines on best practices in educational multimedia design, derived from the Virtual Labs Project at Stanford University. The development of a multimedia module consists of five phases: (1) understand the learning problem and the users needs; (2) design the content to harness the enabling technologies; (3) build multimedia materials with web style standards and

Perilipin polymorphism interacts with dietary carbohydrates to modulate anthropometric traits in Hispanics of Caribbean origin

USDA-ARS?s Scientific Manuscript database

Perilipin (PLIN) is the major protein surrounding lipid droplets in adipocytes and regulates adipocyte metabolism by modulating the interaction between lipases and triacylglycerol stores. Associations between PLIN gene polymorphisms and obesity risk have been described, but interactions with die...

Effects of Web-Based Interactive Modules on Engineering Students' Learning Motivations

ERIC Educational Resources Information Center

Bai, Haiyan; Aman, Amjad; Xu, Yunjun; Orlovskaya, Nina; Zhou, Mingming

2016-01-01

The purpose of this study is to assess the impact of a newly developed modules, Interactive Web-Based Visualization Tools for Gluing Undergraduate Fuel Cell Systems Courses system (IGLU), on learning motivations of engineering students using two samples (n[subscript 1] = 144 and n[subscript 2] = 135) from senior engineering classes. The…

Neuroticism modulates the effects of intranasal vasopressin treatment on the neural response to positive and negative social interactions.

PubMed

Feng, Chunliang; DeMarco, Ashley C; Haroon, Ebrahim; Rilling, James K

2015-07-01

Neuroticism is a fundamental personality trait associated with proneness to feel negative affect. Here we ask how Neuroticism influences the neural response to positive and negative social interactions and how Neuroticism modulates the effect of intranasal oxytocin (OT) and vasopressin (AVP) on the neural response to social interactions. In a double-blind, placebo-controlled study, 153 male participants were randomized to receive 24 IU intranasal OT, 20 IU AVP or placebo. Afterwards, they were imaged with fMRI while playing an iterated Prisoner's Dilemma Game. On a different day, subjects completed the NEO personality inventory to measure Neuroticism. Neuroticism was positively correlated with the neural response to negative social interactions in the anterior cingulate cortex/medial prefrontal cortex and with the neural response to positive social interactions in the insula, indicating that Neuroticism modulates neuropsychological processing of both negative and positive social interactions. Neuroticism did not modulate the effect of intranasal OT treatment on the neural response to either positive or negative social interactions. On the other hand, AVP treatment significantly interacted with Neuroticism to modulate the BOLD response to both positive and negative social interactions. Specifically, AVP increased anterior cingulate cortex/medial prefrontal cortex and lateral temporal lobe responses to negative social interactions to a greater extent in participants scoring high rather than low on Neuroticism. AVP also increased the insula response to positive social interactions to a greater extent in participants scoring high rather than low on Neuroticism. These results imply that AVP may increase emotion regulation in response to negative social interactions and the salience of positive social interactions to a greater extent in individuals high compared to low in Neuroticism. The current findings urge caution against uniform clinical application of nonapeptides

Chromatin loops as allosteric modulators of enhancer-promoter interactions.

PubMed

Doyle, Boryana; Fudenberg, Geoffrey; Imakaev, Maxim; Mirny, Leonid A

2014-10-01

The classic model of eukaryotic gene expression requires direct spatial contact between a distal enhancer and a proximal promoter. Recent Chromosome Conformation Capture (3C) studies show that enhancers and promoters are embedded in a complex network of looping interactions. Here we use a polymer model of chromatin fiber to investigate whether, and to what extent, looping interactions between elements in the vicinity of an enhancer-promoter pair can influence their contact frequency. Our equilibrium polymer simulations show that a chromatin loop, formed by elements flanking either an enhancer or a promoter, suppresses enhancer-promoter interactions, working as an insulator. A loop formed by elements located in the region between an enhancer and a promoter, on the contrary, facilitates their interactions. We find that different mechanisms underlie insulation and facilitation; insulation occurs due to steric exclusion by the loop, and is a global effect, while facilitation occurs due to an effective shortening of the enhancer-promoter genomic distance, and is a local effect. Consistently, we find that these effects manifest quite differently for in silico 3C and microscopy. Our results show that looping interactions that do not directly involve an enhancer-promoter pair can nevertheless significantly modulate their interactions. This phenomenon is analogous to allosteric regulation in proteins, where a conformational change triggered by binding of a regulatory molecule to one site affects the state of another site.

Modulation by clamping: Kv4 and KChIP interactions.

PubMed

Wang, Kewei

2008-10-01

The rapidly inactivating (A-type) potassium channels regulate membrane excitability that defines the fundamental mechanism of neuronal functions such as pain signaling. Cytosolic Kv channel-interacting proteins KChIPs that belong to neuronal calcium sensor (NCS) family of calcium binding EF-hand proteins co-assemble with Kv4 (Shal) alpha subunits to form a native complex that encodes major components of neuronal somatodendritic A-type K+ current, I(SA), in neurons and transient outward current, I(TO), in cardiac myocytes. The specific binding of auxiliary KChIPs to the Kv4 N-terminus results in modulation of gating properties, surface expression and subunit assembly of Kv4 channels. Here, I attempt to emphasize the interaction between KChIPs and Kv4 based on recent progress made in understanding the structure complex in which a single KChIP1 molecule laterally clamps two neighboring Kv4.3 N-termini in a 4:4 manner. Greater insights into molecular mechanism between KChIPs and Kv4 interaction may provide therapeutic potentials of designing compounds aimed at disrupting the protein-protein interaction for treatment of membrane excitability-related disorders.

Ligand-Receptor Interaction Modulates the Energy Landscape of Enzyme-Instructed Self-Assembly of Small Molecules.

PubMed

Haburcak, Richard; Shi, Junfeng; Du, Xuewen; Yuan, Dan; Xu, Bing

2016-11-30

The concurrence of enzymatic reaction and ligand-receptor interactions is common for proteins, but rare for small molecules and has yet to be explored. Here we show that ligand-receptor interaction modulates the morphology of molecular assemblies formed by enzyme-instructed assembly of small molecules. While the absence of ligand-receptor interaction allows enzymatic dephosphorylation of a precursor to generate the hydrogelator that self-assembles to form long nanofibers, the presence of the ligand-receptor interaction biases the pathway to form precipitous aggregates containing short nanofibers. While the hydrogelators self-assemble to form nanofibers or nanoribbons that are unable to bind with the ligand (i.e., vancomycin), the addition of surfactant breaks up the assemblies to restore the ligand-receptor interaction. In addition, an excess amount of the ligands can disrupt the nanofibers and result in the precipitates. As the first example of the use of ligand-receptor interaction to modulate the kinetics of enzymatic self-assembly, this work not only provides a solution to evaluate the interaction between aggregates and target molecules but also offers new insight for understanding the emergent behavior of sophisticated molecular systems having multiple and parallel processes.

Cooperative DNA Recognition Modulated by an Interplay between Protein-Protein Interactions and DNA-Mediated Allostery

PubMed Central

Merino, Felipe; Bouvier, Benjamin; Cojocaru, Vlad

2015-01-01

Highly specific transcriptional regulation depends on the cooperative association of transcription factors into enhanceosomes. Usually, their DNA-binding cooperativity originates from either direct interactions or DNA-mediated allostery. Here, we performed unbiased molecular simulations followed by simulations of protein-DNA unbinding and free energy profiling to study the cooperative DNA recognition by OCT4 and SOX2, key components of enhanceosomes in pluripotent cells. We found that SOX2 influences the orientation and dynamics of the DNA-bound configuration of OCT4. In addition SOX2 modifies the unbinding free energy profiles of both DNA-binding domains of OCT4, the POU specific and POU homeodomain, despite interacting directly only with the first. Thus, we demonstrate that the OCT4-SOX2 cooperativity is modulated by an interplay between protein-protein interactions and DNA-mediated allostery. Further, we estimated the change in OCT4-DNA binding free energy due to the cooperativity with SOX2, observed a good agreement with experimental measurements, and found that SOX2 affects the relative DNA-binding strength of the two OCT4 domains. Based on these findings, we propose that available interaction partners in different biological contexts modulate the DNA exploration routes of multi-domain transcription factors such as OCT4. We consider the OCT4-SOX2 cooperativity as a paradigm of how specificity of transcriptional regulation is achieved through concerted modulation of protein-DNA recognition by different types of interactions. PMID:26067358

Cooperative DNA Recognition Modulated by an Interplay between Protein-Protein Interactions and DNA-Mediated Allostery.

PubMed

Merino, Felipe; Bouvier, Benjamin; Cojocaru, Vlad

2015-06-01

Highly specific transcriptional regulation depends on the cooperative association of transcription factors into enhanceosomes. Usually, their DNA-binding cooperativity originates from either direct interactions or DNA-mediated allostery. Here, we performed unbiased molecular simulations followed by simulations of protein-DNA unbinding and free energy profiling to study the cooperative DNA recognition by OCT4 and SOX2, key components of enhanceosomes in pluripotent cells. We found that SOX2 influences the orientation and dynamics of the DNA-bound configuration of OCT4. In addition SOX2 modifies the unbinding free energy profiles of both DNA-binding domains of OCT4, the POU specific and POU homeodomain, despite interacting directly only with the first. Thus, we demonstrate that the OCT4-SOX2 cooperativity is modulated by an interplay between protein-protein interactions and DNA-mediated allostery. Further, we estimated the change in OCT4-DNA binding free energy due to the cooperativity with SOX2, observed a good agreement with experimental measurements, and found that SOX2 affects the relative DNA-binding strength of the two OCT4 domains. Based on these findings, we propose that available interaction partners in different biological contexts modulate the DNA exploration routes of multi-domain transcription factors such as OCT4. We consider the OCT4-SOX2 cooperativity as a paradigm of how specificity of transcriptional regulation is achieved through concerted modulation of protein-DNA recognition by different types of interactions.

Online interactive teaching modules enhance quantitative proficiency of introductory biology students.

PubMed

Thompson, Katerina V; Nelson, Kären C; Marbach-Ad, Gili; Keller, Michael; Fagan, William F

2010-01-01

There is widespread agreement within the scientific and education communities that undergraduate biology curricula fall short in providing students with the quantitative and interdisciplinary problem-solving skills they need to obtain a deep understanding of biological phenomena and be prepared fully to contribute to future scientific inquiry. MathBench Biology Modules were designed to address these needs through a series of interactive, Web-based modules that can be used to supplement existing course content across the biological sciences curriculum. The effect of the modules was assessed in an introductory biology course at the University of Maryland. Over the course of the semester, students showed significant increases in quantitative skills that were independent of previous math course work. Students also showed increased comfort with solving quantitative problems, whether or not they ultimately arrived at the correct answer. A survey of spring 2009 graduates indicated that those who had experienced MathBench in their course work had a greater appreciation for the role of mathematics in modern biology than those who had not used MathBench. MathBench modules allow students from diverse educational backgrounds to hone their quantitative skills, preparing them for more complex mathematical approaches in upper-division courses.

Oxytocin receptors (OXTR) and early parental care: An interaction that modulates psychiatric disorders.

PubMed

Cataldo, Ilaria; Azhari, Atiqah; Lepri, Bruno; Esposito, Gianluca

2017-10-21

Oxytocin plays an important role in the modulation of social behavior in both typical and atypical contexts. Also, the quality of early parental care sets the foundation for long-term psychosocial development. Here, we review studies that investigated how oxytocin receptor (OXTR) interacts with early parental care experiences to influence the development of psychiatric disorders. Using Pubmed, Scopus and PsycInfo databases, we utilized the keyword "OXTR" before subsequently searching for specific OXTR single nucleotide polymorphisms (SNPs), generating a list of 598 studies in total. The papers were catalogued in a database and filtered for gene-environment interaction, psychiatric disorders and involvement of parental care. In particular, rs53576 and rs2254298 were found to be significantly involved in gene-environment interactions that modulated risk for psychopathology and the following psychiatric disorders: disruptive behavior, depression, anxiety, eating disorder and borderline personality disorder. These results illustrate the importance of OXTR in mediating the impact of parental care on the emergence of psychopathology. Copyright © 2017 Elsevier Ltd. All rights reserved.

BioSIGHT: Interactive Visualization Modules for Science Education

NASA Technical Reports Server (NTRS)

Wong, Wee Ling

1998-01-01

Redefining science education to harness emerging integrated media technologies with innovative pedagogical goals represents a unique challenge. The Integrated Media Systems Center (IMSC) is the only engineering research center in the area of multimedia and creative technologies sponsored by the National Science Foundation. The research program at IMSC is focused on developing advanced technologies that address human-computer interfaces, database management, and high- speed network capabilities. The BioSIGHT project at IMSC is a demonstration technology project in the area of education that seeks to address how such emerging multimedia technologies can make an impact on science education. The scope of this project will help solidify NASA's commitment for the development of innovative educational resources that promotes science literacy for our students and the general population as well. These issues must be addressed as NASA marches towards the goal of enabling human space exploration that requires an understanding of life sciences in space. The IMSC BioSIGHT lab was established with the purpose of developing a novel methodology that will map a high school biology curriculum into a series of interactive visualization modules that can be easily incorporated into a space biology curriculum. Fundamental concepts in general biology must be mastered in order to allow a better understanding and application for space biology. Interactive visualization is a powerful component that can capture the students' imagination, facilitate their assimilation of complex ideas, and help them develop integrated views of biology. These modules will augment the role of the teacher and will establish the value of student-centered interactivity, both in an individual setting as well as in a collaborative learning environment. Students will be able to interact with the content material, explore new challenges, and perform virtual laboratory simulations. The BioSIGHT effort is truly cross

PIPE: a protein–protein interaction passage extraction module for BioCreative challenge

PubMed Central

Chu, Chun-Han; Su, Yu-Chen; Chen, Chien Chin; Hsu, Wen-Lian

2016-01-01

Identifying the interactions between proteins mentioned in biomedical literatures is one of the frequently discussed topics of text mining in the life science field. In this article, we propose PIPE, an interaction pattern generation module used in the Collaborative Biocurator Assistant Task at BioCreative V (http://www.biocreative.org/) to capture frequent protein-protein interaction (PPI) patterns within text. We also present an interaction pattern tree (IPT) kernel method that integrates the PPI patterns with convolution tree kernel (CTK) to extract PPIs. Methods were evaluated on LLL, IEPA, HPRD50, AIMed and BioInfer corpora using cross-validation, cross-learning and cross-corpus evaluation. Empirical evaluations demonstrate that our method is effective and outperforms several well-known PPI extraction methods. Database URL: PMID:27524807

Denaturing high-performance liquid chromatography for mutation detection and genotyping.

PubMed

Fackenthal, Donna Lee; Chen, Pei Xian; Howe, Ted; Das, Soma

2013-01-01

Denaturing high-performance liquid chromatography (DHPLC) is an accurate and efficient screening technique used for detecting DNA sequence changes by heteroduplex analysis. It can also be used for genotyping of single nucleotide polymorphisms (SNPs). The high sensitivity of DHPLC has made this technique one of the most reliable approaches to mutation analysis and, therefore, used in various areas of genetics, both in the research and clinical arena. This chapter describes the methods used for mutation detection analysis and the genotyping of SNPs by DHPLC on the WAVE™ system from Transgenomic Inc. ("WAVE" and "DNASep" are registered trademarks, and "Navigator" is a trademark, of Transgenomic, used with permission. All other trademarks are property of the respective owners).

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

PubMed

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

Interacting Brain Systems Modulate Memory Consolidation

PubMed Central

McIntyre, Christa K.; McGaugh, James L.; Williams, Cedric L.

2011-01-01

Emotional arousal influences the consolidation of long-term memory. This review discusses experimental approaches and relevant findings that provide the foundation for current understanding of coordinated interactions between arousal activated peripheral hormones and the brain processes that modulate memory formation. Rewarding or aversive experiences release the stress hormones epinephrine (adrenalin) and glucocorticoids from the adrenal glands into the bloodstream. The effect of these hormones on memory consolidation depends upon binding of norepinephrine to beta-adrenergic receptors in the basolateral complex of the amygdala (BLA). Much evidence indicates that the stress hormones influence release of norepinephrine in the BLA through peripheral actions on the vagus nerve which stimulates, through polysynaptic connections, cells of the locus coeruleus to release norepinephrine. The BLA influences memory storage by actions on synapses, distributed throughout the brain, that are engaged in sensory and cognitive processing at the time of amygdala activation. The implications of the activation of these stress-activated memory processes are discussed in relation to stress-related memory disorders. PMID:22085800

A Novel Interhemispheric Interaction: Modulation of Neuronal Cooperativity in the Visual Areas

PubMed Central

Carmeli, Cristian; Lopez-Aguado, Laura; Schmidt, Kerstin E.; De Feo, Oscar; Innocenti, Giorgio M.

2007-01-01

Background The cortical representation of the visual field is split along the vertical midline, with the left and the right hemi-fields projecting to separate hemispheres. Connections between the visual areas of the two hemispheres are abundant near the representation of the visual midline. It was suggested that they re-establish the functional continuity of the visual field by controlling the dynamics of the responses in the two hemispheres. Methods/Principal Findings To understand if and how the interactions between the two hemispheres participate in processing visual stimuli, the synchronization of responses to identical or different moving gratings in the two hemi-fields were studied in anesthetized ferrets. The responses were recorded by multiple electrodes in the primary visual areas and the synchronization of local field potentials across the electrodes were analyzed with a recent method derived from dynamical system theory. Inactivating the visual areas of one hemisphere modulated the synchronization of the stimulus-driven activity in the other hemisphere. The modulation was stimulus-specific and was consistent with the fine morphology of callosal axons in particular with the spatio-temporal pattern of activity that axonal geometry can generate. Conclusions/Significance These findings describe a new kind of interaction between the cerebral hemispheres and highlight the role of axonal geometry in modulating aspects of cortical dynamics responsible for stimulus detection and/or categorization. PMID:18074012

Online Interactive Teaching Modules Enhance Quantitative Proficiency of Introductory Biology Students

PubMed Central

Nelson, Kären C.; Marbach-Ad, Gili; Keller, Michael; Fagan, William F.

2010-01-01

There is widespread agreement within the scientific and education communities that undergraduate biology curricula fall short in providing students with the quantitative and interdisciplinary problem-solving skills they need to obtain a deep understanding of biological phenomena and be prepared fully to contribute to future scientific inquiry. MathBench Biology Modules were designed to address these needs through a series of interactive, Web-based modules that can be used to supplement existing course content across the biological sciences curriculum. The effect of the modules was assessed in an introductory biology course at the University of Maryland. Over the course of the semester, students showed significant increases in quantitative skills that were independent of previous math course work. Students also showed increased comfort with solving quantitative problems, whether or not they ultimately arrived at the correct answer. A survey of spring 2009 graduates indicated that those who had experienced MathBench in their course work had a greater appreciation for the role of mathematics in modern biology than those who had not used MathBench. MathBench modules allow students from diverse educational backgrounds to hone their quantitative skills, preparing them for more complex mathematical approaches in upper-division courses. PMID:20810959

BinTree Seeking: A Novel Approach to Mine Both Bi-Sparse and Cohesive Modules in Protein Interaction Networks

PubMed Central

Shen, Hong-Bin

2011-01-01

Modern science of networks has brought significant advances to our understanding of complex systems biology. As a representative model of systems biology, Protein Interaction Networks (PINs) are characterized by a remarkable modular structures, reflecting functional associations between their components. Many methods were proposed to capture cohesive modules so that there is a higher density of edges within modules than those across them. Recent studies reveal that cohesively interacting modules of proteins is not a universal organizing principle in PINs, which has opened up new avenues for revisiting functional modules in PINs. In this paper, functional clusters in PINs are found to be able to form unorthodox structures defined as bi-sparse module. In contrast to the traditional cohesive module, the nodes in the bi-sparse module are sparsely connected internally and densely connected with other bi-sparse or cohesive modules. We present a novel protocol called the BinTree Seeking (BTS) for mining both bi-sparse and cohesive modules in PINs based on Edge Density of Module (EDM) and matrix theory. BTS detects modules by depicting links and nodes rather than nodes alone and its derivation procedure is totally performed on adjacency matrix of networks. The number of modules in a PIN can be automatically determined in the proposed BTS approach. BTS is tested on three real PINs and the results demonstrate that functional modules in PINs are not dominantly cohesive but can be sparse. BTS software and the supporting information are available at: www.csbio.sjtu.edu.cn/bioinf/BTS/. PMID:22140454

Ingroup favoritism or the black sheep effect: Perceived intentions modulate subjective responses to aggressive interactions.

PubMed

Wang, Lei; Zheng, Jiehui; Meng, Liang; Lu, Qiang; Ma, Qingguo

2016-07-01

Social categorization plays an important role in provoking the victim's responses to aggressive interactions. Pioneering studies suggested that uncertainty in the perpetrator's hostile intention influences whether ingroup favoritism or the black sheep effect (ingroup strictness) will be manifested to a greater extent. However, when the hostile intention is ambiguous, subjective perception of the perpetrator's intention may still be quite different due to the inherent information gap between participants, and this discrepancy in perceived intentions may further modulate subjective responses to social aggression. In the present study, subjects played as responders of the Ultimatum Game, and received varied offers proposed by either ingroup or outgroup members. Electrophysiological results showed that, when proposers were perceived to be intentional, unfair offers from ingroups elicited significantly larger Feedback-related Negativity (FRN) than those from outgroups, potentially providing neural evidence for the black sheep effect. The opposite FRN pattern was observed when proposers were perceived to be unintentional, which might suggest ingroup favoritism. Interestingly, despite contrary neural patterns, perceived intentions did not modulate behavioral response to aggressive interactions. Thus, converging results suggested that, when the perpetrator's hostile intention remained ambiguous, perceived intentions modulated the victim's electrophysiological response while not the rational behavioral response to aggressive interactions. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Interactive E-learning module in pharmacology: a pilot project at a rural medical college in India.

PubMed

Gaikwad, Nitin; Tankhiwale, Suresh

2014-01-01

Many medical educators are experimenting with innovative ways of E-learning. E-learning provides opportunities to students for self-directed learning in addition to other advantages. In this study, we designed and evaluated an interactive E-learning module in pharmacology for effectiveness, acceptability and feasibility, with the aim of promoting active learning in this fact-filled subject. A quasi-experimental single-group pre-test/post-test study was conducted with fourth-semester students of the second professionals course (II MBBS), selected using non-probability convenience sampling method. An E-learning module in endocrine pharmacology was designed to comprise three units of interactive PowerPoint presentations. The pre-validated presentations were uploaded on the website according to a predefined schedule and the 42 registered students were encouraged to self-learning using these interactive presentations. Cognitive gain was assessed using an online pre- and post-test for each unit. Students' perceptions were recorded using an online feedback questionnaire on a 5-point Likert scale. Finally, focused group discussion was conducted to further explore students' views on E-learning activity. Significant attrition was observed during the E-learning activity. Of the 42 registered students, only 16 students completed the entire E-learning module. The summed average score of all three units (entire module) was increased significantly from 38.42 % (summed average pre-test score: 11.56/30 ± 2.90) to 66.46 % (summed average post-test score: 19.94/30 ± 6.13). The class-average normalized gain for the entire module was 0.4542 (45.42). The students accepted this E-learning activity well as they perceived it to be innovative, convenient, flexible and useful. The average rating was between 4 (agree) and 5 (strongly agree). The interactive E-learning module in pharmacology was moderately effective and well perceived by the students. The simple, cost-effective and

Modulation of 14-3-3/Phosphotarget Interaction by Physiological Concentrations of Phosphate and Glycerophosphates

PubMed Central

Sluchanko, Nikolai N.; Chebotareva, Natalia A.; Gusev, Nikolai B.

2013-01-01

Molecular mechanisms governing selective binding of a huge number of various phosphorylated protein partners to 14-3-3 remain obscure. Phosphate can bind to 14-3-3 and therefore being present at high intracellular concentration, which undergoes significant changes under physiological conditions, phosphate can theoretically regulate interaction of 14-3-3 with phosphorylated targets. In order to check this hypothesis we analyzed effect of phosphate and other natural abundant anions on interaction of 14-3-3 with phosphorylated human small heat shock protein HspB6 (Hsp20) participating in regulation of different intracellular processes. Inorganic phosphate, glycerol-1-phosphate and glycerol-2-phosphate at physiologically relevant concentrations (5-15 mM) significantly destabilized complexes formed by 14-3-3ζ and phosphorylated HspB6 (pHspB6), presumably, via direct interaction with the substrate-binding site of 14-3-3. Phosphate also destabilized complexes between pHspB6 and 14-3-3γ or the monomeric mutant form of 14-3-3ζ. Inorganic sulfate and pyrophosphate were less effective in modulation of 14-3-3 interaction with its target protein. The inhibitory effect of all anions on pHspB6/14-3-3 interaction was concentration-dependent. It is hypothesized that physiological changes in phosphate anions concentration can modulate affinity and specificity of interaction of 14-3-3 with its multiple targets and therefore the actual phosphointeractome of 14-3-3. PMID:23977325

Modulation of 14-3-3/phosphotarget interaction by physiological concentrations of phosphate and glycerophosphates.

PubMed

Sluchanko, Nikolai N; Chebotareva, Natalia A; Gusev, Nikolai B

2013-01-01

Molecular mechanisms governing selective binding of a huge number of various phosphorylated protein partners to 14-3-3 remain obscure. Phosphate can bind to 14-3-3 and therefore being present at high intracellular concentration, which undergoes significant changes under physiological conditions, phosphate can theoretically regulate interaction of 14-3-3 with phosphorylated targets. In order to check this hypothesis we analyzed effect of phosphate and other natural abundant anions on interaction of 14-3-3 with phosphorylated human small heat shock protein HspB6 (Hsp20) participating in regulation of different intracellular processes. Inorganic phosphate, glycerol-1-phosphate and glycerol-2-phosphate at physiologically relevant concentrations (5-15 mM) significantly destabilized complexes formed by 14-3-3ζ and phosphorylated HspB6 (pHspB6), presumably, via direct interaction with the substrate-binding site of 14-3-3. Phosphate also destabilized complexes between pHspB6 and 14-3-3γ or the monomeric mutant form of 14-3-3ζ. Inorganic sulfate and pyrophosphate were less effective in modulation of 14-3-3 interaction with its target protein. The inhibitory effect of all anions on pHspB6/14-3-3 interaction was concentration-dependent. It is hypothesized that physiological changes in phosphate anions concentration can modulate affinity and specificity of interaction of 14-3-3 with its multiple targets and therefore the actual phosphointeractome of 14-3-3.

Sensing small molecule interactions with lipid membranes by local pH modulation.

PubMed

Huang, Da; Zhao, Tao; Xu, Wei; Yang, Tinglu; Cremer, Paul S

2013-11-05

Herein, we utilized a label-free sensing platform based on pH modulation to detect the interactions between tetracaine, a positively charged small molecule used as a local anesthetic, and planar supported lipid bilayers (SLBs). The SLBs were patterned inside a flow cell, allowing for various concentrations of tetracaine to be introduced over the surface in a buffer solution. Studies with membranes containing POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) yielded an equilibrium dissociation constant value of Kd = 180 ± 47 μm for this small molecule-membrane interaction. Adding cholesterol to the SLBs decreased the affinity between tetracaine and the bilayers, while this interaction tightened when POPE (1-hexadecanoyl-2-(9-Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine) was added. Studies were also conducted with three negatively charged membrane lipids, POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt)), POPS (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine (sodium salt)), and ganglioside GM1. All three measurements gave rise to a similar tightening of the apparent Kd value compared with pure POPC membranes. The lack of chemical specificity with the identity of the negatively charged lipid indicated that the tightening was largely electrostatic. Through a direct comparison with ITC measurements, it was found that the pH modulation sensor platform offers a facile, inexpensive, highly sensitive, and rapid method for the detection of interactions between putative drug candidates and lipid bilayers. As such, this technique may potentially be exploited as a screen for drug development and analysis.

Aldolase directly interacts with ARNO and modulates cell morphology and acidic vesicle distribution

PubMed Central

Merkulova, Maria; Hurtado-Lorenzo, Andrés; Hosokawa, Hiroyuki; Zhuang, Zhenjie; Brown, Dennis; Ausiello, Dennis A.

2011-01-01

Previously, we demonstrated that the vacuolar-type H+-ATPase (V-ATPase) a2-subunit functions as an endosomal pH sensor that interacts with the ADP-ribosylation factor (Arf) guanine nucleotide exchange factor, ARNO. In the present study, we showed that ARNO directly interacts not only with the a2-subunit but with all a-isoforms (a1–a4) of the V-ATPase, indicating a widespread regulatory interaction between V-ATPase and Arf GTPases. We then extended our search for other ARNO effectors that may modulate V-ATPase-dependent vesicular trafficking events and actin cytoskeleton remodeling. Pull-down experiments using cytosol of mouse proximal tubule cells (MTCs) showed that ARNO interacts with aldolase, but not with other enzymes of the glycolytic pathway. Direct interaction of aldolase with the pleckstrin homology domain of ARNO was revealed by pull-down assays using recombinant proteins, and surface plasmon resonance revealed their high avidity interaction with a dissociation constant: KD = 2.84 × 10−10 M. MTC cell fractionation revealed that aldolase is also associated with membranes of early endosomes. Functionally, aldolase knockdown in HeLa cells produced striking morphological changes accompanied by long filamentous cell protrusions and acidic vesicle redistribution. However, the 50% knockdown we achieved did not modulate the acidification capacity of endosomal/lysosomal compartments. Finally, a combination of small interfering RNA knockdown and overexpression revealed that the expression of aldolase is inversely correlated with gelsolin levels in HeLa cells. In summary, we have shown that aldolase forms a complex with ARNO/Arf6 and the V-ATPase and that it may contribute to remodeling of the actin cytoskeleton and/or the trafficking and redistribution of V-ATPase-dependent acidic compartments via a combination of protein-protein interaction and gene expression mechanisms. PMID:21307348

Disentangling the co-structure of multilayer interaction networks: degree distribution and module composition in two-layer bipartite networks.

PubMed

Astegiano, Julia; Altermatt, Florian; Massol, François

2017-11-13

Species establish different interactions (e.g. antagonistic, mutualistic) with multiple species, forming multilayer ecological networks. Disentangling network co-structure in multilayer networks is crucial to predict how biodiversity loss may affect the persistence of multispecies assemblages. Existing methods to analyse multilayer networks often fail to consider network co-structure. We present a new method to evaluate the modular co-structure of multilayer networks through the assessment of species degree co-distribution and network module composition. We focus on modular structure because of its high prevalence among ecological networks. We apply our method to two Lepidoptera-plant networks, one describing caterpillar-plant herbivory interactions and one representing adult Lepidoptera nectaring on flowers, thereby possibly pollinating them. More than 50% of the species established either herbivory or visitation interactions, but not both. These species were over-represented among plants and lepidopterans, and were present in most modules in both networks. Similarity in module composition between networks was high but not different from random expectations. Our method clearly delineates the importance of interpreting multilayer module composition similarity in the light of the constraints imposed by network structure to predict the potential indirect effects of species loss through interconnected modular networks.

Drug-Like Protein–Protein Interaction Modulators: Challenges and Opportunities for Drug Discovery and Chemical Biology

PubMed Central

Villoutreix, Bruno O; Kuenemann, Melaine A; Poyet, Jean-Luc; Bruzzoni-Giovanelli, Heriberto; Labbé, Céline; Lagorce, David; Sperandio, Olivier; Miteva, Maria A

2014-01-01

Fundamental processes in living cells are largely controlled by macromolecular interactions and among them, protein–protein interactions (PPIs) have a critical role while their dysregulations can contribute to the pathogenesis of numerous diseases. Although PPIs were considered as attractive pharmaceutical targets already some years ago, they have been thus far largely unexploited for therapeutic interventions with low molecular weight compounds. Several limiting factors, from technological hurdles to conceptual barriers, are known, which, taken together, explain why research in this area has been relatively slow. However, this last decade, the scientific community has challenged the dogma and became more enthusiastic about the modulation of PPIs with small drug-like molecules. In fact, several success stories were reported both, at the preclinical and clinical stages. In this review article, written for the 2014 International Summer School in Chemoinformatics (Strasbourg, France), we discuss in silico tools (essentially post 2012) and databases that can assist the design of low molecular weight PPI modulators (these tools can be found at www.vls3d.com). We first introduce the field of protein–protein interaction research, discuss key challenges and comment recently reported in silico packages, protocols and databases dedicated to PPIs. Then, we illustrate how in silico methods can be used and combined with experimental work to identify PPI modulators. PMID:25254076

In-Depth Study of the Interaction, Sensitivity, and Gating Modulation by PUFAs on K+ Channels; Interaction and New Targets

PubMed Central

Moreno, Cristina; de la Cruz, Alicia; Valenzuela, Carmen

2016-01-01

Voltage gated potassium channels (KV) are membrane proteins that allow selective flow of K+ ions in a voltage-dependent manner. These channels play an important role in several excitable cells as neurons, cardiomyocytes, and vascular smooth muscle. Over the last 20 years, it has been shown that omega-3 polyunsaturated fatty acids (PUFAs) enhance or decrease the activity of several cardiac KV channels. PUFAs-dependent modulation of potassium ion channels has been reported to be cardioprotective. However, the precise cellular mechanism underlying the cardiovascular benefits remained unclear in part because new PUFAs targets and signaling pathways continue being discovered. In this review, we will focus on recent data available concerning the following aspects of the KV channel modulation by PUFAs: (i) the exact residues involved in PUFAs-KV channels interaction; (ii) the structural PUFAs determinants important for their effects on KV channels; (iii) the mechanism of the gating modulation of KV channels and, finally, (iv) the PUFAs modulation of a few new targets present in smooth muscle cells (SMC), KCa1.1, K2P, and KATP channels, involved in vascular relaxation. PMID:27933000

Use of live interactive webcasting for an international postgraduate module in ehealth: case study evaluation.

PubMed

Jones, Ray B; Maramba, Inocencio; Boulos, Maged N Kamel; Alexander, Tara

2009-11-13

Producing "traditional" e-learning can be time consuming, and in a topic such as eHealth, it may have a short shelf-life. Students sometimes report feeling isolated and lacking in motivation. Synchronous methods can play an important part in any blended approach to learning. The aim was to develop, deliver, and evaluate an international postgraduate module in eHealth using live interactive webcasting. We developed a hybrid solution for live interactive webcasting using a scan converter, mixer, and digitizer, and video server to embed a presenter-controlled talking head or copy of the presenter's computer screen (normally a PowerPoint slide) in a student chat room. We recruited 16 students from six countries and ran weekly 2.5-hour live sessions for 10 weeks. The content included the use of computers by patients, patient access to records, different forms of e-learning for patients and professionals, research methods in eHealth, geographic information systems, and telehealth. All sessions were recorded-presentations as video files and the student interaction as text files. Students were sent an email questionnaire of mostly open questions seeking their views of this form of learning. Responses were collated and anonymized by a colleague who was not part of the teaching team. Sessions were generally very interactive, with most students participating actively in breakout or full-class discussions. In a typical 2.5-hour session, students posted about 50 messages each. Two students did not complete all sessions; one withdrew from the pressure of work after session 6, and one from illness after session 7. Fourteen of the 16 responded to the feedback questionnaire. Most students (12/14) found the module useful or very useful, and all would recommend the module to others. All liked the method of delivery, in particular the interactivity, the variety of students, and the "closeness" of the group. Most (11/14) felt "connected" with the other students on the course. Many

Interaction between total body gamma-irradiation and choline deficiency triggers immediate modulation of choline and choline-containing moieties.

PubMed

Batra, Vipen; Kislay, Binita; Devasagayam, Thomas Paul Asir

2011-12-01

The objective of this study was to examine the effect of 60Co-gamma (γ) radiation on acute phase modulation, if any, of choline and choline-containing moieties in choline-deficient subjects. Corresponding results could provide information that might be useful in the management of adverse effects of γ-radiation. Male Swiss mice maintained on a choline-sufficient diet (CSD) and choline-free diet (CFD) based on AIN-93M formula, were subjected to whole body γ-irradiation (2-6 Gy). Liver, serum and brain samples from each group were then tested for: (i) Alterations in choline and choline-containing moieties such as phosphatidylcholine (PC) and sphingomyeline (SM); and (ii) modulation of choline profile modulating enzymes such as phospholipase D (PLD) and total sphingomyelinase (t-SMase). Liver and brain samples were also subjected to histo-pathological examinations. No significant changes were observed in folate, choline, choline-containing moieties and choline-modulating enzymes in choline-sufficient mice. In contrast, interaction between cytotoxic effects of γ-radiation and choline deficiency modulated choline and choline-containing moieties. Feeding CFD reduced hepatic concentrations of choline, PC and SM whereas PLD and t-SMase activities were significantly raised. The decrease in liver choline and choline-containing moieties was accompanied by an increase in blood choline concentration. Despite choline deficiency, the level of choline and acetylcholine synthesizing enzyme choline acetyltransfease (ChAT) significantly increased in the brain. We propose that choline deprivation and γ-radiation interact to modulate choline reserves of hepatic tissue, which might release choline to blood. Our studies also clearly showed that interaction between choline deficiency and γ-radiation might substantially enhance liver adipogenesis.

Apollo program soil mechanics experiment. [interaction of the lunar module with the lunar surface

NASA Technical Reports Server (NTRS)

Scott, R. F.

1975-01-01

The soil mechanics investigation was conducted to obtain information relating to the landing interaction of the lunar module (LM) with the lunar surface, and lunar soil erosion caused by the spacecraft engine exhaust. Results obtained by study of LM landing performance on each Apollo mission are summarized.

Stochastic genome-nuclear lamina interactions: modulating roles of Lamin A and BAF.

PubMed

Kind, Jop; van Steensel, Bas

2014-01-01

The nuclear lamina (NL) is thought to aid in the spatial organization of interphase chromosomes by providing an anchoring platform for hundreds of large genomic regions named lamina associated domains (LADs). Recently, a new live-cell imaging approach demonstrated directly that LAD-NL interactions are dynamic and in part stochastic. Here we discuss implications of these new findings and introduce Lamin A and BAF as potential modulators of stochastic LAD positioning.

Modulating surface rheology by electrostatic protein/polysaccharide interactions.

PubMed

Ganzevles, Renate A; Zinoviadou, Kyriaki; van Vliet, Ton; Cohen, Martien A; de Jongh, Harmen H

2006-11-21

There is a large interest in mixed protein/polysaccharide layers at air-water and oil-water interfaces because of their ability to stabilize foams and emulsions. Mixed protein/polysaccharide adsorbed layers at air-water interfaces can be prepared either by adsorption of soluble protein/polysaccharide complexes or by sequential adsorption of complexes or polysaccharides to a previously formed protein layer. Even though the final protein and polysaccharide bulk concentrations are the same, the behavior of the adsorbed layers can be very different, depending on the method of preparation. The surface shear modulus of a sequentially formed beta-lactoglobulin/pectin layer can be up to a factor of 6 higher than that of a layer made by simultaneous adsorption. Furthermore, the surface dilatational modulus and surface shear modulus strongly (up to factors of 2 and 7, respectively) depend on the bulk -lactoglobulin/pectin mixing ratio. On the basis of the surface rheological behavior, a mechanistic understanding of how the structure of the adsorbed layers depends on the protein/polysaccharide interaction in bulk solution, mixing ratio, ionic strength, and order of adsorption to the interface (simultaneous or sequential) is derived. Insight into the effect of protein/polysaccharide interactions on the properties of adsorbed layers provides a solid basis to modulate surface rheological behavior.

Solar array module plasma interactions experiment (SAMPIE) - Science and technology objectives

NASA Technical Reports Server (NTRS)

Hillard, G. B.; Ferguson, Dale C.

1993-01-01

The solar array module plasma interactions experiment (SAMPIE) is an approved NASA flight experiment manifested for Shuttle deployment in early 1994. The SAMPIE experiment is designed to investigate the interaction of high voltage space power systems with ionospheric plasma. To study the behavior of solar cells, a number of solar cell coupons (representing design technologies of current interest) will be biased to high voltages to measure both arcing and current collection. Various theories of arc suppression will be tested by including several specially modified cell coupons. Finally, SAMPIE will include experiments to study the basic nature of arcing and current collection. This paper describes the rationale for a space flight experiment, the measurements to be made, and the significance of the expected results. A future paper will present a detailed discussion of the engineering design.

Impact of Interactive e-Learning Modules on Appropriateness of Imaging Referrals: A Multicenter, Randomized, Crossover Study.

PubMed

Velan, Gary M; Goergen, Stacy K; Grimm, Jane; Shulruf, Boaz

2015-11-01

Health care expenditure on diagnostic imaging investigations is increasing, and many tests are ordered inappropriately. Validated clinical decision rules (CDRs) for certain conditions are available to aid in assessing the need for imaging. However, awareness and utilization of CDRs are lacking. This study compared the efficacy and perceived impact of interactive e-learning modules versus static versions of CDRs, for learning about appropriate imaging referrals. A multicenter, randomized, crossover trial was performed; participants were volunteer medical students and recent graduates. In week 1, group 1 received an e-learning module on appropriate imaging referrals for pulmonary embolism; group 2 received PDF versions of relevant CDRs, and an online quiz with feedback. In week 2, the groups crossed over, focusing on imaging referrals for cervical spine trauma in adults. Online assessments were administered to both groups at the end of each week, and participants completed an online questionnaire at the end of the trial. Group 1 (e-learning module) performed significantly better on the pulmonary embolism knowledge assessment. After the crossover, participants in group 2 (e-learning module) were significantly more likely to improve their scores in the assessment of cervical spine trauma knowledge. Both groups gave positive evaluations of the e-learning modules. Interactive e-learning was significantly more effective for learning in this cohort, compared with static CDRs. We believe that the authentic clinical scenarios, feedback, and integration provided by the e-learning modules contributed to their impact. This study has implications for implementation of e-learning tools to facilitate appropriate referrals for imaging investigations in clinical practice. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Mothers' multimodal information processing is modulated by multimodal interactions with their infants.

PubMed

Tanaka, Yukari; Fukushima, Hirokata; Okanoya, Kazuo; Myowa-Yamakoshi, Masako

2014-10-17

Social learning in infancy is known to be facilitated by multimodal (e.g., visual, tactile, and verbal) cues provided by caregivers. In parallel with infants' development, recent research has revealed that maternal neural activity is altered through interaction with infants, for instance, to be sensitive to infant-directed speech (IDS). The present study investigated the effect of mother- infant multimodal interaction on maternal neural activity. Event-related potentials (ERPs) of mothers were compared to non-mothers during perception of tactile-related words primed by tactile cues. Only mothers showed ERP modulation when tactile cues were incongruent with the subsequent words, and only when the words were delivered with IDS prosody. Furthermore, the frequency of mothers' use of those words was correlated with the magnitude of ERP differentiation between congruent and incongruent stimuli presentations. These results suggest that mother-infant daily interactions enhance multimodal integration of the maternal brain in parenting contexts.

Designing Interactive Electronic Module in Chemistry Lessons

NASA Astrophysics Data System (ADS)

Irwansyah, F. S.; Lubab, I.; Farida, I.; Ramdhani, M. A.

2017-09-01

This research aims to design electronic module (e-module) oriented to the development of students’ chemical literacy on the solution colligative properties material. This research undergoes some stages including concept analysis, discourse analysis, storyboard design, design development, product packaging, validation, and feasibility test. Overall, this research undertakes three main stages, namely, Define (in the form of preliminary studies); Design (designing e-module); Develop (including validation and model trial). The concept presentation and visualization used in this e-module is oriented to chemical literacy skills. The presentation order carries aspects of scientific context, process, content, and attitude. Chemists and multi media experts have done the validation to test the initial quality of the products and give a feedback for the product improvement. The feasibility test results stated that the content presentation and display are valid and feasible to be used with the value of 85.77% and 87.94%. These values indicate that this e-module oriented to students’ chemical literacy skills for the solution colligative properties material is feasible to be used.

Azobenzene dye-coupled quadruply hydrogen-bonding modules as colorimetric indicators for supramolecular interactions.

PubMed

Zhang, Yagang; Zimmerman, Steven C

2012-01-01

The facile coupling of azobenzene dyes to the quadruply hydrogen-bonding modules 2,7-diamido-1,8-naphthyridine (DAN) and 7-deazaguanine urea (DeUG) is described. The coupling of azobenzene dye 2 to mono-amido DAN units 4, 7, and 9 was effected by classic 4-(dimethylamino)pyridine (DMAP)-catalyzed peptide synthesis with N-(3-dimethylaminopropyl)-N'-ethyl carbodiimide hydrochloride (EDC) as activating agent, affording the respective amide products 5, 8, and 10 in 60-71% yield. The amide linkage was formed through either the aliphatic or aromatic ester group of 2, allowing both the flexibility and absorption maximum to be tuned. Azobenzene dye 1 was coupled to the DeUG unit 11 by Steglich esterification to afford the product amide 12 in 35% yield. Alternatively, azobenzene dye 16 underwent a room-temperature copper-catalyzed azide-alkyne Huisgen cycloaddition with DeUG alkyne 17 to give triazole 18 in 71% yield. Azobenzene coupled DAN modules 5, 8, and 10 are bright orange-red in color, and azobenzene coupled DeUG modules 12 and 18 are orange-yellow in color. Azobenzene coupled DAN and DeUG modules were successfully used as colorimetric indicators for specific DAN-DeUG and DAN-UPy (2-ureido-4(1H)-pyrimidone) quadruply hydrogen-bonding interactions.

Azobenzene dye-coupled quadruply hydrogen-bonding modules as colorimetric indicators for supramolecular interactions

PubMed Central

Zhang, Yagang

2012-01-01

Summary The facile coupling of azobenzene dyes to the quadruply hydrogen-bonding modules 2,7-diamido-1,8-naphthyridine (DAN) and 7-deazaguanine urea (DeUG) is described. The coupling of azobenzene dye 2 to mono-amido DAN units 4, 7, and 9 was effected by classic 4-(dimethylamino)pyridine (DMAP)-catalyzed peptide synthesis with N-(3-dimethylaminopropyl)-N’-ethyl carbodiimide hydrochloride (EDC) as activating agent, affording the respective amide products 5, 8, and 10 in 60–71% yield. The amide linkage was formed through either the aliphatic or aromatic ester group of 2, allowing both the flexibility and absorption maximum to be tuned. Azobenzene dye 1 was coupled to the DeUG unit 11 by Steglich esterification to afford the product amide 12 in 35% yield. Alternatively, azobenzene dye 16 underwent a room-temperature copper-catalyzed azide–alkyne Huisgen cycloaddition with DeUG alkyne 17 to give triazole 18 in 71% yield. Azobenzene coupled DAN modules 5, 8, and 10 are bright orange–red in color, and azobenzene coupled DeUG modules 12 and 18 are orange–yellow in color. Azobenzene coupled DAN and DeUG modules were successfully used as colorimetric indicators for specific DAN–DeUG and DAN–UPy (2-ureido-4(1H)-pyrimidone) quadruply hydrogen-bonding interactions. PMID:22509220

Default Network Modulation and Large-Scale Network Interactivity in Healthy Young and Old Adults

PubMed Central

Schacter, Daniel L.

2012-01-01

We investigated age-related changes in default, attention, and control network activity and their interactions in young and old adults. Brain activity during autobiographical and visuospatial planning was assessed using multivariate analysis and with intrinsic connectivity networks as regions of interest. In both groups, autobiographical planning engaged the default network while visuospatial planning engaged the attention network, consistent with a competition between the domains of internalized and externalized cognition. The control network was engaged for both planning tasks. In young subjects, the control network coupled with the default network during autobiographical planning and with the attention network during visuospatial planning. In old subjects, default-to-control network coupling was observed during both planning tasks, and old adults failed to deactivate the default network during visuospatial planning. This failure is not indicative of default network dysfunction per se, evidenced by default network engagement during autobiographical planning. Rather, a failure to modulate the default network in old adults is indicative of a lower degree of flexible network interactivity and reduced dynamic range of network modulation to changing task demands. PMID:22128194

Mothers' multimodal information processing is modulated by multimodal interactions with their infants

PubMed Central

Tanaka, Yukari; Fukushima, Hirokata; Okanoya, Kazuo; Myowa-Yamakoshi, Masako

2014-01-01

Social learning in infancy is known to be facilitated by multimodal (e.g., visual, tactile, and verbal) cues provided by caregivers. In parallel with infants' development, recent research has revealed that maternal neural activity is altered through interaction with infants, for instance, to be sensitive to infant-directed speech (IDS). The present study investigated the effect of mother- infant multimodal interaction on maternal neural activity. Event-related potentials (ERPs) of mothers were compared to non-mothers during perception of tactile-related words primed by tactile cues. Only mothers showed ERP modulation when tactile cues were incongruent with the subsequent words, and only when the words were delivered with IDS prosody. Furthermore, the frequency of mothers' use of those words was correlated with the magnitude of ERP differentiation between congruent and incongruent stimuli presentations. These results suggest that mother-infant daily interactions enhance multimodal integration of the maternal brain in parenting contexts. PMID:25322936

Protein-solvent preferential interactions, protein hydration, and the modulation of biochemical reactions by solvent components.

PubMed

Timasheff, Serge N

2002-07-23

Solvent additives (cosolvents, osmolytes) modulate biochemical reactions if, during the course of the reaction, there is a change in preferential interactions of solvent components with the reacting system. Preferential interactions can be expressed in terms of preferential binding of the cosolvent or its preferential exclusion (preferential hydration). The driving force is the perturbation by the protein of the chemical potential of the cosolvent. It is shown that the measured change of the amount of water in contact with protein during the course of the reaction modulated by an osmolyte is a change in preferential hydration that is strictly a measure of the cosolvent chemical potential perturbation by the protein in the ternary water-protein-cosolvent system. It is not equal to the change in water of hydration, because water of hydration is a reflection strictly of protein-water forces in a binary system. There is no direct relation between water of preferential hydration and water of hydration.

Intracellular calcium levels determine differential modulation of allosteric interactions within G protein-coupled receptor heteromers.

PubMed

Navarro, Gemma; Aguinaga, David; Moreno, Estefania; Hradsky, Johannes; Reddy, Pasham P; Cortés, Antoni; Mallol, Josefa; Casadó, Vicent; Mikhaylova, Marina; Kreutz, Michael R; Lluís, Carme; Canela, Enric I; McCormick, Peter J; Ferré, Sergi

2014-11-20

The pharmacological significance of the adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromer is well established and it is being considered as an important target for the treatment of Parkinson’s disease and other neuropsychiatric disorders. However, the physiological factors that control its distinctive biochemical properties are still unknown. We demonstrate that different intracellular Ca2+ levels exert a differential modulation of A2AR-D2R heteromer-mediated adenylyl-cyclase and MAPK signaling in striatal cells. This depends on the ability of low and high Ca2+ levels to promote a selective interaction of the heteromer with the neuronal Ca2+-binding proteins NCS-1 and calneuron-1, respectively. These Ca2+-binding proteins differentially modulate allosteric interactions within the A2AR-D2R heteromer, which constitutes a unique cellular device that integrates extracellular (adenosine and dopamine) and intracellular (Ca+2) signals to produce a specific functional response.

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

PubMed Central

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

2014-01-01

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

The Goals and Development of an Interactive Web Module for a Teacher Education Course.

ERIC Educational Resources Information Center

Schnorr, Donna; Bracken, Nicole; Hazari, Sunil

The World Wide Web has become a promising medium for delivery of instruction. This paper describes a case study in which the Internet was used to supplement teacher education course instruction via an Interactive Web module. The goals of using such a medium for facilitating teaching and enhancing learning are described as they relate to learning…

Autism Tendencies and Psychosis Proneness Interactively Modulate Saliency Cost

PubMed Central

Abu-Akel, Ahmad; Apperly, Ian A.; Wood, Stephen J.; Hansen, Peter C.; Mevorach, Carmel

2017-01-01

Atypical responses to salient information are a candidate endophenotype for both autism and psychosis spectrum disorders. The present study investigated the costs and benefits of such atypicalities for saliency-based selection in a large cohort of neurotypical adults in whom both autism and psychosis expressions were assessed. Two experiments found that autism tendencies and psychosis proneness interactively modulated the cost incurred in the presence of a task-irrelevant salient distractor. Specifically, expressions of autism and psychosis had opposing effects on responses to salient information such that the benefits associated with high expressions for autism offset costs associated with high expressions for psychosis. The opposing influences observed on saliency cost may be driven by distinct attentional mechanisms that are differentially affected by expressions for autism and psychosis. PMID:27217269

Envelope Interactions in Multi-Channel Amplitude Modulation Frequency Discrimination by Cochlear Implant Users.

PubMed

Galvin, John J; Oba, Sandra I; Başkent, Deniz; Chatterjee, Monita; Fu, Qian-Jie

2015-01-01

Previous cochlear implant (CI) studies have shown that single-channel amplitude modulation frequency discrimination (AMFD) can be improved when coherent modulation is delivered to additional channels. It is unclear whether the multi-channel advantage is due to increased loudness, multiple envelope representations, or to component channels with better temporal processing. Measuring envelope interference may shed light on how modulated channels can be combined. In this study, multi-channel AMFD was measured in CI subjects using a 3-alternative forced-choice, non-adaptive procedure ("which interval is different?"). For the reference stimulus, the reference AM (100 Hz) was delivered to all 3 channels. For the probe stimulus, the target AM (101, 102, 104, 108, 116, 132, 164, 228, or 256 Hz) was delivered to 1 of 3 channels, and the reference AM (100 Hz) delivered to the other 2 channels. The spacing between electrodes was varied to be wide or narrow to test different degrees of channel interaction. Results showed that CI subjects were highly sensitive to interactions between the reference and target envelopes. However, performance was non-monotonic as a function of target AM frequency. For the wide spacing, there was significantly less envelope interaction when the target AM was delivered to the basal channel. For the narrow spacing, there was no effect of target AM channel. The present data were also compared to a related previous study in which the target AM was delivered to a single channel or to all 3 channels. AMFD was much better with multiple than with single channels whether the target AM was delivered to 1 of 3 or to all 3 channels. For very small differences between the reference and target AM frequencies (2-4 Hz), there was often greater sensitivity when the target AM was delivered to 1 of 3 channels versus all 3 channels, especially for narrowly spaced electrodes. Besides the increased loudness, the present results also suggest that multiple envelope

Use of Live Interactive Webcasting for an International Postgraduate Module in eHealth: Case Study Evaluation

PubMed Central

Maramba, Inocencio; Boulos, Maged N Kamel; Alexander, Tara

2009-01-01

Background Producing “traditional” e-learning can be time consuming, and in a topic such as eHealth, it may have a short shelf-life. Students sometimes report feeling isolated and lacking in motivation. Synchronous methods can play an important part in any blended approach to learning. Objective The aim was to develop, deliver, and evaluate an international postgraduate module in eHealth using live interactive webcasting. Methods We developed a hybrid solution for live interactive webcasting using a scan converter, mixer, and digitizer, and video server to embed a presenter-controlled talking head or copy of the presenter’s computer screen (normally a PowerPoint slide) in a student chat room. We recruited 16 students from six countries and ran weekly 2.5-hour live sessions for 10 weeks. The content included the use of computers by patients, patient access to records, different forms of e-learning for patients and professionals, research methods in eHealth, geographic information systems, and telehealth. All sessions were recorded—presentations as video files and the student interaction as text files. Students were sent an email questionnaire of mostly open questions seeking their views of this form of learning. Responses were collated and anonymized by a colleague who was not part of the teaching team. Results Sessions were generally very interactive, with most students participating actively in breakout or full-class discussions. In a typical 2.5-hour session, students posted about 50 messages each. Two students did not complete all sessions; one withdrew from the pressure of work after session 6, and one from illness after session 7. Fourteen of the 16 responded to the feedback questionnaire. Most students (12/14) found the module useful or very useful, and all would recommend the module to others. All liked the method of delivery, in particular the interactivity, the variety of students, and the “closeness” of the group. Most (11/14) felt �

Host-Pathogen interactions modulated by small RNAs.

PubMed

Islam, Waqar; Islam, Saif Ul; Qasim, Muhammad; Wang, Liande

2017-07-03

Biological processes such as defense mechanisms and microbial offense strategies are regulated through RNA induced interference in eukaryotes. Genetic mutations are modulated through biogenesis of small RNAs which directly impacts upon host development. Plant defense mechanisms are regulated and supported by a diversified group of small RNAs which are involved in streamlining several RNA interference pathways leading toward the initiation of pathogen gene silencing mechanisms. In the similar context, pathogens also utilize the support of small RNAs to launch their offensive attacks. Also there are strong evidences about the active involvement of these RNAs in symbiotic associations. Interestingly, small RNAs are not limited to the individuals in whom they are produced; they also show cross kingdom influences through variable interactions with other species thus leading toward the inter-organismic gene silencing. The phenomenon is understandable in the microbes which utilize these mechanisms to overcome host defense line. Understanding the mechanism of triggering host defense strategies can be a valuable step toward the generation of disease resistant host plants. We think that the cross kingdom trafficking of small RNA is an interesting insight that is needed to be explored for its vitality.

Host-Pathogen interactions modulated by small RNAs

PubMed Central

Islam, Waqar; Islam, Saif ul; Qasim, Muhammad; Wang, Liande

2017-01-01

ABSTRACT Biological processes such as defense mechanisms and microbial offense strategies are regulated through RNA induced interference in eukaryotes. Genetic mutations are modulated through biogenesis of small RNAs which directly impacts upon host development. Plant defense mechanisms are regulated and supported by a diversified group of small RNAs which are involved in streamlining several RNA interference pathways leading toward the initiation of pathogen gene silencing mechanisms. In the similar context, pathogens also utilize the support of small RNAs to launch their offensive attacks. Also there are strong evidences about the active involvement of these RNAs in symbiotic associations. Interestingly, small RNAs are not limited to the individuals in whom they are produced; they also show cross kingdom influences through variable interactions with other species thus leading toward the inter-organismic gene silencing. The phenomenon is understandable in the microbes which utilize these mechanisms to overcome host defense line. Understanding the mechanism of triggering host defense strategies can be a valuable step toward the generation of disease resistant host plants. We think that the cross kingdom trafficking of small RNA is an interesting insight that is needed to be explored for its vitality. PMID:28430077

GABAergic modulation of human social interaction in a prisoner's dilemma model by acute administration of alprazolam.

PubMed

Lane, Scott D; Gowin, Joshua L

2009-10-01

Recent work in neuroeconomics has used game theory paradigms to examine neural systems that subserve human social interaction and decision making. Attempts to modify social interaction through pharmacological manipulation have been less common. Here we show dose-dependent modification of human social behavior in a prisoner's dilemma model after acute administration of the γ-aminobutyric acid (GABA)-A modulating benzodiazepine alprazolam. Nine healthy adults received doses of placebo, 0.5, 1.0, and 2.0 mg alprazolam in a counterbalanced within-subject design, while completing multiple test blocks per day on an iterated prisoner's dilemma game. During test blocks in which peak subjective effects of alprazolam were reported, cooperative choices were significantly decreased as a function of dose. Consistent with previous reports showing that high acute doses of GABA-modulating drugs are associated with violence and other antisocial behavior, our data suggest that at sufficiently high doses, alprazolam can decrease cooperation. These behavioral changes may be facilitated by changes in inhibitory control facilitated by GABA. Game theory paradigms may prove useful in behavioral pharmacology studies seeking to measure social interaction, and may help inform the emerging field of neuroeconomics.

Comparison of Modules of Wild Type and Mutant Huntingtin and TP53 Protein Interaction Networks: Implications in Biological Processes and Functions

PubMed Central

Basu, Mahashweta; Bhattacharyya, Nitai P.; Mohanty, Pradeep K.

2013-01-01

Disease-causing mutations usually change the interacting partners of mutant proteins. In this article, we propose that the biological consequences of mutation are directly related to the alteration of corresponding protein protein interaction networks (PPIN). Mutation of Huntingtin (HTT) which causes Huntington's disease (HD) and mutations to TP53 which is associated with different cancers are studied as two example cases. We construct the PPIN of wild type and mutant proteins separately and identify the structural modules of each of the networks. The functional role of these modules are then assessed by Gene Ontology (GO) enrichment analysis for biological processes (BPs). We find that a large number of significantly enriched () GO terms in mutant PPIN were absent in the wild type PPIN indicating the gain of BPs due to mutation. Similarly some of the GO terms enriched in wild type PPIN cease to exist in the modules of mutant PPIN, representing the loss. GO terms common in modules of mutant and wild type networks indicate both loss and gain of BPs. We further assign relevant biological function(s) to each module by classifying the enriched GO terms associated with it. It turns out that most of these biological functions in HTT networks are already known to be altered in HD and those of TP53 networks are altered in cancers. We argue that gain of BPs, and the corresponding biological functions, are due to new interacting partners acquired by mutant proteins. The methodology we adopt here could be applied to genetic diseases where mutations alter the ability of the protein to interact with other proteins. PMID:23741403

Coulomb-interaction induced coupling of Landau levels in intrinsic and modulation-doped quantum wells

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

Paul, J.; Stevens, C. E.; Zhang, H.

We have performed two-dimensional Fourier transform spectroscopy on intrinsic and modulation doped quantum wells in external magnetic fields up to 10 T. In the undoped sample, the strong Coulomb interactions and the increasing separations of the electron and hole charge distributions with increasing magnetic fields lead to a nontrivial in-plane dispersion of the magneto-excitons. Thus, the discrete and degenerate Landau levels are coupled to a continuum. The signature of this continuum is the emergence of elongated spectral line shapes at the Landau level energies, which are exposed by the multidimensional nature of our technique. Surprisingly, the elongation of the peaksmore » is completely absent in the lowest Landau level spectra obtained from the modulation doped quantum well at high fields.« less

Coulomb-interaction induced coupling of Landau levels in intrinsic and modulation-doped quantum wells

NASA Astrophysics Data System (ADS)

Paul, J.; Stevens, C. E.; Zhang, H.; Dey, P.; McGinty, D.; McGill, S. A.; Smith, R. P.; Reno, J. L.; Turkowski, V.; Perakis, I. E.; Hilton, D. J.; Karaiskaj, D.

2017-06-01

We have performed two-dimensional Fourier transform spectroscopy on intrinsic and modulation doped quantum wells in external magnetic fields up to 10 T. In the undoped sample, the strong Coulomb interactions and the increasing separations of the electron and hole charge distributions with increasing magnetic fields lead to a nontrivial in-plane dispersion of the magneto-excitons. Thus, the discrete and degenerate Landau levels are coupled to a continuum. The signature of this continuum is the emergence of elongated spectral line shapes at the Landau level energies, which are exposed by the multidimensional nature of our technique. Surprisingly, the elongation of the peaks is completely absent in the lowest Landau level spectra obtained from the modulation doped quantum well at high fields.

Coulomb-interaction induced coupling of Landau levels in intrinsic and modulation-doped quantum wells

DOE PAGES

Paul, J.; Stevens, C. E.; Zhang, H.; ...

2017-06-28

We have performed two-dimensional Fourier transform spectroscopy on intrinsic and modulation doped quantum wells in external magnetic fields up to 10 T. In the undoped sample, the strong Coulomb interactions and the increasing separations of the electron and hole charge distributions with increasing magnetic fields lead to a nontrivial in-plane dispersion of the magneto-excitons. Thus, the discrete and degenerate Landau levels are coupled to a continuum. The signature of this continuum is the emergence of elongated spectral line shapes at the Landau level energies, which are exposed by the multidimensional nature of our technique. Surprisingly, the elongation of the peaksmore » is completely absent in the lowest Landau level spectra obtained from the modulation doped quantum well at high fields.« less

Supramolecular Assembly of Comb-like Macromolecules Induced by Chemical Reactions that Modulate the Macromolecular Interactions In Situ.

PubMed

Xia, Hongwei; Fu, Hailin; Zhang, Yanfeng; Shih, Kuo-Chih; Ren, Yuan; Anuganti, Murali; Nieh, Mu-Ping; Cheng, Jianjun; Lin, Yao

2017-08-16

Supramolecular polymerization or assembly of proteins or large macromolecular units by a homogeneous nucleation mechanism can be quite slow and require specific solution conditions. In nature, protein assembly is often regulated by molecules that modulate the electrostatic interactions of the protein subunits for various association strengths. The key to this regulation is the coupling of the assembly process with a reversible or irreversible chemical reaction that occurs within the constituent subunits. However, realizing this complex process by the rational design of synthetic molecules or macromolecules remains a challenge. Herein, we use a synthetic polypeptide-grafted comb macromolecule to demonstrate how the in situ modulation of interactions between the charged macromolecules affects their resulting supramolecular structures. The kinetics of structural formation was studied and can be described by a generalized model of nucleated polymerization containing secondary pathways. Basic thermodynamic analysis indicated the delicate role of the electrostatic interactions between the charged subunits in the reaction-induced assembly process. This approach may be applicable for assembling a variety of ionic soft matters that are amenable to chemical reactions in situ.

Mycoplasma fermentans and TNF-β interact to amplify immune-modulating cytokines in human lung fibroblasts

PubMed Central

Fabisiak, James P.; Gao, Fei; Thomson, Robyn G.; Strieter, Robert M.; Watkins, Simon C.; Dauber, James H.

2010-01-01

Mycoplasma can establish latent infections and are associated with arthritis, leukemia, and chronic lung disease. We developed an experimental model in which lung cells are deliberately infected with Mycoplasma fermentans. Human lung fibroblasts (HLF) were exposed to live M. fermentans and immune-modulating cytokine release was assessed with and without known inducers of cytokine production. M. fermentans increased IL-6, IL-8/CXCL8, MCP-1/CCL2, and Gro-α/CXCL1 production. M. fermentans interacted with TNF-β to release more IL-6, CXCL8, and CXCL1 than predicted by the responses to either stimulus alone. The effects of live infection were recapitulated by exposure to M. fermentans-derived macrophage-activating lipopeptide-2 (MALP-2), a Toll-like receptor-2- and receptor-6-specific ligand. The synergistic effect of combined stimuli was more pronounced with prolonged incubations. Preexposure to TNF-β sensitized the cells to subsequent MALP-2 challenge, but preexposure to MALP-2 did not alter the IL-6 response to TNF-β. Exposure to M. fermentans or MALP-2 did not enhance nuclear localization, DNA binding, or transcriptional activity of NF-κB and did not modulate early NF-κB activation in response to TNF-β. Application of specific inhibitors of various MAPKs suggested that p38 and JNK/stress-activated protein kinase were involved in early IL-6 release after exposure to TNF-β and M. fermentans, respectively. The combined response to M. fermentans and TNF-β, however, was uniquely sensitive to delayed application of SP-600125, suggesting that JNK/stress-activated protein kinase contributes to the amplification of IL-6 release. Thus M. fermentans interacts with stimuli such as TNF-β to amplify lung cell production of immune-modulating cytokines. The mechanisms accounting for this interaction can now be dissected with the use of this in vitro model. PMID:16751226

Different impressions of other agents obtained through social interaction uniquely modulate dorsal and ventral pathway activities in the social human brain.

PubMed

Takahashi, Hideyuki; Terada, Kazunori; Morita, Tomoyo; Suzuki, Shinsuke; Haji, Tomoki; Kozima, Hideki; Yoshikawa, Masahiro; Matsumoto, Yoshio; Omori, Takashi; Asada, Minoru; Naito, Eiichi

2014-09-01

Internal (neuronal) representations in the brain are modified by our experiences, and this phenomenon is not unique to sensory and motor systems. Here, we show that different impressions obtained through social interaction with a variety of agents uniquely modulate activity of dorsal and ventral pathways of the brain network that mediates human social behavior. We scanned brain activity with functional magnetic resonance imaging (fMRI) in 16 healthy volunteers when they performed a simple matching-pennies game with a human, human-like android, mechanical robot, interactive robot, and a computer. Before playing this game in the scanner, participants experienced social interactions with each opponent separately and scored their initial impressions using two questionnaires. We found that the participants perceived opponents in two mental dimensions: one represented "mind-holderness" in which participants attributed anthropomorphic impressions to some of the opponents that had mental functions, while the other dimension represented "mind-readerness" in which participants characterized opponents as intelligent. Interestingly, this "mind-readerness" dimension correlated to participants frequently changing their game tactic to prevent opponents from envisioning their strategy, and this was corroborated by increased entropy during the game. We also found that the two factors separately modulated activity in distinct social brain regions. Specifically, mind-holderness modulated activity in the dorsal aspect of the temporoparietal junction (TPJ) and medial prefrontal and posterior paracingulate cortices, while mind-readerness modulated activity in the ventral aspect of TPJ and the temporal pole. These results clearly demonstrate that activity in social brain networks is modulated through pre-scanning experiences of social interaction with a variety of agents. Furthermore, our findings elucidated the existence of two distinct functional networks in the social human brain

Interaction of dengue virus nonstructural protein 5 with Daxx modulates RANTES production

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

Khunchai, Sasiprapa; Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok; Junking, Mutita

Highlights: Black-Right-Pointing-Pointer For the first time how DENV NS5 increases RANTES production. Black-Right-Pointing-Pointer DENV NS5 physically interacts with human Daxx. Black-Right-Pointing-Pointer Nuclear localization of NS5 is required for Daxx interaction and RANTES production. -- Abstract: Dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS), caused by dengue virus (DENV) infection, are important public health problems in the tropical and subtropical regions. Abnormal hemostasis and plasma leakage are the main patho-physiological changes in DHF/DSS. A remarkably increased production of cytokines, the so called 'cytokine storm', is observed in the patients with DHF/DSS. A complex interaction between DENV proteinsmore » and the host immune response contributes to cytokine production. However, the molecular mechanism(s) by which DENV nonstructural protein 5 (NS5) mediates these responses has not been fully elucidated. In the present study, yeast two-hybrid assay was performed to identify host proteins interacting with DENV NS5 and a death-domain-associate protein (Daxx) was identified. The in vivo relevance of this interaction was suggested by co-immunoprecipitation and nuclear co-localization of these two proteins in HEK293 cells expressing DENV NS5. HEK293 cells expressing DENV NS5-K/A, which were mutated at the nuclear localization sequences (NLS), were created to assess its functional roles in nuclear translocation, Daxx interaction, and cytokine production. In the absence of NLS, DENV NS5 could neither translocate into the nucleus nor interact with Daxx to increase the DHF-associated cytokine, RANTES (CCL5) production. This work demonstrates the interaction between DENV NS5 and Daxx and the role of the interaction on the modulation of RANTES production.« less

Magnetic properties of cylindrical diameter modulated Ni80Fe20 nanowires: interaction and coercive fields

NASA Astrophysics Data System (ADS)

Salem, Mohamed Shaker; Sergelius, Philip; Corona, Rosa M.; Escrig, Juan; Görlitz, Detlef; Nielsch, Kornelius

2013-04-01

Magnetic properties of cylindrical Ni80Fe20 nanowires with modulated diameters are investigated theoretically as a function of their geometrical parameters and compared with those produced inside the pores of anodic alumina membranes by pulsed electrodeposition. We observe that the Ni80Fe20 nanowires with modulated diameters reverse their magnetization via the nucleation and propagation of a vortex domain wall. The system begins generating vortex domains in the nanowire ends and in the transition region between the two segments to minimize magnetostatic energy generated by surfaces perpendicular to the initial magnetization of the sample. Besides, we observed an increase of the coercivity for the sample with equal volumes in relation to the sample with equal lengths. Finally, the interaction field is stronger in the case of constant volume segments. These structures could be used to control the motions of magnetic domain walls. In this way, these nanowires with modulated diameters can be an alternative to store information or even perform logic functions.

Envelope Interactions in Multi-Channel Amplitude Modulation Frequency Discrimination by Cochlear Implant Users

PubMed Central

2015-01-01

Rationale Previous cochlear implant (CI) studies have shown that single-channel amplitude modulation frequency discrimination (AMFD) can be improved when coherent modulation is delivered to additional channels. It is unclear whether the multi-channel advantage is due to increased loudness, multiple envelope representations, or to component channels with better temporal processing. Measuring envelope interference may shed light on how modulated channels can be combined. Methods In this study, multi-channel AMFD was measured in CI subjects using a 3-alternative forced-choice, non-adaptive procedure (“which interval is different?”). For the reference stimulus, the reference AM (100 Hz) was delivered to all 3 channels. For the probe stimulus, the target AM (101, 102, 104, 108, 116, 132, 164, 228, or 256 Hz) was delivered to 1 of 3 channels, and the reference AM (100 Hz) delivered to the other 2 channels. The spacing between electrodes was varied to be wide or narrow to test different degrees of channel interaction. Results Results showed that CI subjects were highly sensitive to interactions between the reference and target envelopes. However, performance was non-monotonic as a function of target AM frequency. For the wide spacing, there was significantly less envelope interaction when the target AM was delivered to the basal channel. For the narrow spacing, there was no effect of target AM channel. The present data were also compared to a related previous study in which the target AM was delivered to a single channel or to all 3 channels. AMFD was much better with multiple than with single channels whether the target AM was delivered to 1 of 3 or to all 3 channels. For very small differences between the reference and target AM frequencies (2–4 Hz), there was often greater sensitivity when the target AM was delivered to 1 of 3 channels versus all 3 channels, especially for narrowly spaced electrodes. Conclusions Besides the increased loudness, the present results

Interactions between amplitude modulation and frequency modulation processing: Effects of age and hearing loss.

PubMed

Paraouty, Nihaad; Ewert, Stephan D; Wallaert, Nicolas; Lorenzi, Christian

2016-07-01

Frequency modulation (FM) and amplitude modulation (AM) detection thresholds were measured for a 500-Hz carrier frequency and a 5-Hz modulation rate. For AM detection, FM at the same rate as the AM was superimposed with varying FM depth. For FM detection, AM at the same rate was superimposed with varying AM depth. The target stimuli always contained both amplitude and frequency modulations, while the standard stimuli only contained the interfering modulation. Young and older normal-hearing listeners, as well as older listeners with mild-to-moderate sensorineural hearing loss were tested. For all groups, AM and FM detection thresholds were degraded in the presence of the interfering modulation. AM detection with and without interfering FM was hardly affected by either age or hearing loss. While aging had an overall detrimental effect on FM detection with and without interfering AM, there was a trend that hearing loss further impaired FM detection in the presence of AM. Several models using optimal combination of temporal-envelope cues at the outputs of off-frequency filters were tested. The interfering effects could only be predicted for hearing-impaired listeners. This indirectly supports the idea that, in addition to envelope cues resulting from FM-to-AM conversion, normal-hearing listeners use temporal fine-structure cues for FM detection.

A gut feeling: Microbiome-brain-immune interactions modulate social and affective behaviors.

PubMed

Sylvia, Kristyn E; Demas, Gregory E

2018-03-01

The expression of a wide range of social and affective behaviors, including aggression and investigation, as well as anxiety- and depressive-like behaviors, involves interactions among many different physiological systems, including the neuroendocrine and immune systems. Recent work suggests that the gut microbiome may also play a critical role in modulating behavior and likely functions as an important integrator across physiological systems. Microbes within the gut may communicate with the brain via both neural and humoral pathways, providing numerous avenues of research in the area of the gut-brain axis. We are now just beginning to understand the intricate relationships among the brain, microbiome, and immune system and how they work in concert to influence behavior. The effects of different forms of experience (e.g., changes in diet, immune challenge, and psychological stress) on the brain, gut microbiome, and the immune system have often been studied independently. Though because these systems do not work in isolation, it is essential to shift our focus to the connections among them as we move forward in our investigations of the gut-brain axis, the shaping of behavioral phenotypes, and the possible clinical implications of these interactions. This review summarizes the recent progress the field has made in understanding the important role the gut microbiome plays in the modulation of social and affective behaviors, as well as some of the intricate mechanisms by which the microbiome may be communicating with the brain and immune system. Copyright © 2018 Elsevier Inc. All rights reserved.

GABAergic modulation of human social interaction in a prisoner’s dilemma model via acute administration of alprazolam

PubMed Central

Lane, Scott D.; Gowin, Joshua L.

2010-01-01

Recent work in neuroeconomics has utilized game theory paradigms to examine neural systems that subserve human social interaction and decision making. Attempts to modify social interaction through pharmacological manipulation have been less common. Here we show dose-dependent modification of human social behavior in a prisoner’s dilemma (PD) model following acute administration of the GABA-A modulating benzodiazepine alprazolam. Nine healthy adults received doses of placebo, 0.5, 1.0, and 2.0 mg alprazolam in a counterbalanced within-subject design, while completing multiple test blocks per day on an iterated PD game. During test blocks in which peak subjective effects of alprazolam were reported, cooperative choices were significantly decreased as a function of dose. Consistent with previous reports showing that high acute doses of GABA-modulating drugs are associated with violence and other antisocial behavior, our data suggest that at sufficiently high doses, alprazolam can decrease cooperation. These behavioral changes may be facilitated by changes in inhibitory control facilitated by GABA. Game theory paradigms may prove useful in behavioral pharmacology studies seeking to measure social interaction, and may help inform the emerging field of neuroeconomics. PMID:19667972

Integrating Module - NEMS Documentation

EIA Publications

2014-01-01

Provides an overview of the complete National Energy Modeling System (NEMS) model, and includes brief descriptions of the modules with which the Integrating Module interacts. The emphasis and focus, however, is on the structure and function of the Integrating Module of NEMS.

Conformation Change in a Self-recognizing Autotransporter Modulates Bacterial Cell-Cell Interaction*

PubMed Central

Girard, Victoria; Côté, Jean-Philippe; Charbonneau, Marie-Ève; Campos, Manuel; Berthiaume, Frédéric; Hancock, Mark A.; Siddiqui, Nadeem; Mourez, Michael

2010-01-01

Bacteria mostly live as multicellular communities, although they are unicellular organisms, yet the mechanisms that tie individual bacteria together are often poorly understood. The adhesin involved in diffuse adherence (AIDA-I) is an adhesin of diarrheagenic Escherichia coli strains. AIDA-I also mediates bacterial auto-aggregation and biofilm formation and thus could be important for the organization of communities of pathogens. Using purified protein and whole bacteria, we provide direct evidence that AIDA-I promotes auto-aggregation by interacting with itself. Using various biophysical and biochemical techniques, we observed a conformational change in the protein during AIDA-AIDA interactions, strengthening the notion that this is a highly specific interaction. The self-association of AIDA-I is of high affinity but can be modulated by sodium chloride. We observe that a bile salt, sodium deoxycholate, also prevents AIDA-I oligomerization and bacterial auto-aggregation. Thus, we propose that AIDA-I, and most likely other similar autotransporters such as antigen 43 (Ag43) and TibA, organize bacterial communities of pathogens through a self-recognition mechanism that is sensitive to the environment. This could permit bacteria to switch between multicellular and unicellular lifestyles to complete their infection. PMID:20123991

Autism Tendencies and Psychosis Proneness Interactively Modulate Saliency Cost.

PubMed

Abu-Akel, Ahmad; Apperly, Ian A; Wood, Stephen J; Hansen, Peter C; Mevorach, Carmel

2017-01-01

Atypical responses to salient information are a candidate endophenotype for both autism and psychosis spectrum disorders. The present study investigated the costs and benefits of such atypicalities for saliency-based selection in a large cohort of neurotypical adults in whom both autism and psychosis expressions were assessed. Two experiments found that autism tendencies and psychosis proneness interactively modulated the cost incurred in the presence of a task-irrelevant salient distractor. Specifically, expressions of autism and psychosis had opposing effects on responses to salient information such that the benefits associated with high expressions for autism offset costs associated with high expressions for psychosis. The opposing influences observed on saliency cost may be driven by distinct attentional mechanisms that are differentially affected by expressions for autism and psychosis. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Deliberate or unintended: Intentions modulate empathic responses to others' economic payoffs in social interactions.

PubMed

Ma, Qingguo; Meng, Liang; Shen, Qiang

2017-12-01

Previous studies examining empathy have revealed the neural substrates of how the physical pain of others is represented in the human brain. However, little is known about the empathic modulation of behavioral and neural responses to others' economic payoffs, especially in the social context. In the present study, we engaged participants in a revised Dictator Game as observers who observe the powerless players receiving varied offers proposed by the dominant players, establishing the link between empathy and fairness perception. Results showed that unfair division schemes elicited a more pronounced FRN than fair ones only if a human agent proposed the initial offer. In addition, observers sacrificed their own payments to adjust unfair proposals, especially when a human agent proposed the offer. Thus, results of the current study demonstrated that perceived intention modulates behavioral and neural responses to others' economic payoffs in social interactions.

Modulation of the Conformational Dynamics of Apo-Adenylate Kinase through a π-Cation Interaction.

PubMed

Halder, Ritaban; Manna, Rabindra Nath; Chakraborty, Sandipan; Jana, Biman

2017-06-15

Large-scale conformational transition from open to closed state of adenylate kinase (ADK) is essential for its catalytic cycle. Apo-ADK undergoes conformational transition in a way that closely resembles an open-to-closed conformational transition. Here, equilibrium simulations, free-energy simulations, and quantum mechanics/molecular mechanics (QM/MM) calculations in combination with several bioinformatics approaches have been used to explore the molecular origin of this conformational transition in apo-ADK. In addition to its conventional open state, Escherichia coli apo-ADK adopts conformations that resemble a closed-like intermediate, the "half-open-half-closed" (HOHC) state, and a π-cation interaction can account for the stability of this HOHC state. Energetics and the electronic properties of this π-cation interaction have been explored using QM/MM calculations. Upon rescinding the π-cation interaction, the conformational landscape of the apo-ADK changes completely. The apo-ADK population is shifted completely toward the open state. This π-cation interaction is highly conserved in bacterial ADK; the cationic guanidinium moiety of a conserved ARG interacts with the delocalized π-electron cloud of either PHE or TYR. Interestingly, this study demonstrates the modulation of a principal protein dynamics by a conserved specific π-cation interaction across different organisms.

Hepatitis B virus X protein modulates peroxisome proliferator-activated receptor gamma through protein-protein interaction.

PubMed

Choi, Youn-Hee; Kim, Ha-il; Seong, Je Kyung; Yu, Dae-Yeul; Cho, Hyeseong; Lee, Mi-Ock; Lee, Jae Myun; Ahn, Yong-ho; Kim, Se Jong; Park, Jeon Han

2004-01-16

Ligand activation of peroxisome proliferator-activated receptor gamma (PPARgamma) has been reported to induce growth inhibition and apoptosis in various cancers including hepatocellular carcinoma (HCC). However, the effect of hepatitis B virus X protein (HBx) on PPARgamma activation has not been characterized in hepatitis B virus (HBV)-associated HCC. Herein, we demonstrated that HBx counteracted growth inhibition caused by PPARgamma ligand in HBx-associated HCC cells. We found that HBx bound to DNA binding domain of PPARgamma and HBx/PPARgamma interaction blocked nuclear localization and binding to recognition site of PPARgamma. HBx significantly suppressed a PPARgamma-mediated transactivation. These results suggest that HBx modulates PPARgamma function through protein-protein interaction.

Nanomaterials modulate stem cell differentiation: biological interaction and underlying mechanisms.

PubMed

Wei, Min; Li, Song; Le, Weidong

2017-10-25

Stem cells are unspecialized cells that have the potential for self-renewal and differentiation into more specialized cell types. The chemical and physical properties of surrounding microenvironment contribute to the growth and differentiation of stem cells and consequently play crucial roles in the regulation of stem cells' fate. Nanomaterials hold great promise in biological and biomedical fields owing to their unique properties, such as controllable particle size, facile synthesis, large surface-to-volume ratio, tunable surface chemistry, and biocompatibility. Over the recent years, accumulating evidence has shown that nanomaterials can facilitate stem cell proliferation and differentiation, and great effort is undertaken to explore their possible modulating manners and mechanisms on stem cell differentiation. In present review, we summarize recent progress in the regulating potential of various nanomaterials on stem cell differentiation and discuss the possible cell uptake, biological interaction and underlying mechanisms.

The RecX protein interacts with the RecA protein and modulates its activity in Herbaspirillum seropedicae

PubMed Central

Galvão, C.W.; Souza, E.M.; Etto, R.M.; Pedrosa, F.O.; Chubatsu, L.S.; Yates, M.G.; Schumacher, J.; Buck, M.; Steffens, M.B.R.

2012-01-01

DNA repair is crucial to the survival of all organisms. The bacterial RecA protein is a central component in the SOS response and in recombinational and SOS DNA repairs. The RecX protein has been characterized as a negative modulator of RecA activity in many bacteria. The recA and recX genes of Herbaspirillum seropedicae constitute a single operon, and evidence suggests that RecX participates in SOS repair. In the present study, we show that the H. seropedicae RecX protein (RecXHs) can interact with the H. seropedicae RecA protein (RecAHs) and that RecAHs possesses ATP binding, ATP hydrolyzing and DNA strand exchange activities. RecXHs inhibited 90% of the RecAHs DNA strand exchange activity even when present in a 50-fold lower molar concentration than RecAHs. RecAHs ATP binding was not affected by the addition of RecX, but the ATPase activity was reduced. When RecXHs was present before the formation of RecA filaments (RecA-ssDNA), inhibition of ATPase activity was substantially reduced and excess ssDNA also partially suppressed this inhibition. The results suggest that the RecXHs protein negatively modulates the RecAHs activities by protein-protein interactions and also by DNA-protein interactions. PMID:23044625

Disparate bilingual experiences modulate task-switching advantages: A diffusion-model analysis of the effects of interactional context on switch costs.

PubMed

Hartanto, Andree; Yang, Hwajin

2016-05-01

Drawing on the adaptive control hypothesis (Green & Abutalebi, 2013), we investigated whether bilinguals' disparate interactional contexts modulate task-switching performance. Fifty-eight bilinguals within the single-language context (SLC) and 75 bilinguals within the dual-language context (DLC) were compared in a typical task-switching paradigm. Given that DLC bilinguals switch between languages within the same context, while SLC bilinguals speak only one language in one environment and therefore rarely switch languages, we hypothesized that the two groups' stark difference in their interactional contexts of conversational exchanges would lead to differences in switch costs. As predicted, DLC bilinguals showed smaller switch costs than SLC bilinguals. Our diffusion-model analyses suggest that DLC bilinguals' benefits in switch costs are more likely driven by task-set reconfiguration than by proactive interference. Our findings underscore the modulating role of the interactional context of conversational exchanges in task switching. Copyright © 2016 Elsevier B.V. All rights reserved.

IGF2BP3 modulates the interaction of invasion-associated transcripts with RISC

PubMed Central

Ennajdaoui, Hanane; Howard, Jonathan M.; Sterne-Weiler, Timothy; Jahanbani, Fereshteh; Coyne, Doyle J.; Uren, Philip J.; Dargyte, Marija; Katzman, Sol; Draper, Jolene M.; Wallace, Andrew; Cazarez, Oscar; Burns, Suzanne C.; Qiao, Mei; Hinck, Lindsay; Smith, Andrew D.; Toloue, Masoud M.; Blencowe, Benjamin J.; Penalva, Luiz O.F.; Sanford, Jeremy R.

2016-01-01

Summary Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) expression correlates with malignancy. But its role(s) in pathogenesis remain enigmatic. Here, we interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC) cells. Using a combination of genome-wide approaches we identify 164 direct mRNA targets of IGF2BP3. These transcripts encode proteins enriched for functions such as cell migration, proliferation and adhesion. Loss of IGF2BP3 reduced PDAC cell invasiveness and remodeled focal adhesion junctions. Individual-nucleotide resolution crosslinking immunoprecipitation (iCLIP) revealed significant overlap of IGF2BP3 and miRNA binding sites. IGF2BP3 promotes association of the RNA induced silencing complex (RISC) with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating miRNA-mRNA interactions. PMID:27210763

Identification of Unstable Network Modules Reveals Disease Modules Associated with the Progression of Alzheimer’s Disease

PubMed Central

Kikuchi, Masataka; Ogishima, Soichi; Miyamoto, Tadashi; Miyashita, Akinori; Kuwano, Ryozo; Nakaya, Jun; Tanaka, Hiroshi

2013-01-01

Alzheimer’s disease (AD), the most common cause of dementia, is associated with aging, and it leads to neuron death. Deposits of amyloid β and aberrantly phosphorylated tau protein are known as pathological hallmarks of AD, but the underlying mechanisms have not yet been revealed. A high-throughput gene expression analysis previously showed that differentially expressed genes accompanying the progression of AD were more down-regulated than up-regulated in the later stages of AD. This suggested that the molecular networks and their constituent modules collapsed along with AD progression. In this study, by using gene expression profiles and protein interaction networks (PINs), we identified the PINs expressed in three brain regions: the entorhinal cortex (EC), hippocampus (HIP) and superior frontal gyrus (SFG). Dividing the expressed PINs into modules, we examined the stability of the modules with AD progression and with normal aging. We found that in the AD modules, the constituent proteins, interactions and cellular functions were not maintained between consecutive stages through all brain regions. Interestingly, the modules were collapsed with AD progression, specifically in the EC region. By identifying the modules that were affected by AD pathology, we found the transcriptional regulation-associated modules that interact with the proteasome-associated module via UCHL5 hub protein, which is a deubiquitinating enzyme. Considering PINs as a system made of network modules, we found that the modules relevant to the transcriptional regulation are disrupted in the EC region, which affects the ubiquitin-proteasome system. PMID:24348898

Modulation of Caenorhabditis elegans immune response and modification of Shigella endotoxin upon interaction.

PubMed

Kesika, Periyanaina; Prasanth, Mani Iyer; Balamurugan, Krishnaswamy

2015-04-01

To analyze the pathogenesis at both physiological and molecular level using the model organism, Caenorhabditis elegans at different developmental stages in response to Shigella spp. and its pathogen associated molecular patterns such as lipopolysaccharide. The solid plate and liquid culture-based infection assays revealed that Shigella spp. infects C. elegans and had an impact on the brood size and pharyngeal pumping rate. LPS of Shigella spp. was toxic to C. elegans. qPCR analysis revealed that host innate immune genes have been modulated upon Shigella spp. infections and its LPS challenges. Non-destructive analysis was performed to kinetically assess the alterations in LPS during interaction of Shigella spp. with C. elegans. The modulation of innate immune genes attributed the surrendering of host immune system to Shigella spp. by favoring the infection. LPS appeared to have a major role in Shigella-mediated pathogenesis and Shigella employs a tactic behavior of modifying its LPS content to escape from the recognition of host immune system. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Time-dependent modulation of galactic cosmic rays by merged interaction regions

NASA Technical Reports Server (NTRS)

Perko, J. S.

1993-01-01

Models that solve the one-dimensional, solar modulation equation have reproduced the 11-year galactic cosmic ray using functional representations of global merged interaction regions (MIRs). This study extends those results to the solution of the modulation equation with explicit time dependence. The magnetometers on Voyagers 1 and 2 provide local magnetic field intensities at regular intervals, from which one calculates the ratio of the field intensity to the average local field. These ratios in turn are inverted to form diffusion coefficients. Strung together in radius and time, these coefficents then fall and rise with the strength of the interplanetary magnetic field, becoming representations of MIRs. These diffusion coefficients, calculated locally, propagate unchanged from approx. 10 AU to the outer boundary (120 AU). Inside 10 AU, all parameters, including the diffusion coefficient are assumed constant in time and space. The model reproduces the time-intensity profiles of Voyager 2 and Pioneer 10. Radial gradient data from 1982-1990 between Pioneer 10 and Voyager 2 are about the same magnitude as those calculated in the model. It is also shows agreement in rough magnitude with the radial gradient between Pioneer 10 and 1 AU. When coupled with enhanced, time-dependent solar wind speed at the probe's high latitude, as measured by independent observers, the model also follows Voyager 1's time-intensity profile reasonably well, providing a natural source the model also follows Voyager 1's time-intensity profile reasonably well, providing a natural source for the observed negative latitudinal gradients. The model exhibits the 11-year cyclical cosmic ray intensity behavior at all radii, including 1 AU, not just at the location of the spacecraft where the magnetic fields are measured. In addition, the model's point of cosmic ray maximum correctly travels at the solar wind speed, illustrating the well-known propagation of modulation. Finally, at least in the inner

Integrating Anatomy Training into Radiation Oncology Residency: Considerations for Developing a Multidisciplinary, Interactive Learning Module for Adult Learners

ERIC Educational Resources Information Center

Labranche, Leah; Johnson, Marjorie; Palma, David; D'Souza, Leah; Jaswal, Jasbir

2015-01-01

Radiation oncologists require an in-depth understanding of anatomical relationships for modern clinical practice, although most do not receive formal anatomy training during residency. To fulfill the need for instruction in relevant anatomy, a series of four multidisciplinary, interactive learning modules were developed for a cohort of radiation…

PyrE, an interactive fire module within the NASA-GISS Earth System Model

NASA Astrophysics Data System (ADS)

Mezuman, K.; Bauer, S. E.; Tsigaridis, K.

2017-12-01

Fires directly affect the composition of the atmosphere and Earth's radiation balance by emitting a suite of reactive gases and particles. Having an interactive fire module in an Earth System Model allows us to study the natural and anthropogenic drivers, feedbacks, and interactions of biomass burning in different time periods. To do so we have developed PyrE, the NASA-GISS interactive fire emissions model. PyrE uses the flammability, ignition, and suppression parameterization proposed by Pechony and Shindell (2009), and is coupled to a burned area and surface recovery parameterization. The burned area calculation follows CLM's approach (Li et al., 2012), paired with an offline recovery scheme based on Ent's Terrestrial Biosphere Model (Ent TBM) carbon pool turnover time. PyrE is driven by environmental variables calculated by climate simulations, population density data, MODIS fire counts and LAI retrievals, as well as GFED4s emissions. Since the model development required extensive use of reference datasets, in addition to comparing it to GFED4s BA, we evaluate it by studying the effect of fires on atmospheric composition and climate. Our results show good agreement globally, with some regional differences. Finally, we quantify the present day fire radiative forcing. The development of PyrE allowed us for the first time to interactively simulate climate and fire activity with GISS-ModelE3

Biotic Interactions in Microbial Communities as Modulators of Biogeochemical Processes: Methanotrophy as a Model System

PubMed Central

Ho, Adrian; Angel, Roey; Veraart, Annelies J.; Daebeler, Anne; Jia, Zhongjun; Kim, Sang Yoon; Kerckhof, Frederiek-Maarten; Boon, Nico; Bodelier, Paul L. E.

2016-01-01

Microbial interaction is an integral component of microbial ecology studies, yet the role, extent, and relevance of microbial interaction in community functioning remains unclear, particularly in the context of global biogeochemical cycles. While many studies have shed light on the physico-chemical cues affecting specific processes, (micro)biotic controls and interactions potentially steering microbial communities leading to altered functioning are less known. Yet, recent accumulating evidence suggests that the concerted actions of a community can be significantly different from the combined effects of individual microorganisms, giving rise to emergent properties. Here, we exemplify the importance of microbial interaction for ecosystem processes by analysis of a reasonably well-understood microbial guild, namely, aerobic methane-oxidizing bacteria (MOB). We reviewed the literature which provided compelling evidence for the relevance of microbial interaction in modulating methane oxidation. Support for microbial associations within methane-fed communities is sought by a re-analysis of literature data derived from stable isotope probing studies of various complex environmental settings. Putative positive interactions between active MOB and other microbes were assessed by a correlation network-based analysis with datasets covering diverse environments where closely interacting members of a consortium can potentially alter the methane oxidation activity. Although, methanotrophy is used as a model system, the fundamentals of our postulations may be applicable to other microbial guilds mediating other biogeochemical processes. PMID:27602021

IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC.

PubMed

Ennajdaoui, Hanane; Howard, Jonathan M; Sterne-Weiler, Timothy; Jahanbani, Fereshteh; Coyne, Doyle J; Uren, Philip J; Dargyte, Marija; Katzman, Sol; Draper, Jolene M; Wallace, Andrew; Cazarez, Oscar; Burns, Suzanne C; Qiao, Mei; Hinck, Lindsay; Smith, Andrew D; Toloue, Masoud M; Blencowe, Benjamin J; Penalva, Luiz O F; Sanford, Jeremy R

2016-05-31

Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) expression correlates with malignancy, but its role(s) in pathogenesis remains enigmatic. We interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC) cells. Using a combination of genome-wide approaches, we have identified 164 direct mRNA targets of IGF2BP3. These transcripts encode proteins enriched for functions such as cell migration, proliferation, and adhesion. Loss of IGF2BP3 reduced PDAC cell invasiveness and remodeled focal adhesion junctions. Individual nucleotide resolution crosslinking immunoprecipitation (iCLIP) revealed significant overlap of IGF2BP3 and microRNA (miRNA) binding sites. IGF2BP3 promotes association of the RNA-induced silencing complex (RISC) with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating miRNA-mRNA interactions. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

A role for direct interactions in the modulation of rhodopsin by -3 polyunsaturated lipids

NASA Astrophysics Data System (ADS)

Grossfield, Alan; Feller, Scott E.; Pitman, Michael C.

2006-03-01

Rhodopsin, the G protein-coupled receptor primarily responsible for sensing light, is found in an environment rich in polyunsaturated lipid chains and cholesterol. Biophysical experiments have shown that lipid unsaturation and cholesterol both have significant effects on rhodopsin's stability and function; -3 polyunsaturated chains, such as docosahexaenoic acid (DHA), destabilize rhodopsin and enhance the kinetics of the photocycle, whereas cholesterol has the opposite effect. Here, we use molecular dynamics simulations to investigate the possibility that polyunsaturated chains modulate rhodopsin stability and kinetics via specific direct interactions. By analyzing the results of 26 independent 100-ns simulations of dark-adapted rhodopsin, we found that DHA routinely forms tight associations with the protein in a small number of specific locations qualitatively different from the nonspecific interactions made by saturated chains and cholesterol. Furthermore, the presence of tightly packed DHA molecules tends to weaken the interhelical packing. These results are consistent with recent NMR work, which proposes that rhodopsin binds DHA, and they suggest a molecular rationale for DHA's effects on rhodopsin stability and kinetics. cholesterol | molecular dynamics | fatty acid | protein-lipid interactions

The RecX protein interacts with the RecA protein and modulates its activity in Herbaspirillum seropedicae.

PubMed

Galvão, C W; Souza, E M; Etto, R M; Pedrosa, F O; Chubatsu, L S; Yates, M G; Schumacher, J; Buck, M; Steffens, M B R

2012-12-01

DNA repair is crucial to the survival of all organisms. The bacterial RecA protein is a central component in the SOS response and in recombinational and SOS DNA repairs. The RecX protein has been characterized as a negative modulator of RecA activity in many bacteria. The recA and recX genes of Herbaspirillum seropedicae constitute a single operon, and evidence suggests that RecX participates in SOS repair. In the present study, we show that the H. seropedicae RecX protein (RecX Hs) can interact with the H. seropedicaeRecA protein (RecA Hs) and that RecA Hs possesses ATP binding, ATP hydrolyzing and DNA strand exchange activities. RecX Hs inhibited 90% of the RecA Hs DNA strand exchange activity even when present in a 50-fold lower molar concentration than RecA Hs. RecA Hs ATP binding was not affected by the addition of RecX, but the ATPase activity was reduced. When RecX Hs was present before the formation of RecA filaments (RecA-ssDNA), inhibition of ATPase activity was substantially reduced and excess ssDNA also partially suppressed this inhibition. The results suggest that the RecX Hs protein negatively modulates the RecA Hs activities by protein-protein interactions and also by DNA-protein interactions.

Assigning protein functions by comparative genome analysis protein phylogenetic profiles

DOEpatents

Pellegrini, Matteo; Marcotte, Edward M.; Thompson, Michael J.; Eisenberg, David; Grothe, Robert; Yeates, Todd O.

2003-05-13

A computational method system, and computer program are provided for inferring functional links from genome sequences. One method is based on the observation that some pairs of proteins A' and B' have homologs in another organism fused into a single protein chain AB. A trans-genome comparison of sequences can reveal these AB sequences, which are Rosetta Stone sequences because they decipher an interaction between A' and B. Another method compares the genomic sequence of two or more organisms to create a phylogenetic profile for each protein indicating its presence or absence across all the genomes. The profile provides information regarding functional links between different families of proteins. In yet another method a combination of the above two methods is used to predict functional links.

Processing module operating methods, processing modules, and communications systems

DOEpatents

McCown, Steven Harvey; Derr, Kurt W.; Moore, Troy

2014-09-09

A processing module operating method includes using a processing module physically connected to a wireless communications device, requesting that the wireless communications device retrieve encrypted code from a web site and receiving the encrypted code from the wireless communications device. The wireless communications device is unable to decrypt the encrypted code. The method further includes using the processing module, decrypting the encrypted code, executing the decrypted code, and preventing the wireless communications device from accessing the decrypted code. Another processing module operating method includes using a processing module physically connected to a host device, executing an application within the processing module, allowing the application to exchange user interaction data communicated using a user interface of the host device with the host device, and allowing the application to use the host device as a communications device for exchanging information with a remote device distinct from the host device.

Telescience operations with the solar array module plasma interaction experiment

NASA Technical Reports Server (NTRS)

Wald, Lawrence W.; Bibyk, Irene K.

1995-01-01

The Solar Array Module Plasma Interactions Experiment (SAMPIE) is a flight experiment that flew on the Space Shuttle Columbia (STS-62) in March 1994, as part of the OAST-2 mission. The overall objective of SAMPIE was to determine the adverse environmental interactions within the space plasma of low earth orbit (LEO) on modern solar cells and space power system materials which are artificially biased to high positive and negative direct current (DC) voltages. The two environmental interactions of interest included high voltage arcing from the samples to the space plasma and parasitic current losses. High voltage arcing can cause physical damage to power system materials and shorten expected hardware life. parasitic current losses can reduce power system efficiency because electric currents generated in a power system drain into the surrounding plasma via parasitic resistance. The flight electronics included two programmable high voltage DC power supplies to bias the experiment samples, instruments to measure the surrounding plasma environment in the STS cargo bay, and the on-board data acquisition system (DAS). The DAS provided in-flight experiment control, data storage, and communications through the Goddard Space Flight Center (GSFC) Hitchhiker flight avionics to the GSFC Payload Operations Control Center (POCC). The DAS and the SAMPIE POCC computer systems were designed for telescience operations; this paper will focus on the experiences of the SAMPIE team regarding telescience development and operations from the GSFC POCC during STS-62. The SAMPIE conceptual development, hardware design, and system verification testing were accomplished at the NASA Lewis Research Center (LeRC). SAMPIE was developed under the In-Space Technology Experiment Program (IN-STEP), which sponsors NASA, industry, and university flight experiments designed to enable and enhance space flight technology. The IN-STEP Program is sponsored by the Office of Space Access and Technology (OSAT).

Just enough, but not too much interactivity leads to better clinical skills performance after a computer assisted learning module.

PubMed

Kalet, A L; Song, H S; Sarpel, U; Schwartz, R; Brenner, J; Ark, T K; Plass, J

2012-01-01

Well-designed computer-assisted instruction (CAI) can potentially transform medical education. Yet little is known about whether specific design features such as direct manipulation of the content yield meaningful gains in clinical learning. We designed three versions of a multimedia module on the abdominal exam incorporating different types of interactivity. As part of their physical diagnosis course, 162 second-year medical students were randomly assigned (1:1:1) to Watch, Click or Drag versions of the abdominal exam module. First, students' prior knowledge, spatial ability, and prior experience with abdominal exams were assessed. After using the module, students took a posttest; demonstrated the abdominal exam on a standardized patient; and wrote structured notes of their findings. Data from 143 students were analyzed. Baseline measures showed no differences among groups regarding prior knowledge, experience, or spatial ability. Overall there was no difference in knowledge across groups. However, physical exam scores were significantly higher for students in the Click group. A mid-range level of behavioral interactivity was associated with small to moderate improvements in performance of clinical skills. These improvements were likely mediated by enhanced engagement with the material, within the bounds of learners' cognitive capacity. These findings have implications for the design of CAI materials to teach procedural skills.

Interacting Network of the Gap Junction (GJ) Protein Connexin43 (Cx43) is Modulated by Ischemia and Reperfusion in the Heart.

PubMed

Martins-Marques, Tania; Anjo, Sandra Isabel; Pereira, Paulo; Manadas, Bruno; Girão, Henrique

2015-11-01

The coordinated and synchronized cardiac muscle contraction relies on an efficient gap junction-mediated intercellular communication (GJIC) between cardiomyocytes, which involves the rapid anisotropic impulse propagation through connexin (Cx)-containing channels, namely of Cx43, the most abundant Cx in the heart. Expectedly, disturbing mechanisms that affect channel activity, localization and turnover of Cx43 have been implicated in several cardiomyopathies, such as myocardial ischemia. Besides gap junction-mediated intercellular communication, Cx43 has been associated with channel-independent functions, including modulation of cell adhesion, differentiation, proliferation and gene transcription. It has been suggested that the role played by Cx43 is dictated by the nature of the proteins that interact with Cx43. Therefore, the characterization of the Cx43-interacting network and its dynamics is vital to understand not only the molecular mechanisms underlying pathological malfunction of gap junction-mediated intercellular communication, but also to unveil novel and unanticipated biological functions of Cx43. In the present report, we applied a quantitative SWATH-MS approach to characterize the Cx43 interactome in rat hearts subjected to ischemia and ischemia-reperfusion. Our results demonstrate that, in the heart, Cx43 interacts with proteins related with various biological processes such as metabolism, signaling and trafficking. The interaction of Cx43 with proteins involved in gene transcription strengthens the emerging concept that Cx43 has a role in gene expression regulation. Importantly, our data shows that the interactome of Cx43 (Connexome) is differentially modulated in diseased hearts. Overall, the characterization of Cx43-interacting network may contribute to the establishment of new therapeutic targets to modulate cardiac function in physiological and pathological conditions. Data are available via ProteomeXchange with identifier PXD002331. © 2015 by

The HMI™ module: a new tool to study the Host-Microbiota Interaction in the human gastrointestinal tract in vitro.

PubMed

Marzorati, Massimo; Vanhoecke, Barbara; De Ryck, Tine; Sadaghian Sadabad, Mehdi; Pinheiro, Iris; Possemiers, Sam; Van den Abbeele, Pieter; Derycke, Lara; Bracke, Marc; Pieters, Jan; Hennebel, Tom; Harmsen, Hermie J; Verstraete, Willy; Van de Wiele, Tom

2014-05-22

Recent scientific developments have shed more light on the importance of the host-microbe interaction, particularly in the gut. However, the mechanistic study of the host-microbe interplay is complicated by the intrinsic limitations in reaching the different areas of the gastrointestinal tract (GIT) in vivo. In this paper, we present the technical validation of a new device--the Host-Microbiota Interaction (HMI) module--and the evidence that it can be used in combination with a gut dynamic simulator to evaluate the effect of a specific treatment at the level of the luminal microbial community and of the host surface colonization and signaling. The HMI module recreates conditions that are physiologically relevant for the GIT: i) a mucosal area to which bacteria can adhere under relevant shear stress (3 dynes cm(-2)); ii) the bilateral transport of low molecular weight metabolites (4 to 150 kDa) with permeation coefficients ranging from 2.4 × 10(-6) to 7.1 × 10(-9) cm sec(-1); and iii) microaerophilic conditions at the bottom of the growing biofilm (PmO2 = 2.5 × 10(-4) cm sec(-1)). In a long-term study, the host's cells in the HMI module were still viable after a 48-hour exposure to a complex microbial community. The dominant mucus-associated microbiota differed from the luminal one and its composition was influenced by the treatment with a dried product derived from yeast fermentation. The latter--with known anti-inflammatory properties--induced a decrease of pro-inflammatory IL-8 production between 24 and 48 h. The study of the in vivo functionality of adhering bacterial communities in the human GIT and of the localized effect on the host is frequently hindered by the complexity of reaching particular areas of the GIT. The HMI module offers the possibility of co-culturing a gut representative microbial community with enterocyte-like cells up to 48 h and may therefore contribute to the mechanistic understanding of host-microbiome interactions.

Developing Classroom Interactions Which Signal Effective Teaching. A Module for Undergraduate Instruction in Teacher Education in the RAFT Program at Mississippi State University.

ERIC Educational Resources Information Center

Handley, Herbert M., Ed.

In this module, developed by the Research Applications for Teaching (RAFT) project, preservice teachers study the major types of classroom interactions which occur between teachers and students and review the research findings showing how these interactions are related to effective teaching. Much effort is spent on describing procedures for…

Modulation of frontostriatal interaction aligns with reduced primary reward processing under serotonergic drugs.

PubMed

Abler, Birgit; Grön, Georg; Hartmann, Antonie; Metzger, Coraline; Walter, Martin

2012-01-25

Recently, functional interactions between anteroventral prefrontal cortex and nucleus accumbens (NAcc) have been shown to relate to behavior counteracting reward-desiring (Diekhof and Gruber, 2010). Downregulation of the reward system by serotonin has also been suggested as the mode of action accounting for unsatisfactory effects of serotonin reuptake inhibitors (SSRIs) such as insufficient alleviation or even increase of anhedonia, and loss of interest. However, understanding of the in vivo mechanisms of SSRI-related alteration of the human reward system is still incomplete. Using functional magnetic resonance imaging (fMRI) within a double-blind cross-over within-subjects study design and administering the SSRI paroxetine, the dopamine/norepinephrine reuptake inhibitor bupropione, and placebo for 7 d each, we investigated a group of 18 healthy male subjects. Under paroxetine, subjects showed significantly decreased activation of the bilateral NAcc during processing of primary rewards (erotic videos), but not under bupropion. Similar to the previous study, analysis of psychophysiological interactions revealed that this downregulation relied on negative interactions between left and right NAcc fMRI signals and the bilateral anteroventral prefrontal cortex that now were significantly enhanced under paroxetine and reduced under bupropion. Individual drug-dependent modulations of interacting brain regions were significantly associated with individual expressions of impulsivity as a personality trait. Our results corroborate and extend previous insights on interregional crosstalk from secondary to primary rewards and demonstrate parallels between active inhibitory control of and serotonergic effects on the dopaminergic reward system's activity.

Rho differentially regulates the Hippo pathway by modulating the interaction between Amot and Nf2 in the blastocyst.

PubMed

Shi, Xianle; Yin, Zixi; Ling, Bin; Wang, Lingling; Liu, Chang; Ruan, Xianhui; Zhang, Weiyu; Chen, Lingyi

2017-11-01

The Hippo pathway modulates the transcriptional activity of Yap to regulate the differentiation of the inner cell mass (ICM) and the trophectoderm (TE) in blastocysts. Yet how Hippo signaling is differentially regulated in ICM and TE cells is poorly understood. Through an inhibitor/activator screen, we have identified Rho as a negative regulator of Hippo in TE cells, and PKA as a positive regulator of Hippo in ICM cells. We further elucidated a novel mechanism by which Rho suppresses Hippo, distinct from the prevailing view that Rho inhibits Hippo signaling through modulating cytoskeleton remodeling and/or cell polarity. Active Rho prevents the phosphorylation of Amot Ser176, thus stabilizing the interaction between Amot and F-actin, and restricting the binding between Amot and Nf2. Moreover, Rho attenuates the interaction between Amot and Nf2 by binding to the coiled-coil domain of Amot. By blocking the association of Nf2 and Amot, Rho suppresses Hippo in TE cells. © 2017. Published by The Company of Biologists Ltd.

Modulation of TEL transcription activity by interaction with the ubiquitin-conjugating enzyme UBC9

PubMed Central

Chakrabarti, Subhra Ranjan; Sood, Rashmi; Ganguly, Surajit; Bohlander, Stefan; Shen, Zhiyuan; Nucifora, Giuseppina

1999-01-01

The E-26 transforming specific (ETS)-related gene TEL, also known as ETV6, is involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. The encoded protein contains two functional domains: a helix–loop–helix (HLH) domain (also known as pointed domain) located at the N terminus and a DNA-binding domain located at the C terminus. The HLH domain is involved in protein–protein interaction with itself and other members of the ETS family of transcription factors such as FLI1. TEL is a transcription factor, and we and others have shown that it is a repressor of gene expression. To understand further the role of TEL in the cell, we have used an in vivo interaction system to identify proteins that interact with TEL. We show that a protein, UBC9, interacts specifically with TEL in vitro and in vivo. UBC9 is a member of the family of ubiquitin-conjugating enzymes. These enzymes usually are involved in proteosome-mediated degradation; however, our data suggest that interaction of TEL with UBC9 does not lead to TEL degradation. Our studies show that UBC9 binds to TEL exclusively through the HLH domain of TEL. We also show that TEL expressed as fusion to the DNA-binding domain of Gal4 completely represses a Gal4-responsive promoter, but that the coexpression of UBC9 in the same system restores the activity of the promoter. Targeted point mutation of conserved amino acids in UBC9 essential for enzymatic ubiquitination of proteins does not affect interaction nor transcriptional activity. Based on our data, we conclude that UBC9 physically interacts with TEL through the HLH domain and that the interaction leads to modulation of the transcription activity of TEL. PMID:10377438

Sanguinarine interacts with chromatin, modulates epigenetic modifications, and transcription in the context of chromatin.

PubMed

Selvi B, Ruthrotha; Pradhan, Suman Kalyan; Shandilya, Jayasha; Das, Chandrima; Sailaja, Badi Sri; Shankar G, Naga; Gadad, Shrikanth S; Reddy, Ashok; Dasgupta, Dipak; Kundu, Tapas K

2009-02-27

DNA-binding anticancer agents cause alteration in chromatin structure and dynamics. We report the dynamic interaction of the DNA intercalator and potential anticancer plant alkaloid, sanguinarine (SGR), with chromatin. Association of SGR with different levels of chromatin structure was enthalpy driven with micromolar dissociation constant. Apart from DNA, it binds with comparable affinity with core histones and induces chromatin aggregation. The dual binding property of SGR leads to inhibition of core histone modifications. Although it potently inhibits H3K9 methylation by G9a in vitro, H3K4 and H3R17 methylation are more profoundly inhibited in cells. SGR inhibits histone acetylation both in vitro and in vivo. It does not affect the in vitro transcription from DNA template but significantly represses acetylation-dependent chromatin transcription. SGR-mediated repression of epigenetic marks and the alteration of chromatin geography (nucleography) also result in the modulation of global gene expression. These data, conclusively, show an anticancer DNA binding intercalator as a modulator of chromatin modifications and transcription in the chromatin context.

Siderophore biosynthesis coordinately modulated the virulence-associated interactive metabolome of uropathogenic Escherichia coli and human urine

PubMed Central

Su, Qiao; Guan, Tianbing; Lv, Haitao

2016-01-01

Uropathogenic Escherichia coli (UPEC) growth in women’s bladders during urinary tract infection (UTI) incurs substantial chemical exchange, termed the “interactive metabolome”, which primarily accounts for the metabolic costs (utilized metabolome) and metabolic donations (excreted metabolome) between UPEC and human urine. Here, we attempted to identify the individualized interactive metabolome between UPEC and human urine. We were able to distinguish UPEC from non-UPEC by employing a combination of metabolomics and genetics. Our results revealed that the interactive metabolome between UPEC and human urine was markedly different from that between non-UPEC and human urine, and that UPEC triggered much stronger perturbations in the interactive metabolome in human urine. Furthermore, siderophore biosynthesis coordinately modulated the individualized interactive metabolome, which we found to be a critical component of UPEC virulence. The individualized virulence-associated interactive metabolome contained 31 different metabolites and 17 central metabolic pathways that were annotated to host these different metabolites, including energetic metabolism, amino acid metabolism, and gut microbe metabolism. Changes in the activities of these pathways mechanistically pinpointed the virulent capability of siderophore biosynthesis. Together, our findings provide novel insights into UPEC virulence, and we propose that siderophores are potential targets for further discovery of drugs to treat UPEC-induced UTI. PMID:27076285

Siderophore biosynthesis coordinately modulated the virulence-associated interactive metabolome of uropathogenic Escherichia coli and human urine.

PubMed

Su, Qiao; Guan, Tianbing; Lv, Haitao

2016-04-14

Uropathogenic Escherichia coli (UPEC) growth in women's bladders during urinary tract infection (UTI) incurs substantial chemical exchange, termed the "interactive metabolome", which primarily accounts for the metabolic costs (utilized metabolome) and metabolic donations (excreted metabolome) between UPEC and human urine. Here, we attempted to identify the individualized interactive metabolome between UPEC and human urine. We were able to distinguish UPEC from non-UPEC by employing a combination of metabolomics and genetics. Our results revealed that the interactive metabolome between UPEC and human urine was markedly different from that between non-UPEC and human urine, and that UPEC triggered much stronger perturbations in the interactive metabolome in human urine. Furthermore, siderophore biosynthesis coordinately modulated the individualized interactive metabolome, which we found to be a critical component of UPEC virulence. The individualized virulence-associated interactive metabolome contained 31 different metabolites and 17 central metabolic pathways that were annotated to host these different metabolites, including energetic metabolism, amino acid metabolism, and gut microbe metabolism. Changes in the activities of these pathways mechanistically pinpointed the virulent capability of siderophore biosynthesis. Together, our findings provide novel insights into UPEC virulence, and we propose that siderophores are potential targets for further discovery of drugs to treat UPEC-induced UTI.

The alpha subunit of Go interacts with promyelocytic leukemia zinc finger protein and modulates its functions.

PubMed

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.

Differential Modulation of Functional Dynamics and Allosteric Interactions in the Hsp90-Cochaperone Complexes with p23 and Aha1: A Computational Study

PubMed Central

Blacklock, Kristin; Verkhivker, Gennady M.

2013-01-01

Allosteric interactions of the molecular chaperone Hsp90 with a large cohort of cochaperones and client proteins allow for molecular communication and event coupling in signal transduction networks. The integration of cochaperones into the Hsp90 system is driven by the regulatory mechanisms that modulate the progression of the ATPase cycle and control the recruitment of the Hsp90 clientele. In this work, we report the results of computational modeling of allosteric regulation in the Hsp90 complexes with the cochaperones p23 and Aha1. By integrating protein docking, biophysical simulations, modeling of allosteric communications, protein structure network analysis and the energy landscape theory we have investigated dynamics and stability of the Hsp90-p23 and Hsp90-Aha1 interactions in direct comparison with the extensive body of structural and functional experiments. The results have revealed that functional dynamics and allosteric interactions of Hsp90 can be selectively modulated by these cochaperones via specific targeting of the regulatory hinge regions that could restrict collective motions and stabilize specific chaperone conformations. The protein structure network parameters have quantified the effects of cochaperones on conformational stability of the Hsp90 complexes and identified dynamically stable communities of residues that can contribute to the strengthening of allosteric interactions. According to our results, p23-mediated changes in the Hsp90 interactions may provide “molecular brakes” that could slow down an efficient transmission of the inter-domain allosteric signals, consistent with the functional role of p23 in partially inhibiting the ATPase cycle. Unlike p23, Aha1-mediated acceleration of the Hsp90-ATPase cycle may be achieved via modulation of the equilibrium motions that facilitate allosteric changes favoring a closed dimerized form of Hsp90. The results of our study have shown that Aha1 and p23 can modulate the Hsp90-ATPase activity

A Structural Perspective on the Modulation of Protein-Protein Interactions with Small Molecules.

PubMed

Demirel, Habibe Cansu; Dogan, Tunca; Tuncbag, Nurcan

2018-05-31

Protein-protein interactions (PPIs) are the key components in many cellular processes including signaling pathways, enzymatic reactions and epigenetic regulation. Abnormal interactions of some proteins may be pathogenic and cause various disorders including cancer and neurodegenerative diseases. Although inhibiting PPIs with small molecules is a challenging task, it gained an increasing interest because of its strong potential for drug discovery and design. The knowledge of the interface as well as the structural and chemical characteristics of the PPIs and their roles in the cellular pathways are necessary for a rational design of small molecules to modulate PPIs. In this study, we review the recent progress in the field and detail the physicochemical properties of PPIs including binding hot spots with a focus on structural methods. Then, we review recent approaches for structural prediction of PPIs. Finally, we revisit the concept of targeting PPIs in a systems biology perspective and we refer to the non-structural approaches, usually employed when the structural information is not present. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cancer-adipose tissue interaction and fluid flow synergistically modulate cell kinetics, HER2 expression, and trastuzumab efficacy in gastric cancer.

PubMed

Akutagawa, Takashi; Aoki, Shigehisa; Yamamoto-Rikitake, Mihoko; Iwakiri, Ryuichi; Fujimoto, Kazuma; Toda, Shuji

2018-04-25

Early local tumor invasion in gastric cancer results in likely encounters between cancer cells and submucosal and subserosal adipose tissue, but these interactions remain to be clarified. Microenvironmental mechanical forces, such as fluid flow, are known to modulate normal cell kinetics, but the effects of fluid flow on gastric cancer cells are poorly understood. We analyzed the cell kinetics and chemosensitivity in gastric cancer using a simple in vitro model that simultaneously replicated the cancer-adipocyte interaction and physical microenvironment. Gastric cancer cells (MKN7 and MKN74) were seeded on rat adipose tissue fragment-embedded discs or collagen discs alone. To generate fluid flow, samples were placed on a rotatory shaker in a CO 2 incubator. Proliferation, apoptosis, invasion, and motility-related molecules were analyzed by morphometry and immunostaining. Proteins were evaluated by western blot analysis. Chemosensitivity was investigated by trastuzumab treatment. Adipose tissue and fluid flow had a positive synergistic effect on the proliferative potential and invasive capacity of gastric cancer cells, and adipose tissue inhibited apoptosis in these cells. Adipose tissue upregulated ERK1/2 signaling in gastric cancer cells, but downregulated p38 signaling. Notably, adipose tissue and fluid flow promoted membranous and cytoplasmic HER2 expression and modulated chemosensitivity to trastuzumab in gastric cancer cells. We have demonstrated that cancer-adipocyte interaction and physical microenvironment mutually modulate gastric cancer cell kinetics. Further elucidation of the microenvironmental regulation in gastric cancer will be very important for the development of strategies involving molecular targeted therapy.

Interactions between target location and reward size modulate the rate of microsaccades in monkeys

PubMed Central

Tokiyama, Stefanie; Lisberger, Stephen G.

2015-01-01

We have studied how rewards modulate the occurrence of microsaccades by manipulating the size of an expected reward and the location of the cue that sets the expectations for future reward. We found an interaction between the size of the reward and the location of the cue. When monkeys fixated on a cue that signaled the size of future reward, the frequency of microsaccades was higher if the monkey expected a large vs. a small reward. When the cue was presented at a site in the visual field that was remote from the position of fixation, reward size had the opposite effect: the frequency of microsaccades was lower when the monkey was expecting a large reward. The strength of pursuit initiation also was affected by reward size and by the presence of microsaccades just before the onset of target motion. The gain of pursuit initiation increased with reward size and decreased when microsaccades occurred just before or after the onset of target motion. The effect of the reward size on pursuit initiation was much larger than any indirect effects reward might cause through modulation of the rate of microsaccades. We found only a weak relationship between microsaccade direction and the location of the exogenous cue relative to fixation position, even in experiments where the location of the cue indicated the direction of target motion. Our results indicate that the expectation of reward is a powerful modulator of the occurrence of microsaccades, perhaps through attentional mechanisms. PMID:26311180

Gauge interaction as periodicity modulation

NASA Astrophysics Data System (ADS)

Dolce, Donatello

2012-06-01

The paper is devoted to a geometrical interpretation of gauge invariance in terms of the formalism of field theory in compact space-time dimensions (Dolce, 2011) [8]. In this formalism, the kinematic information of an interacting elementary particle is encoded on the relativistic geometrodynamics of the boundary of the theory through local transformations of the underlying space-time coordinates. Therefore gauge interactions are described as invariance of the theory under local deformations of the boundary. The resulting local variations of the field solution are interpreted as internal transformations. The internal symmetries of the gauge theory turn out to be related to corresponding space-time local symmetries. In the approximation of local infinitesimal isometric transformations, Maxwell's kinematics and gauge invariance are inferred directly from the variational principle. Furthermore we explicitly impose periodic conditions at the boundary of the theory as semi-classical quantization condition in order to investigate the quantum behavior of gauge interaction. In the abelian case the result is a remarkable formal correspondence with scalar QED.

Masking release for words in amplitude-modulated noise as a function of modulation rate and task

PubMed Central

Buss, Emily; Whittle, Lisa N.; Grose, John H.; Hall, Joseph W.

2009-01-01

For normal-hearing listeners, masked speech recognition can improve with the introduction of masker amplitude modulation. The present experiments tested the hypothesis that this masking release is due in part to an interaction between the temporal distribution of cues necessary to perform the task and the probability of those cues temporally coinciding with masker modulation minima. Stimuli were monosyllabic words masked by speech-shaped noise, and masker modulation was introduced via multiplication with a raised sinusoid of 2.5–40 Hz. Tasks included detection, three-alternative forced-choice identification, and open-set identification. Overall, there was more masking release associated with the closed than the open-set tasks. The best rate of modulation also differed as a function of task; whereas low modulation rates were associated with best performance for the detection and three-alternative identification tasks, performance improved with modulation rate in the open-set task. This task-by-rate interaction was also observed when amplitude-modulated speech was presented in a steady masker, and for low- and high-pass filtered speech presented in modulated noise. These results were interpreted as showing that the optimal rate of amplitude modulation depends on the temporal distribution of speech cues and the information required to perform a particular task. PMID:19603883

Plume-Free Stream Interaction Heating Effects During Orion Crew Module Reentry

NASA Technical Reports Server (NTRS)

Marichalar, J.; Lumpkin, F.; Boyles, K.

2012-01-01

During reentry of the Orion Crew Module (CM), vehicle attitude control will be performed by firing reaction control system (RCS) thrusters. Simulation of RCS plumes and their interaction with the oncoming flow has been difficult for the analysis community due to the large scarf angles of the RCS thrusters and the unsteady nature of the Orion capsule backshell environments. The model for the aerothermal database has thus relied on wind tunnel test data to capture the heating effects of thruster plume interactions with the freestream. These data are only valid for the continuum flow regime of the reentry trajectory. A Direct Simulation Monte Carlo (DSMC) analysis was performed to study the vehicle heating effects that result from the RCS thruster plume interaction with the oncoming freestream flow at high altitudes during Orion CM reentry. The study was performed with the DSMC Analysis Code (DAC). The inflow boundary conditions for the jets were obtained from Data Parallel Line Relaxation (DPLR) computational fluid dynamics (CFD) solutions. Simulations were performed for the roll, yaw, pitch-up and pitch-down jets at altitudes of 105 km, 125 km and 160 km as well as vacuum conditions. For comparison purposes (see Figure 1), the freestream conditions were based on previous DAC simulations performed without active RCS to populate the aerodynamic database for the Orion CM. Other inputs to the analysis included a constant Orbital reentry velocity of 7.5 km/s and angle of attack of 160 degrees. The results of the study showed that the interaction effects decrease quickly with increasing altitude. Also, jets with highly scarfed nozzles cause more severe heating compared to the nozzles with lower scarf angles. The difficulty of performing these simulations was based on the maximum number density and the ratio of number densities between the freestream and the plume for each simulation. The lowest altitude solutions required a substantial amount of computational resources

The ER Contact Proteins VAPA/B Interact with Multiple Autophagy Proteins to Modulate Autophagosome Biogenesis.

PubMed

Zhao, Yan G; Liu, Nan; Miao, Guangyan; Chen, Yong; Zhao, Hongyu; Zhang, Hong

2018-04-23

The endoplasmic reticulum (ER) is the site of biogenesis of the isolation membrane (IM, autophagosome precursor) and forms extensive contacts with IMs during their expansion into double-membrane autophagosomes. Little is known about the molecular mechanism underlying the formation and/or maintenance of the ER/IM contact. The integral ER proteins VAPA and VAPB (VAPs) participate in establishing ER contacts with multiple membranes by interacting with different tethers. Here, we demonstrate that VAPs also modulate ER/IM contact formation. Depletion of VAPs impairs progression of IMs into autophagosomes. Upon autophagy induction, VAPs are recruited to autophagosome formation sites on the ER, a process mediated by their interactions with FIP200 and PI(3)P. VAPs directly interact with FIP200 and ULK1 through their conserved FFAT motifs and stabilize the ULK1/FIP200 complex at the autophagosome formation sites on the ER. The formation of ULK1 puncta is significantly reduced by VAPA/B depletion. VAPs also interact with WIPI2 and enhance the formation of the WIPI2/FIP200 ER/IM tethering complex. Depletion of VMP1, which increases the ER/IM contact, greatly elevates the interaction of VAPs with these autophagy proteins. The VAPB P56S mutation, which is associated with amyotrophic lateral sclerosis, reduces the ULK1/FIP200 interaction and impairs autophagy at an early step, similar to the effect seen in VAPA/B-depleted cells. Our study reveals that VAPs directly interact with multiple ATG proteins, thereby contributing to ER/IM contact formation for autophagosome biogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

MINE: Module Identification in Networks

PubMed Central

2011-01-01

Background Graphical models of network associations are useful for both visualizing and integrating multiple types of association data. Identifying modules, or groups of functionally related gene products, is an important challenge in analyzing biological networks. However, existing tools to identify modules are insufficient when applied to dense networks of experimentally derived interaction data. To address this problem, we have developed an agglomerative clustering method that is able to identify highly modular sets of gene products within highly interconnected molecular interaction networks. Results MINE outperforms MCODE, CFinder, NEMO, SPICi, and MCL in identifying non-exclusive, high modularity clusters when applied to the C. elegans protein-protein interaction network. The algorithm generally achieves superior geometric accuracy and modularity for annotated functional categories. In comparison with the most closely related algorithm, MCODE, the top clusters identified by MINE are consistently of higher density and MINE is less likely to designate overlapping modules as a single unit. MINE offers a high level of granularity with a small number of adjustable parameters, enabling users to fine-tune cluster results for input networks with differing topological properties. Conclusions MINE was created in response to the challenge of discovering high quality modules of gene products within highly interconnected biological networks. The algorithm allows a high degree of flexibility and user-customisation of results with few adjustable parameters. MINE outperforms several popular clustering algorithms in identifying modules with high modularity and obtains good overall recall and precision of functional annotations in protein-protein interaction networks from both S. cerevisiae and C. elegans. PMID:21605434

Estrogen Receptor Folding Modulates cSrc Kinase SH2 Interaction via a Helical Binding Mode.

PubMed

Nieto, Lidia; Tharun, Inga M; Balk, Mark; Wienk, Hans; Boelens, Rolf; Ottmann, Christian; Milroy, Lech-Gustav; Brunsveld, Luc

2015-11-20

The estrogen receptors (ERs) feature, next to their transcriptional role, important nongenomic signaling actions, with emerging clinical relevance. The Src Homology 2 (SH2) domain mediated interaction between cSrc kinase and ER plays a key role in this; however the molecular determinants of this interaction have not been elucidated. Here, we used phosphorylated ER peptide and semisynthetic protein constructs in a combined biochemical and structural study to, for the first time, provide a quantitative and structural characterization of the cSrc SH2-ER interaction. Fluorescence polarization experiments delineated the SH2 binding motif in the ER sequence. Chemical shift perturbation analysis by nuclear magnetic resonance (NMR) together with molecular dynamics (MD) simulations allowed us to put forward a 3D model of the ER-SH2 interaction. The structural basis of this protein-protein interaction has been compared with that of the high affinity SH2 binding sequence GpYEEI. The ER features a different binding mode from that of the "two-pronged plug two-hole socket" model in the so-called specificity determining region. This alternative binding mode is modulated via the folding of ER helix 12, a structural element directly C-terminal of the key phosphorylated tyrosine. The present findings provide novel molecular entries for understanding nongenomic ER signaling and targeting the corresponding disease states.

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

PubMed

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

2012-01-01

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

Cancer Cell Biology: A Student-Centered Instructional Module Exploring the Use of Multimedia to Enrich Interactive, Constructivist Learning of Science

PubMed Central

Bockholt, Susanne M.; West, J. Paige; Bollenbacher, Walter E.

2003-01-01

Multimedia has the potential of providing bioscience education novel learning environments and pedagogy applications to foster student interest, involve students in the research process, advance critical thinking/problem-solving skills, and develop conceptual understanding of biological topics. Cancer Cell Biology, an interactive, multimedia, problem-based module, focuses on how mutations in protooncogenes and tumor suppressor genes can lead to uncontrolled cell proliferation by engaging students as research scientists/physicians with the task of diagnosing the molecular basis of tumor growth for a group of patients. The process of constructing the module, which was guided by scientist and student feedback/responses, is described. The completed module and insights gained from its development are presented as a potential “multimedia pedagogy” for the development of other multimedia science learning environments. PMID:12822037

Phototropism: a "simple" physiological response modulated by multiple interacting photosensory-response pathways.

PubMed

Liscum, E; Stowe-Evans, E L

2000-09-01

Phototropism is the process by which plants reorient growth of various organs, most notably stems, in response to lateral differences in light quantity and/or quality. The ubiquitous nature of the phototropic response in the plant kingdom implies that it provides some adaptive evolutionary advantage. Upon visual inspection it is tempting to surmise that phototropic curvatures result from a relatively simple growth response to a directional stimulus. However, detailed photophysiological, and more recently genetic and molecular, studies have demonstrated that phototropism is in fact regulated by complex interactions among several photosensory systems. At least two receptors, phototropin and a presently unidentified receptor, appear to mediate the primary photoreception of directional blue light cues in dark-grown plants. PhyB may also function as a primary receptor to detect lateral increases in far-red light in neighbor-avoidance responses of light-grown plants. Phytochromes (phyA and phyB at a minimum) also appear to function as secondary receptors to regulate adaptation processes that ultimately modulate the magnitude of curvature induced by primary photoperception. As a result of the interactions of these multiple photosensory systems plants are able to maximize the adaptive advantage of the phototropic response in ever changing light environments.

The HMI™ module: a new tool to study the Host-Microbiota Interaction in the human gastrointestinal tract in vitro

PubMed Central

2014-01-01

Background Recent scientific developments have shed more light on the importance of the host-microbe interaction, particularly in the gut. However, the mechanistic study of the host-microbe interplay is complicated by the intrinsic limitations in reaching the different areas of the gastrointestinal tract (GIT) in vivo. In this paper, we present the technical validation of a new device - the Host-Microbiota Interaction (HMI) module - and the evidence that it can be used in combination with a gut dynamic simulator to evaluate the effect of a specific treatment at the level of the luminal microbial community and of the host surface colonization and signaling. Results The HMI module recreates conditions that are physiologically relevant for the GIT: i) a mucosal area to which bacteria can adhere under relevant shear stress (3 dynes cm−2); ii) the bilateral transport of low molecular weight metabolites (4 to 150 kDa) with permeation coefficients ranging from 2.4 × 10−6 to 7.1 × 10−9 cm sec−1; and iii) microaerophilic conditions at the bottom of the growing biofilm (PmO2 = 2.5 × 10−4 cm sec−1). In a long-term study, the host’s cells in the HMI module were still viable after a 48-hour exposure to a complex microbial community. The dominant mucus-associated microbiota differed from the luminal one and its composition was influenced by the treatment with a dried product derived from yeast fermentation. The latter - with known anti-inflammatory properties - induced a decrease of pro-inflammatory IL-8 production between 24 and 48 h. Conclusions The study of the in vivo functionality of adhering bacterial communities in the human GIT and of the localized effect on the host is frequently hindered by the complexity of reaching particular areas of the GIT. The HMI module offers the possibility of co-culturing a gut representative microbial community with enterocyte-like cells up to 48 h and may therefore contribute to the mechanistic understanding of

Control-structure interaction study for the Space Station solar dynamic power module

NASA Technical Reports Server (NTRS)

Cheng, J.; Ianculescu, G.; Ly, J.; Kim, M.

1991-01-01

The authors investigate the feasibility of using a conventional PID (proportional plus integral plus derivative) controller design to perform the pointing and tracking functions for the Space Station Freedom solar dynamic power module. Using this simple controller design, the control/structure interaction effects were also studied without assuming frequency bandwidth separation. From the results, the feasibility of a simple solar dynamic control solution with a reduced-order model, which satisfies the basic system pointing and stability requirements, is suggested. However, the conventional control design approach is shown to be very much influenced by the order of reduction of the plant model, i.e., the number of the retained elastic modes from the full-order model. This suggests that, for complex large space structures, such as the Space Station Freedom solar dynamic, the conventional control system design methods may not be adequate.

Development of Land Analysis System display modules

NASA Technical Reports Server (NTRS)

Gordon, Douglas; Hollaren, Douglas; Huewe, Laurie

1986-01-01

The Land Analysis System (LAS) display modules were developed to allow a user to interactively display, manipulate, and store image and image related data. To help accomplish this task, these modules utilize the Transportable Applications Executive and the Display Management System software to interact with the user and the display device. The basic characteristics of a display are outlined and some of the major modifications and additions made to the display management software are discussed. Finally, all available LAS display modules are listed along with a short description of each.

Allosteric Modulation of Chemoattractant Receptors

PubMed Central

Allegretti, Marcello; Cesta, Maria Candida; Locati, Massimo

2016-01-01

Chemoattractants control selective leukocyte homing via interactions with a dedicated family of related G protein-coupled receptor (GPCR). Emerging evidence indicates that the signaling activity of these receptors, as for other GPCR, is influenced by allosteric modulators, which interact with the receptor in a binding site distinct from the binding site of the agonist and modulate the receptor signaling activity in response to the orthosteric ligand. Allosteric modulators have a number of potential advantages over orthosteric agonists/antagonists as therapeutic agents and offer unprecedented opportunities to identify extremely selective drug leads. Here, we resume evidence of allosterism in the context of chemoattractant receptors, discussing in particular its functional impact on functional selectivity and probe/concentration dependence of orthosteric ligands activities. PMID:27199992

Application of mass spectrometry technologies for the discovery of low-molecular weight modulators of enzymes and protein-protein interactions.

PubMed

Zehender, Hartmut; Mayr, Lorenz M

2007-10-01

In recent years, mass spectrometry has gained widespread use as an assay and screening technology in drug discovery because it enables sensitive, label-free detection of low-molecular weight modulators of biomolecules as well as sensitive and accurate detection of high-molecular weight modifications of biomolecules. Electrospray and matrix-assisted laser desorption ionization are the most widely used ionization techniques to identify chemical compounds interfering with enzymatic function, receptor-ligand binding or molecules modulating a protein-protein interaction of interest. Mass spectrometry based techniques are no longer restricted to screening in biochemical assay systems but have now become also applicable to imaging of biomolecules and chemical compounds in cell-based assay systems and even in highly complex tissue sections.

Electrochemical capacitance modulation in an interacting mesoscopic capacitor induced by internal charge transfer

NASA Astrophysics Data System (ADS)

Liu, Wei; He, Jianhong; Guo, Huazhong; Gao, Jie

2018-04-01

We report experiments on the dynamic response of an interacting mesoscopic capacitor consisting of a quantum dot with two confined spin-split levels of the lowest Landau level. In high magnetic fields, states inside the dot are regulated by a mixture of Coulomb interaction and Landau-level quantization, and electrons distribute on two spatially separated regions. Quantum point contact voltage and magnetic field are employed to manipulate the number and distribution of electrons inside the quantum dot. We find that the periodicity of the electrochemical capacitance oscillations is dominated by the charging energy, and their amplitudes, due to internal charge transfer and strong internal capacitive coupling, show rich variations of modulations. Magnetocapacitance displays a sawtoothlike manner and may differ in tooth directions for different voltages, which, we demonstrate, result from a sawtoothlike electrochemical potential change induced by internal charge transfer and field-sensitive electrostatic potential. We further build a charge stability diagram, which, together with all other capacitance properties, is consistently interpreted in terms of a double-dot model. The demonstrated technique is of interest as a tool for fast and sensitive charge state readout of a double-quantum-dot qubit in the gigahertz frequency quantum electronics.

Interferometric modulation of quantum cascade interactions

NASA Astrophysics Data System (ADS)

Cusumano, Stefano; Mari, Andrea; Giovannetti, Vittorio

2018-05-01

We consider many-body quantum systems dissipatively coupled by a cascade network, i.e., a setup in which interactions are mediated by unidirectional environmental modes propagating through a linear optical interferometer. In particular we are interested in the possibility of inducing different effective interactions by properly engineering an external dissipative network of beam splitters and phase shifters. In this work we first derive the general structure of the master equation for a symmetric class of translation-invariant cascade networks. Then we show how, by tuning the parameters of the interferometer, one can exploit interference effects to tailor a large variety of many-body interactions.

The integration of audio-tactile information is modulated by multimodal social interaction with physical contact in infancy.

PubMed

Tanaka, Yukari; Kanakogi, Yasuhiro; Kawasaki, Masahiro; Myowa, Masako

2018-04-01

Interaction between caregivers and infants is multimodal in nature. To react interactively and smoothly to such multimodal signals, infants must integrate all these signals. However, few empirical infant studies have investigated how multimodal social interaction with physical contact facilitates multimodal integration, especially regarding audio - tactile (A-T) information. By using electroencephalogram (EEG) and event-related potentials (ERPs), the present study investigated how neural processing involved in A-T integration is modulated by tactile interaction. Seven- to 8-months-old infants heard one pseudoword both whilst being tickled (multimodal 'A-T' condition), and not being tickled (unimodal 'A' condition). Thereafter, their EEG was measured during the perception of the same words. Compared to the A condition, the A-T condition resulted in enhanced ERPs and higher beta-band activity within the left temporal regions, indicating neural processing of A-T integration. Additionally, theta-band activity within the middle frontal region was enhanced, which may reflect enhanced attention to social information. Furthermore, differential ERPs correlated with the degree of engagement in the tickling interaction. We provide neural evidence that the integration of A-T information in infants' brains is facilitated through tactile interaction with others. Such plastic changes in neural processing may promote harmonious social interaction and effective learning in infancy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

PubMed

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

2014-10-01

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

Imaging contrast and tip-sample interaction of non-contact amplitude modulation atomic force microscopy with Q-control

NASA Astrophysics Data System (ADS)

Shi, Shuai; Guo, Dan; Luo, Jianbin

2017-10-01

Active quality factor (Q) exhibits many promising properties in dynamic atomic force microscopy. Energy dissipation and image contrasts are investigated in the non-contact amplitude modulation atomic force microscopy (AM-AFM) with an active Q-control circuit in the ambient air environment. Dissipated power and virial were calculated to compare the highly nonlinear interaction of tip-sample and image contrasts with different Q gain values. Greater free amplitudes and lower effective Q values show better contrasts for the same setpoint ratio. Active quality factor also can be employed to change tip-sample interaction force in non-contact regime. It is meaningful that non-destructive and better contrast images can be realized in non-contact AM-AFM by applying an active Q-control to the dynamic system.

"iBIM"--internet-based interactive modules: an easy and interesting learning tool for general surgery residents.

PubMed

Azer, Nader; Shi, Xinzhe; de Gara, Chris; Karmali, Shahzeer; Birch, Daniel W

2014-04-01

The increased use of information technology supports a resident- centred educational approach that promotes autonomy, flexibility and time management and helps residents to assess their competence, promoting self-awareness. We established a web-based e-learning tool to introduce general surgery residents to bariatric surgery and evaluate them to determine the most appropriate implementation strategy for Internet-based interactive modules (iBIM) in surgical teaching. Usernames and passwords were assigned to general surgery residents at the University of Alberta. They were directed to the Obesity101 website and prompted to complete a multiple-choice precourse test. Afterwards, they were able to access the interactive modules. Residents could review the course material as often as they wanted before completing a multiple-choice postcourse test and exit survey. We used paired t tests to assess the difference between pre- and postcourse scores. Out of 34 residents who agreed to participate in the project, 12 completed the project (35.3%). For these 12 residents, the precourse mean score was 50 ± 17.3 and the postcourse mean score was 67 ± 14 (p = 0.020). Most residents who participated in this study recommended using the iBIMs as a study tool for bariatric surgery. Course evaluation scores suggest this novel approach was successful in transferring knowledge to surgical trainees. Further development of this tool and assessment of implementation strategies will determine how iBIM in bariatric surgery may be integrated into the curriculum.

Driving the need to feed: Insight into the collaborative interaction between ghrelin and endocannabinoid systems in modulating brain reward systems.

PubMed

Edwards, Alexander; Abizaid, Alfonso

2016-07-01

Independent stimulation of either the ghrelin or endocannabinoid system promotes food intake and increases adiposity. Given the similar distribution of their receptors in feeding associated brain regions and organs involved in metabolism, it is not surprising that evidence of their interaction and its importance in modulating energy balance has emerged. This review documents the relationship between ghrelin and endocannabinoid systems within the periphery and hypothalamus (HYP) before presenting evidence suggesting that these two systems likewise work collaboratively within the ventral tegmental area (VTA) to modulate non-homeostatic feeding. Mechanisms, consistent with current evidence and local infrastructure within the VTA, will be proposed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Capsule expression in Streptococcus mitis modulates interaction with oral keratinocytes and alters susceptibility to human antimicrobial peptides.

PubMed

Rukke, H V; Engen, S A; Schenck, K; Petersen, F C

2016-08-01

Streptococcus mitis is a colonizer of the oral cavity and the nasopharynx, and is closely related to Streptococcus pneumoniae. Both species occur in encapsulated and unencapsulated forms, but in S. mitis the role of the capsule in host interactions is mostly unknown. Therefore, the aim of this study was to examine how capsule expression in S. mitis can modulate interactions with the host with relevance for colonization. The S. mitis type strain, as well as two mutants of the type strain, an isogenic capsule deletion mutant, and a capsule switch mutant expressing the serotype 4 capsule of S. pneumoniae TIGR4, were used. Wild-type and capsule deletion strains of S. pneumoniae TIGR4 were included for comparison. We found that capsule production in S. mitis reduced adhesion to oral and lung epithelial cells. Further, exposure of oral epithelial cells to encapsulated S. mitis resulted in higher interleukin-6 and CXCL-8 transcription levels relative to the unencapsulated mutant. Capsule expression in S. mitis increased the sensitivity to human neutrophil peptide 1-3 but reduced the sensitivity to human β-defensin-3 and cathelicidin. This was in contrast with S. pneumoniae in which capsule expression has been generally associated with increased sensitivity to human antimicrobial peptides (AMPs). Collectively, these findings indicate that capsule expression in S. mitis is important in modulating interactions with epithelial cells, and is associated with increased or reduced susceptibility to AMPs depending on the nature of the AMP. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

HSP27 phosphorylation modulates TRAIL-induced activation of Src-Akt/ERK signaling through interaction with β-arrestin2.

PubMed

Qi, Shimei; Xin, Yinqiang; Qi, Zhilin; Xu, Yimiao; Diao, Ying; Lan, Lei; Luo, Lan; Yin, Zhimin

2014-03-01

Heat shock protein 27 (HSP27) regulates critical cellular functions such as development, differentiation, cell growth and apoptosis. A variety of stimuli induce the phosphorylation of HSP27, which affects its cellular functions. However, most previous studies focused on the role of HSP27 protein itself in apoptosis, the particular role of its phosphorylation state in signaling transduction remains largely unclear. In the present study, we reported that HSP27 phosphorylation modulated TRAIL-triggered pro-survival signaling transduction. In HeLa cells, suppression of HSP27 phosphorylation by specific inhibitor KRIBB3 or MAPKAPK2 (MK2) knockdown and by overexpression of non-phosphorylatable HSP27(3A) mutant demonstrated that hindered HSP27 phosphorylation enhanced the TRAIL-induced apoptosis. In addition, reduced HSP27 phosphorylation by KRIBB3 treatment or MK2 knockdown attenuated the TRAIL-induced activation of Akt and ERK survival signaling through suppressing the phosphorylation of Src. By overexpression of HSP27(15A) or HSP27(78/82A) phosphorylation mutant, we further showed that phosphorylation of HSP27 at serine 78/82 residues was essential to TRAIL-triggered Src-Akt/ERK signaling transduction. Co-immunoprecipitation and confocal microscopy showed that HSP27 interacted with Src and scaffolding protein β-arrestin2 in response of TRAIL stimulation and suppression of HSP27 phosphorylation apparently disrupted the TRAIL-induced interaction of HSP27 and Src or interaction of HSP27 and β-arrestin2. We further demonstrated that β-arrestin2 mediated HSP27 action on TRAIL-induced Src activation, which was achieved by recruiting signaling complex of HSP27/β-arrestin2/Src in response to TRAIL. Taken together, our study revealed that HSP27 phosphorylation modulates TRAIL-triggered activation of Src-Akt/ERK pro-survival signaling via interacting with β-arrestin2 in HeLa cells. Copyright © 2013 Elsevier Inc. All rights reserved.

High-throughput analysis of peptide binding modules

PubMed Central

Liu, Bernard A.; Engelmann, Brett; Nash, Piers D.

2014-01-01

Modular protein interaction domains that recognize linear peptide motifs are found in hundreds of proteins within the human genome. Some protein interaction domains such as SH2, 14-3-3, Chromo and Bromo domains serve to recognize post-translational modification of amino acids (such as phosphorylation, acetylation, methylation etc.) and translate these into discrete cellular responses. Other modules such as SH3 and PDZ domains recognize linear peptide epitopes and serve to organize protein complexes based on localization and regions of elevated concentration. In both cases, the ability to nucleate specific signaling complexes is in large part dependent on the selectivity of a given protein module for its cognate peptide ligand. High throughput analysis of peptide-binding domains by peptide or protein arrays, phage display, mass spectrometry or other HTP techniques provides new insight into the potential protein-protein interactions prescribed by individual or even whole families of modules. Systems level analyses have also promoted a deeper understanding of the underlying principles that govern selective protein-protein interactions and how selectivity evolves. Lastly, there is a growing appreciation for the limitations and potential pitfalls of high-throughput analysis of protein-peptide interactomes. This review will examine some of the common approaches utilized for large-scale studies of protein interaction domains and suggest a set of standards for the analysis and validation of datasets from large-scale studies of peptide-binding modules. We will also highlight how data from large-scale studies of modular interaction domain families can provide insight into systems level properties such as the linguistics of selective interactions. PMID:22610655

Modulation in prototropism of the photosensitizer Harmane by host:guest interactions between β-cyclodextrin and surfactants.

PubMed

Paul, Bijan K; Ray, Debarati; Ganguly, Aniruddha; Guchhait, Nikhil

2013-12-01

The present contribution demonstrates the photophysics of a prospective cancer cell photosensitizer Harmane (HM) belonging to the family of β-carboline in mixed microheterogeneous environments of β-cyclodextrin (β-CD) and surfactants having varying surface charges using steady-state and time-resolved fluorescence spectroscopic techniques. The remarkable modulations in prototropic activities of the micelle-bound drug in the presence of β-CD evinces for disruption of the micellar structural integrity by β-CD. The results are meticulously discussed in relevance to the effect of a potential drug delivery vehicle (CD) on the membrane-mimetic micellar system. Further, application of an extrinsic fluorescence probe for monitoring such interactions is fraught by the possibilities of no less than three equilibria that can operate simultaneously viz., (i) surfactant-cyclodextrin, (ii) surfactant-fluorophore and (iii) cyclodextrin-fluorophore. This aspect highlights the enormous importance of the issue of suitability of the fluorescence probe to study such complicated systems and interaction phenomena. Also the varying interaction scenario of β-CD with the nature of the surfactant highlights the importance of precise knowledge of the strength and locus of drug binding in delineating such complex interactions. The results of the present investigation advocate for the potential applicability of the drug (HM) itself as a fluorescence reporter in study of such complex microheterogeneous interactions. Copyright © 2013 Elsevier Inc. All rights reserved.

Long-range functional interactions of anterior insula and medial frontal cortex are differently modulated by visuospatial and inductive reasoning tasks.

PubMed

Ebisch, Sjoerd J H; Mantini, Dante; Romanelli, Roberta; Tommasi, Marco; Perrucci, Mauro G; Romani, Gian Luca; Colom, Roberto; Saggino, Aristide

2013-09-01

The brain is organized into functionally specific networks as characterized by intrinsic functional relationships within discrete sets of brain regions. However, it is poorly understood whether such functional networks are dynamically organized according to specific task-states. The anterior insular cortex (aIC)-dorsal anterior cingulate cortex (dACC)/medial frontal cortex (mFC) network has been proposed to play a central role in human cognitive abilities. The present functional magnetic resonance imaging (fMRI) study aimed at testing whether functional interactions of the aIC-dACC/mFC network in terms of temporally correlated patterns of neural activity across brain regions are dynamically modulated by transitory, ongoing task demands. For this purpose, functional interactions of the aIC-dACC/mFC network are compared during two distinguishable fluid reasoning tasks, Visualization and Induction. The results show an increased functional coupling of bilateral aIC with visual cortices in the occipital lobe during the Visualization task, whereas coupling of mFC with right anterior frontal cortex was enhanced during the Induction task. These task-specific modulations of functional interactions likely reflect ability related neural processing. Furthermore, functional connectivity strength between right aIC and right dACC/mFC reliably predicts general task performance. The findings suggest that the analysis of long-range functional interactions may provide complementary information about brain-behavior relationships. On the basis of our results, it is proposed that the aIC-dACC/mFC network contributes to the integration of task-common and task-specific information based on its within-network as well as its between-network dynamic functional interactions. Copyright © 2013 Elsevier Inc. All rights reserved.

SOX2 O-GlcNAcylation alters its protein-protein interactions and genomic occupancy to modulate gene expression in pluripotent cells

PubMed Central

Myers, Samuel A; Peddada, Sailaja; Chatterjee, Nilanjana; Friedrich, Tara; Tomoda, Kiichrio; Krings, Gregor; Thomas, Sean; Maynard, Jason; Broeker, Michael; Thomson, Matthew; Pollard, Katherine; Yamanaka, Shinya; Burlingame, Alma L; Panning, Barbara

2016-01-01

The transcription factor SOX2 is central in establishing and maintaining pluripotency. The processes that modulate SOX2 activity to promote pluripotency are not well understood. Here, we show SOX2 is O-GlcNAc modified in its transactivation domain during reprogramming and in mouse embryonic stem cells (mESCs). Upon induction of differentiation SOX2 O-GlcNAcylation at serine 248 is decreased. Replacing wild type with an O-GlcNAc-deficient SOX2 (S248A) increases reprogramming efficiency. ESCs with O-GlcNAc-deficient SOX2 exhibit alterations in gene expression. This change correlates with altered protein-protein interactions and genomic occupancy of the O-GlcNAc-deficient SOX2 compared to wild type. In addition, SOX2 O-GlcNAcylation impairs the SOX2-PARP1 interaction, which has been shown to regulate ESC self-renewal. These findings show that SOX2 activity is modulated by O-GlcNAc, and provide a novel regulatory mechanism for this crucial pluripotency transcription factor. DOI: http://dx.doi.org/10.7554/eLife.10647.001 PMID:26949256

Plasma Protein Corona Modulates the Vascular Wall Interaction of Drug Carriers in a Material and Donor Specific Manner

PubMed Central

Sobczynski, Daniel J.; Charoenphol, Phapanin; Heslinga, Michael J.; Onyskiw, Peter J.; Namdee, Katawut; Thompson, Alex J.; Eniola-Adefeso, Omolola

2014-01-01

The nanoscale plasma protein interaction with intravenously injected particulate carrier systems is known to modulate their organ distribution and clearance from the bloodstream. However, the role of this plasma protein interaction in prescribing the adhesion of carriers to the vascular wall remains relatively unknown. Here, we show that the adhesion of vascular-targeted poly(lactide-co-glycolic-acid) (PLGA) spheres to endothelial cells is significantly inhibited in human blood flow, with up to 90% reduction in adhesion observed relative to adhesion in simple buffer flow, depending on the particle size and the magnitude and pattern of blood flow. This reduced PLGA adhesion in blood flow is linked to the adsorption of certain high molecular weight plasma proteins on PLGA and is donor specific, where large reductions in particle adhesion in blood flow (>80% relative to buffer) is seen with ∼60% of unique donor bloods while others exhibit moderate to no reductions. The depletion of high molecular weight immunoglobulins from plasma is shown to successfully restore PLGA vascular wall adhesion. The observed plasma protein effect on PLGA is likely due to material characteristics since the effect is not replicated with polystyrene or silica spheres. These particles effectively adhere to the endothelium at a higher level in blood over buffer flow. Overall, understanding how distinct plasma proteins modulate the vascular wall interaction of vascular-targeted carriers of different material characteristics would allow for the design of highly functional delivery vehicles for the treatment of many serious human diseases. PMID:25229244

The alpha subunit of Go modulates cell proliferation and differentiation through interactions with Necdin.

PubMed

Ju, Hyunhee; Lee, Sujin; Kang, Sunghak; Kim, Sung-Soo; Ghil, Sungho

2014-07-10

Heterotrimeric GTP-binding proteins (G-proteins) play an important role in mediating signal transduction generated by neurotransmitters or hormones. Go, a member of the Gi/Go subfamily, is the most abundant G-protein found in the brain. Recently, the alpha subunit of Go (Gαo) was characterized as an inducer of neuronal differentiation. However, its underlying molecular mechanisms have remained unclear to date, since the downstream effectors of Gαo are ambiguous. A neurally differentiated embryonal carcinoma-derived protein (Necdin) was isolated as an interacting partner for Gαo from a mouse brain cDNA library using yeast two-hybrid screening. Interactions between the proteins were confirmed with several affinity binding assays, both in vitro and in vivo. Necdin interacted directly and preferentially with activated Gαo, compared to wild-type protein. Interestingly, Gαo did not interact with Gαi, despite high sequence homology between the two proteins. We subsequently analyzed whether Gαo modulates the cellular activities of Necdin. Notably, expression of Gαo significantly augmented Necdin-mediated cellular responses, such as proliferation and differentiation. Moreover, activation of type 1 cannabinoid receptor (CB1R), a Gi/oα-coupled receptor, augmented cell growth suppression, which was mediated by Gαo and Necdin in U87MG cells containing CB1R, Gαo, and Necdin as normal components. These results collectively suggest that Necdin is a candidate downstream effector for Gαo. Our findings provide novel insights into the cellular roles of Gαo and its coupled receptor.

A new level of regulation in gluconeogenesis: metabolic state modulates the intracellular localization of aldolase B and its interaction with liver fructose-1,6-bisphosphatase.

PubMed

Droppelmann, Cristian A; Sáez, Doris E; Asenjo, Joel L; Yáñez, Alejandro J; García-Rocha, Mar; Concha, Ilona I; Grez, Manuel; Guinovart, Joan J; Slebe, Juan C

2015-12-01

Understanding how glucose metabolism is finely regulated at molecular and cellular levels in the liver is critical for knowing its relationship to related pathologies, such as diabetes. In order to gain insight into the regulation of glucose metabolism, we studied the liver-expressed isoforms aldolase B and fructose-1,6-bisphosphatase-1 (FBPase-1), key enzymes in gluconeogenesis, analysing their cellular localization in hepatocytes under different metabolic conditions and their protein-protein interaction in vitro and in vivo. We observed that glucose, insulin, glucagon and adrenaline differentially modulate the intracellular distribution of aldolase B and FBPase-1. Interestingly, the in vitro protein-protein interaction analysis between aldolase B and FBPase-1 showed a specific and regulable interaction between them, whereas aldolase A (muscle isozyme) and FBPase-1 showed no interaction. The affinity of the aldolase B and FBPase-1 complex was modulated by intermediate metabolites, but only in the presence of K(+). We observed a decreased association constant in the presence of adenosine monophosphate, fructose-2,6-bisphosphate, fructose-6-phosphate and inhibitory concentrations of fructose-1,6-bisphosphate. Conversely, the association constant of the complex increased in the presence of dihydroxyacetone phosphate (DHAP) and non-inhibitory concentrations of fructose-1,6-bisphosphate. Notably, in vivo FRET studies confirmed the interaction between aldolase B and FBPase-1. Also, the co-expression of aldolase B and FBPase-1 in cultured cells suggested that FBPase-1 guides the cellular localization of aldolase B. Our results provide further evidence that metabolic conditions modulate aldolase B and FBPase-1 activity at the cellular level through the regulation of their interaction, suggesting that their association confers a catalytic advantage for both enzymes. © 2015 Authors; published by Portland Press Limited.

GLADIATOR: a global approach for elucidating disease modules.

PubMed

Silberberg, Yael; Kupiec, Martin; Sharan, Roded

2017-05-26

Understanding the genetic basis of disease is an important challenge in biology and medicine. The observation that disease-related proteins often interact with one another has motivated numerous network-based approaches for deciphering disease mechanisms. In particular, protein-protein interaction networks were successfully used to illuminate disease modules, i.e., interacting proteins working in concert to drive a disease. The identification of these modules can further our understanding of disease mechanisms. We devised a global method for the prediction of multiple disease modules simultaneously named GLADIATOR (GLobal Approach for DIsease AssociaTed mOdule Reconstruction). GLADIATOR relies on a gold-standard disease phenotypic similarity to obtain a pan-disease view of the underlying modules. To traverse the search space of potential disease modules, we applied a simulated annealing algorithm aimed at maximizing the correlation between module similarity and the gold-standard phenotypic similarity. Importantly, this optimization is employed over hundreds of diseases simultaneously. GLADIATOR's predicted modules highly agree with current knowledge about disease-related proteins. Furthermore, the modules exhibit high coherence with respect to functional annotations and are highly enriched with known curated pathways, outperforming previous methods. Examination of the predicted proteins shared by similar diseases demonstrates the diverse role of these proteins in mediating related processes across similar diseases. Last, we provide a detailed analysis of the suggested molecular mechanism predicted by GLADIATOR for hyperinsulinism, suggesting novel proteins involved in its pathology. GLADIATOR predicts disease modules by integrating knowledge of disease-related proteins and phenotypes across multiple diseases. The predicted modules are functionally coherent and are more in line with current biological knowledge compared to modules obtained using previous disease

Norepinephrine versus Dopamine and their Interaction in Modulating Synaptic Function in the Prefrontal Cortex

PubMed Central

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

2016-01-01

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. PMID:26790349

Multiple effects of S13 in modulating the strength of intersubunit interactions in the ribosome during translation.

PubMed

Cukras, Anthony R; Green, Rachel

2005-05-27

The ribosomal protein S13 is found in the head region of the small subunit, where it interacts with the central protuberance of the large ribosomal subunit and with the P site-bound tRNA through its extended C terminus. The bridging interactions between the large and small subunits are dynamic, and are thought to be critical in orchestrating the molecular motions of the translation cycle. S13 provides a direct link between the tRNA-binding site and the movements in the head of the small subunit seen during translocation, thereby providing a possible pathway of signal transduction. We have created and characterized an rpsM(S13)-deficient strain of Escherichia coli and have found significant defects in subunit association, initiation and translocation through in vitro assays of S13-deficient ribosomes. Targeted mutagenesis of specific bridge and tRNA contact elements in S13 provides evidence that these two interaction domains play critical roles in maintaining the fidelity of translation. This ribosomal protein thus appears to play a non-essential, yet important role by modulating subunit interactions in multiple steps of the translation cycle.

Cosmic ray modulation and merged interaction regions

NASA Technical Reports Server (NTRS)

Burlaga, L. F.; Goldstein, M. L.; Mcdonald, F. B.

1985-01-01

Beyond several AU, interactions among shocks and streams give rise to merged interaction regions in which the magnetic field is turbulent. The integral intensity of . 75 MeV/Nuc cosmic rays at Voyager is generally observed to decrease when a merged interaction region moves past the spacecraft and to increase during the passage of a rarefaction region. When the separation between interaction regions is relatively large, the cosmic ray intensity tends to increase on a scale of a few months. This was the case at Voyager 1 from July 1, 1983 to May 1, 1984, when the spacecraft moved from 16.7 to 19.6 AU. Changes in cosmic ray intensity were related to the magnetic field strength in a simple way. It is estimated that the diffusion coefficient in merged interaction regions at this distance is similar to 0.6 x 10 to the 22nd power sq cm/s.

Investigation of allosteric modulation mechanism of metabotropic glutamate receptor 1 by molecular dynamics simulations, free energy and weak interaction analysis

NASA Astrophysics Data System (ADS)

Bai, Qifeng; Yao, Xiaojun

2016-02-01

Metabotropic glutamate receptor 1 (mGlu1), which belongs to class C G protein-coupled receptors (GPCRs), can be coupled with G protein to transfer extracellular signal by dimerization and allosteric regulation. Unraveling the dimer packing and allosteric mechanism can be of great help for understanding specific regulatory mechanism and designing more potential negative allosteric modulator (NAM). Here, we report molecular dynamics simulation studies of the modulation mechanism of FITM on the wild type, T815M and Y805A mutants of mGlu1 through weak interaction analysis and free energy calculation. The weak interaction analysis demonstrates that van der Waals (vdW) and hydrogen bonding play an important role on the dimer packing between six cholesterol molecules and mGlu1 as well as the interaction between allosteric sites T815, Y805 and FITM in wild type, T815M and Y805A mutants of mGlu1. Besides, the results of free energy calculations indicate that secondary binding pocket is mainly formed by the residues Thr748, Cys746, Lys811 and Ser735 except for FITM-bound pocket in crystal structure. Our results can not only reveal the dimer packing and allosteric regulation mechanism, but also can supply useful information for the design of potential NAM of mGlu1.

Interactions Between Anandamide and Corticotropin-Releasing Factor Signaling Modulate Human Amygdala Function and Risk for Anxiety Disorders: An Imaging Genetics Strategy for Modeling Molecular Interactions.

PubMed

Demers, Catherine H; Drabant Conley, Emily; Bogdan, Ryan; Hariri, Ahmad R

2016-09-01

Preclinical models reveal that stress-induced amygdala activity and impairment in fear extinction reflect reductions in anandamide driven by corticotropin-releasing factor receptor type 1 (CRF1) potentiation of the anandamide catabolic enzyme fatty acid amide hydrolase. Here, we provide clinical translation for the importance of these molecular interactions using an imaging genetics strategy to examine whether interactions between genetic polymorphisms associated with differential anandamide (FAAH rs324420) and CRF1 (CRHR1 rs110402) signaling modulate amygdala function and anxiety disorder diagnosis. Analyses revealed that individuals with a genetic background predicting relatively high anandamide and CRF1 signaling exhibited blunted basolateral amygdala habituation, which further mediated increased risk for anxiety disorders among these same individuals. The convergence of preclinical and clinical data suggests that interactions between anandamide and CRF1 represent a fundamental molecular mechanism regulating amygdala function and anxiety. Our results further highlight the potential of imaging genetics to powerfully translate complex preclinical findings to clinically meaningful human phenotypes. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

ABC multidrug transporters: target for modulation of drug pharmacokinetics and drug-drug interactions.

PubMed

Marquez, Béatrice; Van Bambeke, Françoise

2011-05-01

Nine proteins of the ABC superfamily (P-glycoprotein, 7 MRPs and BCRP) are involved in multidrug transport. Being localised at the surface of endothelial or epithelial cells, they expel drugs back to the external medium (if located at the apical side [P-glycoprotein, BCRP, MRP2, MRP4 in the kidney]) or to the blood (if located at the basolateral side [MRP1, MRP3, MRP4, MRP5]), modulating thereby their absorption, distribution, and elimination. In the CNS, most transporters are oriented to expel drugs to the blood. Transporters also cooperate with Phase I/Phase II metabolism enzymes by eliminating drug metabolites. Their major features are (i) their capacity to recognize drugs belonging to unrelated pharmacological classes, and (ii) their redundancy, a single molecule being possibly substrate for different transporters. This ensures an efficient protection of the body against invasion by xenobiotics. Competition for transport is now characterized as a mechanism of interaction between co-administered drugs, one molecule limiting the transport of the other, potentially affecting bioavailability, distribution, and/or elimination. Again, this mechanism reinforces drug interactions mediated by cytochrome P450 inhibition, as many substrates of P-glycoprotein and CYP3A4 are common. Induction of the expression of genes coding for MDR transporters is another mechanism of drug interaction, which could affect all drug substrates of the up-regulated transporter. Overexpression of MDR transporters confers resistance to anticancer agents and other therapies. All together, these data justify why studying drug active transport should be part of the evaluation of new drugs, as recently recommended by the FDA.

A Mitochondrial ATP synthase Subunit Interacts with TOR Signaling to Modulate Protein Homeostasis and Lifespan in Drosophila

PubMed Central

Sun, Xiaoping; Wheeler, Charles T.; Yolitz, Jason; Laslo, Mara; Alberico, Thomas; Sun, Yaning; Song, Qisheng; Zou, Sige

2014-01-01

SUMMARY Diet composition is a critical determinant of lifespan and nutrient imbalance is detrimental health. However, how nutrients interact with genetic factors to modulate lifespan remains elusive. We investigated how diet composition influences mitochondrial ATP synthase subunit d (ATPsyn-d) in modulating lifespan in Drosophila. ATPsyn-d knockdown extended lifespan in females fed low carbohydrate-to-protein (C:P) diets, but not the high C:P ratio diet. This extension was associated with increased resistance to oxidative stress, transcriptional changes in metabolism, proteostasis and immune genes, reduced protein damage and aggregation, and reduced phosphorylation of S6K and ERK in TOR and MAPK signaling, respectively. ATPsyn-d knockdown did not extend lifespan in females with reduced TOR signaling induced genetically by Tsc2 overexpression or pharmacologically by rapamycin. Our data reveal a link among diet, mitochondria, MAPK and TOR signaling in aging and stresses the importance of considering genetic background and diet composition in implementing interventions for promoting healthy aging. PMID:25220459

Interactions of GSK-3β with mitochondrial permeability transition pore modulators during preconditioning: age-associated differences.

PubMed

Zhu, Jiang; Rebecchi, Mario J; Glass, Peter S A; Brink, Peter R; Liu, Lixin

2013-04-01

Anesthetic preconditioning (APC) and ischemic preconditioning (IPC) are lost with normal aging. Here, we investigated age-related difference between phosphoglycogen synthase kinase-3beta (pGSK-3β) and pGSK-3β with modulators of mitochondrial permeability transition pore, including adenine nucleotide translocase (ANT), cyclophilin-D, or voltage-dependent anion channel. APC or IPC significantly increased pGSK-3β in the young groups in both the cytosol and the mitochondria and also significantly increased pGSK-3β in co-immunoprecipitates with ANT. Importantly, the level of cyclophilin-D in co-immunoprecipitates with ANT was significantly decreased in the young APC and IPC groups, but not in old rats. We also found that APC or IPC significantly prolonged mitochondrial permeability transition pore opening time in the young cardiomyocytes under oxidative stress, but not in the elderly. Attenuation of APC or IPC protection in the aging heart is associated with failure to reduce ANT-cyclophilin-D interactions and to decreased pGSK-3β responsiveness of ANT, critical modulators of mitochondrial permeability transition pore.

Odorant binding protein 69a connects social interaction to modulation of social responsiveness in Drosophila.

PubMed

Bentzur, Assa; Shmueli, Anat; Omesi, Liora; Ryvkin, Julia; Knapp, Jon-Michael; Parnas, Moshe; Davis, Fred P; Shohat-Ophir, Galit

2018-04-01

Living in a social environment requires the ability to respond to specific social stimuli and to incorporate information obtained from prior interactions into future ones. One of the mechanisms that facilitates social interaction is pheromone-based communication. In Drosophila melanogaster, the male-specific pheromone cis-vaccenyl acetate (cVA) elicits different responses in male and female flies, and functions to modulate behavior in a context and experience-dependent manner. Although it is the most studied pheromone in flies, the mechanisms that determine the complexity of the response, its intensity and final output with respect to social context, sex and prior interaction, are still not well understood. Here we explored the functional link between social interaction and pheromone-based communication and discovered an odorant binding protein that links social interaction to sex specific changes in cVA related responses. Odorant binding protein 69a (Obp69a) is expressed in auxiliary cells and secreted into the olfactory sensilla. Its expression is inversely regulated in male and female flies by social interactions: cVA exposure reduces its levels in male flies and increases its levels in female flies. Increasing or decreasing Obp69a levels by genetic means establishes a functional link between Obp69a levels and the extent of male aggression and female receptivity. We show that activation of cVA-sensing neurons is sufficeint to regulate Obp69a levels in the absence of cVA, and requires active neurotransmission between the sensory neuron to the second order olfactory neuron. The cross-talk between sensory neurons and non-neuronal auxiliary cells at the olfactory sensilla, represents an additional component in the machinery that promotes behavioral plasticity to the same sensory stimuli in male and female flies.

Integrin-linked kinase interactions with ELMO2 modulate cell polarity.

PubMed

Ho, Ernest; Irvine, Tames; Vilk, Gregory J A; Lajoie, Gilles; Ravichandran, Kodi S; D'Souza, Sudhir J A; Dagnino, Lina

2009-07-01

Cell polarization is a key prerequisite for directed migration during development, tissue regeneration, and metastasis. Integrin-linked kinase (ILK) is a scaffold protein essential for cell polarization, but very little is known about the precise mechanisms whereby ILK modulates polarization in normal epithelia. Elucidating these mechanisms is essential to understand tissue morphogenesis, transformation, and repair. Here we identify a novel ILK protein complex that includes Engulfment and Cell Motility 2 (ELMO2). We also demonstrate the presence of RhoG in ILK-ELMO2 complexes, and the localization of this multiprotein species specifically to the leading lamellipodia of polarized cells. Significantly, the ability of RhoG to bind ELMO is crucial for ILK induction of cell polarization, and the joint expression of ILK and ELMO2 synergistically promotes the induction of front-rear polarity and haptotactic migration. This places RhoG-ELMO2-ILK complexes in a key position for the development of cell polarity and forward movement. Although ILK is a component of many diverse multiprotein species that may contribute to cell polarization, expression of dominant-negative ELMO2 mutants is sufficient to abolish the ability of ILK to promote cell polarization. Thus, its interaction with ELMO2 and RhoG is essential for the ability of ILK to induce front-rear cell polarity.

A Comparison of Two Objective Measures of Binaural Processing: The Interaural Phase Modulation Following Response and the Binaural Interaction Component.

PubMed

Haywood, Nicholas R; Undurraga, Jaime A; Marquardt, Torsten; McAlpine, David

2015-12-30

There has been continued interest in clinical objective measures of binaural processing. One commonly proposed measure is the binaural interaction component (BIC), which is obtained typically by recording auditory brainstem responses (ABRs)-the BIC reflects the difference between the binaural ABR and the sum of the monaural ABRs (i.e., binaural - (left + right)). We have recently developed an alternative, direct measure of sensitivity to interaural time differences, namely, a following response to modulations in interaural phase difference (the interaural phase modulation following response; IPM-FR). To obtain this measure, an ongoing diotically amplitude-modulated signal is presented, and the interaural phase difference of the carrier is switched periodically at minima in the modulation cycle. Such periodic modulations to interaural phase difference can evoke a steady state following response. BIC and IPM-FR measurements were compared from 10 normal-hearing subjects using a 16-channel electroencephalographic system. Both ABRs and IPM-FRs were observed most clearly from similar electrode locations-differential recordings taken from electrodes near the ear (e.g., mastoid) in reference to a vertex electrode (Cz). Although all subjects displayed clear ABRs, the BIC was not reliably observed. In contrast, the IPM-FR typically elicited a robust and significant response. In addition, the IPM-FR measure required a considerably shorter recording session. As the IPM-FR magnitude varied with interaural phase difference modulation depth, it could potentially serve as a correlate of perceptual salience. Overall, the IPM-FR appears a more suitable clinical measure than the BIC. © The Author(s) 2015.

Vitamins K interact with N-terminus α-synuclein and modulate the protein fibrillization in vitro. Exploring the interaction between quinones and α-synuclein.

PubMed

da Silva, Fernanda Luna; Coelho Cerqueira, Eduardo; de Freitas, Mônica Santos; Gonçalves, Daniela Leão; Costa, Lilian Terezinha; Follmer, Cristian

2013-01-01

In the last decades, a series of compounds, including quinones and polyphenols, has been described as having anti-fibrillogenic action on α-synuclein (α-syn) whose aggregation is associated to the pathogenesis of Parkinson's disease (PD). Most of these molecules act as promiscuous anti-amyloidogenic agents, interacting with the diverse amyloidogenic proteins (mostly unfolded) through non-specific hydrophobic interactions. Herein we investigated the effect of the vitamins K (phylloquinone, menaquinone and menadione), which are 1,4-naphthoquinone (1,4-NQ) derivatives, on α-syn aggregation, comparing them with other anti-fibrillogenic molecules such as quinones, polyphenols and lipophilic vitamins. Vitamins K delayed α-syn fibrillization in substoichiometric concentrations, leading to the formation of short, sheared fibrils and amorphous aggregates, which are less prone to produce leakage of synthetic vesicles. In seeding conditions, menadione and 1,4-NQ significantly inhibited fibrils elongation, which could be explained by their ability to destabilize preformed fibrils of α-syn. Bidimensional NMR experiments indicate that a specific site at the N-terminal α-syn (Gly31/Lys32) is involved in the interaction with vitamins K, which is corroborated by previous studies suggesting that Lys is a key residue in the interaction with quinones. Together, our data suggest that 1,4-NQ, recently showed up by our group as a potential scaffold for designing new monoamine oxidase inhibitors, is also capable to modulate α-syn fibrillization in vitro. Copyright © 2012 Elsevier Ltd. All rights reserved.

Coherent population trapping with polarization modulation

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

Yun, Peter, E-mail: enxue.yun@obspm.fr; Guérandel, Stéphane; Clercq, Emeric de

Coherent population trapping (CPT) is extensively studied for future vapor cell clocks of high frequency stability. In the constructive polarization modulation CPT scheme, a bichromatic laser field with polarization and phase synchronously modulated is applied on an atomic medium. A high contrast CPT signal is observed in this so-called double-modulation configuration, due to the fact that the atomic population does not leak to the extreme Zeeman states, and that the two CPT dark states, which are produced successively by the alternate polarizations, add constructively. Here, we experimentally investigate CPT signal dynamics first in the usual configuration, a single circular polarization.more » The double-modulation scheme is then addressed in both cases: one pulse Rabi interaction and two pulses Ramsey interaction. The impact and the optimization of the experimental parameters involved in the time sequence are reviewed. We show that a simple seven-level model explains the experimental observations. The double-modulation scheme yields a high contrast similar to the one of other high contrast configurations like push-pull optical pumping or crossed linear polarization scheme, with a setup allowing a higher compactness. The constructive polarization modulation is attractive for atomic clock, atomic magnetometer, and high precision spectroscopy applications.« less

De novo designed library of linear helical peptides: an exploratory tool in the discovery of protein-protein interaction modulators.

PubMed

Bonache, M Ángeles; Balsera, Beatriz; López-Méndez, Blanca; Millet, Oscar; Brancaccio, Diego; Gómez-Monterrey, Isabel; Carotenuto, Alfonso; Pavone, Luigi M; Reille-Seroussi, Marie; Gagey-Eilstein, Nathalie; Vidal, Michel; de la Torre-Martinez, Roberto; Fernández-Carvajal, Asia; Ferrer-Montiel, Antonio; García-López, M Teresa; Martín-Martínez, Mercedes; de Vega, M Jesús Pérez; González-Muñiz, Rosario

2014-05-12

Protein-protein interactions (PPIs) have emerged as important targets for pharmaceutical intervention because of their essential role in numerous physiological and pathological processes, but screening efforts using small-molecules have led to very low hit rates. Linear peptides could represent a quick and effective approach to discover initial PPI hits, particularly if they have inherent ability to adopt specific peptide secondary structures. Here, we address this hypothesis through a linear helical peptide library, composed of four sublibraries, which was designed by theoretical predictions of helicity (Agadir software). The 13-mer peptides of this collection fixes either a combination of three aromatic or two aromatic and one aliphatic residues on one face of the helix (Ac-SSEEX(5)ARNX(9)AAX(12)N-NH2), since these are structural features quite common at PPIs interfaces. The 81 designed peptides were conveniently synthesized by parallel solid-phase methodologies, and the tendency of some representative library components to adopt the intended secondary structure was corroborated through CD and NMR experiments. As proof of concept in the search for PPI modulators, the usefulness of this library was verified on the widely studied p53-MDM2 interaction and on the communication between VEGF and its receptor Flt-1, two PPIs for which a hydrophobic α-helix is essential for the interaction. We have demonstrated here that, in both cases, selected peptides from the library, containing the right hydrophobic sequence of the hot-spot in one of the protein partners, are able to interact with the complementary protein. Moreover, we have discover some new, quite potent inhibitors of the VEGF-Flt-1 interaction, just by replacing one of the aromatic residues of the initial F(5)Y(9)Y(12) peptide by W, in agreement with previous results on related antiangiogenic peptides. Finally, the HTS evaluation of the full collection on thermoTRPs has led to a few antagonists of TRPV1 and TRPA

The Application of Ligand-Mapping Molecular Dynamics Simulations to the Rational Design of Peptidic Modulators of Protein-Protein Interactions.

PubMed

Tan, Yaw Sing; Spring, David R; Abell, Chris; Verma, Chandra S

2015-07-14

A computational ligand-mapping approach to detect protein surface pockets that interact with hydrophobic moieties is presented. In this method, we incorporated benzene molecules into explicit solvent molecular dynamics simulations of various protein targets. The benzene molecules successfully identified the binding locations of hydrophobic hot-spot residues and all-hydrocarbon cross-links from known peptidic ligands. They also unveiled cryptic binding sites that are occluded by side chains and the protein backbone. Our results demonstrate that ligand-mapping molecular dynamics simulations hold immense promise to guide the rational design of peptidic modulators of protein-protein interactions, including that of stapled peptides, which show promise as an exciting new class of cell-penetrating therapeutic molecules.

RNA Modulates the Interaction between Influenza A Virus NS1 and Human PABP1.

PubMed

Arias-Mireles, Bryan H; de Rozieres, Cyrus M; Ly, Kevin; Joseph, Simpson

2018-05-25

Nonstructural protein 1 (NS1) is a multifunctional protein involved in preventing host-interferon response in influenza A virus (IAV). Previous studies have indicated that NS1 also stimulates the translation of viral mRNA by binding to conserved sequences in the viral 5'-UTR. Additionally, NS1 binds to poly(A) binding protein 1 (PABP1) and eukaryotic initiation factor 4G (eIF4G). The interaction of NS1 with the viral 5'-UTR, PABP1, and eIF4G has been suggested to specifically enhance the translation of viral mRNAs. In contrast, we report that NS1 does not directly bind to sequences in the viral 5'-UTR, indicating that NS1 is not responsible for providing the specificity to stimulate viral mRNA translation. We also monitored the interaction of NS1 with PABP1 using a new, quantitative FRET assay. Our data show that NS1 binds to PABP1 with high affinity; however, the binding of double-stranded RNA (dsRNA) to NS1 weakens the binding of NS1 to PABP1. Correspondingly, the binding of PABP1 to NS1 weakens the binding of NS1 to double-stranded RNA (dsRNA). In contrast, the affinity of PABP1 for binding to poly(A) RNA is not significantly changed by NS1. We propose that the modulation of NS1·PABP1 interaction by dsRNA may be important for the viral cycle.

Intrasteric inhibition mediates the interaction of the I/LWEQ module proteins Talin1, Talin2, Hip1, and Hip12 with actin.

PubMed

Senetar, Melissa A; Foster, Stanley J; McCann, Richard O

2004-12-14

The I/LWEQ module superfamily is a class of actin-binding proteins that contains a conserved C-terminal actin-binding element known as the I/LWEQ module. I/LWEQ module proteins include the metazoan talins, the cellular slime mold talin homologues TalA and TalB, fungal Sla2p, and the metazoan Sla2 homologues Hip1 and Hip12 (Hip1R). These proteins possess a similar modular organization that includes an I/LWEQ module at their C-termini and either a FERM domain or an ENTH domain at their N-termini. As a result of this modular organization, I/LWEQ module proteins may serve as linkers between cellular compartments, such as the plasma membrane and the endocytic machinery, and the actin cytoskeleton. Previous studies have shown that I/LWEQ module proteins bind to F-actin. In this report, we have determined the affinity of the I/LWEQ module proteins Talin1, Talin2, huntingtin interacting protein-1 (Hip1), and the Hip1-related protein (Hip1R/Hip12) for F-actin and identified a conserved structural element that interferes with the actin binding capacity of these proteins. Our data support the hypothesis that the actin-binding determinants in native talin and other I/LWEQ module proteins are cryptic and indicate that the actin binding capacities of Talin1, Talin2, Hip1, and Hip12 are regulated by intrasteric occlusion of primary actin-binding determinants within the I/LWEQ module. We have also found that the I/LWEQ module contains a dimerization motif and stabilizes actin filaments against depolymerization. This activity may contribute to the function of talin in cell adhesion and the roles of Hip1, Hip12 (Hip1R), and Sla2p in endocytosis.

Loss of Cbl-PI3K Interaction Modulates the Periosteal Response to Fracture by Enhancing Osteogenic Commitment and Differentiation

PubMed Central

Scanlon, Vanessa; Walia, Bhavita; Yu, Jungeun; Hansen, Marc; Drissi, Hicham; Maye, Peter; Sanjay, Archana

2018-01-01

The periosteum contains multipotent skeletal progenitors that contribute to bone repair. The signaling pathways regulating the response of periosteal cells to fracture are largely unknown. Phosphatidylinositol-3 Kinase (PI3K), a prominent lipid kinase, is a major signaling protein downstream of several factors that regulate osteoblast differentiation. Cbl is an E3 ubiquitin ligase and a major adaptor protein that binds to the p85 regulatory subunit and modulates PI3K activity. Substitution of tyrosine 737 to phenylalanine (Y737F) in Cbl abolishes the interaction between Cbl and the p85 subunit without affecting the Cbl’s ubiquitin ligase function. Here, we investigated the role of PI3K signaling during the very early stages of fracture healing using OsterixRFP reporter mice. We found that the absence of PI3K regulation by Cbl resulted in robust periosteal thickening, with increased proliferation of periosteal cells. While the multipotent properties of periosteal progenitors to differentiate into chondrocytes and adipocytes did not change, osteogenic differentiation in the absence of Cbl-PI3K interaction was highly augmented. The increased stability and nuclear localization of Osterix observed in periosteal cells lacking Cbl-PI3K interaction may explain this enhanced osteogenic differentiation since the expression of Osterix transcriptional target genes including osteocalcin and BSP are increased in YF cells. Overall, our findings highlight a hitherto unexplored and novel role for Cbl and PI3K in modulating the osteogenic response of periosteal cells during the early stages of fracture repair. PMID:27884787

Loss of Cbl-PI3K interaction modulates the periosteal response to fracture by enhancing osteogenic commitment and differentiation.

PubMed

Scanlon, Vanessa; Walia, Bhavita; Yu, Jungeun; Hansen, Marc; Drissi, Hicham; Maye, Peter; Sanjay, Archana

2017-02-01

The periosteum contains multipotent skeletal progenitors that contribute to bone repair. The signaling pathways regulating the response of periosteal cells to fracture are largely unknown. Phosphatidylinositol-3 Kinase (PI3K), a prominent lipid kinase, is a major signaling protein downstream of several factors that regulate osteoblast differentiation. Cbl is an E3 ubiquitin ligase and a major adaptor protein that binds to the p85 regulatory subunit and modulates PI3K activity. Substitution of tyrosine 737 to phenylalanine (Y737F) in Cbl abolishes the interaction between Cbl and p85 subunit without affecting the Cbl's ubiquitin ligase function. Here, we investigated the role of PI3K signaling during the very early stages of fracture healing using Osterix RFP reporter mice. We found that the absence of PI3K regulation by Cbl resulted in robust periosteal thickening, with increased proliferation of periosteal cells. While the multipotent properties of periosteal progenitors to differentiate into chondrocytes and adipocytes did not change, osteogenic differentiation in the absence of Cbl-PI3K interaction was highly augmented. The increased stability and nuclear localization of Osterix observed in periosteal cells lacking Cbl-PI3K interaction may explain this enhanced osteogenic differentiation since the expression of Osterix transcriptional target genes including osteocalcin and BSP are increased in YF cells. Overall, our findings highlight a hitherto unexplored and novel role for Cbl and PI3K in modulating the osteogenic response of periosteal cells during the early stages of fracture repair. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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.

Two autonomous structural modules in the fimbrial shaft adhesin FimA mediate Actinomyces interactions with streptococci and host cells during oral biofilm development

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

Mishra, Arunima; Devarajan, Bharanidharan; Reardon, Melissa E.

2011-09-06

By combining X-ray crystallography and modelling, we describe here the atomic structure of distinct adhesive moieties of FimA, the shaft fimbrillin of Actinomyces type 2 fimbriae, which uniquely mediates the receptor-dependent intercellular interactions between Actinomyces and oral streptococci as well as host cells during the development of oral biofilms. The FimA adhesin is built with three IgG-like domains, each of which harbours an intramolecular isopeptide bond, previously described in several Gram-positive pilins. Genetic and biochemical studies demonstrate that although these isopeptide bonds are dispensable for fimbrial assembly, cell-cell interactions and biofilm formation, they contribute significantly to the proteolytic stability ofmore » FimA. Remarkably, FimA harbours two autonomous adhesive modules, which structurally resemble the Staphylococcus aureus Cna B domain. Each isolated module can bind the plasma glycoprotein asialofetuin as well as the polysaccharide receptors present on the surface of oral streptococci and epithelial cells. Thus, FimA should serve as an excellent paradigm for the development of therapeutic strategies and elucidating the precise molecular mechanisms underlying the interactions between cellular receptors and Gram-positive fimbriae.« less

Two Autonomous Structural Modules in the Fimbrial Shaft Adhesin FimA Mediate Actinomyces Interactions with Streptococci and Host Cells during Oral Biofilm Development

PubMed Central

Mishra, Arunima; Devarajan, Bharanidharan; Reardon, Melissa E.; Dwivedi, Prabhat; Krishnan, Vengadesan; Cisar, John O.; Das, Asis; Narayana, Sthanam V. L; Ton-That, Hung

2011-01-01

By combining X-ray crystallography and modeling, we describe here the atomic structure of distinct adhesive moieties of FimA, the shaft fimbrillin of Actinomyces type 2 fimbriae, which uniquely mediates the receptor-dependent intercellular interactions between Actinomyces and oral streptococci as well as host cells during the development of oral biofilms. The FimA adhesin is built with three IgG-like domains, each of which harbors an intramolecular isopeptide bond, previously described in several Gram-positive pilins. Genetic and biochemical studies demonstrate that although these isopeptide bonds are dispensable for fimbrial assembly, cell-cell interactions and biofilm formation, they contribute significantly to the proteolytic stability of FimA. Remarkably, FimA harbors two autonomous adhesive modules, which structurally resemble the Staphylococcus aureus Cna B domain. Each isolated module can bind the plasma glycoprotein asialofetuin as well as the polysaccharide receptors present on the surface of oral streptococci and epithelial cells. Thus, FimA should serve as an excellent paradigm for the development of therapeutic strategies and elucidating the precise molecular mechanisms underlying the interactions between cellular receptors and Gram-positive fimbriae. PMID:21696465

High and Low Computer Self-Efficacy Groups and Their Learning Behavior from Self-Regulated Learning Perspective While Engaged in Interactive Learning Modules

ERIC Educational Resources Information Center

Santoso, Harry B.; Lawanto, Oenardi; Becker, Kurt; Fang, Ning; Reeve, Edward M.

2014-01-01

The purpose of this research was to investigate high school students' computer self-efficacy (CSE) and learning behavior in a self-regulated learning (SRL) framework while utilizing an interactive learning module. The researcher hypothesizes that CSE is reflected on cognitive actions and metacognitive strategies while the students are engaged with…

Bayesian module identification from multiple noisy networks.

PubMed

Zamani Dadaneh, Siamak; Qian, Xiaoning

2016-12-01

Module identification has been studied extensively in order to gain deeper understanding of complex systems, such as social networks as well as biological networks. Modules are often defined as groups of vertices in these networks that are topologically cohesive with similar interaction patterns with the rest of the vertices. Most of the existing module identification algorithms assume that the given networks are faithfully measured without errors. However, in many real-world applications, for example, when analyzing protein-protein interaction networks from high-throughput profiling techniques, there is significant noise with both false positive and missing links between vertices. In this paper, we propose a new model for more robust module identification by taking advantage of multiple observed networks with significant noise so that signals in multiple networks can be strengthened and help improve the solution quality by combining information from various sources. We adopt a hierarchical Bayesian model to integrate multiple noisy snapshots that capture the underlying modular structure of the networks under study. By introducing a latent root assignment matrix and its relations to instantaneous module assignments in all the observed networks to capture the underlying modular structure and combine information across multiple networks, an efficient variational Bayes algorithm can be derived to accurately and robustly identify the underlying modules from multiple noisy networks. Experiments on synthetic and protein-protein interaction data sets show that our proposed model enhances both the accuracy and resolution in detecting cohesive modules, and it is less vulnerable to noise in the observed data. In addition, it shows higher power in predicting missing edges compared to individual-network methods.

Preliminary Results from the Flight of the Solar Array Module Plasma Interactions Experiment (SAMPIE)

NASA Technical Reports Server (NTRS)

Ferguson, Dale C.; Hillard, G. Barry

1994-01-01

SAMPIE, the Solar Array Module Plasma Interactions Experiment, flew in the Space Shuttle Columbia payload bay as part of the OAST-2 mission on STS-62, March, 1994. SAMPIE biased samples of solar arrays and space power materials to varying potentials with respect to the surrounding space plasma, and recorded the plasma currents collected and the arcs which occurred, along with a set of plasma diagnostics data. A large set of high quality data was obtained on the behavior of solar arrays and space power materials in the space environment. This paper is the first report on the data SAMPIE telemetered to the ground during the mission. It will be seen that the flight data promise to help determine arcing thresholds, snapover potentials and floating potentials for arrays and spacecraft in LEO.

Chlorella vulgaris and Pseudomonas putida interaction modulates phosphate trafficking for reduced arsenic uptake in rice (Oryza sativa L.).

PubMed

Srivastava, Suchi; Srivastava, Sonal; Bist, Vidisha; Awasthi, Surabhi; Chauhan, Reshu; Chaudhry, Vasvi; Singh, Poonam C; Dwivedi, Sanjay; Niranjan, Abhishek; Agrawal, Lalit; Chauhan, Puneet Singh; Tripathi, Rudra Deo; Nautiyal, Chandra Shekhar

2018-06-05

Rice grown in arsenic (As) contaminated areas contributes to high dietary exposure of As inducing multiple adverse effects on human health. The As contamination and application of phosphate fertilizers during seedling stage creates a high P and As stress condition. The flooded paddy fields are also conducive for algal growth and microbial activity. The present study proposes potential role of microalgae, Chlorella vulgaris (CHL) and bacteria, Pseudomonas putida (RAR) on rice plant grown under excess As and phosphate (P) conditions. The results show synchronized interaction of CHL + RAR which, reduces As uptake through enhanced P:As and reduced As:biomass ratio by modulating P trafficking. Gene expression analysis of different phosphate transporters exhibited correlation with reduced As uptake and other essential metals. The balancing of reactive oxygen species (ROS), proline accumulation, hormone modulation, and As sequestration in microbial biomass were elucidated as possible mechanisms of As detoxification. The study concludes that RAR and CHL combination mitigates the As stress during P-enriched conditions in rice by: (i) reducing As availability, (ii) modulating the As uptake, and (iii) improving detoxification mechanism of the plant. The study will be important in assessing the role and applicability of P solubilizing biofertilizers in these conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

Novel Entropically Driven Conformation-specific Interactions with Tomm34 Protein Modulate Hsp70 Protein Folding and ATPase Activities*

PubMed Central

Durech, Michal; Trcka, Filip; Man, Petr; Blackburn, Elizabeth A.; Hernychova, Lenka; Dvorakova, Petra; Coufalova, Dominika; Kavan, Daniel; Vojtesek, Borivoj; Muller, Petr

2016-01-01

Co-chaperones containing tetratricopeptide repeat (TPR) domains enable cooperation between Hsp70 and Hsp90 to maintain cellular proteostasis. Although the details of the molecular interactions between some TPR domains and heat shock proteins are known, we describe a novel mechanism by which Tomm34 interacts with and coordinates Hsp70 activities. In contrast to the previously defined Hsp70/Hsp90-organizing protein (Hop), Tomm34 interaction is dependent on the Hsp70 chaperone cycle. Tomm34 binds Hsp70 in a complex process; anchorage of the Hsp70 C terminus by the TPR1 domain is accompanied by additional contacts formed exclusively in the ATP-bound state of Hsp70 resulting in a high affinity entropically driven interaction. Tomm34 induces structural changes in determinants within the Hsp70-lid subdomain and modulates Hsp70/Hsp40-mediated refolding and Hsp40-stimulated Hsp70 ATPase activity. Because Tomm34 recruits Hsp90 through its TPR2 domain, we propose a model in which Tomm34 enables Hsp70/Hsp90 scaffolding and influences the Hsp70 chaperone cycle, providing an additional role for co-chaperones that contain multiple TPR domains in regulating protein homeostasis. PMID:26944342

Prefrontal activity during working memory is modulated by the interaction of variation in CB1 and COX2 coding genes and correlates with frequency of cannabis use.

PubMed

Taurisano, Paolo; Antonucci, Linda A; Fazio, Leonardo; Rampino, Antonio; Romano, Raffaella; Porcelli, Annamaria; Masellis, Rita; Colizzi, Marco; Quarto, Tiziana; Torretta, Silvia; Di Giorgio, Annabella; Pergola, Giulio; Bertolino, Alessandro; Blasi, Giuseppe

2016-08-01

The CB1 cannabinoid receptor is targeted in the brain by endocannabinoids under physiological conditions as well as by delta9-tetrahydrocannabinol under cannabis use. Furthermore, its signaling appears to affect brain cognitive processing. Recent findings highlight a crucial role of cyclooxygenase-2 (COX-2) in the mechanism of intraneuronal CB1 signaling transduction, while others indicate that two single nucleotide polymorphisms (SNPs) (rs1406977 and rs20417) modulate expression of CB1 (CNR1) and COX-2 (PTGS2) coding genes, respectively. Here, our aim was to use fMRI to investigate in healthy humans whether these SNPs interact in modulating prefrontal activity during working memory processing and if this modulation is linked with cannabis use. We recruited 242 healthy subjects genotyped for CNR1 rs1406977 and PTGS2 rs20417 that performed the N-back working memory task during fMRI and were interviewed using the Cannabis Experience Questionnaire (CEQ). We found that the interaction between CNR1 rs1406977 and PTGS2 rs20417 is associated with dorsolateral prefrontal cortex (DLPFC) activity such that specific genotype configurations (CNR1 C carriers/PTGS2 C carriers and CNR1 TT/PTGS2 GG) predict lower cortical response versus others in spite of similar behavioral accuracy. Furthermore, DLPFC activity in the cluster associated with the CNR1 by PTGS2 interaction was negatively correlated with behavioral efficiency and positively correlated with frequency of cannabis use in cannabis users. These results suggest that a genetically modulated balancing of signaling within the CB1-COX-2 pathway may reflect on more or less efficient patterns of prefrontal activity during working memory. Frequency of cannabis use may be a factor for further modulation of CNR1/PTGS2-mediated cortical processing associated with this cognitive process. Copyright © 2016 Elsevier Ltd. All rights reserved.

Developing an On-Line Interactive Health Psychology Module

ERIC Educational Resources Information Center

Upton, Dominic; Cooper, Carol

2006-01-01

On-line teaching material in health psychology was developed which ensured a range of students could access appropriate material for their course and level of study. This material has been developed around the concept of smaller "content chunks" which can be combined into whole units of learning (topics), and ultimately, a module. On the…

Differential network analysis reveals the genome-wide landscape of estrogen receptor modulation in hormonal cancers

PubMed Central

Hsiao, Tzu-Hung; Chiu, Yu-Chiao; Hsu, Pei-Yin; Lu, Tzu-Pin; Lai, Liang-Chuan; Tsai, Mong-Hsun; Huang, Tim H.-M.; Chuang, Eric Y.; Chen, Yidong

2016-01-01

Several mutual information (MI)-based algorithms have been developed to identify dynamic gene-gene and function-function interactions governed by key modulators (genes, proteins, etc.). Due to intensive computation, however, these methods rely heavily on prior knowledge and are limited in genome-wide analysis. We present the modulated gene/gene set interaction (MAGIC) analysis to systematically identify genome-wide modulation of interaction networks. Based on a novel statistical test employing conjugate Fisher transformations of correlation coefficients, MAGIC features fast computation and adaption to variations of clinical cohorts. In simulated datasets MAGIC achieved greatly improved computation efficiency and overall superior performance than the MI-based method. We applied MAGIC to construct the estrogen receptor (ER) modulated gene and gene set (representing biological function) interaction networks in breast cancer. Several novel interaction hubs and functional interactions were discovered. ER+ dependent interaction between TGFβ and NFκB was further shown to be associated with patient survival. The findings were verified in independent datasets. Using MAGIC, we also assessed the essential roles of ER modulation in another hormonal cancer, ovarian cancer. Overall, MAGIC is a systematic framework for comprehensively identifying and constructing the modulated interaction networks in a whole-genome landscape. MATLAB implementation of MAGIC is available for academic uses at https://github.com/chiuyc/MAGIC. PMID:26972162

A mitochondrial ATP synthase subunit interacts with TOR signaling to modulate protein homeostasis and lifespan in Drosophila.

PubMed

Sun, Xiaoping; Wheeler, Charles T; Yolitz, Jason; Laslo, Mara; Alberico, Thomas; Sun, Yaning; Song, Qisheng; Zou, Sige

2014-09-25

Diet composition is a critical determinant of lifespan, and nutrient imbalance is detrimental to health. However, how nutrients interact with genetic factors to modulate lifespan remains elusive. We investigated how diet composition influences mitochondrial ATP synthase subunit d (ATPsyn-d) in modulating lifespan in Drosophila. ATPsyn-d knockdown extended lifespan in females fed low carbohydrate-to-protein (C:P) diets but not the high C:P ratio diet. This extension was associated with increased resistance to oxidative stress; transcriptional changes in metabolism, proteostasis, and immune genes; reduced protein damage and aggregation, and reduced phosphorylation of S6K and ERK in TOR and mitogen-activated protein kinase (MAPK) signaling, respectively. ATPsyn-d knockdown did not extend lifespan in females with reduced TOR signaling induced genetically by Tsc2 overexpression or pharmacologically by rapamycin. Our data reveal a link among diet, mitochondria, and MAPK and TOR signaling in aging and stresses the importance of considering genetic background and diet composition in implementing interventions for promoting healthy aging. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

EGFR-SGLT1 interaction does not respond to EGFR modulators, but inhibition of SGLT1 sensitizes prostate cancer cells to EGFR tyrosine kinase inhibitors.

PubMed

Ren, Jiangong; Bollu, Lakshmi R; Su, Fei; Gao, Guang; Xu, Lei; Huang, Wei-Chien; Hung, Mien-Chie; Weihua, Zhang

2013-09-01

Overexpression of epidermal growth factor receptor (EGFR) is associated with poor prognosis in malignant tumors. Sodium/glucose co-transporter 1 (SGLT1) is an active glucose transporter that is overexpressed in many cancers including prostate cancer. Previously, we found that EGFR interacts with and stabilizes SGLT1 in cancer cells. In this study, we determined the micro-domain of EGFR that is required for its interaction with SGLT1 and the effects of activation/inactivation of EGFR on EGFR-SGLT1 interaction, measured the expression of EGFR and SGLT1 in prostate cancer tissues, and tested the effect of inhibition of SGLT1 on the sensitivity of prostate cancer cells to EGFR tyrosine inhibitors. We found that the autophosphorylation region (978-1210 amino acids) of EGFR was required for its sufficient interaction with SGLT1 and that this interaction was independent of EGFR's tyrosine kinase activity. Most importantly, the EGFR-SGLT1 interaction does not respond to EGFR tyrosine kinase modulators (EGF and tyrosine kinase inhibitors). EGFR and SGLT1 co-localized in prostate cancer tissues, and inhibition of SGLT1 by a SGLT1 inhibitor (Phlorizin) sensitized prostate cancer cells to EGFR inhibitors (Gefitinib and Erlotinib). These data suggest that EGFR in cancer cells can exist as either a tyrosine kinase modulator responsive status or an irresponsive status. SGLT1 is a protein involved in EGFR's functions that are irresponsive to EGFR tyrosine kinase inhibitors and, therefore, the EGFR-SGLT1 interaction might be a novel target for prostate cancer therapy. © 2013 Wiley Periodicals, Inc. This article is a U.S. Government work and is in the public domain in the USA.

Integrin-linked Kinase Interactions with ELMO2 Modulate Cell Polarity

PubMed Central

Ho, Ernest; Irvine, Tames; Vilk, Gregory J.A.; Lajoie, Gilles; Ravichandran, Kodi S.; D'Souza, Sudhir J.A.

2009-01-01

Cell polarization is a key prerequisite for directed migration during development, tissue regeneration, and metastasis. Integrin-linked kinase (ILK) is a scaffold protein essential for cell polarization, but very little is known about the precise mechanisms whereby ILK modulates polarization in normal epithelia. Elucidating these mechanisms is essential to understand tissue morphogenesis, transformation, and repair. Here we identify a novel ILK protein complex that includes Engulfment and Cell Motility 2 (ELMO2). We also demonstrate the presence of RhoG in ILK–ELMO2 complexes, and the localization of this multiprotein species specifically to the leading lamellipodia of polarized cells. Significantly, the ability of RhoG to bind ELMO is crucial for ILK induction of cell polarization, and the joint expression of ILK and ELMO2 synergistically promotes the induction of front-rear polarity and haptotactic migration. This places RhoG–ELMO2–ILK complexes in a key position for the development of cell polarity and forward movement. Although ILK is a component of many diverse multiprotein species that may contribute to cell polarization, expression of dominant-negative ELMO2 mutants is sufficient to abolish the ability of ILK to promote cell polarization. Thus, its interaction with ELMO2 and RhoG is essential for the ability of ILK to induce front-rear cell polarity. PMID:19439446

Interactive Scene Analysis Module - A sensor-database fusion system for telerobotic environments

NASA Technical Reports Server (NTRS)

Cooper, Eric G.; Vazquez, Sixto L.; Goode, Plesent W.

1992-01-01

Accomplishing a task with telerobotics typically involves a combination of operator control/supervision and a 'script' of preprogrammed commands. These commands usually assume that the location of various objects in the task space conform to some internal representation (database) of that task space. The ability to quickly and accurately verify the task environment against the internal database would improve the robustness of these preprogrammed commands. In addition, the on-line initialization and maintenance of a task space database is difficult for operators using Cartesian coordinates alone. This paper describes the Interactive Scene' Analysis Module (ISAM) developed to provide taskspace database initialization and verification utilizing 3-D graphic overlay modelling, video imaging, and laser radar based range imaging. Through the fusion of taskspace database information and image sensor data, a verifiable taskspace model is generated providing location and orientation data for objects in a task space. This paper also describes applications of the ISAM in the Intelligent Systems Research Laboratory (ISRL) at NASA Langley Research Center, and discusses its performance relative to representation accuracy and operator interface efficiency.

Defined surface immobilization of glycosaminoglycan molecules for probing and modulation of cell-material interactions.

PubMed

Wang, Kai; Luo, Ying

2013-07-08

As one important category of biological molecules on the cell surface and in the extracellular matrix (ECM), glycosaminoglycans (GAGs) have been widely studied for biomedical applications. With the understanding that the biological functions of GAGs are driven by the complex dynamics of physiological and pathological processes, methodologies are desired to allow the elucidation of cell-GAG interactions with molecular level precision. In this study, a microtiter plate-based system was devised through a new surface modification strategy involving polydopamine (PDA) and GAG molecules functionalized with hydrazide chemical groups. A small library of GAGs including hyaluronic acid (with different molecular weights), heparin, and chondroitin sulfate was successfully immobilized via defined binding sites onto the microtiter plate surface under facile aqueous conditions. The methodology then allowed parallel studies of the GAG-modified surfaces in a high-throughput format. The results show that immobilized GAGs possess distinct properties to mediate protein adsorption, cell adhesion, and inflammatory responses, with each property showing dependence on the type and molecular weight of specific GAG molecules. The PDA-assisted immobilization of hydrazide-functionalized GAGs allows biomimetic attachment of GAG molecules and retains their bioactivity, providing a new methodology to systematically probe fundamental cell-GAG interactions to modulate the bioactivity and biocompatibility of biomaterials.

Identifying interactions between chemical entities in biomedical text.

PubMed

Lamurias, Andre; Ferreira, João D; Couto, Francisco M

2014-10-23

Interactions between chemical compounds described in biomedical text can be of great importance to drug discovery and design, as well as pharmacovigilance. We developed a novel system, \\"Identifying Interactions between Chemical Entities\\" (IICE), to identify chemical interactions described in text. Kernel-based Support Vector Machines first identify the interactions and then an ensemble classifier validates and classifies the type of each interaction. This relation extraction module was evaluated with the corpus released for the DDI Extraction task of SemEval 2013, obtaining results comparable to state-of-the-art methods for this type of task. We integrated this module with our chemical named entity recognition module and made the whole system available as a web tool at www.lasige.di.fc.ul.pt/webtools/iice.

Identifying interactions between chemical entities in biomedical text.

PubMed

Lamurias, Andre; Ferreira, João D; Couto, Francisco M

2014-12-01

Interactions between chemical compounds described in biomedical text can be of great importance to drug discovery and design, as well as pharmacovigilance. We developed a novel system, "Identifying Interactions between Chemical Entities" (IICE), to identify chemical interactions described in text. Kernel-based Support Vector Machines first identify the interactions and then an ensemble classifier validates and classifies the type of each interaction. This relation extraction module was evaluated with the corpus released for the DDI Extraction task of SemEval 2013, obtaining results comparable to stateof- the-art methods for this type of task. We integrated this module with our chemical named entity recognition module and made the whole system available as a web tool at www.lasige.di.fc.ul.pt/webtools/iice.

A protein isolated from human oviductal tissue in vitro secretion, identified as human lactoferrin, interacts with spermatozoa and oocytes and modulates gamete interaction.

PubMed

Zumoffen, C M; Gil, R; Caille, A M; Morente, C; Munuce, M J; Ghersevich, S A

2013-05-01

Is lactoferrin (LF) (detected in oviductal secretion) able to bind to oocytes and sperm and modulate gamete interaction? LF binds to zona pellucida (ZP) and spermatozoa (depending upon the capacitation stage and acrosome status) and inhibits gamete interaction in vitro. Proteins from human oviductal tissue secretion modulate gamete interaction and parameters of sperm function in vitro and some of them bind to sperm, but they remain to be isolated and identified. Proteins were isolated from human oviductal tissue secretion using their sperm membrane binding ability. One of the isolated proteins was identified as human LF and immunolocalized in tubal tissues. LF expression was analyzed in native oviductal fluid and oviduct epithelial cells (at different phases of the menstrual cycle: proliferative, periovulatory and secretory). In addition, the LF binding sites on spermatozoa (at different capacitation and acrosome reaction stages) and on ZP and the dose-dependent effect of LF on gamete interaction were investigated. All experiments were performed at least three times. Tubal tissues obtained from premenopausal patients (scheduled for hysterectomy, n = 23) were cultured in DMEM/Ham's F12 medium and conditioned media (CM) were collected. Motile spermatozoa were obtained by swim-up from normozoospermic semen samples from healthy donors (n = 4). An affinity chromatography with sperm membrane extracts was used to isolate proteins from CM. Isolated proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophresis and further identified by nano liquid chromatography tandem mass spectrometry peptide sequencing. The presence of LF in oviductal tissue was investigated by immunohistochemistry and immunofluorescence and was detected in native oviductal fluid and oviduct epithelial cells homogenates by western blot. LF binding sites on gametes were investigated by incubating gametes with the protein coupled to fluorescein isothiocyanate (FITC). The acrosome

Preliminary results from the flight of the Solar Array Module Plasma Interactions Experiment (SAMPIE)

NASA Technical Reports Server (NTRS)

Ferguson, Dale C.; Hillard, G. Barry

1994-01-01

SAMPIE, the Solar Array Module Plasma Interactions Experiment, flew in the Space Shuttle Columbia payload bay as part of the Office of Aeronautics and Space Technology-2 (OAST-2) mission on STS-62, March, 1994. SAMPIE biased samples of solar arrays and space power materials to varying potentials with respect to the surrounding space plasma, and recorded the plasma currents collected and the arcs which occurred, along with a set of plasma diagnostics data. A large set of high quality data was obtained on the behavior of solar arrays and space power materials in the space environment. This paper is the first report on the data SAMPIE telemetered to the ground during the mission. It will be seen that the flight data promise to help determine arcing thresholds, snapover potentials, and floating potentials for arrays and spacecraft in LEO.

Excavation of attractor modules for nasopharyngeal carcinoma via integrating systemic module inference with attract method.

PubMed

Jiang, T; Jiang, C-Y; Shu, J-H; Xu, Y-J

2017-07-10

The molecular mechanism of nasopharyngeal carcinoma (NPC) is poorly understood and effective therapeutic approaches are needed. This research aimed to excavate the attractor modules involved in the progression of NPC and provide further understanding of the underlying mechanism of NPC. Based on the gene expression data of NPC, two specific protein-protein interaction networks for NPC and control conditions were re-weighted using Pearson correlation coefficient. Then, a systematic tracking of candidate modules was conducted on the re-weighted networks via cliques algorithm, and a total of 19 and 38 modules were separately identified from NPC and control networks, respectively. Among them, 8 pairs of modules with similar gene composition were selected, and 2 attractor modules were identified via the attract method. Functional analysis indicated that these two attractor modules participate in one common bioprocess of cell division. Based on the strategy of integrating systemic module inference with the attract method, we successfully identified 2 attractor modules. These attractor modules might play important roles in the molecular pathogenesis of NPC via affecting the bioprocess of cell division in a conjunct way. Further research is needed to explore the correlations between cell division and NPC.

Environmental factors as modulators of neurodegeneration: insights from gene-environment interactions in Huntington's disease.

PubMed

Mo, Christina; Hannan, Anthony J; Renoir, Thibault

2015-05-01

Unlike many other neurodegenerative diseases with established gene-environment interactions, Huntington's disease (HD) is viewed as a disorder governed by genetics. The cause of the disease is a highly penetrant tandem repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. In the year 2000, a pioneering study showed that the disease could be delayed in transgenic mice by enriched housing conditions. This review describes subsequent human and preclinical studies identifying environmental modulation of motor, cognitive, affective and other symptoms found in HD. Alongside the behavioral observations we also discuss potential mechanisms and the relevance to other neurodegenerative disorders, including Alzheimer's and Parkinson's disease. In mouse models of HD, increased sensorimotor and cognitive stimulation can delay or ameliorate various endophenotypes. Potential mechanisms include increased trophic support, synaptic plasticity, adult neurogenesis, and other forms of experience-dependent cellular plasticity. Subsequent clinical investigations support a role for lifetime activity levels in modulating the onset and progression of HD. Stress can accelerate memory and olfactory deficits and exacerbate cellular dysfunctions in HD mice. In the absence of effective treatments to slow the course of HD, environmental interventions offer feasible approaches to delay the disease, however further preclinical and human studies are needed in order to generate clinical recommendations. Environmental interventions could be combined with future pharmacological therapies and stimulate the identification of enviromimetics, drugs which mimic or enhance the beneficial effects of cognitive stimulation and physical activity. Copyright © 2015. Published by Elsevier Ltd.

You Look Human, But Act Like a Machine: Agent Appearance and Behavior Modulate Different Aspects of Human-Robot Interaction.

PubMed

Abubshait, Abdulaziz; Wiese, Eva

2017-01-01

Gaze following occurs automatically in social interactions, but the degree to which gaze is followed depends on whether an agent is perceived to have a mind, making its behavior socially more relevant for the interaction. Mind perception also modulates the attitudes we have toward others, and determines the degree of empathy, prosociality, and morality invested in social interactions. Seeing mind in others is not exclusive to human agents, but mind can also be ascribed to non-human agents like robots, as long as their appearance and/or behavior allows them to be perceived as intentional beings. Previous studies have shown that human appearance and reliable behavior induce mind perception to robot agents, and positively affect attitudes and performance in human-robot interaction. What has not been investigated so far is whether different triggers of mind perception have an independent or interactive effect on attitudes and performance in human-robot interaction. We examine this question by manipulating agent appearance (human vs. robot) and behavior (reliable vs. random) within the same paradigm and examine how congruent (human/reliable vs. robot/random) versus incongruent (human/random vs. robot/reliable) combinations of these triggers affect performance (i.e., gaze following) and attitudes (i.e., agent ratings) in human-robot interaction. The results show that both appearance and behavior affect human-robot interaction but that the two triggers seem to operate in isolation, with appearance more strongly impacting attitudes, and behavior more strongly affecting performance. The implications of these findings for human-robot interaction are discussed.

Interaction of a common painkiller piroxicam and copper-piroxicam with chromatin causes structural alterations accompanied by modulation at the epigenomic/genomic level.

PubMed

Goswami, Sathi; Sanyal, Sulagna; Chakraborty, Payal; Das, Chandrima; Sarkar, Munna

2017-08-01

NSAIDs are the most common class of painkillers and anti-inflammatory agents. They also show other functions like chemoprevention and chemosuppression for which they act at the protein but not at the genome level since they are mostly anions at physiological pH, which prohibit their approach to the poly-anionic DNA. Complexing the drugs with bioactive metal obliterate their negative charge and allow them to bind to the DNA, thereby, opening the possibility of genome level interaction. To test this hypothesis, we present the interaction of a traditional NSAID, Piroxicam and its copper complex with core histone and chromatin. Spectroscopy, DLS, and SEM studies were applied to see the effect of the interaction on the structure of histone/chromatin. This was coupled with MTT assay, immunoblot analysis, confocal microscopy, micro array analysis and qRT-PCR. The interaction of Piroxicam and its copper complex with histone/chromatin results in structural alterations. Such structural alterations can have different biological manifestations, but to test our hypothesis, we have focused only on the accompanied modulations at the epigenomic/genomic level. The complex, showed alteration of key epigenetic signatures implicated in transcription in the global context, although Piroxicam caused no significant changes. We have correlated such alterations caused by the complex with the changes in global gene expression and validated the candidate gene expression alterations. Our results provide the proof of concept that DNA binding ability of the copper complexes of a traditional NSAID, opens up the possibility of modulations at the epigenomic/genomic level. Copyright © 2017 Elsevier B.V. All rights reserved.

Ionic Gel Modulation of RKKY Interactions in Synthetic Anti-Ferromagnetic Nanostructures for Low Power Wearable Spintronic Devices.

PubMed

Yang, Qu; Zhou, Ziyao; Wang, Liqian; Zhang, Hongjia; Cheng, Yuxin; Hu, Zhongqiang; Peng, Bin; Liu, Ming

2018-05-01

To meet the demand of developing compatible and energy-efficient flexible spintronics, voltage manipulation of magnetism on soft substrates is in demand. Here, a voltage tunable flexible field-effect transistor structure by ionic gel (IG) gating in perpendicular synthetic anti-ferromagnetic nanostructure is demonstrated. As a result, the interlayer Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction can be tuned electrically at room temperature. With a circuit gating voltage, anti-ferromagnetic (AFM) ordering is enhanced or converted into an AFM-ferromagnetic (FM) intermediate state, accompanying with the dynamic domain switching. This IG gating process can be repeated stably at different curvatures, confirming an excellent mechanical property. The IG-induced modification of interlayer exchange coupling is related to the change of Fermi level aroused by the disturbance of itinerant electrons. The voltage modulation of RKKY interaction with excellent flexibility proposes an application potential for wearable spintronic devices with energy efficiency and ultralow operation voltage. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

FUS Phase Separation Is Modulated by a Molecular Chaperone and Methylation of Arginine Cation-π Interactions.

PubMed

Qamar, Seema; Wang, GuoZhen; Randle, Suzanne J; Ruggeri, Francesco Simone; Varela, Juan A; Lin, Julie Qiaojin; Phillips, Emma C; Miyashita, Akinori; Williams, Declan; Ströhl, Florian; Meadows, William; Ferry, Rodylyn; Dardov, Victoria J; Tartaglia, Gian G; Farrer, Lindsay A; Kaminski Schierle, Gabriele S; Kaminski, Clemens F; Holt, Christine E; Fraser, Paul E; Schmitt-Ulms, Gerold; Klenerman, David; Knowles, Tuomas; Vendruscolo, Michele; St George-Hyslop, Peter

2018-04-19

Reversible phase separation underpins the role of FUS in ribonucleoprotein granules and other membrane-free organelles and is, in part, driven by the intrinsically disordered low-complexity (LC) domain of FUS. Here, we report that cooperative cation-π interactions between tyrosines in the LC domain and arginines in structured C-terminal domains also contribute to phase separation. These interactions are modulated by post-translational arginine methylation, wherein arginine hypomethylation strongly promotes phase separation and gelation. Indeed, significant hypomethylation, which occurs in FUS-associated frontotemporal lobar degeneration (FTLD), induces FUS condensation into stable intermolecular β-sheet-rich hydrogels that disrupt RNP granule function and impair new protein synthesis in neuron terminals. We show that transportin acts as a physiological molecular chaperone of FUS in neuron terminals, reducing phase separation and gelation of methylated and hypomethylated FUS and rescuing protein synthesis. These results demonstrate how FUS condensation is physiologically regulated and how perturbations in these mechanisms can lead to disease. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Dense module enumeration in biological networks

NASA Astrophysics Data System (ADS)

Tsuda, Koji; Georgii, Elisabeth

2009-12-01

Analysis of large networks is a central topic in various research fields including biology, sociology, and web mining. Detection of dense modules (a.k.a. clusters) is an important step to analyze the networks. Though numerous methods have been proposed to this aim, they often lack mathematical rigorousness. Namely, there is no guarantee that all dense modules are detected. Here, we present a novel reverse-search-based method for enumerating all dense modules. Furthermore, constraints from additional data sources such as gene expression profiles or customer profiles can be integrated, so that we can systematically detect dense modules with interesting profiles. We report successful applications in human protein interaction network analyses.

Interaction between personality traits and cerebrospinal fluid biomarkers of Alzheimer's disease pathology modulates cognitive performance.

PubMed

Tautvydaitė, Domilė; Kukreja, Deepti; Antonietti, Jean-Philippe; Henry, Hugues; von Gunten, Armin; Popp, Julius

2017-02-02

During adulthood, personality characteristics may contribute to the individual capacity to compensate the impact of developing cerebral Alzheimer's disease (AD) pathology on cognitive impairment in later life. In this study we aimed to investigate whether and how premorbid personality traits interact with cerebrospinal fluid (CSF) markers of AD pathology to predict cognitive performance in subjects with mild cognitive impairment or mild AD dementia and in participants with normal cognition. One hundred and ten subjects, of whom 66 were patients with mild cognitive impairment or mild AD dementia and 44 were healthy controls, had a comprehensive medical and neuropsychological examination as well as lumbar puncture to measure CSF biomarkers of AD pathology (amyloid beta 1-42 , phosphorylated tau and total-tau). Participants' proxies completed the Revised NEO Personality Inventory, Form R to retrospectively assess subjects' premorbid personality. In hierarchical multivariate regression analyses, including age, gender, education, APOEε4 status and cognitive level, premorbid neuroticism, conscientiousness and agreeableness modulated the effect of CSF biomarkers on cognitive performance. Low premorbid openness independently predicted lower levels of cognitive functioning after controlling for biomarker concentrations. Our findings suggest that specific premorbid personality traits are associated with cerebral AD pathology and modulate its impact on cognitive performance. Considering personality characteristics may help to appraise a person's cognitive reserve and the risk of cognitive decline in later life.

Critical Analysis of an e-Learning and Interactive Teaching Module with Respect to the Interpretation of Emergency Computed Tomography of the Brain.

PubMed

Groth, Michael; Barthe, Käthe Greta; Riemer, Martin; Ernst, Marielle; Herrmann, Jochen; Fiehler, Jens; Buhk, Jan-Hendrik

2018-04-01

 To compare the learning benefit of three different teaching strategies on the interpretation of emergency cerebral computed tomography (CT) pathologies by medical students.  Three groups of students with different types of teaching (e-learning, interactive teaching, and standard curricular education in neuroradiology) were tested with respect to the detection of seven CT pathologies. The test results of each group were compared for each CT pathology using the chi-square test. A p-value ≤ 0.05 was considered to be significant.  Opposed to the results of the comparison group (curricular education), the e-learning group and interactive teaching tutorial group both showed a significantly better performance in detecting hyperdense middle cerebral artery sign (p = 0.001 and p < 0.0001) as well as subarachnoid hemorrhage (p = 0.03 and p = 0.001) on CT. Moreover, an increase in performance for the detection of subdural hematoma and skull fracture could be observed for both the interactive teaching group and the e-learning group, with statistical significance in the latter (p = 0.03 and p < 0.0001, respectively). No statistically significant differences were found for the detection of intracranial and epidural hemorrhage, as well as midline shift, among the groups studied.  Our study demonstrates potential learning benefits for both the interactive teaching tutorial and e-learning module group with respect to reading CT scans with slightly different advantages. Thus, the introduction of new learning methods in radiological education might be reasonable at an undergraduate stage but requires learning content-based considerations.   · E-learning can offer benefits regarding the reading of cerebral CT scans by students. · Interactive tutorial can offer benefits regarding the reading of cerebral CT scans by students. · E-learning and interactive tutorial feature different strengths for student learning in radiology. · Application of

Biphasic patterns of diversification and the emergence of modules

PubMed Central

Mittenthal, Jay; Caetano-Anollés, Derek; Caetano-Anollés, Gustavo

2012-01-01

The intricate molecular and cellular structure of organisms converts energy to work, which builds and maintains structure. Evolving structure implements modules, in which parts are tightly linked. Each module performs characteristic functions. In this work we propose that a module can emerge through two phases of diversification of parts. Early in the first phase of this biphasic pattern, the parts have weak linkage—they interact weakly and associate variously. The parts diversify and compete. Under selection for performance, interactions among the parts increasingly constrain their structure and associations. As many variants are eliminated, parts self-organize into modules with tight linkage. Linkage may increase in response to exogenous stresses as well as endogenous processes. In the second phase of diversification, variants of the module and its functions evolve and become new parts for a new cycle of generation of higher-level modules. This linkage hypothesis can interpret biphasic patterns in the diversification of protein domain structure, RNA and protein shapes, and networks in metabolism, codes, and embryos, and can explain hierarchical levels of structural organization that are widespread in biology. PMID:22891076

Interaction of cholinesterase modulators with DNA and their cytotoxic activity.

PubMed

Janockova, Jana; Gulasova, Zuzana; Plsikova, Jana; Musilek, Kamil; Kuca, Kamil; Mikes, Jaromir; Culka, Lubomir; Fedorocko, Peter; Kozurkova, Maria

2014-03-01

This research was focused on a study of the binding properties of a series of cholinesterase reactivators compounds K075 (1), K027 (2) and inhibitors compounds K524, K009 and 7-MEOTA (3-5) with calf thymus DNA. The nature of the interactions between compounds 1-5 and DNA were studied using spectroscopic techniques (UV-vis, fluorescence spectroscopy and circular dichroism). The binding constants for complexes of cholinesterase modulators with DNA were determined from UV-vis spectroscopic titrations (K=0.5 × 10(4)-8.9 × 10(5)M(-1)). The ability of the prepared analogues to relax topoisomerase I was studied with electrophoretic techniques and it was proved that ligands 4 and 5 inhibited this enzyme at a concentration of 30 μM. The biological activity of the novel compounds was assessed through an examination of changes in cell cycle distribution, mitochondrial membrane potential and cellular viability. Inhibitors 3-5 exhibited a cytotoxic effect on HL-60 (human acute promyelocytic leukaemia) cell culture, demonstrated a tendency to affect mitochondrial physiology and viability, and also forced cells to accumulate in the G1/G0-phase of the cell cycle. The cholinesterase reactivators 1 and 2 were found relatively save from the point of view of DNA binding, whereas cholinesterase inhibitors 3-5 resulted as strong DNA binding agents that limit their plausible use. Copyright © 2013 Elsevier B.V. All rights reserved.

Cannabidiol Modulates Fear Memory Formation Through Interactions with Serotonergic Transmission in the Mesolimbic System

PubMed Central

Norris, Christopher; Loureiro, Michael; Kramar, Cecilia; Zunder, Jordan; Renard, Justine; Rushlow, Walter; Laviolette, Steven R

2016-01-01

Emerging evidence suggests that the largest phytochemical component of cannabis, cannabidiol (CBD), may possess pharmacotherapeutic properties in the treatment of neuropsychiatric disorders. CBD has been reported to functionally interact with both the mesolimbic dopamine (DA) and serotonergic (5-HT) receptor systems. However, the underlying mechanisms by which CBD may modulate emotional processing are not currently understood. Using a combination of in vivo electrophysiological recording and fear conditioning in rats, the present study aimed to characterize the behavioral, neuroanatomical, and pharmacological effects of CBD within the mesolimbic pathway, and its possible functional interactions with 5-HT and DAergic transmission. Using targeted microinfusions of CBD into the shell region of the mesolimbic nucleus accumbens (NASh), we report that intra-NASh CBD potently blocks the formation of conditioned freezing behaviors. These effects were challenged with DAergic, cannabinoid CB1 receptor, and serotonergic (5-HT1A) transmission blockade, but only 5-HT1A blockade restored associative conditioned freezing behaviors. In vivo intra-ventral tegmental area (VTA) electrophysiological recordings revealed that behaviorally effective doses of intra-NASh CBD elicited a predominant decrease in spontaneous DAergic neuronal frequency and bursting activity. These neuronal effects were reversed by simultaneous blockade of 5-HT1A receptor transmission. Finally, using a functional contralateral disconnection procedure, we demonstrated that the ability of intra-NASh CBD to block the formation of conditioned freezing behaviors was dependent on intra-VTA GABAergic transmission substrates. Our findings demonstrate a novel NAc→VTA circuit responsible for the behavioral and neuronal effects of CBD within the mesolimbic system via functional interactions with serotonergic 5-HT1A receptor signaling. PMID:27296152

Cellular DEAD-box RNA helicase DDX6 modulates interaction of miR-122 with the 5' untranslated region of hepatitis C virus RNA.

PubMed

Biegel, Jason M; Henderson, Eric; Cox, Erica M; Bonenfant, Gaston; Netzband, Rachel; Kahn, Samantha; Eager, Rachel; Pager, Cara T

2017-07-01

Hepatitis C virus (HCV) subverts the cellular DEAD-box RNA helicase DDX6 to promote virus infection. Using polysome gradient analysis and the subgenomic HCV Renilla reporter replicon genome, we determined that DDX6 does not affect HCV translation. Rather expression of the subgenomic HCV Renilla luciferase reporter at late times, as well as labeling of newly synthesized viral RNA with 4-thiouridine showed that DDX6 modulates replication. Because DDX6 is an effector protein of the microRNA pathway, we also investigated its role in miR-122-directed HCV gene expression. Similar to sequestering miR-122, depletion of DDX6 modulated HCV RNA stability. Interestingly, miR-122-HCV RNA interaction assays with mutant HCV genomes sites and compensatory exogenous miR-122 showed that DDX6 affects the function of miR-122 at one particular binding site. We propose that DDX6 facilitates the miR-122 interaction with HCV 5' UTR, which is necessary for stabilizing the viral genome and the switch between translation and replication. Copyright © 2017 Elsevier Inc. All rights reserved.

Heat Shock Partially Dissociates the Overlapping Modules of the Yeast Protein-Protein Interaction Network: A Systems Level Model of Adaptation

PubMed Central

Mihalik, Ágoston; Csermely, Peter

2011-01-01

Network analysis became a powerful tool giving new insights to the understanding of cellular behavior. Heat shock, the archetype of stress responses, is a well-characterized and simple model of cellular dynamics. S. cerevisiae is an appropriate model organism, since both its protein-protein interaction network (interactome) and stress response at the gene expression level have been well characterized. However, the analysis of the reorganization of the yeast interactome during stress has not been investigated yet. We calculated the changes of the interaction-weights of the yeast interactome from the changes of mRNA expression levels upon heat shock. The major finding of our study is that heat shock induced a significant decrease in both the overlaps and connections of yeast interactome modules. In agreement with this the weighted diameter of the yeast interactome had a 4.9-fold increase in heat shock. Several key proteins of the heat shock response became centers of heat shock-induced local communities, as well as bridges providing a residual connection of modules after heat shock. The observed changes resemble to a ‘stratus-cumulus’ type transition of the interactome structure, since the unstressed yeast interactome had a globally connected organization, similar to that of stratus clouds, whereas the heat shocked interactome had a multifocal organization, similar to that of cumulus clouds. Our results showed that heat shock induces a partial disintegration of the global organization of the yeast interactome. This change may be rather general occurring in many types of stresses. Moreover, other complex systems, such as single proteins, social networks and ecosystems may also decrease their inter-modular links, thus develop more compact modules, and display a partial disintegration of their global structure in the initial phase of crisis. Thus, our work may provide a model of a general, system-level adaptation mechanism to environmental changes. PMID:22022244

The AC photovoltaic module is here!

NASA Astrophysics Data System (ADS)

Strong, Steven J.; Wohlgemuth, John H.; Wills, Robert H.

1997-02-01

This paper describes the design, development, and performance results of a large-area photovoltaic module whose electrical output is ac power suitable for direct connection to the utility grid. The large-area ac PV module features a dedicated, integrally mounted, high-efficiency dc-to-ac power inverter with a nominal output of 250 watts (STC) at 120 Vac, 60 H, that is fully compatible with utility power. The module's output is connected directly to the building's conventional ac distribution system without need for any dc wiring, string combiners, dc ground-fault protection or additional power-conditioning equipment. With its advantages, the ac photovoltaic module promises to become a universal building block for use in all utility-interactive PV systems. This paper discusses AC Module design aspects and utility interface issues (including islanding).

A mental retardation gene, motopsin/neurotrypsin/prss12, modulates hippocampal function and social interaction

PubMed Central

Mitsui, Shinichi; Osako, Yoji; Yokoi, Fumiaki; Dang, Mai T.; Yuri, Kazunari; Li, Yuqing; Yamaguchi, Nozomi

2010-01-01

Motopsin is a mosaic serine protease secreted from neuronal cells in various brain regions including the hippocampus. The loss of motopsin function causes nonsyndromic mental retardation in humans and impairs long-term memory formation in Drosophila. To understand motopsin’s function in the mammalian brain, motopsin knockout mice were generated. Motopsin knockout mice did not have significant deficit in memory formation, as was tested using in the Morris water maze, passive avoidance, and Y-maze tests. A social recognition test showed that the motopsin knockout mice had the ability to recognize two stimulator mice, suggesting normal social memory. In a social novelty test, motopsin knockout mice spent a longer time investigating a familiar mouse than wild-type mice did. In a resident-intruder test, motopsin knockout mice showed prolonged social interaction compared to wild-type mice. Consistent with the behavioral deficit, spine density was significantly decreased on apical dendrites, but not on basal dendrites, of hippocampal pyramidal neurons of motopsin knockout mice. In contrast, pyramidal neurons at the cingulate cortex showed normal spine density. Spatial learning and social interaction induced the phosphorylation of cAMP responsive element binding protein (CREB) in hippocampal neurons of wild-type mice, whereas the phosphorylation of CREB was markedly decreased in mutant mouse brains. Our results indicate that an extracellular protease, motopsin, preferentially affects social behaviors, and modulates the functions of hippocampal neurons. PMID:20092579

A mental retardation gene, motopsin/neurotrypsin/prss12, modulates hippocampal function and social interaction.

PubMed

Mitsui, Shinichi; Osako, Yoji; Yokoi, Fumiaki; Dang, Mai T; Yuri, Kazunari; Li, Yuqing; Yamaguchi, Nozomi

2009-12-01

Motopsin is a mosaic serine protease secreted from neuronal cells in various brain regions, including the hippocampus. The loss of motopsin function causes nonsyndromic mental retardation in humans and impairs long-term memory formation in Drosophila. To understand motopsin's function in the mammalian brain, motopsin knockout (KO) mice were generated. Motopsin KO mice did not have significant deficits in memory formation, as tested using the Morris water maze, passive avoidance and Y-maze tests. A social recognition test showed that the motopsin KO mice had the ability to recognize two stimulator mice, suggesting normal social memory. In a social novelty test, motopsin KO mice spent a longer time investigating a familiar mouse than wild-type (WT) mice did. In a resident-intruder test, motopsin KO mice showed prolonged social interaction as compared with WT mice. Consistent with the behavioral deficit, spine density was significantly decreased on apical dendrites, but not on basal dendrites, of hippocampal pyramidal neurons of motopsin KO mice. In contrast, pyramidal neurons at the cingulate cortex showed normal spine density. Spatial learning and social interaction induced the phosphorylation of cAMP-responsive element-binding protein (CREB) in hippocampal neurons of WT mice, whereas the phosphorylation of CREB was markedly decreased in mutant mouse brains. Our results indicate that an extracellular protease, motopsin, preferentially affects social behaviors, and modulates the functions of hippocampal neurons.

An Interactive Medical Knowledge Assistant

NASA Astrophysics Data System (ADS)

Czejdo, Bogdan D.; Baszun, Mikolaj

This paper describes an interactive medical knowledge assistant that can help a doctor or a patient in making important health related decisions. The system is Web based and consists of several modules, including a medical knowledge base, a doctor interface module, patient interface module and a the main module of the medical knowledge assistant. The medical assistant is designed to help interpret the fuzzy data using rough sets approach. The patient interface includes sub-system for real time monitoring of patients' health parameters and sending them to the main module of the medical knowledge assistant.

Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs

NASA Astrophysics Data System (ADS)

Dror, Ron O.; Green, Hillary F.; Valant, Celine; Borhani, David W.; Valcourt, James R.; Pan, Albert C.; Arlow, Daniel H.; Canals, Meritxell; Lane, J. Robert; Rahmani, Raphaël; Baell, Jonathan B.; Sexton, Patrick M.; Christopoulos, Arthur; Shaw, David E.

2013-11-01

The design of G-protein-coupled receptor (GPCR) allosteric modulators, an active area of modern pharmaceutical research, has proved challenging because neither the binding modes nor the molecular mechanisms of such drugs are known. Here we determine binding sites, bound conformations and specific drug-receptor interactions for several allosteric modulators of the M2 muscarinic acetylcholine receptor (M2 receptor), a prototypical family A GPCR, using atomic-level simulations in which the modulators spontaneously associate with the receptor. Despite substantial structural diversity, all modulators form cation-π interactions with clusters of aromatic residues in the receptor extracellular vestibule, approximately 15Å from the classical, `orthosteric' ligand-binding site. We validate the observed modulator binding modes through radioligand binding experiments on receptor mutants designed, on the basis of our simulations, either to increase or to decrease modulator affinity. Simulations also revealed mechanisms that contribute to positive and negative allosteric modulation of classical ligand binding, including coupled conformational changes of the two binding sites and electrostatic interactions between ligands in these sites. These observations enabled the design of chemical modifications that substantially alter a modulator's allosteric effects. Our findings thus provide a structural basis for the rational design of allosteric modulators targeting muscarinic and possibly other GPCRs.

Wikis for a Collaborative Problem-Solving (CPS) Module for Secondary School Science

ERIC Educational Resources Information Center

DeWitt, Dorothy; Alias, Norlidah; Siraj, Saedah; Spector, Jonathan Michael

2017-01-01

Collaborative problem solving (CPS) can support online learning by enabling interactions for social and cognitive processes. Teachers may not have sufficient knowledge to support such interactions, so support needs to be designed into learning modules for this purpose. This study investigates to what extent an online module for teaching nutrition…

Perceived live interaction modulates the developing social brain.

PubMed

Rice, Katherine; Moraczewski, Dustin; Redcay, Elizabeth

2016-09-01

Although children's social development is embedded in social interaction, most developmental neuroscience studies have examined responses to non-interactive social stimuli (e.g. photographs of faces). The neural mechanisms of real-world social behavior are of special interest during middle childhood (roughly ages 7-13), a time of increased social complexity and competence coinciding with structural and functional social brain development. Evidence from adult neuroscience studies suggests that social interaction may alter neural processing, but no neuroimaging studies in children have directly examined the effects of live social-interactive context on social cognition. In the current study of middle childhood, we compare the processing of two types of speech: speech that children believed was presented over a real-time audio-feed by a social partner and speech that they believed was recorded. Although in reality all speech was prerecorded, perceived live speech resulted in significantly greater neural activation in regions associated with social cognitive processing. These findings underscore the importance of using ecologically-valid and interactive methods to understand the developing social brain. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Complex interactions between cis-regulatory modules in native conformation are critical for Drosophila snail expression

PubMed Central

Dunipace, Leslie; Ozdemir, Anil; Stathopoulos, Angelike

2011-01-01

It has been shown in several organisms that multiple cis-regulatory modules (CRMs) of a gene locus can be active concurrently to support similar spatiotemporal expression. To understand the functional importance of such seemingly redundant CRMs, we examined two CRMs from the Drosophila snail gene locus, which are both active in the ventral region of pre-gastrulation embryos. By performing a deletion series in a ∼25 kb DNA rescue construct using BAC recombineering and site-directed transgenesis, we demonstrate that the two CRMs are not redundant. The distal CRM is absolutely required for viability, whereas the proximal CRM is required only under extreme conditions such as high temperature. Consistent with their distinct requirements, the CRMs support distinct expression patterns: the proximal CRM exhibits an expanded expression domain relative to endogenous snail, whereas the distal CRM exhibits almost complete overlap with snail except at the anterior-most pole. We further show that the distal CRM normally limits the increased expression domain of the proximal CRM and that the proximal CRM serves as a `damper' for the expression levels driven by the distal CRM. Thus, the two CRMs interact in cis in a non-additive fashion and these interactions may be important for fine-tuning the domains and levels of gene expression. PMID:21813571

RM-SORN: a reward-modulated self-organizing recurrent neural network.

PubMed

Aswolinskiy, Witali; Pipa, Gordon

2015-01-01

Neural plasticity plays an important role in learning and memory. Reward-modulation of plasticity offers an explanation for the ability of the brain to adapt its neural activity to achieve a rewarded goal. Here, we define a neural network model that learns through the interaction of Intrinsic Plasticity (IP) and reward-modulated Spike-Timing-Dependent Plasticity (STDP). IP enables the network to explore possible output sequences and STDP, modulated by reward, reinforces the creation of the rewarded output sequences. The model is tested on tasks for prediction, recall, non-linear computation, pattern recognition, and sequence generation. It achieves performance comparable to networks trained with supervised learning, while using simple, biologically motivated plasticity rules, and rewarding strategies. The results confirm the importance of investigating the interaction of several plasticity rules in the context of reward-modulated learning and whether reward-modulated self-organization can explain the amazing capabilities of the brain.

Synchronous Oscillations in Van Der Pol Generator with Modulated Natural Frequency

NASA Astrophysics Data System (ADS)

Nimets, A. Yu.; Vavriv, D. M.

2015-12-01

The synchronous operation of Van Der Pole generator with the low-frequency modulated natural frequency has been investigated. The presence of low-frequency modulation is shown to lead to formation of additional synchronization regions. The appearance of such regions is found to be caused by threefrequency resonances resulted from the interaction between oscillations of the generator natural frequency, modulation frequency and synchronized signal frequency. Characteristics of synchronous oscillations due to the below mentioned three-frequency interaction are obtained and comparison with the case of synchronization of oscillator on the main mode made.

Ecological modules and roles of species in heathland plant-insect flower visitor networks.

PubMed

Dupont, Yoko L; Olesen, Jens M

2009-03-01

1. Co-existing plants and flower-visiting animals often form complex interaction networks. A long-standing question in ecology and evolutionary biology is how to detect nonrandom subsets (compartments, blocks, modules) of strongly interacting species within such networks. Here we use a network analytical approach to (i) detect modularity in pollination networks, (ii) investigate species composition of modules, and (iii) assess the stability of modules across sites. 2. Interactions between entomophilous plants and their flower-visitors were recorded throughout the flowering season at three heathland sites in Denmark, separated by >or= 10 km. Among sites, plant communities were similar, but composition of flower-visiting insect faunas differed. Visitation frequencies of visitor species were recorded as a measure of insect abundance. 3. Qualitative (presence-absence) interaction networks were tested for modularity. Modules were identified, and species classified into topological roles (peripherals, connectors, or hubs) using 'functional cartography by simulated annealing', a method recently developed by Guimerà & Amaral (2005a). 4. All networks were significantly modular. Each module consisted of 1-6 plant species and 18-54 insect species. Interactions aggregated around one or two hub plant species, which were largely identical at the three study sites. 5. Insect species were categorized in taxonomic groups, mostly at the level of orders. When weighted by visitation frequency, each module was dominated by one or few insect groups. This pattern was consistent across sites. 6. Our study adds support to the conclusion that certain plant species and flower-visitor groups are nonrandomly and repeatedly associated. Within a network, these strongly interacting subgroups of species may exert reciprocal selection pressures on each other. Thus, modules may be candidates for the long-sought key units of co-evolution.

A holistic view of crystalline silicon module reliability

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

Hanoka, J.I.

1995-11-01

Several aspects of module reliability are discussed, particularly with reference to the encapsulant and its interaction with the metallization and interconnection of a module. A need to look at the module as a whole single unit is stressed. Also, the issue of a slight light degradation effect in crystalline silicon cells is discussed. A model for this is mentioned and it may well be that polycrystalline cells with dislocations may have an advantage.

Electron spin-echo envelope modulation (ESEEM) reveals water and phosphate interactions with the KcsA potassium channel.

PubMed

Cieslak, John A; Focia, Pamela J; Gross, Adrian

2010-02-23

Electron spin-echo envelope modulation (ESEEM) spectroscopy is a well-established technique for the study of naturally occurring paramagnetic metal centers. The technique has been used to study copper complexes, hemes, enzyme mechanisms, micellar water content, and water permeation profiles in membranes, among other applications. In the present study, we combine ESEEM spectroscopy with site-directed spin labeling (SDSL) and X-ray crystallography in order to evaluate the technique's potential as a structural tool to describe the native environment of membrane proteins. Using the KcsA potassium channel as a model system, we demonstrate that deuterium ESEEM can detect water permeation along the lipid-exposed surface of the KcsA outer helix. We further demonstrate that (31)P ESEEM is able to identify channel residues that interact with the phosphate headgroup of the lipid bilayer. In combination with X-ray crystallography, the (31)P data may be used to define the phosphate interaction surface of the protein. The results presented here establish ESEEM as a highly informative technique for SDSL studies of membrane proteins.

The relative vertex clustering value - a new criterion for the fast discovery of functional modules in protein interaction networks

PubMed Central

2015-01-01

Background Cellular processes are known to be modular and are realized by groups of proteins implicated in common biological functions. Such groups of proteins are called functional modules, and many community detection methods have been devised for their discovery from protein interaction networks (PINs) data. In current agglomerative clustering approaches, vertices with just a very few neighbors are often classified as separate clusters, which does not make sense biologically. Also, a major limitation of agglomerative techniques is that their computational efficiency do not scale well to large PINs. Finally, PIN data obtained from large scale experiments generally contain many false positives, and this makes it hard for agglomerative clustering methods to find the correct clusters, since they are known to be sensitive to noisy data. Results We propose a local similarity premetric, the relative vertex clustering value, as a new criterion allowing to decide when a node can be added to a given node's cluster and which addresses the above three issues. Based on this criterion, we introduce a novel and very fast agglomerative clustering technique, FAC-PIN, for discovering functional modules and protein complexes from a PIN data. Conclusions Our proposed FAC-PIN algorithm is applied to nine PIN data from eight different species including the yeast PIN, and the identified functional modules are validated using Gene Ontology (GO) annotations from DAVID Bioinformatics Resources. Identified protein complexes are also validated using experimentally verified complexes. Computational results show that FAC-PIN can discover functional modules or protein complexes from PINs more accurately and more efficiently than HC-PIN and CNM, the current state-of-the-art approaches for clustering PINs in an agglomerative manner. PMID:25734691

Dynamic e-Learning Modules for Student Lecture Preparation

ERIC Educational Resources Information Center

McIntyre, Timothy; Wegener, Margaret; McGrath, Dominic

2018-01-01

We have developed and demonstrated the effectiveness of a set of online interactive learning modules to accompany physics courses at first- and second-year university levels. Students access the modules prior to attending lectures to familiarize themselves with content which is then discussed and reaffirmed in class. Student surveys and access…

3D extracellular matrix interactions modulate tumour cell growth, invasion and angiogenesis in engineered tumour microenvironments.

PubMed

Taubenberger, Anna V; Bray, Laura J; Haller, Barbara; Shaposhnykov, Artem; Binner, Marcus; Freudenberg, Uwe; Guck, Jochen; Werner, Carsten

2016-05-01

Interactions between tumour cells and extracellular matrix proteins of the tumour microenvironment play crucial roles in cancer progression. So far, however, there are only a few experimental platforms available that allow us to study these interactions systematically in a mechanically defined three-dimensional (3D) context. Here, we have studied the effect of integrin binding motifs found within common extracellular matrix (ECM) proteins on 3D breast (MCF-7) and prostate (PC-3, LNCaP) cancer cell cultures, and co-cultures with endothelial and mesenchymal stromal cells. For this purpose, matrix metalloproteinase-degradable biohybrid poly(ethylene) glycol-heparin hydrogels were decorated with the peptide motifs RGD, GFOGER (collagen I), or IKVAV (laminin-111). Over 14days, cancer spheroids of 100-200μm formed. While the morphology of poorly invasive MCF-7 and LNCaP cells was not modulated by any of the peptide motifs, the aggressive PC-3 cells exhibited an invasive morphology when cultured in hydrogels comprising IKVAV and GFOGER motifs compared to RGD motifs or nonfunctionalised controls. PC-3 (but not MCF-7 and LNCaP) cell growth and endothelial cell infiltration were also significantly enhanced in IKVAV and GFOGER presenting gels. Taken together, we have established a 3D culture model that allows for dissecting the effect of biochemical cues on processes relevant to early cancer progression. These findings provide a basis for more mechanistic studies that may further advance our understanding of how ECM modulates cancer cell invasion and how to ultimately interfere with this process. Threedimensional in vitro cancer models have generated great interest over the past decade. However, most models are not suitable to systematically study the effects of environmental cues on cancer development and progression. To overcome this limitation, we have developed an innovative hydrogel platform to study the interactions between breast and prostate cancer cells and

Modulation of [3H]DAGO binding by substance P (SP) and SP fragments in the mouse brain and spinal cord via MU1 interactions.

PubMed

Krumins, S A; Kim, D C; Seybold, V S; Larson, A A

1989-01-01

Binding of [3H]DAGO to fresh, frozen or beta-funaltrexamine (beta-FNA) pretreated membranes of mouse brain and spinal cord was extensively studied using substance P (SP) or SP fragments as potential competitors and/or modulators. The objective was to determine whether SP exerts its analgesic effect by interacting with mu opioid receptors. The affinity of DAGO was reduced and binding capacity was increased in the presence of SP or the N-terminal SP fragments SP(1-9) and SP(1-4) but not the C-terminal SP fragment SP(5-11). Because sub-nanomolar concentrations of SP or N-terminal SP fragments displaced [3H] DAGO binding to a minor but detectable degree, it is suggested that SP interacts with mu 1 sites through its N-terminus portion. The effect of SP on DAGO binding was less in the spinal cord compared to the rest of the brain. Modulation of DAGO binding by SP was enhanced in the brain after pretreatment of membranes with the narcotic antagonist beta-FNA. These results suggest a novel mechanism for the analgesic action of SP.

Thin film lithium niobate electro-optic modulator with terahertz operating bandwidth.

PubMed

Mercante, Andrew J; Shi, Shouyuan; Yao, Peng; Xie, Linli; Weikle, Robert M; Prather, Dennis W

2018-05-28

We present a thin film crystal ion sliced (CIS) LiNbO 3 phase modulator that demonstrates an unprecedented measured electro-optic (EO) response up to 500 GHz. Shallow rib waveguides are utilized for guiding a single transverse electric (TE) optical mode, and Au coplanar waveguides (CPWs) support the modulating radio frequency (RF) mode. Precise index matching between the co-propagating RF and optical modes is responsible for the device's broadband response, which is estimated to extend even beyond 500 GHz. Matching the velocities of these co-propagating RF and optical modes is realized by cladding the modulator's interaction region in a thin UV15 polymer layer, which increases the RF modal index. The fabricated modulator possesses a tightly confined optical mode, which lends itself to a strong interaction between the modulating RF field and the guided optical carrier; resulting in a measured DC half-wave voltage of 3.8 V·cm -1 . The design, fabrication, and characterization of our broadband modulator is presented in this work.

Macrogenomic engineering via modulation of the scaling of chromatin packing density.

PubMed

Almassalha, Luay M; Bauer, Greta M; Wu, Wenli; Cherkezyan, Lusik; Zhang, Di; Kendra, Alexis; Gladstein, Scott; Chandler, John E; VanDerway, David; Seagle, Brandon-Luke L; Ugolkov, Andrey; Billadeau, Daniel D; O'Halloran, Thomas V; Mazar, Andrew P; Roy, Hemant K; Szleifer, Igal; Shahabi, Shohreh; Backman, Vadim

2017-11-01

Many human diseases result from the dysregulation of the complex interactions between tens to thousands of genes. However, approaches for the transcriptional modulation of many genes simultaneously in a predictive manner are lacking. Here, through the combination of simulations, systems modelling and in vitro experiments, we provide a physical regulatory framework based on chromatin packing-density heterogeneity for modulating the genomic information space. Because transcriptional interactions are essentially chemical reactions, they depend largely on the local physical nanoenvironment. We show that the regulation of the chromatin nanoenvironment allows for the predictable modulation of global patterns in gene expression. In particular, we show that the rational modulation of chromatin density fluctuations can lead to a decrease in global transcriptional activity and intercellular transcriptional heterogeneity in cancer cells during chemotherapeutic responses to achieve near-complete cancer cell killing in vitro. Our findings represent a 'macrogenomic engineering' approach to modulating the physical structure of chromatin for whole-scale transcriptional modulation.

To Modulate and Be Modulated: Estrogenic Influences on Auditory Processing of Communication Signals within a Socio-Neuro-Endocrine Framework

PubMed Central

Yoder, Kathleen M.; Vicario, David S.

2012-01-01

Gonadal hormones modulate behavioral responses to sexual stimuli, and communication signals can also modulate circulating hormone levels. In several species, these combined effects appear to underlie a two-way interaction between circulating gonadal hormones and behavioral responses to socially salient stimuli. Recent work in songbirds has shown that manipulating local estradiol levels in the auditory forebrain produces physiological changes that affect discrimination of conspecific vocalizations and can affect behavior. These studies provide new evidence that estrogens can directly alter auditory processing and indirectly alter the behavioral response to a stimulus. These studies show that: 1. Local estradiol action within an auditory area is necessary for socially-relevant sounds to induce normal physiological responses in the brains of both sexes; 2. These physiological effects occur much more quickly than predicted by the classical time-frame for genomic effects; 3. Estradiol action within the auditory forebrain enables behavioral discrimination among socially-relevant sounds in males; and 4. Estradiol is produced locally in the male brain during exposure to particular social interactions. The accumulating evidence suggests a socio-neuro-endocrinology framework in which estradiol is essential to auditory processing, is increased by a socially relevant stimulus, acts rapidly to shape perception of subsequent stimuli experienced during social interactions, and modulates behavioral responses to these stimuli. Brain estrogens are likely to function similarly in both songbird sexes because aromatase and estrogen receptors are present in both male and female forebrain. Estrogenic modulation of perception in songbirds and perhaps other animals could fine-tune male advertising signals and female ability to discriminate them, facilitating mate selection by modulating behaviors. Keywords: Estrogens, Songbird, Social Context, Auditory Perception PMID:22201281

Motivational salience and genetic variability of dopamine D2 receptor expression interact in the modulation of interference processing

PubMed Central

Richter, Anni; Richter, Sylvia; Barman, Adriana; Soch, Joram; Klein, Marieke; Assmann, Anne; Libeau, Catherine; Behnisch, Gusalija; Wüstenberg, Torsten; Seidenbecher, Constanze I.; Schott, Björn H.

2013-01-01

Dopamine has been implicated in the fine-tuning of complex cognitive and motor function and also in the anticipation of future rewards. This dual function of dopamine suggests that dopamine might be involved in the generation of active motivated behavior. The DRD2 TaqIA polymorphism of the dopamine D2 receptor gene (rs1800497) has previously been suggested to affect striatal function with carriers of the less common A1 allele exhibiting reduced striatal D2 receptor density and increased risk for addiction. Here we aimed to investigate the influences of DRD2 TaqIA genotype on the modulation of interference processing by reward and punishment. Forty-six young, healthy volunteers participated in a behavioral experiment, and 32 underwent functional magnetic resonance imaging (fMRI). Participants performed a flanker task with a motivation manipulation (monetary reward, monetary loss, neither, or both). Reaction times (RTs) were shorter in motivated flanker trials, irrespective of congruency. In the fMRI experiment motivation was associated with reduced prefrontal activation during incongruent vs. congruent flanker trials, possibly reflecting increased processing efficiency. DRD2 TaqIA genotype did not affect overall RTs, but interacted with motivation on the congruency-related RT differences, with A1 carriers showing smaller interference effects to reward alone and A2 homozygotes exhibiting a specific interference reduction during combined reward (REW) and punishment trials (PUN). In fMRI, anterior cingulate activity showed a similar pattern of genotype-related modulation. Additionally, A1 carriers showed increased anterior insula activation relative to A2 homozygotes. Our results point to a role for genetic variations of the dopaminergic system in individual differences of cognition-motivation interaction. PMID:23760450

Gene-to-gene interactions regulate endogenous pain modulation in fibromyalgia patients and healthy controls—antagonistic effects between opioid and serotonin-related genes

PubMed Central

Tour, Jeanette; Löfgren, Monika; Mannerkorpi, Kaisa; Gerdle, Björn; Larsson, Anette; Palstam, Annie; Bileviciute-Ljungar, Indre; Bjersing, Jan; Martin, Ingvar; Ernberg, Malin; Schalling, Martin; Kosek, Eva

2017-01-01

Abstract Chronic pain is associated with dysfunctional endogenous pain modulation, involving both central opioid and serotonergic (5-HT) signaling. Fibromyalgia (FM) is a chronic pain syndrome, characterized by widespread musculoskeletal pain and reduced exercise-induced hypoalgesia (EIH). In this study, we assessed the effects of 3 functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls. Subjects were genotyped regarding the mu-opioid receptor (OPRM1) gene (rs1799971), the serotonin transporter (5-HTT) gene (5-HTTLPR/rs25531), and the serotonin-1a receptor (5-HT1a) gene (rs6296). The patients with FM had increased pain sensitivity and reduced EIH compared with healthy controls. None of the polymorphisms had an effect on EIH on their own. We found significant gene-to-gene interactions between OPRM1 x 5-HTT and OPRM1 x 5-HT1a regarding activation of EIH, with no statistically significant difference between groups. Better EIH was found in individuals with genetically inferred strong endogenous opioid signaling (OPRM1 G) in combination with weak 5-HT tone (5-HTT low/5-HT1a G), compared with strong 5-HT tone (5-HTT high/5-HT1a CC). Based on the proposed mechanisms of these genetic variants, the findings indicate antagonistic interactions between opioid and serotonergic mechanisms during EIH. Moreover, despite different baseline pain level, similar results were detected in FM and controls, not supporting an altered interaction between opioid and 5-HT mechanisms as the basis for dysfunction of EIH in patients with FM. In summary, our results suggest that, by genetic association, the mu-opioid receptor interacts with 2 major serotonergic structures involved in 5-HT reuptake and release, to modulate EIH. PMID:28282362

Gene-to-gene interactions regulate endogenous pain modulation in fibromyalgia patients and healthy controls-antagonistic effects between opioid and serotonin-related genes.

PubMed

Tour, Jeanette; Löfgren, Monika; Mannerkorpi, Kaisa; Gerdle, Björn; Larsson, Anette; Palstam, Annie; Bileviciute-Ljungar, Indre; Bjersing, Jan; Martin, Ingvar; Ernberg, Malin; Schalling, Martin; Kosek, Eva

2017-07-01

Chronic pain is associated with dysfunctional endogenous pain modulation, involving both central opioid and serotonergic (5-HT) signaling. Fibromyalgia (FM) is a chronic pain syndrome, characterized by widespread musculoskeletal pain and reduced exercise-induced hypoalgesia (EIH). In this study, we assessed the effects of 3 functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls. Subjects were genotyped regarding the mu-opioid receptor (OPRM1) gene (rs1799971), the serotonin transporter (5-HTT) gene (5-HTTLPR/rs25531), and the serotonin-1a receptor (5-HT1a) gene (rs6296). The patients with FM had increased pain sensitivity and reduced EIH compared with healthy controls. None of the polymorphisms had an effect on EIH on their own. We found significant gene-to-gene interactions between OPRM1 x 5-HTT and OPRM1 x 5-HT1a regarding activation of EIH, with no statistically significant difference between groups. Better EIH was found in individuals with genetically inferred strong endogenous opioid signaling (OPRM1 G) in combination with weak 5-HT tone (5-HTT low/5-HT1a G), compared with strong 5-HT tone (5-HTT high/5-HT1a CC). Based on the proposed mechanisms of these genetic variants, the findings indicate antagonistic interactions between opioid and serotonergic mechanisms during EIH. Moreover, despite different baseline pain level, similar results were detected in FM and controls, not supporting an altered interaction between opioid and 5-HT mechanisms as the basis for dysfunction of EIH in patients with FM. In summary, our results suggest that, by genetic association, the mu-opioid receptor interacts with 2 major serotonergic structures involved in 5-HT reuptake and release, to modulate EIH.

Measuring ECS Interaction with Biomembranes.

PubMed

Angelucci, Clotilde B; Sabatucci, Annalaura; Dainese, Enrico

2016-01-01

Understanding the correct interaction among the different components of the endocannabinoid system (ECS) is fundamental for a proper assessment of the function of endocannabinoids (eCBs) as signaling molecules. The knowledge of how membrane environment is able to modulate intracellular trafficking of eCBs and their interacting proteins holds a huge potential in unraveling new mechanisms of ECS modulation.Here, fluorescence resonance energy transfer (FRET) technique is applied to measure the binding affinity of ECS proteins to model membranes (i.e., large unilamellar vesicles, LUVs). In particular, we describe in details the paradigmatic example of the interaction of recombinant rat FAAH-ΔTM with LUVs constituted by 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC).

A mental retardation gene, motopsin/prss12, modulates cell morphology by interaction with seizure-related gene 6.

PubMed

Mitsui, Shinichi; Hidaka, Chiharu; Furihata, Mutsuo; Osako, Yoji; Yuri, Kazunari

2013-07-12

A serine protease, motopsin (prss12), plays a significant role in cognitive function and the development of the brain, since the loss of motopsin function causes severe mental retardation in humans and enhances social behavior in mice. Motopsin is activity-dependently secreted from neuronal cells, is captured around the synaptic cleft, and cleaves a proteoglycan, agrin. The multi-domain structure of motopsin, consisting of a signal peptide, a proline-rich domain, a kringle domain, three scavenger receptor cysteine-rich domains, and a protease domain at the C-terminal, suggests the interaction with other molecules through these domains. To identify a protein interacting with motopsin, we performed yeast two-hybrid screening and found that seizure-related gene 6 (sez-6), a transmembrane protein on the plasma membrane of neuronal cells, bound to the proline-rich/kringle domain of motopsin. Pull-down and immunoprecipitation analyses indicated the interaction between these proteins. Immunocytochemical and immunohistochemical analyses suggested the co-localization of motopsin and sez-6 at neuronal cells in the developmental mouse brain and at motor neurons in the anterior horn of human spinal cords. Transient expression of motopsin in neuro2a cells increased the number and length of neurites as well as the level of neurite branching. Interestingly, co-expression of sez-6 with motopsin restored the effect of motopsin at the basal level, while sez-6 expression alone showed no effects on cell morphology. Our results suggest that the interaction of motopsin and sez-6 modulates the neuronal cell morphology. Copyright © 2013 Elsevier Inc. All rights reserved.

The all-optical modulator in dielectric-loaded waveguide with graphene-silicon heterojunction structure

NASA Astrophysics Data System (ADS)

Sun, Feiying; Xia, Liangping; Nie, Changbin; Shen, Jun; Zou, Yixuan; Cheng, Guiyu; Wu, Hao; Zhang, Yong; Wei, Dongshan; Yin, Shaoyun; Du, Chunlei

2018-04-01

All-optical modulators based on graphene show great promise for on-chip optical interconnects. However, the modulation performance of all-optical modulators is usually based on the interaction between graphene and the fiber, limiting their potential in high integration. Based on this point, an all-optical modulator in a dielectric-loaded waveguide (DLW) with a graphene-silicon heterojunction structure (GSH) is proposed. The DLW raises the waveguide mode, which provides a strong light-graphene interaction. Sufficient tuning of the graphene Fermi energy beyond the Pauli blocking effect is obtained with the presented GSH structure. Under the modulation light with a wavelength of 532 nm and a power of 60 mW, a modulation efficiency of 0.0275 dB µm-1 is achieved for light with a communication wavelength of 1.55 µm in the experiment. This modulator has the advantage of having a compact footprint, which may make it a candidate for achieving a highly integrated all-optical modulator.

Teaching Radiology Physics Interactively with Scientific Notebook Software.

PubMed

Richardson, Michael L; Amini, Behrang

2018-06-01

The goal of this study is to demonstrate how the teaching of radiology physics can be enhanced with the use of interactive scientific notebook software. We used the scientific notebook software known as Project Jupyter, which is free, open-source, and available for the Macintosh, Windows, and Linux operating systems. We have created a scientific notebook that demonstrates multiple interactive teaching modules we have written for our residents using the Jupyter notebook system. Scientific notebook software allows educators to create teaching modules in a form that combines text, graphics, images, data, interactive calculations, and image analysis within a single document. These notebooks can be used to build interactive teaching modules, which can help explain complex topics in imaging physics to residents. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Ion-Specific Modulation of Interfacial Interaction Potentials between Solid Substrates and Cell-Sized Particles Mediated via Zwitterionic, Super-Hydrophilic Poly(sulfobetaine) Brushes.

PubMed

Higaki, Yuji; Fröhlich, Benjamin; Yamamoto, Akihisa; Murakami, Ryo; Kaneko, Makoto; Takahara, Atsushi; Tanaka, Motomu

2017-02-16

Zwitterionic polymer brushes draw increasing attention not only because of their superhydrophilic, self-cleaning capability but also due to their excellent antifouling capacity. We investigated the ion-specific modulation of the interfacial interaction potential via densely packed, uniform poly(sulfobetaine) brushes. The vertical Brownian motion of a cell-sized latex particle was monitored by microinterferometry, yielding the effective interfacial interaction potentials V(Δh) and the autocorrelation function of height fluctuation. The potential curvature V″(Δh) exhibited a monotonic increase according to the increase in monovalent salt concentrations, implying the sharpening of the potential confinement. An opposite tendency was observed in CaCl 2 solutions, suggesting that the ion specific modulation cannot be explained by the classical Hofmeister series. When the particle fluctuation was monitored in the presence of free sulfobetaine molecules, the increase in [sulfobetaine] resulted in a distinct increase in hydrodynamic friction. This was never observed in all the other salt solutions, suggesting the interference of zwitterionic pairing of sulfobetaine side chains by the intercalation of sulfobetaine molecules into the brush layer. Furthermore, poly(sulfobetaine) brushes exhibited a very low V″(Δh) and hydrodynamic friction to human erythrocytes, which seems to explain the excellent blood repellency of zwitterionic polymer materials.

PV modules for ground testing

NASA Technical Reports Server (NTRS)

1986-01-01

The main objective was to design and build a minimum of three photovoltaic test panels for plasma interaction experiments. These experiments are intended to provide data on the interactions between high-voltage solar arrays and the space plasma environment. Data gathered will significantly contribute to the development of design criteria for the space station solar arrays. Electrical isolation between the solar cell strings and the module mounting plate is required for high-voltage bias.

Does the Relative Strength of Grouping Principles Modulate the Interactions between them?

PubMed

Montoro, Pedro R; Luna, Dolores

2015-06-05

This study examines the influence of the relative strength of grouping principles on interactions between the intrinsic principle of proximity and the extrinsic principle of common region in the process of perceptual organization. Cooperation and competition between intrinsic and extrinsic principles were examined by presenting the principle either alone or conjoined with another principle. The relative grouping strength of the principles operating alone was varied in two different groups of participants so that it was similar for one group and very different for the other group. Results showed that, when principles acting alone had different strengths, the grouping effect of the strongest principle was similar to that of the cooperation condition, and the effect of the weakest principle was similar to that of competing conjoined principles. In contrast, when the strength of principles acting alone was similar, the effect of conjoined cooperating principles was greater than that of either principle acting alone. Moreover, the effect of conjoined competing principles was smaller than that of either principle operating alone. Results show that cooperation and competition between intrinsic and extrinsic principles are modulated by the relative grouping strength of principles acting alone. Furthermore, performance in these conditions could be predicted on the basis of performance in single-principle conditions.

Artificial neural network-based exploration of gene-nutrient interactions in folate and xenobiotic metabolic pathways that modulate susceptibility to breast cancer.

PubMed

Naushad, Shaik Mohammad; Ramaiah, M Janaki; Pavithrakumari, Manickam; Jayapriya, Jaganathan; Hussain, Tajamul; Alrokayan, Salman A; Gottumukkala, Suryanarayana Raju; Digumarti, Raghunadharao; Kutala, Vijay Kumar

2016-04-15

In the current study, an artificial neural network (ANN)-based breast cancer prediction model was developed from the data of folate and xenobiotic pathway genetic polymorphisms along with the nutritional and demographic variables to investigate how micronutrients modulate susceptibility to breast cancer. The developed ANN model explained 94.2% variability in breast cancer prediction. Fixed effect models of folate (400 μg/day) and B12 (6 μg/day) showed 33.3% and 11.3% risk reduction, respectively. Multifactor dimensionality reduction analysis showed the following interactions in responders to folate: RFC1 G80A × MTHFR C677T (primary), COMT H108L × CYP1A1 m2 (secondary), MTR A2756G (tertiary). The interactions among responders to B12 were RFC1G80A × cSHMT C1420T and CYP1A1 m2 × CYP1A1 m4. ANN simulations revealed that increased folate might restore ER and PR expression and reduce the promoter CpG island methylation of extra cellular superoxide dismutase and BRCA1. Dietary intake of folate appears to confer protection against breast cancer through its modulating effects on ER and PR expression and methylation of EC-SOD and BRCA1. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed Central

2010-01-01

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

Periodically modulated single-photon transport in one-dimensional waveguide

NASA Astrophysics Data System (ADS)

Li, Xingmin; Wei, L. F.

2018-03-01

Single-photon transport along a one-dimension waveguide interacting with a quantum system (e.g., two-level atom) is a very useful and meaningful simplified model of the waveguide-based optical quantum devices. Thus, how to modulate the transport of the photons in the waveguide structures by adjusting certain external parameters should be particularly important. In this paper, we discuss how such a modulation could be implemented by periodically driving the energy splitting of the interacting atom and the atom-photon coupling strength. By generalizing the well developed time-independent full quantum mechanical theory in real space to the time-dependent one, we show that various sideband-transmission phenomena could be observed. This means that, with these modulations the photon has certain probabilities to transmit through the scattering atom in the other energy sidebands. Inversely, by controlling the sideband transmission the periodic modulations of the single photon waveguide devices could be designed for the future optical quantum information processing applications.

An integrative approach to inferring biologically meaningful gene modules.

PubMed

Cho, Ji-Hoon; Wang, Kai; Galas, David J

2011-07-26

The ability to construct biologically meaningful gene networks and modules is critical for contemporary systems biology. Though recent studies have demonstrated the power of using gene modules to shed light on the functioning of complex biological systems, most modules in these networks have shown little association with meaningful biological function. We have devised a method which directly incorporates gene ontology (GO) annotation in construction of gene modules in order to gain better functional association. We have devised a method, Semantic Similarity-Integrated approach for Modularization (SSIM) that integrates various gene-gene pairwise similarity values, including information obtained from gene expression, protein-protein interactions and GO annotations, in the construction of modules using affinity propagation clustering. We demonstrated the performance of the proposed method using data from two complex biological responses: 1. the osmotic shock response in Saccharomyces cerevisiae, and 2. the prion-induced pathogenic mouse model. In comparison with two previously reported algorithms, modules identified by SSIM showed significantly stronger association with biological functions. The incorporation of semantic similarity based on GO annotation with gene expression and protein-protein interaction data can greatly enhance the functional relevance of inferred gene modules. In addition, the SSIM approach can also reveal the hierarchical structure of gene modules to gain a broader functional view of the biological system. Hence, the proposed method can facilitate comprehensive and in-depth analysis of high throughput experimental data at the gene network level.

An integrative approach to inferring biologically meaningful gene modules

PubMed Central

2011-01-01

Background The ability to construct biologically meaningful gene networks and modules is critical for contemporary systems biology. Though recent studies have demonstrated the power of using gene modules to shed light on the functioning of complex biological systems, most modules in these networks have shown little association with meaningful biological function. We have devised a method which directly incorporates gene ontology (GO) annotation in construction of gene modules in order to gain better functional association. Results We have devised a method, Semantic Similarity-Integrated approach for Modularization (SSIM) that integrates various gene-gene pairwise similarity values, including information obtained from gene expression, protein-protein interactions and GO annotations, in the construction of modules using affinity propagation clustering. We demonstrated the performance of the proposed method using data from two complex biological responses: 1. the osmotic shock response in Saccharomyces cerevisiae, and 2. the prion-induced pathogenic mouse model. In comparison with two previously reported algorithms, modules identified by SSIM showed significantly stronger association with biological functions. Conclusions The incorporation of semantic similarity based on GO annotation with gene expression and protein-protein interaction data can greatly enhance the functional relevance of inferred gene modules. In addition, the SSIM approach can also reveal the hierarchical structure of gene modules to gain a broader functional view of the biological system. Hence, the proposed method can facilitate comprehensive and in-depth analysis of high throughput experimental data at the gene network level. PMID:21791051

A computational study of anion-modulated cation-π interactions.

PubMed

Carrazana-García, Jorge A; Rodríguez-Otero, Jesús; Cabaleiro-Lago, Enrique M

2012-05-24

The interaction of anions with cation-π complexes formed by the guanidinium cation and benzene was thoroughly studied by means of computational methods. Potential energy surface scans were performed in order to evaluate the effect of the anion coming closer to the cation-π pair. Several structures of guanidinium-benzene complexes and anion approaching directions were examined. Supermolecule calculations were performed on ternary complexes formed by guanidinium, benzene, and one anion and the interaction energy was decomposed into its different two- and three-body contributions. The interaction energies were further dissected into their electrostatic, exchange, repulsion, polarization and dispersion contributions by means of local molecular orbital energy decomposition analysis. The results confirm that, besides the electrostatic cation-anion attraction, the effect of the anion over the cation-π interaction is mainly due to polarization and can be rationalized following the changes in the anion-π and the nonadditive (three-body) terms of the interaction. When the cation and the anion are on the same side of the π system, the three-body interaction is anticooperative, but when the anion and the cation are on opposite sides of the π system, the three-body interaction is cooperative. As far as we know, this is the first study where this kind of analysis is carried out with a structured cation as guanidinium with a significant biological interest.

AIM: a comprehensive Arabidopsis interactome module database and related interologs in plants.

PubMed

Wang, Yi; Thilmony, Roger; Zhao, Yunjun; Chen, Guoping; Gu, Yong Q

2014-01-01

Systems biology analysis of protein modules is important for understanding the functional relationships between proteins in the interactome. Here, we present a comprehensive database named AIM for Arabidopsis (Arabidopsis thaliana) interactome modules. The database contains almost 250,000 modules that were generated using multiple analysis methods and integration of microarray expression data. All the modules in AIM are well annotated using multiple gene function knowledge databases. AIM provides a user-friendly interface for different types of searches and offers a powerful graphical viewer for displaying module networks linked to the enrichment annotation terms. Both interactive Venn diagram and power graph viewer are integrated into the database for easy comparison of modules. In addition, predicted interologs from other plant species (homologous proteins from different species that share a conserved interaction module) are available for each Arabidopsis module. AIM is a powerful systems biology platform for obtaining valuable insights into the function of proteins in Arabidopsis and other plants using the modules of the Arabidopsis interactome. Database URL:http://probes.pw.usda.gov/AIM Published by Oxford University Press 2014. This work is written by US Government employees and is in the public domain in the US.

Social interaction with a tutor modulates responsiveness of specific auditory neurons in juvenile zebra finches.

PubMed

Yanagihara, Shin; Yazaki-Sugiyama, Yoko

2018-04-12

Behavioral states of animals, such as observing the behavior of a conspecific, modify signal perception and/or sensations that influence state-dependent higher cognitive behavior, such as learning. Recent studies have shown that neuronal responsiveness to sensory signals is modified when animals are engaged in social interactions with others or in locomotor activities. However, how these changes produce state-dependent differences in higher cognitive function is still largely unknown. Zebra finches, which have served as the premier songbird model, learn to sing from early auditory experiences with tutors. They also learn from playback of recorded songs however, learning can be greatly improved when song models are provided through social communication with tutors (Eales, 1989; Chen et al., 2016). Recently we found a subset of neurons in the higher-level auditory cortex of juvenile zebra finches that exhibit highly selective auditory responses to the tutor song after song learning, suggesting an auditory memory trace of the tutor song (Yanagihara and Yazaki-Sugiyama, 2016). Here we show that auditory responses of these selective neurons became greater when juveniles were paired with their tutors, while responses of non-selective neurons did not change. These results suggest that social interaction modulates cortical activity and might function in state-dependent song learning. Copyright © 2018 Elsevier B.V. All rights reserved.

Socio-ecological transitions trigger fire regime shifts and modulate fire-climate interactions in the Sierra Nevada, CA, 1600-2015 CE

NASA Astrophysics Data System (ADS)

Trouet, V.; Taylor, A. H.; Skinner, C. N.; Stephens, S.

2016-12-01

In California, large wildfires cause significant socio-ecological impacts and they incur high federal funding costs for fire suppression. Future fire activity is projected to increase with climate change, but anthropogenic effects can modulate or even override climatic effects causing large uncertainty in fire projections. We developed a 415-year fire history record (1600-2015 CE) based on tree-ring fire-scar data from 29 sites throughout the Sierra Nevada, California. Changes in socio-ecological systems from the Native American to the current period drove large historical fire regime shifts in our record and socio-ecological conditions amplified and buffered fire response to climate. Fire activity was highest and fire-climate relationships were strongest after Native American depopulation - following mission establishment ca. 1775 CE - reduced the self-limiting effect of Native American burns on fire spread. With the Gold Rush and Euro-American immigration (ca. 1865 CE), area burned declined and the strong multidecadal relationship between temperature and fire decayed and then disappeared after implementation of fire suppression (ca. 1900 CE). The past anthropogenic modulation of fire-climate relationships underscores the need for nuanced representations of human-fire interactions to improve the skill of future fire-climate projections. In California, large wildfires cause significant socio-ecological impacts and they incur high federal funding costs for fire suppression. Future fire activity is projected to increase with climate change, but anthropogenic effects can modulate or even override climatic effects causing large uncertainty in fire projections. We developed a 415-year fire history record (1600-2015 CE) based on tree-ring fire-scar data from 29 sites throughout the Sierra Nevada, California. Changes in socio-ecological systems from the Native American to the current period drove large historical fire regime shifts in our record and socio

Investigating local network interactions underlying first- and second-order processing.

PubMed

Ellemberg, Dave; Allen, Harriet A; Hess, Robert F

2004-01-01

We compared the spatial lateral interactions for first-order cues to those for second-order cues, and investigated spatial interactions between these two types of cues. We measured the apparent modulation depth of a target Gabor at fixation, in the presence and the absence of horizontally flanking Gabors. The Gabors' gratings were either added to (first-order) or multiplied with (second-order) binary 2-D noise. Apparent "contrast" or modulation depth (i.e., the perceived difference between the high and low luminance regions for the first-order stimulus, or between the high and low contrast regions for the second-order stimulus) was measured with a modulation depth-matching paradigm. For each observer, the first- and second-order Gabors were equated for apparent modulation depth without the flankers. Our results indicate that at the smallest inter-element spacing, the perceived reduction in modulation depth is significantly smaller for the second-order than for the first-order stimuli. Further, lateral interactions operate over shorter distances and the spatial frequency and orientation tuning of the suppression effect are broader for second- than first-order stimuli. Finally, first- and second-order information interact in an asymmetrical fashion; second-order flankers do not reduce the apparent modulation depth of the first-order target, whilst first-order flankers reduce the apparent modulation depth of the second-order target.

Why study gene-environment interactions?

USDA-ARS?s Scientific Manuscript database

PURPOSE OF REVIEW: We examine the reasons for investigating gene-environment interactions and address recent reports evaluating interactions between genes and environmental modulators in relation to cardiovascular disease and its common risk factors. RECENT FINDINGS: Studies focusing on smoking, phy...

PKB/Akt modulates TGF-beta signalling through a direct interaction with Smad3.

PubMed

Remy, Ingrid; Montmarquette, Annie; Michnick, Stephen W

2004-04-01

Transforming growth factor beta (TGF-beta) has a major role in cell proliferation, differentiation and apoptosis in many cell types. Integration of the TGF-beta pathway with other signalling cascades that control the same cellular processes may modulate TGF-beta responses. Here we report the discovery of a new functional link between TGF-beta and growth factor signalling pathways, mediated by a physical interaction between the serine-threonine kinase PKB (protein kinase B)/Akt and the transcriptional activator Smad3. Formation of the complex is induced by insulin, but inhibited by TGF-beta stimulation, placing PKB-Smad3 at a point of convergence between these two pathways. PKB inhibits Smad3 by preventing its phosphorylation, binding to Smad4 and nuclear translocation. In contrast, Smad3 does not inhibit PKB. Inhibition of Smad3 by PKB occurs through a kinase-activity-independent mechanism, resulting in a decrease in Smad3-mediated transcription and protection of cells against TGF-beta-induced apoptosis. Consistently, knockdown of the endogenous PKB gene with small-interfering RNA (siRNA) has the opposite effect. Our results suggest a very simple mechanism for the integration of signals arising from growth-factor- and TGF-beta-mediated pathways.

Interaction of multiple networks modulated by the working memory training based on real-time fMRI

NASA Astrophysics Data System (ADS)

Shen, Jiahui; Zhang, Gaoyan; Zhu, Chaozhe; Yao, Li; Zhao, Xiaojie

2015-03-01

Neuroimaging studies of working memory training have identified the alteration of brain activity as well as the regional interactions within the functional networks such as central executive network (CEN) and default mode network (DMN). However, how the interaction within and between these multiple networks is modulated by the training remains unclear. In this paper, we examined the interaction of three training-induced brain networks during working memory training based on real-time functional magnetic resonance imaging (rtfMRI). Thirty subjects assigned to the experimental and control group respectively participated in two times training separated by seven days. Three networks including silence network (SN), CEN and DMN were identified by the training data with the calculated function connections within each network. Structural equation modeling (SEM) approach was used to construct the directional connectivity patterns. The results showed that the causal influences from the percent signal changes of target ROI to the SN were positively changed in both two groups, as well as the causal influence from the SN to CEN was positively changed in experimental group but negatively changed in control group from the SN to DMN. Further correlation analysis of the changes in each network with the behavioral improvements showed that the changes in SN were stronger positively correlated with the behavioral improvement of letter memory task. These findings indicated that the SN was not only a switch between the target ROI and the other networks in the feedback training but also an essential factor to the behavioral improvement.

FIBER AND INTEGRATED OPTICS: Radio-frequency electrooptic modulation in optical fibers

NASA Astrophysics Data System (ADS)

Bulyuk, A. N.

1992-10-01

The electrooptic interaction in single-mode optical fibers with both linear and circular birefringe is analyzed. In most cases, a large interaction length imposes a limit on the modulation frequency. A circular birefringence in an optical fiber may lead to an effective coupling of polarization normal modes if a phase-matching condition is satisfied. Through an appropriate choice of polarization states of the light at the entrance and exit of the device, one can achieve a polarization modulation or a frequency shift of the light. There are possible applications in rf polarization modulators, devices for shifting the frequency of light, and detectors of electromagnetic fields.

Unstart coupling mechanism analysis of multiple-modules hypersonic inlet.

PubMed

Hu, Jichao; Chang, Juntao; Wang, Lei; Cao, Shibin; Bao, Wen

2013-01-01

The combination of multiplemodules in parallel manner is an important way to achieve the much higher thrust of scramjet engine. For the multiple-modules scramjet engine, when inlet unstarted oscillatory flow appears in a single-module engine due to high backpressure, how to interact with each module by massflow spillage, and whether inlet unstart occurs in other modules are important issues. The unstarted flowfield and coupling characteristic for a three-module hypersonic inlet caused by center module II and side module III were, conducted respectively. The results indicate that the other two hypersonic inlets are forced into unstarted flow when unstarted phenomenon appears on a single-module hypersonic inlet due to high backpressure, and the reversed flow in the isolator dominates the formation, expansion, shrinkage, and disappearance of the vortexes, and thus, it is the major factor of unstart coupling of multiple-modules hypersonic inlet. The coupling effect among multiple modules makes hypersonic inlet be more likely unstarted.

Unstart Coupling Mechanism Analysis of Multiple-Modules Hypersonic Inlet

PubMed Central

Wang, Lei; Cao, Shibin

2013-01-01

The combination of multiplemodules in parallel manner is an important way to achieve the much higher thrust of scramjet engine. For the multiple-modules scramjet engine, when inlet unstarted oscillatory flow appears in a single-module engine due to high backpressure, how to interact with each module by massflow spillage, and whether inlet unstart occurs in other modules are important issues. The unstarted flowfield and coupling characteristic for a three-module hypersonic inlet caused by center module II and side module III were, conducted respectively. The results indicate that the other two hypersonic inlets are forced into unstarted flow when unstarted phenomenon appears on a single-module hypersonic inlet due to high backpressure, and the reversed flow in the isolator dominates the formation, expansion, shrinkage, and disappearance of the vortexes, and thus, it is the major factor of unstart coupling of multiple-modules hypersonic inlet. The coupling effect among multiple modules makes hypersonic inlet be more likely unstarted. PMID:24348146

Using Surface Enhanced Raman Scattering to Analyze the Interactions of Protein Receptors with Bacterial Quorum Sensing Modulators

PubMed Central

2015-01-01

Many members of the LuxR family of quorum sensing (QS) transcriptional activators, including LasR of Pseudomonas aeruginosa, are believed to require appropriate acyl-homoserine lactone (acyl-HSL) ligands to fold into an active conformation. The failure to purify ligand-free LuxR homologues in nonaggregated form at the high concentrations required for their structural characterization has limited the understanding of the mechanisms by which QS receptors are activated. Surface-enhanced Raman scattering (SERS) is a vibrational spectroscopy technique that can be applied to study proteins at extremely low concentrations in their active state. The high sensitivity of SERS has allowed us to detect molecular interactions between the ligand-binding domain of LasR (LasRLBD) as a soluble apoprotein and modulators of P. aeruginosa QS. We found that QS activators and inhibitors produce differential SERS fingerprints in LasRLBD, and in combination with molecular docking analysis provide insight into the relevant interaction mechanism. This study reveals signal-specific structural changes in LasR upon ligand binding, thereby confirming the applicability of SERS to analyze ligand-induced conformational changes in proteins. PMID:25927541

Bifidobacterium breve - HT-29 cell line interaction: modulation of TNF-α induced gene expression.

PubMed

Boesten, R J; Schuren, F H J; Willemsen, L E M; Vriesema, A; Knol, J; De Vos, W M

2011-06-01

To provide insight in the molecular basis for intestinal host-microbe interactions, we determined the genome-wide transcriptional response of human intestinal epithelial cells following exposure to cells of Bifidobacterium breve. To select an appropriate test system reflecting inflammatory conditions, the responsiveness to TNF-α was compared in T84, Caco-2 and HT-29 cells. The highest TNF-α response was observed in HT-29 cells and this cell line was selected for exposure to the B. breve strains M-16V, NR246 and UCC2003. After one hour of bacterial pre-incubation followed by two hours of additional TNF-α stimulation, B. breve M-16V (86%), but to a much lesser extent strains NR246 (50%) or UCC2003 (32%), showed a strain-specific reduction of the HT-29 transcriptional response to the inflammatory treatment. The most important functional groups of genes that were transcriptionally suppressed by the presence of B. breve M-16V, were found to be involved in immune regulation and apoptotic processes. About 54% of the TNF-α induced genes were solely suppressed by the presence of B. breve M-16V. These included apoptosis-related cysteine protease caspase 7 (CASP7), interferon regulatory factor 3 (IRF3), amyloid beta (A4) precursor proteinbinding family A member 1 (APBA1), NADPH oxidase (NOX5), and leukemia inhibitory factor receptor (LIFR). The extracellular IL-8 concentration was determined by an immunological assay but did not change significantly, indicating that B. breve M-16V only partially modulates the TNF-α pathway. In conclusion, this study shows that B. breve strains modulate gene expression in HT-29 cells under inflammatory conditions in a strain-specific way.

The role of merged interaction regions and drafts in the heliospheric modulation of cosmic rays beyond 20 AU - A computer simulation

NASA Technical Reports Server (NTRS)

Potgieter, M. S.; Le Roux, J. A.; Burlaga, L. F.; Mcdonald, F. B.

1993-01-01

Voyager 2 magnetic field measurements are used to simulate merged interaction and rarefaction regions (MIRs and RRs) for 1985-1989 via numerical solutions of the time-dependent, axially symmetric transport equation of cosmic rays in the heliosphere, together with the concurrent use of the wavy neutral sheet as a time-dependent drift parameter. This drift approach was found to be more successful, because it was able to reproduce the intensity levels, the factor modulation, and latitudinal gradients for 1 GeV protons at 23 AU.

Modulation and interactions of charged biomimetic membranes with bivalent ions

NASA Astrophysics Data System (ADS)

Kazadi Badiambile, Adolphe

biomolecules in a dynamic environment and the lack of appropriate physical and biochemical tools. In contrast, biomimetic membrane models that rely on the amphiphilic properties of phospholipids are powerful tools that enable the study of these molecules in vitro. By having control over the different experimental parameters such as temperature and pH, reliable and repeatable experimental conditions can be created. One of the key questions I investigated in this thesis is related to the clustering mechanism of PtdIns(4, 5)P2 into pools or aggregates that enable independent cellular control of this species by geometric separation. The lateral aggregation of PtdIns(4, 5)P2 and its underlying physical causes is still a matter of debate. In the first part of this thesis I introduce the general information on lipid membranes with a special focus on the PtdIns family and their associated signaling events. In addition, I explain the Langmuir-Blodgett film balance (LB) system as tool to study lipid membranes and lipid interactions. In the second chapter, I describe my work on the lateral compressibility of PtdIns(4, 5)P2, PtdIns and DOPG monolayers and its modulation by bivalent ions using Langmuir monolayers. In addition, a theoretical framework of compressibility that depends on a surface potential induced by a planar layer of charged molecules and ions in the bulk was provided. In the third part, I present my work on the excess Gibbs free energy of the lipid systems PtdIns(4, 5)P2 --POPC, PtdIns(4, 5)P2, and POPC as they are modulated by bivalent ions. In the fourth part, I report on my foray in engineering a light-based system that relies on different dye properties to simulate calcium induced calcium release (CICR) that occurs in many cell types. In the final chapter, I provide a general conclusion and present directions for future research that would build on my findings.

Love as a Modulator of Pain

PubMed Central

Tamam, Sofina; Ahmad, Asma Hayati

2017-01-01

Pain is modulated by various factors, the most notable of which is emotions. Since love is an emotion, it can also modulate pain. The answer to the question of whether it enhances or reduces pain needs to be determined. A review was conducted of animal and human studies in which this enigmatic emotion and its interaction with pain was explored. Recent advances in neuroimaging have revealed similarities in brain activation relating to love and pain. At the simplest level, this interaction can be explained by the overlapping network structure in brain functional connectivity, although the explanation is considerably more complex. The effect of love can either result in increased or decreased pain perception. An explanation of the interaction between pain and love relates to the functional connectivity of the brain and to the psychological construct of the individual, as well as to his or her ability to engage resources relating to emotion regulation. In turn, this determines how a person relates to love and reacts to pain. PMID:28814928

Polymorphism and Modulation of Para-Substituted l-Phenylalanine.

PubMed

Sögütoglu, Leyla-Cann; Lutz, Martin; Meekes, Hugo; de Gelder, René; Vlieg, Elias

2017-12-06

The crystal structure of para -methyl-l-phenylalanine at 230 K resembles that of the para-fluorinated analogue from the literature but is commensurately modulated with seven molecules in the asymmetric unit ( Z ' = 7). At 100 K, the superstructure loses its modulation, leading to a unit cell with Z ' = 1, with clear disorder in the phenyl ring orientations. The methyl-substituent in para -methyl-l-phenylalanine has, in contrast to fluorine, no polar interactions with protons of neighboring molecules, which might allow for the well-defined modulation of the crystal structure at 230 K.

Interaction of small G protein signaling modulator 3 with connexin 43 contributes to myocardial infarction in rat hearts.

PubMed

Lee, Chang Youn; Choi, Jung-Won; Shin, Sunhye; Lee, Jiyun; Seo, Hyang-Hee; Lim, Soyeon; Lee, Seahyoung; Joo, Hyun-Chul; Kim, Sang Woo; Hwang, Ki-Chul

2017-09-16

Connexin 43 (Cx43), a ubiquitous connexin expressed in the heart and skin, is associated with a variety of hereditary conditions. Therefore, the characterization of Cx43-interacting proteins and their dynamics is important to understand not only the molecular mechanisms underlying pathological malfunction of gap junction-mediated intercellular communication but also to identify novel and unanticipated biological functions of Cx43. In the present study, we observed potential targets of Cx43 to determine new molecular functions in cardio-protection. MALDI-TOF mass spectrometry analysis of Cx43 co-immunoprecipitated proteins showed that Cx43 interacts with several proteins related to metabolism. In GeneMANIA network analysis, SGSM3, which has not been previously associated with Cx43, was highly correlated with Cx43 in heart functions, and high levels of SGSM3 appeared to induce the turnover of Cx43 through lysosomal degradation in myocardial infarcted rat hearts. Moreover, we confirmed that lysosomal degradation of Cx43 is dependent upon the interaction between SGSM3 and Cx43 in H9c2 cardiomyocytes. The functional importance of the interaction between SGSM3 and Cx43 was confirmed by results showing that Cx43 expression was enhanced by SGSM3 siRNA knockdown in H9c2 cells. In summary, the results of this study elucidate the molecular mechanisms in which Cx43 with SGSM3 is degraded in myocardial infarcted rat hearts, which may contribute to the establishment of new therapeutic targets to modulate cardiac function in physiological and pathological conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

HuR interacts with human immunodeficiency virus type 1 reverse transcriptase, and modulates reverse transcription in infected cells

PubMed Central

Lemay, Julie; Maidou-Peindara, Priscilla; Bader, Thomas; Ennifar, Eric; Rain, Jean-Christophe; Benarous, Richard; Liu, Lang Xia

2008-01-01

Reverse transcription of the genetic material of human immunodeficiency virus type 1 (HIV-1) is a critical step in the replication cycle of this virus. This process, catalyzed by reverse transcriptase (RT), is well characterized at the biochemical level. However, in infected cells, reverse transcription occurs in a multiprotein complex – the reverse transcription complex (RTC) – consisting of viral genomic RNA associated with viral proteins (including RT) and, presumably, as yet uncharacterized cellular proteins. Very little is known about the cellular proteins interacting with the RTC, and with reverse transcriptase in particular. We report here that HIV-1 reverse transcription is affected by the levels of a nucleocytoplasmic shuttling protein – the RNA-binding protein HuR. A direct protein-protein interaction between RT and HuR was observed in a yeast two-hybrid screen and confirmed in vitro by homogenous time-resolved fluorescence (HTRF). We mapped the domain interacting with HuR to the RNAse H domain of RT, and the binding domain for RT to the C-terminus of HuR, partially overlapping the third RRM RNA-binding domain of HuR. HuR silencing with specific siRNAs greatly impaired early and late steps of reverse transcription, significantly inhibiting HIV-1 infection. Moreover, by mutagenesis and immunoprecipitation studies, we could not detect the binding of HuR to the viral RNA. These results suggest that HuR may be involved in and may modulate the reverse transcription reaction of HIV-1, by an as yet unknown mechanism involving a protein-protein interaction with HIV-1 RT. PMID:18544151

Modularity, pollination systems, and interaction turnover in plant-pollinator networks across space.

PubMed

Carstensen, Daniel W; Sabatino, Malena; Morellato, Leonor Patricia C

2016-05-01

Mutualistic interaction networks have been shown to be structurally conserved over space and time while pairwise interactions show high variability. In such networks, modularity is the division of species into compartments, or modules, where species within modules share more interactions with each other than they do with species from other modules. Such a modular structure is common in mutualistic networks and several evolutionary and ecological mechanisms have been proposed as underlying drivers. One prominent explanation is the existence of pollination syndromes where flowers tend to attract certain pollinators as determined by a set of traits. We investigate the modularity of seven community level plant-pollinator networks sampled in rupestrian grasslands, or campos rupestres, in SE Brazil. Defining pollination systems as corresponding groups of flower syndromes and pollinator functional groups, we test the two hypotheses that (1) interacting species from the same pollination system are more often assigned to the same module than interacting species from different pollination systems and; that (2) interactions between species from the same pollination system are more consistent across space than interactions between species from different pollination systems. Specifically we ask (1) whether networks are consistently modular across space; (2) whether interactions among species of the same pollination system occur more often inside modules, compared to interactions among species of different pollination systems, and finally; (3) whether the spatial variation in interaction identity, i.e., spatial interaction rewiring, is affected by trait complementarity among species as indicated by pollination systems. We confirm that networks are consistently modular across space and that interactions within pollination systems principally occur inside modules. Despite a strong tendency, we did not find a significant effect of pollination systems on the spatial consistency of

Search for an Annual Modulation in a p-Type Point Contact Germanium Dark Matter Detector

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

Barbeau, P.S.; Collar, J.I.; Fields, N.

2011-01-01

Fifteen months of cumulative CoGeNT data are examined for indications of an annual modulation, a predicted signature of weakly interacting massive particle (WIMP) interactions. Presently available data support the presence of a modulated component of unknown origin, with parameters prima facie compatible with a galactic halo composed of light-mass WIMPs. Unoptimized estimators yield a statistical significance for a modulation of {approx}2.8{sigma}, limited by the short exposure.

Search for an Annual Modulation in a p-Type Point Contact Germanium Dark Matter Detector

NASA Astrophysics Data System (ADS)

Aalseth, C. E.; Barbeau, P. S.; Colaresi, J.; Collar, J. I.; Diaz Leon, J.; Fast, J. E.; Fields, N.; Hossbach, T. W.; Keillor, M. E.; Kephart, J. D.; Knecht, A.; Marino, M. G.; Miley, H. S.; Miller, M. L.; Orrell, J. L.; Radford, D. C.; Wilkerson, J. F.; Yocum, K. M.

2011-09-01

Fifteen months of cumulative CoGeNT data are examined for indications of an annual modulation, a predicted signature of weakly interacting massive particle (WIMP) interactions. Presently available data support the presence of a modulated component of unknown origin, with parameters prima facie compatible with a galactic halo composed of light-mass WIMPs. Unoptimized estimators yield a statistical significance for a modulation of ˜2.8σ, limited by the short exposure.

Dynamic cross correlation studies of wave particle interactions in ULF phenomena

NASA Technical Reports Server (NTRS)

Mcpherron, R. L.

1979-01-01

Magnetic field observations made by satellites in the earth's magnetic field reveal a wide variety of ULF waves. These waves interact with the ambient particle populations in complex ways, causing modulation of the observed particle fluxes. This modulation is found to be a function of species, pitch angle, energy and time. The characteristics of this modulation provide information concerning the wave mode and interaction process. One important characteristic of wave-particle interactions is the phase of the particle flux modulation relative to the magnetic field variations. To display this phase as a function of time a dynamic cross spectrum program has been developed. The program produces contour maps in the frequency time plane of the cross correlation coefficient between any particle flux time series and the magnetic field vector. This program has been utilized in several studies of ULF wave-particle interactions at synchronous orbit.

Fat mass and obesity-associated (FTO) protein interacts with CaMKII and modulates the activity of CREB signaling pathway.

PubMed

Lin, Li; Hales, Chadwick M; Garber, Kathryn; Jin, Peng

2014-06-15

Polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. FTO is a nuclear protein and its physiological function remains largely unknown, but alterations in its expression in mice influence energy expenditure, food intake and, ultimately, body weight. To understand the molecular functions of FTO, we performed a yeast two-hybrid screen to identify the protein(s) that could directly interact with human FTO protein. Using multiple assays, we demonstrate that FTO interacts with three isoforms of calcium/calmodulin-dependent protein kinase II: α, β and γ, which are protein kinases that phosphorylate a broad range of substrates. This interaction is functional; overexpression of FTO delays the dephosphorylation of cAMP response element-binding protein (CREB) in human neuroblastoma (SK-N-SH) cells, which in turn leads to a dramatic increase in the expression of the CREB targets neuropeptide receptor 1 (NPY1R) and brain-derived neurotrophic factor (BDNF), which already are known to regulate food intake and energy homeostasis. Thus, our results suggest that FTO could modulate obesity by regulating the activity of the CREB signaling pathway. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Modulating interactions between ligand-coated nanoparticles and phase-separated lipid bilayers by varying the ligand density and the surface charge.

PubMed

Chen, Xiaojie; Tieleman, D Peter; Liang, Qing

2018-02-01

The interactions between nanoparticles and lipid bilayers are critical in applications of nanoparticles in nanomedicine, cell imaging, toxicology, and elsewhere. Here, we investigate the interactions between nanoparticles coated with neutral and/or charged ligands and phase-separated lipid bilayers using coarse-grained molecular dynamics simulation. Both penetration and adsorption processes as well as the final distribution of the nanoparticles can be readily modulated by varying the ligand density and the surface charge of the nanoparticles. Completely hydrophobic (neutral) nanoparticles with larger size initially preferentially penetrate into the liquid-disordered region of the lipid bilayer and finally transfer into the liquid-ordered region; partially hydrophilic nanoparticles with low or moderate surface charge tend to either distribute in the liquid-disordered region or be adsorbed on the surface of the lipid bilayer, while strongly hydrophilic nanoparticles with high surface charge always reside on the surface of the lipid bilayer. Interactions of the nanoparticles with the lipid bilayers are affected by the surface charge of nanoparticles, hydrophobic mismatch, bending of the ligands, and the packing state of the lipids. Insight in these factors can be used to improve the efficiency of designing nanoparticles for specific applications.

Improving Intercultural Interactions. Modules for Cross-Cultural Training Programs. Multicultural Aspects of Counseling Series 3.

ERIC Educational Resources Information Center

Brislin, Richard W., Ed.; Yoshida, Tomoko, Ed.

This book contains modules for use in cross-cultural training programs. A module differs from a chapter in that it is a collection of materials that guide the reader both on the content of a defined unit of training and the method of delivery of that content. The modules are grouped into four sections, three corresponding to organizations in which…

NF-κB-Chromatin Interactions Drive Diverse Phenotypes by Modulating Transcriptional Noise

PubMed Central

Wong, Victor C.; Bass, Victor L.; Bullock, M. Elise; Chavali, Arvind K.; Lee, Robin E.C.; Mothes, Walther; Gaudet, Suzanne; Miller-Jensen, Kathryn

2018-01-01

SUMMARY Noisy gene expression generates diverse phenotypes, but little is known about mechanisms that modulate noise. Combining experiments and modeling, we studied how tumor necrosis factor (TNF) initiates noisy expression of latent HIV via the transcription factor nuclear factor κB (NF-κB) and how the HIV genomic integration site modulates noise to generate divergent (low-versus-high) phenotypes of viral activation. We show that TNF-induced transcriptional noise varies more than mean transcript number and that amplification of this noise explains low-versus-high viral activation. For a given integration site, live-cell imaging shows that NF-κB activation correlates with viral activation, but across integration sites, NF-κB activation cannot account for differences in transcriptional noise and phenotypes. Instead, differences in transcriptional noise are associated with differences in chromatin state and RNA polymerase II regulation. We conclude that, whereas NF-κB regulates transcript abundance in each cell, the chromatin environment modulates noise in the population to support diverse HIV activation in response to TNF. PMID:29346759

Genome-Environment Interactions That Modulate Aging: Powerful Targets for Drug Discovery

PubMed Central

Wuttke, Daniel; Wood, Shona H.; Plank, Michael; Vora, Chintan

2012-01-01

Aging is the major biomedical challenge of this century. The percentage of elderly people, and consequently the incidence of age-related diseases such as heart disease, cancer, and neurodegenerative diseases, is projected to increase considerably in the coming decades. Findings from model organisms have revealed that aging is a surprisingly plastic process that can be manipulated by both genetic and environmental factors. Here we review a broad range of findings in model organisms, from environmental to genetic manipulations of aging, with a focus on those with underlying gene-environment interactions with potential for drug discovery and development. One well-studied dietary manipulation of aging is caloric restriction, which consists of restricting the food intake of organisms without triggering malnutrition and has been shown to retard aging in model organisms. Caloric restriction is already being used as a paradigm for developing compounds that mimic its life-extension effects and might therefore have therapeutic value. The potential for further advances in this field is immense; hundreds of genes in several pathways have recently emerged as regulators of aging and caloric restriction in model organisms. Some of these genes, such as IGF1R and FOXO3, have also been associated with human longevity in genetic association studies. The parallel emergence of network approaches offers prospects to develop multitarget drugs and combinatorial therapies. Understanding how the environment modulates aging-related genes may lead to human applications and disease therapies through diet, lifestyle, or pharmacological interventions. Unlocking the capacity to manipulate human aging would result in unprecedented health benefits. PMID:22090473

Angle-dependent modulated spectral peaks of proton beams generated in ultrashort intense laser-solid interactions

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

Su, L. N.; Hu, Z. D.; Zheng, Y.

2014-09-15

Proton acceleration from 4 μm thick aluminum foils irradiated by 30-TW Ti:sapphire laser pulses is investigated using an angle-resolved proton energy spectrometer. We find that a modulated spectral peak at ∼0.82 MeV is presented at 2.5° off the target normal direction. The divergence angle of the modulated zone is 3.8°. Two-dimensional particle-in-cell simulations reveal that self-generated toroidal magnetic field at the rear surface of the target foil is responsible for the modulated spectral feature. The field deflects the low energy protons, resulting in the modulated energy spectrum with certain peaks.

Ginsenoside Re protects against phencyclidine-induced behavioral changes and mitochondrial dysfunction via interactive modulation of glutathione peroxidase-1 and NADPH oxidase in the dorsolateral cortex of mice.

PubMed

Tran, The-Vinh; Shin, Eun-Joo; Dang, Duy-Khanh; Ko, Sung Kwon; Jeong, Ji Hoon; Nah, Seung-Yeol; Jang, Choon-Gon; Lee, Yu Jeung; Toriumi, Kazuya; Nabeshima, Toshitaka; Kim, Hyoung-Chun

2017-12-01

We investigated whether ginsenoside Re (Re) modulates phencyclidine (PCP)-induced sociability deficits and recognition memory impairments to extend our recent finding. We examined the role of GPx-1 gene in the pharmacological activity of Re against mitochondrial dysfunction induced by PCP in the dorsolateral cortex of mice. Since mitochondrial oxidative stress activates NADPH oxidase (PHOX), we applied PHOX inhibitor apocynin for evaluating interactive modulation between GPx-1 and PHOX against PCP neurotoxicity. Sociability deficits and recognition memory impairments induced by PCP were more pronounced in GPx-1 knockout (KO) than in wild type (WT) mice. PCP-induced mitochondrial oxidative stress, mitochondrial dysfunction, and membrane translocation of p47phox were more evident in GPx-1 KO than in WT. Re treatment significantly attenuated PCP-induced neurotoxic changes. Re also significantly attenuated PCP-induced sociability deficits and recognition memory impairments. The attenuation by Re was comparable to that by apocynin. The attenuation was more obvious in GPx-1 KO than in WT. Importantly, apocynin did not show any additional positive effects on the neuroprotective activity of Re, indicating that PHOX is a molecular target for therapeutic activity of Re. Our results suggest that Re requires interactive modulation between GPx activity and PHOX (p47phox) to exhibit neuroprotective potentials against PCP insult. Copyright © 2017 Elsevier Ltd. All rights reserved.

Applied Graph-Mining Algorithms to Study Biomolecular Interaction Networks

PubMed Central

2014-01-01

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

In vitro modulation of the interaction between HA95 and LAP2beta by cAMP signaling.

PubMed

Martins, Sandra B; Marstad, Anne; Collas, Philippe

2003-09-09

The nuclear envelope mediates key functions by interacting with chromatin. We recently reported an interaction between the chromatin- and nuclear matrix-associated protein HA95 and the inner nuclear membrane integral protein LAP2beta, implicated in initiation of DNA replication (Martins et al. (2003) J. Cell Biol. 160, 177-188). Here, we show that in vitro, interaction between HA95 and LAP2beta is modulated by cAMP signaling via PKA. Exposure of an anti-HA95 immune precipitate from interphase HeLa cells to a mitotic extract promotes ATP-dependent release of LAP2beta from the HA95 complex. This coincides with Ser and Thr phosphorylation of HA95 and LAP2beta. Inhibition of PKA with PKI abolishes phosphorylation of HA95 and dissociation of LAP2beta from HA95, although LAPbeta remains phosphorylated. Antagonizing cAMP signaling in mitotic extract also abolishes the release of LAP2beta from HA95; however, disrupting PKA anchoring to A-kinase anchoring proteins has no effect. Inhibition of CDK activity in the extract greatly reduces LAP2beta phosphorylation but does not prevent LAP2beta release from HA95. Inhibition of PKC, MAP kinase, or CaM kinase II does not affect mitotic extract-induced dissociation of LAP2beta from HA95. PKA phosphorylates HA95 but not LAP2beta in vitro and elicits a release of LAP2beta from HA95. CDK1 or PKC phosphorylates LAP2beta within the HA95 complex, but neither kinase induces LAP2beta release. Our results indicate that in vitro, the interaction between HA95 and LAP2beta is influenced by a PKA-mediated phosphorylation of HA95 rather than by CDK1- or PKC-mediated phosphorylation of LAP2beta. This suggests an additional level of regulation of a chromatin-nuclear envelope interaction in dividing cells.

Thalamic synaptic transmission of sensory information modulated by synergistic interaction of adenosine and serotonin.

PubMed

Yang, Ya-Chin; Hu, Chun-Chang; Huang, Chen-Syuan; Chou, Pei-Yu

2014-03-01

The thalamic synapses relay peripheral sensory information to the cortex, and constitute an important part of the thalamocortical network that generates oscillatory activities responsible for different vigilance (sleep and wakefulness) states. However, the modulation of thalamic synaptic transmission by potential sleep regulators, especially by combination of regulators in physiological scenarios, is not fully characterized. We found that somnogen adenosine itself acts similar to wake-promoting serotonin, both decreasing synaptic strength as well as short-term depression, at the retinothalamic synapse. We then combined the two modulators considering the coexistence of them in the hypnagogic (sleep-onset) state. Adenosine plus serotonin results in robust synergistic inhibition of synaptic strength and dramatic transformation of short-term synaptic depression to facilitation. These synaptic effects are not achievable with a single modulator, and are consistent with a high signal-to-noise ratio but a low level of signal transmission through the thalamus appropriate for slow-wave sleep. This study for the first time demonstrates that the sleep-regulatory modulators may work differently when present in combination than present singly in terms of shaping information flow in the thalamocortical network. The major synaptic characters such as the strength and short-term plasticity can be profoundly altered by combination of modulators based on physiological considerations. © 2013 International Society for Neurochemistry.

Static Modulation Wave of Arrays of Halogen Interactions Transduced to a Hierarchy of Nanoscale Change Stimuli of Crystalline Rotors Dynamics.

PubMed

Simonov, Sergey; Zorina, Leokadiya; Wzietek, Pawel; Rodríguez-Fortea, Antonio; Canadell, Enric; Mézière, Cécile; Bastien, Guillaume; Lemouchi, Cyprien; Garcia-Garibay, Miguel A; Batail, Patrick

2018-06-13

Here we present a study where what can be seen as a static modulation wave encompassing four successive arrays of interacting iodine atoms in crystalline 1,4-Bis((4'-(iodoethynyl)phenyl) ethynyl)bicyclo[2,2,2]octane rotors changes the structure from one-half molecule to three-and-a-half molecules in the asymmetric unit below a phase transition at 105 K. The remarkable finding is that the total 1 H spin-lattice relaxation rate, T 1 -1 , of unprecedented complexity to date in molecular rotors, is the weighted sum of the relaxation rates of the four contributing rotors relaxation rates, each with distinguishable exchange frequencies reflecting Arrhenius parameters with different activation barriers ( E a ) and attempt frequencies (τ o -1 ). This allows us to show in tandem with rotor-environment interaction energy calculations how the dynamics of molecular rotors are able to decode structural information from their surroundings with remarkable nanoscale precision.

Stapled Voltage-Gated Calcium Channel (CaV) α-Interaction Domain (AID) Peptides Act As Selective Protein-Protein Interaction Inhibitors of CaV Function.

PubMed

Findeisen, Felix; Campiglio, Marta; Jo, Hyunil; Abderemane-Ali, Fayal; Rumpf, Christine H; Pope, Lianne; Rossen, Nathan D; Flucher, Bernhard E; DeGrado, William F; Minor, Daniel L

2017-06-21

For many voltage-gated ion channels (VGICs), creation of a properly functioning ion channel requires the formation of specific protein-protein interactions between the transmembrane pore-forming subunits and cystoplasmic accessory subunits. Despite the importance of such protein-protein interactions in VGIC function and assembly, their potential as sites for VGIC modulator development has been largely overlooked. Here, we develop meta-xylyl (m-xylyl) stapled peptides that target a prototypic VGIC high affinity protein-protein interaction, the interaction between the voltage-gated calcium channel (Ca V ) pore-forming subunit α-interaction domain (AID) and cytoplasmic β-subunit (Ca V β). We show using circular dichroism spectroscopy, X-ray crystallography, and isothermal titration calorimetry that the m-xylyl staples enhance AID helix formation are structurally compatible with native-like AID:Ca V β interactions and reduce the entropic penalty associated with AID binding to Ca V β. Importantly, electrophysiological studies reveal that stapled AID peptides act as effective inhibitors of the Ca V α 1 :Ca V β interaction that modulate Ca V function in an Ca V β isoform-selective manner. Together, our studies provide a proof-of-concept demonstration of the use of protein-protein interaction inhibitors to control VGIC function and point to strategies for improved AID-based Ca V modulator design.

Stapled Voltage-Gated Calcium Channel (CaV) α-Interaction Domain (AID) Peptides Act As Selective Protein–Protein Interaction Inhibitors of CaV Function

PubMed Central

2017-01-01

For many voltage-gated ion channels (VGICs), creation of a properly functioning ion channel requires the formation of specific protein–protein interactions between the transmembrane pore-forming subunits and cystoplasmic accessory subunits. Despite the importance of such protein–protein interactions in VGIC function and assembly, their potential as sites for VGIC modulator development has been largely overlooked. Here, we develop meta-xylyl (m-xylyl) stapled peptides that target a prototypic VGIC high affinity protein–protein interaction, the interaction between the voltage-gated calcium channel (CaV) pore-forming subunit α-interaction domain (AID) and cytoplasmic β-subunit (CaVβ). We show using circular dichroism spectroscopy, X-ray crystallography, and isothermal titration calorimetry that the m-xylyl staples enhance AID helix formation are structurally compatible with native-like AID:CaVβ interactions and reduce the entropic penalty associated with AID binding to CaVβ. Importantly, electrophysiological studies reveal that stapled AID peptides act as effective inhibitors of the CaVα1:CaVβ interaction that modulate CaV function in an CaVβ isoform-selective manner. Together, our studies provide a proof-of-concept demonstration of the use of protein–protein interaction inhibitors to control VGIC function and point to strategies for improved AID-based CaV modulator design. PMID:28278376

Amplitude Modulations of Acoustic Communication Signals

NASA Astrophysics Data System (ADS)

Turesson, Hjalmar K.

2011-12-01

In human speech, amplitude modulations at 3 -- 8 Hz are important for discrimination and detection. Two different neurophysiological theories have been proposed to explain this effect. The first theory proposes that, as a consequence of neocortical synaptic dynamics, signals that are amplitude modulated at 3 -- 8 Hz are propagated better than un-modulated signals, or signals modulated above 8 Hz. This suggests that neural activity elicited by vocalizations modulated at 3 -- 8 Hz is optimally transmitted, and the vocalizations better discriminated and detected. The second theory proposes that 3 -- 8 Hz amplitude modulations interact with spontaneous neocortical oscillations. Specifically, vocalizations modulated at 3 -- 8 Hz entrain local populations of neurons, which in turn, modulate the amplitude of high frequency gamma oscillations. This suggests that vocalizations modulated at 3 -- 8 Hz should induce stronger cross-frequency coupling. Similar to human speech, we found that macaque monkey vocalizations also are amplitude modulated between 3 and 8 Hz. Humans and macaque monkeys share similarities in vocal production, implying that the auditory systems subserving perception of acoustic communication signals also share similarities. Based on the similarities between human speech and macaque monkey vocalizations, we addressed how amplitude modulated vocalizations are processed in the auditory cortex of macaque monkeys, and what behavioral relevance modulations may have. Recording single neuron activity, as well as, the activity of local populations of neurons allowed us to test both of the neurophysiological theories presented above. We found that single neuron responses to vocalizations amplitude modulated at 3 -- 8 Hz resulted in better stimulus discrimination than vocalizations lacking 3 -- 8 Hz modulations, and that the effect most likely was mediated by synaptic dynamics. In contrast, we failed to find support for the oscillation-based model proposing a

Protein complexes and functional modules in molecular networks

NASA Astrophysics Data System (ADS)

Spirin, Victor; Mirny, Leonid A.

2003-10-01

Proteins, nucleic acids, and small molecules form a dense network of molecular interactions in a cell. Molecules are nodes of this network, and the interactions between them are edges. The architecture of molecular networks can reveal important principles of cellular organization and function, similarly to the way that protein structure tells us about the function and organization of a protein. Computational analysis of molecular networks has been primarily concerned with node degree [Wagner, A. & Fell, D. A. (2001) Proc. R. Soc. London Ser. B 268, 1803-1810; Jeong, H., Tombor, B., Albert, R., Oltvai, Z. N. & Barabasi, A. L. (2000) Nature 407, 651-654] or degree correlation [Maslov, S. & Sneppen, K. (2002) Science 296, 910-913], and hence focused on single/two-body properties of these networks. Here, by analyzing the multibody structure of the network of protein-protein interactions, we discovered molecular modules that are densely connected within themselves but sparsely connected with the rest of the network. Comparison with experimental data and functional annotation of genes showed two types of modules: (i) protein complexes (splicing machinery, transcription factors, etc.) and (ii) dynamic functional units (signaling cascades, cell-cycle regulation, etc.). Discovered modules are highly statistically significant, as is evident from comparison with random graphs, and are robust to noise in the data. Our results provide strong support for the network modularity principle introduced by Hartwell et al. [Hartwell, L. H., Hopfield, J. J., Leibler, S. & Murray, A. W. (1999) Nature 402, C47-C52], suggesting that found modules constitute the "building blocks" of molecular networks.

Search for an Annual Modulation in a p-Type Point Contact Germanium Dark Matter Detector

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

Aalseth, Craig E.; Barbeau, Phil; Colaresi, J.

2011-09-01

Fifteen months of cumulative CoGeNT data are examined for indications of an annual modulation, a predicted signature of Weakly Interacting Massive Particle (WIMP) interactions. Presently available data support the presence of a modulated component of unknown origin, with parameters prima facie compatible with a galactic halo composed of light-mass WIMPs.

Interactive Online Modules and Videos for Learning Geological Concepts at the University of Toronto Department of Earth Sciences

NASA Astrophysics Data System (ADS)

Veglio, E.; Graves, L. W.; Bank, C. G.

2014-12-01

We designed various computer-based applications and videos as educational resources for undergraduate courses at the University of Toronto in the Earth Science Department. These resources were developed in effort to enhance students' self-learning of key concepts as identified by educators at the department. The interactive learning modules and videos were created using the programs MATLAB and Adobe Creative Suite 5 (Photoshop and Premiere) and range from optical mineralogy (extinction and Becke line), petrology (equilibrium melting in 2-phase systems), crystallography (crystal systems), geophysics (gravity anomaly), and geologic history (evolution of Canada). These resources will be made available for students on internal course websites as well as through the University of Toronto Earth Science's website (www.es.utoronto.ca) where appropriate; the video platform YouTube.com may be used to reach a wide audience and promote the material. Usage of the material will be monitored and feedback will be collected over the next academic year in order to gage the use of these interactive learning tools and to assess if these computer-based applications and videos foster student engagement and active learning, and thus offer an enriched learning experience.

Structural modulation of factor VIIa by full-length tissue factor (TF1-263): implication of novel interactions between EGF2 domain and TF.

PubMed

Prasad, Ramesh; Sen, Prosenjit

2018-02-01

Tissue factor (TF)-mediated factor VII (FVII) activation and a subsequent proteolytic TF-FVIIa binary complex formation is the key step initiating the coagulation cascade, with implications in various homeostatic and pathologic scenarios. TF binding allosterically modifies zymogen-like free FVIIa to its highly catalytically active form. As a result of unresolved crystal structure of the full-length TF 1-263 -FVIIa binary complex and free FVIIa, allosteric alterations in FVIIa following its binding to full-length TF and the consequences of these on function are not entirely clear. The present study aims to map and identify structural alterations in FVIIa and TF resulting from full-length TF binding to FVIIa and the key events responsible for enhanced FVIIa activity in coagulation. We constructed the full-length TF 1-263 -FVIIa membrane bound complex using computational modeling and subjected it to molecular dynamics (MD) simulations. MD simulations showed that TF alters the structure of each domain of FVIIa and these combined alterations contribute to enhanced TF-FVIIa activity. Detailed, domain-wise investigation revealed several new non-covalent interactions between TF and FVIIa that were not found in the truncated soluble TF-FVIIa crystal structure. The structural modulation of each FVIIa domain imparted by TF indicated that both inter and intra-domain communication is crucial for allosteric modulation of FVIIa. Our results suggest that these newly formed interactions can provide additional stability to the protease domain and regulate its activity profile by governing catalytic triad (CT) orientation and localization. The unexplored newly formed interactions between EGF2 and TF provides a possible explanation for TF-induced allosteric activation of FVIIa.

N-ethylmaleimide-sensitive factor interacts with the serotonin transporter and modulates its trafficking: implications for pathophysiology in autism

PubMed Central

2014-01-01

Background Changes in serotonin transporter (SERT) function have been implicated in autism. SERT function is influenced by the number of transporter molecules present at the cell surface, which is regulated by various cellular mechanisms including interactions with other proteins. Thus, we searched for novel SERT-binding proteins and investigated whether the expression of one such protein was affected in subjects with autism. Methods Novel SERT-binding proteins were examined by a pull-down system. Alterations of SERT function and membrane expression upon knockdown of the novel SERT-binding protein were studied in HEK293-hSERT cells. Endogenous interaction of SERT with the protein was evaluated in mouse brains. Alterations in the mRNA expression of SERT (SLC6A4) and the SERT-binding protein in the post-mortem brains and the lymphocytes of autism patients were compared to nonclinical controls. Results N-ethylmaleimide-sensitive factor (NSF) was identified as a novel SERT-binding protein. NSF was co-localized with SERT at the plasma membrane, and NSF knockdown resulted in decreased SERT expression at the cell membranes and decreased SERT uptake function. NSF was endogenously co-localized with SERT and interacted with SERT. While SLC6A4 expression was not significantly changed, NSF expression tended to be reduced in post-mortem brains, and was significantly reduced in lymphocytes of autistic subjects, which correlated with the severity of the clinical symptoms. Conclusions These data clearly show that NSF interacts with SERT under physiological conditions and is required for SERT membrane trafficking and uptake function. A possible role for NSF in the pathophysiology of autism through modulation of SERT trafficking, is suggested. PMID:24834316

Cascaded Amplitude Modulations in Sound Texture Perception.

PubMed

McWalter, Richard; Dau, Torsten

2017-01-01

Sound textures, such as crackling fire or chirping crickets, represent a broad class of sounds defined by their homogeneous temporal structure. It has been suggested that the perception of texture is mediated by time-averaged summary statistics measured from early auditory representations. In this study, we investigated the perception of sound textures that contain rhythmic structure, specifically second-order amplitude modulations that arise from the interaction of different modulation rates, previously described as "beating" in the envelope-frequency domain. We developed an auditory texture model that utilizes a cascade of modulation filterbanks that capture the structure of simple rhythmic patterns. The model was examined in a series of psychophysical listening experiments using synthetic sound textures-stimuli generated using time-averaged statistics measured from real-world textures. In a texture identification task, our results indicated that second-order amplitude modulation sensitivity enhanced recognition. Next, we examined the contribution of the second-order modulation analysis in a preference task, where the proposed auditory texture model was preferred over a range of model deviants that lacked second-order modulation rate sensitivity. Lastly, the discriminability of textures that included second-order amplitude modulations appeared to be perceived using a time-averaging process. Overall, our results demonstrate that the inclusion of second-order modulation analysis generates improvements in the perceived quality of synthetic textures compared to the first-order modulation analysis considered in previous approaches.

Diffusion modulation of DNA by toehold exchange

NASA Astrophysics Data System (ADS)

Rodjanapanyakul, Thanapop; Takabatake, Fumi; Abe, Keita; Kawamata, Ibuki; Nomura, Shinichiro M.; Murata, Satoshi

2018-05-01

We propose a method to control the diffusion speed of DNA molecules with a target sequence in a polymer solution. The interaction between solute DNA and diffusion-suppressing DNA that has been anchored to a polymer matrix is modulated by the concentration of the third DNA molecule called the competitor by a mechanism called toehold exchange. Experimental results show that the sequence-specific modulation of the diffusion coefficient is successfully achieved. The diffusion coefficient can be modulated up to sixfold by changing the concentration of the competitor. The specificity of the modulation is also verified under the coexistence of a set of DNA with noninteracting base sequences. With this mechanism, we are able to control the diffusion coefficient of individual DNA species by the concentration of another DNA species. This methodology introduces a programmability to a DNA-based reaction-diffusion system.

Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64+ cells

PubMed Central

Vogel, Stephanie; Grabski, Elena; Buschjäger, Daniela; Klawonn, Frank; Döring, Marius; Wang, Junxi; Fletcher, Erika; Bechmann, Ingo; Witte, Torsten; Durisin, Martin; Schraven, Burkhart; Mangsbo, Sara M.; Schönfeld, Kurt; Czeloth, Niklas; Kalinke, Ulrich

2015-01-01

Treatment of PBMC with the CD4-specific mAb BT-061 induces CD4 down-modulation of T cells. Here we report that addition of BT-061 to purified T cells did not confer this effect, whereas incubation of T cells in BT-061 coated wells restored CD4 down-modulation. These results implied that Fcγ receptor mediated cell-cell interactions played a role. In consistence with this hypothesis PBMC depleted of CD64+ monocytes did not confer CD4 down-modulation of BT-061 decorated T cells. Strikingly, CD4 down-modulation was observed in BT-061 treated synovial fluid punctuated from patients’ inflamed joints that comprised enhanced numbers of CD64+ cells. In contrast, in a circulating whole blood system injection of BT-061 did not induce CD4 down-modulation, due to CD64 saturation by serum IgG. Similarly, tonsil derived mononuclear cells devoid of CD64+ cells did not show CD4 down-modulation, whereas addition of blood derived monocytes restored the effect. Thus, the interaction of BT-061 decorated T cells with CD64+ cells is needed for CD4 down-modulation, implying that in patients BT-061 would primarily induce CD4 down-modulation at inflammatory sites. These results highlight the need not only to examine the interaction of a given mAb with single FcγR, but also the immunological environment that is appropriate to support such interactions. PMID:26670584

Structural and Functional Characterization of the Interaction of Snapin with the Dopamine Transporter: Differential Modulation of Psychostimulant Actions.

PubMed

Erdozain, Amaia M; De Gois, Stéphanie; Bernard, Véronique; Gorgievski, Victor; Pietrancosta, Nicolas; Dumas, Sylvie; Macedo, Carlos E; Vanhoutte, Peter; Ortega, Jorge E; Meana, J Javier; Tzavara, Eleni T; Vialou, Vincent; Giros, Bruno

2018-04-01

The importance of dopamine (DA) neurotransmission is emphasized by its direct implication in several neurological and psychiatric disorders. The DA transporter (DAT), target of psychostimulant drugs, is the key protein that regulates spatial and temporal activity of DA in the synaptic cleft via the rapid reuptake of DA into the presynaptic terminal. There is strong evidence suggesting that DAT-interacting proteins may have a role in its function and regulation. Performing a two-hybrid screening, we identified snapin, a SNARE-associated protein implicated in synaptic transmission, as a new binding partner of the carboxyl terminal of DAT. Our data show that snapin is a direct partner and regulator of DAT. First, we determined the domains required for this interaction in both proteins and characterized the DAT-snapin interface by generating a 3D model. Using different approaches, we demonstrated that (i) snapin is expressed in vivo in dopaminergic neurons along with DAT; (ii) both proteins colocalize in cultured cells and brain and, (iii) DAT and snapin are present in the same protein complex. Moreover, by functional studies we showed that snapin produces a significant decrease in DAT uptake activity. Finally, snapin downregulation in mice produces an increase in DAT levels and transport activity, hence increasing DA concentration and locomotor response to amphetamine. In conclusion, snapin/DAT interaction represents a direct link between exocytotic and reuptake mechanisms and is a potential target for DA transmission modulation.

OGO 5 observations of Pc 5 waves - Particle flux modulations

NASA Technical Reports Server (NTRS)

Kokubun, S.; Kivelson, M. G.; Mcpherron, R. L.; Russell, C. T.; West, H. I., Jr.

1977-01-01

An investigation is conducted concerning the modulations of particle fluxes associated with Pc 5 waves in the region beyond the plasmapause. A study of thermal flux modulations indicates that some of the density enhancements observed are not spatial structures but are spurious features caused by temporal flux variations associated with hydromagnetic waves. A resonance model of the energetic particle flux modulations is discussed. Energetic particle modulations are also considered. The reported observations reveal that modulations are dominant at energies of about 100 keV for electrons and at 100 keV to 1 MeV for protons. This may indicate that the bounce resonance interaction is not important for Pc 5 waves.

Domain-domain interactions determine the gating, permeation, pharmacology, and subunit modulation of the IKs ion channel.

PubMed

Zaydman, Mark A; Kasimova, Marina A; McFarland, Kelli; Beller, Zachary; Hou, Panpan; Kinser, Holly E; Liang, Hongwu; Zhang, Guohui; Shi, Jingyi; Tarek, Mounir; Cui, Jianmin

2014-12-23

Voltage-gated ion channels generate electrical currents that control muscle contraction, encode neuronal information, and trigger hormonal release. Tissue-specific expression of accessory (β) subunits causes these channels to generate currents with distinct properties. In the heart, KCNQ1 voltage-gated potassium channels coassemble with KCNE1 β-subunits to generate the IKs current (Barhanin et al., 1996; Sanguinetti et al., 1996), an important current for maintenance of stable heart rhythms. KCNE1 significantly modulates the gating, permeation, and pharmacology of KCNQ1 (Wrobel et al., 2012; Sun et al., 2012; Abbott, 2014). These changes are essential for the physiological role of IKs (Silva and Rudy, 2005); however, after 18 years of study, no coherent mechanism explaining how KCNE1 affects KCNQ1 has emerged. Here we provide evidence of such a mechanism, whereby, KCNE1 alters the state-dependent interactions that functionally couple the voltage-sensing domains (VSDs) to the pore.

Domain–domain interactions determine the gating, permeation, pharmacology, and subunit modulation of the IKs ion channel

PubMed Central

Zaydman, Mark A; Kasimova, Marina A; McFarland, Kelli; Beller, Zachary; Hou, Panpan; Kinser, Holly E; Liang, Hongwu; Zhang, Guohui; Shi, Jingyi; Tarek, Mounir; Cui, Jianmin

2014-01-01

Voltage-gated ion channels generate electrical currents that control muscle contraction, encode neuronal information, and trigger hormonal release. Tissue-specific expression of accessory (β) subunits causes these channels to generate currents with distinct properties. In the heart, KCNQ1 voltage-gated potassium channels coassemble with KCNE1 β-subunits to generate the IKs current (Barhanin et al., 1996; Sanguinetti et al., 1996), an important current for maintenance of stable heart rhythms. KCNE1 significantly modulates the gating, permeation, and pharmacology of KCNQ1 (Wrobel et al., 2012; Sun et al., 2012; Abbott, 2014). These changes are essential for the physiological role of IKs (Silva and Rudy, 2005); however, after 18 years of study, no coherent mechanism explaining how KCNE1 affects KCNQ1 has emerged. Here we provide evidence of such a mechanism, whereby, KCNE1 alters the state-dependent interactions that functionally couple the voltage-sensing domains (VSDs) to the pore. DOI: http://dx.doi.org/10.7554/eLife.03606.001 PMID:25535795

Identification of common coexpression modules based on quantitative network comparison.

PubMed

Jo, Yousang; Kim, Sanghyeon; Lee, Doheon

2018-06-13

Finding common molecular interactions from different samples is essential work to understanding diseases and other biological processes. Coexpression networks and their modules directly reflect sample-specific interactions among genes. Therefore, identification of common coexpression network or modules may reveal the molecular mechanism of complex disease or the relationship between biological processes. However, there has been no quantitative network comparison method for coexpression networks and we examined previous methods for other networks that cannot be applied to coexpression network. Therefore, we aimed to propose quantitative comparison methods for coexpression networks and to find common biological mechanisms between Huntington's disease and brain aging by the new method. We proposed two similarity measures for quantitative comparison of coexpression networks. Then, we performed experiments using known coexpression networks. We showed the validity of two measures and evaluated threshold values for similar coexpression network pairs from experiments. Using these similarity measures and thresholds, we quantitatively measured the similarity between disease-specific and aging-related coexpression modules and found similar Huntington's disease-aging coexpression module pairs. We identified similar Huntington's disease-aging coexpression module pairs and found that these modules are related to brain development, cell death, and immune response. It suggests that up-regulated cell signalling related cell death and immune/ inflammation response may be the common molecular mechanisms in the pathophysiology of HD and normal brain aging in the frontal cortex.

Designing modulators of 5-hydroxytryptamine signaling to treat abuse disorders.

PubMed

van de Wiel, Sandra M W; Verheij, Michel M; Homberg, Judith R

2014-11-01

There are currently no treatments approved by the FDA to effectively treat cocaine dependence. Research of recent years has gradually revealed the importance of 5-hydroxytryptamine (5-HT) in the reinforcing and rewarding effects of cocaine and the potential for relapse. Brain-derived neurotropic factor (BDNF) is an important modulator of the serotonergic system and 5-HT modulates BDNF expression. Their reciprocal interaction is of crucial importance for synaptic plasticity during long-term cocaine intake. Thus, agents modifying BDNF-5-HT interactions might have therapeutic potential for cocaine dependence by reversing the altered brain structure that underlies relapse after cocaine withdrawal. On the basis of the available literature, the authors propose an interaction between BDNF and the serotonergic system in the response to cocaine and during cocaine intake. Furthermore, they discuss putative therapies that are based on 5-HT and BDNF. Recent studies are beginning to elucidate the role of 5-HT and BDNF in cocaine addiction. Additionally, animal studies modeling addiction-like drug intake will only further help to gain a better understanding of how to treat cocaine addiction. Based on the current evidence, the authors believe that BDNF, as a modulator of the serotonergic pathway, or 5-HT, as a modulator of the BDNF system, represent a valuable target to treat drug addiction, which may yield novel therapeutics in the future.

Metabolic and trophic interactions modulate methane production by Arctic peat microbiota in response to warming

PubMed Central

Tveit, Alexander Tøsdal; Urich, Tim; Frenzel, Peter; Svenning, Mette Marianne

2015-01-01

Arctic permafrost soils store large amounts of soil organic carbon (SOC) that could be released into the atmosphere as methane (CH4) in a future warmer climate. How warming affects the complex microbial network decomposing SOC is not understood. We studied CH4 production of Arctic peat soil microbiota in anoxic microcosms over a temperature gradient from 1 to 30 °C, combining metatranscriptomic, metagenomic, and targeted metabolic profiling. The CH4 production rate at 4 °C was 25% of that at 25 °C and increased rapidly with temperature, driven by fast adaptations of microbial community structure, metabolic network of SOC decomposition, and trophic interactions. Below 7 °C, syntrophic propionate oxidation was the rate-limiting step for CH4 production; above this threshold temperature, polysaccharide hydrolysis became rate limiting. This change was associated with a shift within the functional guild for syntrophic propionate oxidation, with Firmicutes being replaced by Bacteroidetes. Correspondingly, there was a shift from the formate- and H2-using Methanobacteriales to Methanomicrobiales and from the acetotrophic Methanosarcinaceae to Methanosaetaceae. Methanogenesis from methylamines, probably stemming from degradation of bacterial cells, became more important with increasing temperature and corresponded with an increased relative abundance of predatory protists of the phylum Cercozoa. We concluded that Arctic peat microbiota responds rapidly to increased temperatures by modulating metabolic and trophic interactions so that CH4 is always highly produced: The microbial community adapts through taxonomic shifts, and cascade effects of substrate availability cause replacement of functional guilds and functional changes within taxa. PMID:25918393

Interactions Between Flavonoid-Rich Extracts and Sodium Caseinate Modulate Protein Functionality and Flavonoid Bioaccessibility in Model Food Systems.

PubMed

Elegbede, Jennifer L; Li, Min; Jones, Owen G; Campanella, Osvaldo H; Ferruzzi, Mario G

2018-05-01

With growing interest in formulating new food products with added protein and flavonoid-rich ingredients for health benefits, direct interactions between these ingredient classes becomes critical in so much as they may impact protein functionality, product quality, and flavonoids bioavailability. In this study, sodium caseinate (SCN)-based model products (foams and emulsions) were formulated with grape seed extract (GSE, rich in galloylated flavonoids) and green tea extract (GTE, rich in nongalloylated flavonoids), respectively, to assess changes in functional properties of SCN and impacts on flavonoid bioaccessibility. Experiments with pure flavonoids suggested that galloylated flavonoids reduced air-water interfacial tension of 0.01% SCN dispersions more significantly than nongalloylated flavonoids at high concentrations (>50 μg/mL). This observation was supported by changes in stability of 5% SCN foam, which showed that foam stability was increased at high levels of GSE (≥50 μg/mL, P < 0.05) but was not affected by GTE. However, flavonoid extracts had modest effects on SCN emulsion. In addition, galloylated flavonoids had higher bioaccessibility in both SCN foam and emulsion. These results suggest that SCN-flavonoid binding interactions can modulate protein functionality leading to difference in performance and flavonoid bioaccessibility of protein-based products. As information on the beneficial health effects of flavonoids expands, it is likely that usage of these ingredients in consumer foods will increase. However, the necessary levels to provide such benefits may exceed those that begin to impact functionality of the macronutrients such as proteins. Flavonoid inclusion within protein matrices may modulate protein functionality in a food system and modify critical consumer traits or delivery of these beneficial plant-derived components. The product matrices utilized in this study offer relevant model systems to evaluate how fortification with flavonoid

Aspheric Solute Ions Modulate Gold Nanoparticle Interactions in an Aqueous Solution: An Optimal Way to Reversibly Concentrate Functionalized Nanoparticles

PubMed Central

Villarreal, Oscar D; Chen, Liao Y; Whetten, Robert L; Demeler, Borries

2015-01-01

Nanometer-sized gold particles (AuNPs) are of peculiar interest because their behaviors in an aqueous solution are sensitive to changes in environmental factors including the size and shape of the solute ions. In order to determine these important characteristics, we performed all-atom molecular dynamics simulations on the icosahedral Au144 nanoparticles each coated with a homogeneous set of 60 thiolates (4-mercapto-benzoate, pMBA) in eight aqueous solutions having ions of varying sizes and shapes (Na+, K+, tetramethylamonium cation TMA+, trisamonium cation TRS+, Cl−, and OH−). For each solution, we computed the reversible work (potential of mean of force) to bring two nanoparticles together as a function of their separation distance. We found that the behavior of pMBA protected Au144 nanoparticles can be readily modulated by tuning their aqueous environmental factors (pH and solute ion combinations). We examined the atomistic details on how the sizes and shapes of solute ions quantitatively factor in the definitive characteristics of nanoparticle-environment and nanoparticle-nanoparticle interactions. We predict that tuning the concentrations of non-spherical composite ions such as TRS+ in an aqueous solution of AuNPs be an effective means to modulate the aggregation propensity desired in biomedical and other applications of small charged nanoparticles. PMID:26581232

Aspheric Solute Ions Modulate Gold Nanoparticle Interactions in an Aqueous Solution: An Optimal Way To Reversibly Concentrate Functionalized Nanoparticles.

PubMed

Villarreal, Oscar D; Chen, Liao Y; Whetten, Robert L; Demeler, Borries

2015-12-17

Nanometer-sized gold particles (AuNPs) are of peculiar interest because their behaviors in an aqueous solution are sensitive to changes in environmental factors including the size and shape of the solute ions. In order to determine these important characteristics, we performed all-atom molecular dynamics simulations on the icosahedral Au144 nanoparticles each coated with a homogeneous set of 60 thiolates (4-mercaptobenzoate, pMBA) in eight aqueous solutions having ions of varying sizes and shapes (Na(+), K(+), tetramethylamonium cation TMA(+), tris-ammonium cation TRS(+), Cl(-), and OH(-)). For each solution, we computed the reversible work (potential of mean of force) to bring two nanoparticles together as a function of their separation distance. We found that the behavior of pMBA protected Au144 nanoparticles can be readily modulated by tuning their aqueous environmental factors (pH and solute ion combinations). We examined the atomistic details on how the sizes and shapes of solute ions quantitatively factor in the definitive characteristics of nanoparticle-environment and nanoparticle-nanoparticle interactions. We predict that tuning the concentrations of nonspherical composite ions such as TRS(+) in an aqueous solution of AuNPs be an effective means to modulate the aggregation propensity desired in biomedical and other applications of small charged nanoparticles.

Enhanced spatial near-infrared modulation of graphene-loaded perfect absorbers using plasmonic nanoslits.

PubMed

Cai, Yijun; Zhu, Jinfeng; Liu, Qing Huo; Lin, Timothy; Zhou, Jianyang; Ye, Longfang; Cai, Zhiping

2015-12-14

Modulating spatial near-infrared light for ultra-compact electro-optic devices is a critical issue in optical communication and imaging applications. To date, spatial near-infrared modulators based on graphene have been reported, but they showed limited modulation effects due to the relatively weak light-graphene interaction. In combination with graphene and metallic nanoslits, we design a kind of ultrathin near-infrared perfect absorber with enhanced spatial modulation effects and independence on a wide range of incident angles. The modulated spectral shift of central wavelength is up to 258.2 nm in the near-infrared range, which is more promising in applications than state-of-the-art devices. The modulation enhancement is attributed to the plasmonic nanoslit mode, in which the optical electric field is highly concentrated in the deep subwavelength scale and the light-graphene interaction is significantly strengthened. The physical insight is deeply revealed by a combination of equivalent circuit and electromagnetic field analysis. The design principles are not only crucial for spatial near-infrared modulators, but also provide a key guide for developing active near-infrared patch nanoantennas based on graphene.

Pittsburgh Science Technology Society Project: Instruction Modules. Interrelationships Science--Technology--Society.

ERIC Educational Resources Information Center

O'Brien, George, Ed.

This collection of instruction modules studies the interactions of science, technology, and society (STS) using five activity sets. The introduction module includes activities which show students the STS relationships in their world, develop good organizational skills, develop an understanding of who and what a scientist is, develop graphing…

All-optical intensity modulation based on graphene-coated microfibre waveguides

NASA Astrophysics Data System (ADS)

Wang, Ruiduo; Li, Diao; Jiang, Man; Wu, Hao; Xu, Xiang; Ren, Zhaoyu

2018-03-01

We investigate graphene-covered microfibre (GCM) waveguides, and analyse the microfibres' evanescent field distributions in different diameters and lengths by numerically simulation. According to the simulation results, we designed a graphene-based all-optical modulator using 980 nm and Amplified Spontaneous Emission (ASE) lasers, employing the microfibre's evanescent field induced light-graphene interaction. We studied the modulation effect that is influenced by the microfibre's diameter, number of graphene layers, and effective graphene length. Compared to a single graphene layer of shorter length, the double graphene layer with longer length presents stronger absorption and higher modulation depth. Using a 2- μm diameter microfibre covered by ∼0.3 cm double graphene sheets, we achieved a modulation depth of 8.45 dB. This modulator features ease of fabrication, low cost, and a controllable modulation depth.

Immune Modulation During Latent Herpesvirus Infection

PubMed Central

White, Douglas W.; Beard, R. Suzanne; Barton, Erik S.

2011-01-01

Summary Nearly all human beings, by the time they reach adolescence, are infected with multiple herpesviruses. At any given time, this family of viruses accounts for 35–40 billion human infections worldwide, making herpesviruses among the most prevalent pathogens known to exist. Compared to most other viruses, herpesviruses are also unique in that infection lasts the life of the host. Remarkably, despite their prevalence and persistence, little is known about how these viruses interact with their hosts, especially during the clinically asymptomatic phase of infection referred to as latency. This review explores data in human and animal systems that reveal the ability of latent herpesviruses to modulate the immune response to self and environmental antigens. From the perspective of the host, there are both potentially detrimental and surprisingly beneficial effects of this lifelong interaction. The realization that latent herpesvirus infection modulates immune responses in asymptomatic hosts forces us to reconsider what constitutes a ‘normal’ immune system in a healthy individual. PMID:22168421

Representations of pitch and slow modulation in auditory cortex

PubMed Central

Barker, Daphne; Plack, Christopher J.; Hall, Deborah A.

2013-01-01

Iterated ripple noise (IRN) is a type of pitch-evoking stimulus that is commonly used in neuroimaging studies of pitch processing. When contrasted with a spectrally matched Gaussian noise, it is known to produce a consistent response in a region of auditory cortex that includes an area antero-lateral to the primary auditory fields (lateral Heschl's gyrus). The IRN-related response has often been attributed to pitch, although recent evidence suggests that it is more likely driven by slowly varying spectro-temporal modulations not related to pitch. The present functional magnetic resonance imaging (fMRI) study showed that both pitch-related temporal regularity and slow modulations elicited a significantly greater response than a baseline Gaussian noise in an area that has been pre-defined as pitch-responsive. The region was sensitive to both pitch salience and slow modulation salience. The responses to pitch and spectro-temporal modulations interacted in a saturating manner, suggesting that there may be an overlap in the populations of neurons coding these features. However, the interaction may have been influenced by the fact that the two pitch stimuli used (IRN and unresolved harmonic complexes) differed in terms of pitch salience. Finally, the results support previous findings suggesting that the cortical response to IRN is driven in part by slow modulations, not by pitch. PMID:24106464

Inner-outer interactions in a turbulent boundary layer overlying complex roughness

NASA Astrophysics Data System (ADS)

Pathikonda, Gokul; Christensen, Kenneth T.

2017-04-01

Hot-wire measurements were performed in a zero-pressure-gradient turbulent boundary layer overlying both a smooth and a rough wall for the purpose of investigating the details of inner-outer flow interactions. The roughness considered embodies a broad range of topographical scales arranged in an irregular manner and reflects the topographical complexity often encountered in practical flow systems. Single-probe point-wise measurements with a traversing probe were made at two different regions of the rough-wall flow, which was previously shown to be heterogeneous in the spanwise direction, to investigate the distribution of streamwise turbulent kinetic energy and large scale-small scale interactions. In addition, two-probe simultaneous measurements were conducted enabling investigation of inner-outer interactions, wherein the large scales were independently sampled in the outer layer. Roughness-induced changes to the near-wall behavior were investigated, particularly by contrasting the amplitude and frequency modulation effects of inner-outer interactions in the rough-wall flow with well-established smooth-wall flow phenomena. It was observed that the rough-wall flow exhibits both amplitude and frequency modulation features close to the wall in a manner very similar to smooth-wall flow, though the correlated nature of these effects was found to be more intense in the rough-wall flow. In particular, frequency modulation was found to illuminate these enhanced modulation effects in the rough-wall flow. The two-probe measurements helped in evaluating the suitability of the interaction-schematic recently proposed by Baars et al., Exp. Fluids 56, 1 (2015), 10.1007/s00348-014-1876-4 for rough-wall flows. This model was found to be suitable for the rough-wall flow considered herein, and it was found that frequency modulation is a "cleaner" measure of the inner-outer modulation interactions for this rough-wall flow.

The RavA-ViaA Chaperone-Like System Interacts with and Modulates the Activity of the Fumarate Reductase Respiratory Complex.

PubMed

Wong, Keith S; Bhandari, Vaibhav; Janga, Sarath Chandra; Houry, Walid A

2017-01-20

Regulatory ATPase variant A (RavA) is a MoxR AAA+ protein that functions together with a partner protein that we termed VWA interacting with AAA+ ATPase (ViaA) containing a von Willebrand Factor A domain. However, the functional role of RavA-ViaA in the cell is not yet well established. Here, we show that RavA-ViaA are functionally associated with anaerobic respiration in Escherichia coli through interactions with the fumarate reductase (Frd) electron transport complex. Expression analysis of ravA and viaA genes showed that both proteins are co-expressed with multiple anaerobic respiratory genes, many of which are regulated by the anaerobic transcriptional regulator Fnr. Consistently, the expression of both ravA and viaA was found to be dependent on Fnr in cells grown under oxygen-limiting condition. ViaA was found to physically interact with FrdA, the flavin-containing subunit of the Frd complex. Both RavA and the Fe-S-containing subunit of the Frd complex, FrdB, regulate this interaction. Importantly, Frd activity was observed to increase in the absence of RavA and ViaA. This indicates that RavA and ViaA modulate the activity of the Frd complex, signifying a potential regulatory chaperone-like function for RavA-ViaA during bacterial anaerobic respiration with fumarate as the terminal electron acceptor. Copyright © 2016 Elsevier Ltd. All rights reserved.

A biological approach to assembling tissue modules through endothelial capillary network formation.

PubMed

Riesberg, Jeremiah J; Shen, Wei

2015-09-01

To create functional tissues having complex structures, bottom-up approaches to assembling small tissue modules into larger constructs have been emerging. Most of these approaches are based on chemical reactions or physical interactions at the interface between tissue modules. Here we report a biological assembly approach to integrate small tissue modules through endothelial capillary network formation. When adjacent tissue modules contain appropriate extracellular matrix materials and cell types that support robust endothelial capillary network formation, capillary tubules form and grow across the interface, resulting in assembly of the modules into a single, larger construct. It was shown that capillary networks formed in modules of dense fibrin gels seeded with human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs); adjacent modules were firmly assembled into an integrated construct having a strain to failure of 117 ± 26%, a tensile strength of 2208 ± 83 Pa and a Young's modulus of 2548 ± 574 Pa. Under the same culture conditions, capillary networks were absent in modules of dense fibrin gels seeded with either HUVECs or MSCs alone; adjacent modules disconnected even when handled gently. This biological assembly approach eliminates the need for chemical reactions or physical interactions and their associated limitations. In addition, the integrated constructs are prevascularized, and therefore this bottom-up assembly approach may also help address the issue of vascularization, another key challenge in tissue engineering. Copyright © 2015 John Wiley & Sons, Ltd.

In vivo pharmacological interactions between a type II positive allosteric modulator of α7 nicotinic ACh receptors and nicotinic agonists in a murine tonic pain model

PubMed Central

Freitas, K; Negus, SS; Carroll, FI; Damaj, MI

2013-01-01

Background and Purpose The α7 nicotinic ACh receptor subtype is abundantly expressed in the CNS and in the periphery. Recent evidence suggests that α7 nicotinic ACh receptor (nAChR) subtypes, which can be activated by an endogenous cholinergic tone comprising ACh and the α7 agonist choline, play an important role in chronic pain and inflammation. In this study, we evaluated whether type II α7 positive allosteric modulator PNU-120596 induces antinociception on its own and in combination with choline in the formalin pain model. Experimental Approach We assessed the effects of PNU-120596 and choline and the nature of their interactions in the formalin test using an isobolographic analysis. In addition, we evaluated the interaction of PNU-120596 with PHA-54613, an exogenous selective α7 nAChR agonist, in the formalin test. Finally, we assessed the interaction between PNU-120596 and nicotine using acute thermal pain, locomotor activity, body temperature and convulsing activity tests in mice. Key Results We found that PNU-120596 dose-dependently attenuated nociceptive behaviour in the formalin test after systemic administration in mice. In addition, mixtures of PNU-120596 and choline synergistically reduced formalin-induced pain. PNU-120596 enhanced the effects of nicotine and α7 agonist PHA-543613 in the same test. In contrast, PNU-120596 failed to enhance nicotine-induced convulsions, hypomotility and antinociception in acute pain models. Surprisingly, it enhanced nicotine-induced hypothermia via activation of α7 nAChRs. Conclusions and Implications Our results demonstrate that type II α7 positive allosteric modulators produce antinociceptive effects in the formalin test through a synergistic interaction with the endogenous α7 agonist choline. PMID:23004024

Combined effects of potassium chloride and ethanol as mobile phase modulators on hydrophobic interaction and reversed-phase chromatography of three insulin variants.

PubMed

Johansson, Karolina; Frederiksen, Søren S; Degerman, Marcus; Breil, Martin P; Mollerup, Jørgen M; Nilsson, Bernt

2015-02-13

The two main chromatographic modes based on hydrophobicity, hydrophobic interaction chromatography (HIC) and reversed-phase chromatography (RPC), are widely used for both analytical and preparative chromatography of proteins in the pharmaceutical industry. Despite the extensive application of these separation methods, and the vast amount of studies performed on HIC and RPC over the decades, the underlying phenomena remain elusive. As part of a systematic study of the influence of mobile phase modulators in hydrophobicity-based chromatography, we have investigated the effects of both KCl and ethanol on the retention of three insulin variants on two HIC adsorbents and two RPC adsorbents. The focus was on the linear adsorption range, separating the modulator effects from the capacity effects, but some complementary experiments at higher load were included to further investigate observed phenomena. The results show that the modulators have the same effect on the two RPC adsorbents in the linear range, indicating that the modulator concentration only affects the activity of the solute in the mobile phase, and not that of the solute-ligand complex, or that of the ligand. Unfortunately, the HIC adsorbents did not show the same behavior. However, the insulin variants displayed a strong tendency toward self-association on both HIC adsorbents; on one in particular. Since this causes peak fronting, the retention is affected, and this could probably explain the lack of congruity. This conclusion was supported by the results from the non-linear range experiments which were indicative of double-layer adsorption on the HIC adsorbents, while the RPC adsorbents gave the anticipated increased tailing at higher load. Copyright © 2015 Elsevier B.V. All rights reserved.

Sigmund Freud's Personality Theory: Learning Module Employing Computer-Assisted Instruction Technology.

ERIC Educational Resources Information Center

Saavedra, Jose M.

This interactive module contains 33 windows of text and three graphics, in which Freud's topographical (unconscious, pre-conscious, and conscious) and structural (id, ego, and superego) models of the psyche are studied. Seventeen fill-in questions are interspersed within the text. The module stresses the importance of comprehending the concept of…

Polaron spin echo envelope modulations in an organic semiconducting polymer

DOE PAGES

Mkhitaryan, V. V.; Dobrovitski, V. V.

2017-06-01

Here, we present a theoretical analysis of the electron spin echo envelope modulation (ESEEM) spectra of polarons in semiconducting π -conjugated polymers. We show that the contact hyperfine coupling and the dipolar interaction between the polaron and the proton spins give rise to different features in the ESEEM spectra. Our theory enables direct selective probe of different groups of nuclear spins, which affect the polaron spin dynamics. Namely, we demonstrate how the signal from the distant protons (coupled to the polaron spin via dipolar interactions) can be distinguished from the signal coming from the protons residing on the polaron sitemore » (coupled to the polaron spin via contact hyperfine interaction). We propose a method for directly probing the contact hyperfine interaction, that would enable detailed study of the polaron orbital state and its immediate environment. Lastly, we also analyze the decay of the spin echo modulation, and its connection to the polaron transport.« less

Modular analysis of the probabilistic genetic interaction network.

PubMed

Hou, Lin; Wang, Lin; Qian, Minping; Li, Dong; Tang, Chao; Zhu, Yunping; Deng, Minghua; Li, Fangting

2011-03-15

Epistatic Miniarray Profiles (EMAP) has enabled the mapping of large-scale genetic interaction networks; however, the quantitative information gained from EMAP cannot be fully exploited since the data are usually interpreted as a discrete network based on an arbitrary hard threshold. To address such limitations, we adopted a mixture modeling procedure to construct a probabilistic genetic interaction network and then implemented a Bayesian approach to identify densely interacting modules in the probabilistic network. Mixture modeling has been demonstrated as an effective soft-threshold technique of EMAP measures. The Bayesian approach was applied to an EMAP dataset studying the early secretory pathway in Saccharomyces cerevisiae. Twenty-seven modules were identified, and 14 of those were enriched by gold standard functional gene sets. We also conducted a detailed comparison with state-of-the-art algorithms, hierarchical cluster and Markov clustering. The experimental results show that the Bayesian approach outperforms others in efficiently recovering biologically significant modules.

Cascaded Amplitude Modulations in Sound Texture Perception

PubMed Central

McWalter, Richard; Dau, Torsten

2017-01-01

Sound textures, such as crackling fire or chirping crickets, represent a broad class of sounds defined by their homogeneous temporal structure. It has been suggested that the perception of texture is mediated by time-averaged summary statistics measured from early auditory representations. In this study, we investigated the perception of sound textures that contain rhythmic structure, specifically second-order amplitude modulations that arise from the interaction of different modulation rates, previously described as “beating” in the envelope-frequency domain. We developed an auditory texture model that utilizes a cascade of modulation filterbanks that capture the structure of simple rhythmic patterns. The model was examined in a series of psychophysical listening experiments using synthetic sound textures—stimuli generated using time-averaged statistics measured from real-world textures. In a texture identification task, our results indicated that second-order amplitude modulation sensitivity enhanced recognition. Next, we examined the contribution of the second-order modulation analysis in a preference task, where the proposed auditory texture model was preferred over a range of model deviants that lacked second-order modulation rate sensitivity. Lastly, the discriminability of textures that included second-order amplitude modulations appeared to be perceived using a time-averaging process. Overall, our results demonstrate that the inclusion of second-order modulation analysis generates improvements in the perceived quality of synthetic textures compared to the first-order modulation analysis considered in previous approaches. PMID:28955191

The Effects of Noncellulosic Compounds on the Nanoscale Interaction Forces Measured between Carbohydrate-Binding Module and Lignocellulosic Biomass.

PubMed

Arslan, Baran; Colpan, Mert; Ju, Xiaohui; Zhang, Xiao; Kostyukova, Alla; Abu-Lail, Nehal I

2016-05-09

The lack of fundamental understanding of the types of forces that govern how cellulose-degrading enzymes interact with cellulosic and noncellulosic components of lignocellulosic surfaces limits the design of new strategies for efficient conversion of biomass to bioethanol. In a step to improve our fundamental understanding of such interactions, nanoscale forces acting between a model cellulase-a carbohydrate-binding module (CBM) of cellobiohydrolase I (CBH I)-and a set of lignocellulosic substrates with controlled composition were measured using atomic force microscopy (AFM). The three model substrates investigated were kraft (KP), sulfite (SP), and organosolv (OPP) pulped substrates. These substrates varied in their surface lignin coverage, lignin type, and xylan and acetone extractives' content. Our results indicated that the overall adhesion forces of biomass to CBM increased linearly with surface lignin coverage with kraft lignin showing the highest forces among lignin types investigated. When the overall adhesion forces were decoupled into specific and nonspecific component forces via the Poisson statistical model, hydrophobic and Lifshitz-van der Waals (LW) forces dominated the binding forces of CBM to kraft lignin, whereas permanent dipole-dipole interactions and electrostatic forces facilitated the interactions of lignosulfonates to CBM. Xylan and acetone extractives' content increased the attractive forces between CBM and lignin-free substrates, most likely through hydrogen bonding forces. When the substrates treated differently were compared, it was found that both the differences in specific and nonspecific forces between lignin-containing and lignin-free substrates were the least for OPP. Therefore, cellulase enzymes represented by CBM would weakly bind to organosolv lignin. This will facilitate an easy enzyme recovery compared to other substrates treated with kraft or sulfite pulping. Our results also suggest that altering the surface hydrophobicity

Multi-function robots with speech interaction and emotion feedback

NASA Astrophysics Data System (ADS)

Wang, Hongyu; Lou, Guanting; Ma, Mengchao

2018-03-01

Nowadays, the service robots have been applied in many public circumstances; however, most of them still don’t have the function of speech interaction, especially the function of speech-emotion interaction feedback. To make the robot more humanoid, Arduino microcontroller was used in this study for the speech recognition module and servo motor control module to achieve the functions of the robot’s speech interaction and emotion feedback. In addition, W5100 was adopted for network connection to achieve information transmission via Internet, providing broad application prospects for the robot in the area of Internet of Things (IoT).

The Impact of an Interactive Statistics Module on Novices' Development of Scientific Process Skills and Attitudes in a First-Semester Research Foundations Course.

PubMed

Marsan, Lynnsay A; D'Arcy, Christina E; Olimpo, Jeffrey T

2016-12-01

Evidence suggests that incorporating quantitative reasoning exercises into existent curricular frameworks within the science, technology, engineering, and mathematics (STEM) disciplines is essential for novices' development of conceptual understanding and process skills in these domains. Despite this being the case, such studies acknowledge that students often experience difficulty in applying mathematics in the context of scientific problems. To address this concern, the present study sought to explore the impact of active demonstrations and critical reading exercises on novices' comprehension of basic statistical concepts, including hypothesis testing, experimental design, and interpretation of research findings. Students first engaged in a highly interactive height activity that served to intuitively illustrate normal distribution, mean, standard deviation, and sample selection criteria. To enforce practical applications of standard deviation and p -value, student teams were subsequently assigned a figure from a peer-reviewed primary research article and instructed to evaluate the trustworthiness of the data. At the conclusion of this exercise, students presented their evaluations to the class for open discussion and commentary. Quantitative assessment of pre- and post-module survey data indicated a statistically significant increase both in students' scientific reasoning and process skills and in their self-reported confidence in understanding the statistical concepts presented in the module. Furthermore, data indicated that the majority of students (>85%) found the module both interesting and helpful in nature. Future studies will seek to develop additional, novel exercises within this area and to evaluate the impact of such modules across a variety of STEM and non-STEM contexts.

The Impact of an Interactive Statistics Module on Novices’ Development of Scientific Process Skills and Attitudes in a First-Semester Research Foundations Course†

PubMed Central

Marsan, Lynnsay A.; D’Arcy, Christina E.; Olimpo, Jeffrey T.

2016-01-01

Evidence suggests that incorporating quantitative reasoning exercises into existent curricular frameworks within the science, technology, engineering, and mathematics (STEM) disciplines is essential for novices’ development of conceptual understanding and process skills in these domains. Despite this being the case, such studies acknowledge that students often experience difficulty in applying mathematics in the context of scientific problems. To address this concern, the present study sought to explore the impact of active demonstrations and critical reading exercises on novices’ comprehension of basic statistical concepts, including hypothesis testing, experimental design, and interpretation of research findings. Students first engaged in a highly interactive height activity that served to intuitively illustrate normal distribution, mean, standard deviation, and sample selection criteria. To enforce practical applications of standard deviation and p-value, student teams were subsequently assigned a figure from a peer-reviewed primary research article and instructed to evaluate the trustworthiness of the data. At the conclusion of this exercise, students presented their evaluations to the class for open discussion and commentary. Quantitative assessment of pre- and post-module survey data indicated a statistically significant increase both in students’ scientific reasoning and process skills and in their self-reported confidence in understanding the statistical concepts presented in the module. Furthermore, data indicated that the majority of students (>85%) found the module both interesting and helpful in nature. Future studies will seek to develop additional, novel exercises within this area and to evaluate the impact of such modules across a variety of STEM and non-STEM contexts. PMID:28101271

APOA5 Gene Variation Interacts with Dietary Fat Intake to Modulate Obesity and Circulating Triglycerides in a Mediterranean Population12

PubMed Central

Sánchez-Moreno, Carmen; Ordovás, Jose M.; Smith, Caren E.; Baraza, Juan C.; Lee, Yu-Chi; Garaulet, Marta

2011-01-01

APOA5 is one of the strongest regulators of plasma TG concentrations; nevertheless, its mechanisms of action are poorly characterized. Genetic variability at the APOA5 locus has also been associated with increased cardiovascular disease risk; however, this predisposition could be attenuated in the context of a prudent diet as traditionally consumed in the Mediterranean countries. We have investigated the interaction between a single nucleotide polymorphism (SNP) at the APOA5 gene (-1131T > C) and dietary fat that may modulate TG-rich lipoprotein concentrations and anthropometric measures in overweight and obese participants. We recruited 1465 participants from a Spanish population (20–65 y old; BMI 25–40 kg/m2) attending outpatient obesity clinics. Consistent with previous reports, we found an association between the APOA5-1131T > C SNP and TG-rich lipoprotein concentrations that were higher in carriers of the minor allele than in noncarriers (P < 0.001). Moreover, we found a significant genotype-dietary fat interaction for obesity traits. Participants homozygous for the −1131T major allele had a positive association between fat intake and obesity, whereas in those carrying the APOA5−1131C minor allele, higher fat intakes were not associated with higher BMI. Likewise, we found genotype-dietary fat interactions for TG-rich lipoproteins (P < 0.001). In conclusion, we have replicated previous gene-diet interactions between APOA5 -1131T > C SNP and fat intake for obesity traits and detected a novel interaction for TG-rich lipoprotein concentrations. Our data support the hypothesis that the minor C-allele may protect those consuming a high-fat diet from obesity and elevated concentrations of TG-rich lipoproteins. PMID:21209257

Construction of the Zeus forward/rear calorimeter modules at NIKHEF

NASA Astrophysics Data System (ADS)

Blankers, R.; Engelen, J.; Geerinck, H.; Homma, J.; Hunck, P.; Dekoning, N.; Kooijman, P.; Korporaal, A.; Loos, R.; Straver, J.

1990-07-01

The design and assembly procedure of the FCAL/RCAL (Forward (in proton direction) Calorimeter/Rear (in electron direction) Calorimeter) of the Zeus detector to study electron proton interactions at Desy, Hamburg (Germany, F.R.) are detailed. The main components of the modules are described: steel C-frame which provides the overall mechanical module structure; a stack of depleted uranium plates and scintillator plates; wavelength shifter material, mounted in cassettes for the readout of the scintillator light; stainless steel straps which compress the stack and fix it to the C-frame. Finite element techniques for module force calculations are outlined. The module assembly and transport and calibration tools are described.

A universal quantum module for quantum communication, computation, and metrology

NASA Astrophysics Data System (ADS)

Hanks, Michael; Lo Piparo, Nicolò; Trupke, Michael; Schmiedmayer, Jorg; Munro, William J.; Nemoto, Kae

2017-08-01

In this work, we describe a simple module that could be ubiquitous for quantum information based applications. The basic modules comprises a single NV- center in diamond embedded in an optical cavity, where the cavity mediates interactions between photons and the electron spin (enabling entanglement distribution and efficient readout), while the nuclear spins constitutes a long-lived quantum memories capable of storing and processing quantum information. We discuss how a network of connected modules can be used for distributed metrology, communication and computation applications. Finally, we investigate the possible use of alternative diamond centers (SiV/GeV) within the module and illustrate potential advantages.

A global interaction network maps a wiring diagram of cellular function

PubMed Central

Costanzo, Michael; VanderSluis, Benjamin; Koch, Elizabeth N.; Baryshnikova, Anastasia; Pons, Carles; Tan, Guihong; Wang, Wen; Usaj, Matej; Hanchard, Julia; Lee, Susan D.; Pelechano, Vicent; Styles, Erin B.; Billmann, Maximilian; van Leeuwen, Jolanda; van Dyk, Nydia; Lin, Zhen-Yuan; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff S.; Srikumar, Tharan; Bahr, Sondra; Chen, Yiqun; Deshpande, Raamesh; Kurat, Christoph F.; Li, Sheena C.; Li, Zhijian; Usaj, Mojca Mattiazzi; Okada, Hiroki; Pascoe, Natasha; Luis, Bryan-Joseph San; Sharifpoor, Sara; Shuteriqi, Emira; Simpkins, Scott W.; Snider, Jamie; Suresh, Harsha Garadi; Tan, Yizhao; Zhu, Hongwei; Malod-Dognin, Noel; Janjic, Vuk; Przulj, Natasa; Troyanskaya, Olga G.; Stagljar, Igor; Xia, Tian; Ohya, Yoshikazu; Gingras, Anne-Claude; Raught, Brian; Boutros, Michael; Steinmetz, Lars M.; Moore, Claire L.; Rosebrock, Adam P.; Caudy, Amy A.; Myers, Chad L.; Andrews, Brenda; Boone, Charles

2017-01-01

We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing over 23 million double mutants, identifying ~550,000 negative and ~350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell. PMID:27708008

Evaluation of best practices in the design of online evidence-based practice instructional modules*

PubMed Central

Foster, Margaret J.; Shurtz, Suzanne; Pepper, Catherine

2014-01-01

Objectives: The research determined to what extent best practices are being followed by freely available online modules aimed at teaching critical thinking and evidence-based practices (EBPs) in health sciences fields. Methods: In phase I, an evaluation rubric was created after reviewing the literature. Individual rubric questions were assigned point values and grouped into sections, and the sections weighted. Phase II involved searching Internet platforms to locate online EBP modules, which were screened to determine if they met predetermined criteria for inclusion. Phase III comprised a first evaluation, in which two authors assessed each module, followed by a second evaluation of the top-scoring modules by five representatives from different health sciences units. Results: The rubric's 28 questions were categorized into 4 sections: content, design, interactivity, and usability. After retrieving 170 online modules and closely screening 91, 42 were in the first evaluation and 8 modules were in the second evaluation. Modules in the first evaluation earned, on average, 59% of available points; modules in the second earned an average of 68%. Both evaluations had a moderate level of inter-rater reliability. Conclusions: The rubric was effective and reliable in evaluating the modules. Most modules followed best practices for content and usability but not for design and interactivity. Implications: By systematically collecting and evaluating instructional modules, the authors found many potentially useful elements for module creation. Also, by reviewing the limitations of the evaluated modules, the authors were able to anticipate and plan ways to overcome potential issues in module design. PMID:24415917

Cosmic ray modulation and turbulent interaction regions near 11 AU

NASA Technical Reports Server (NTRS)

Burlaga, L. F.; Mcdonald, F. B.; Goldstein, M. L.; Lazarus, A. J.

1985-01-01

When Voyager 2 was near 11 AU, the counting rate of nuclei approx 75 MeV/nucleon decreased during the interval from July, 1982 to November, 1982, and it increased thereafter until August, 1983. A decrease in cosmic ray flux was generally associated with the passage of an interaction region in which the magnetic field strength B was higher than that predicted by the spiral field model, B sub p. Several large enhancements in B/B sup p were associated with merged interaction regions which probably resulted from the interaction of two or more distinct flows. During the passage of interaction regions the cosmic ray intensity decreased at a rate proportional to (B/B sup p -1), and during the passage of rarefaction regions (where B/B sup p 1) the cosmic ray intensity increased at a constant rate. The general form of the cosmic ray intensity profile during this approx 13 month minicycle can be described by integrating these relations using the observed B(t). Latitudinal variations of the interaction regions and of the short-term cosmic ray variations were identified.

Nebulette interacts with filamin C.

PubMed

Holmes, William B; Moncman, Carole L

2008-02-01

The actin-binding proteins, nebulette, and nebulin, are comprised of a four-domain layout containing an acidic N-terminal region, a repeat domain, a serine-rich-linker region, and a Src homology-3 domain. Both proteins contain homologous N-terminal regions that are predicted to be in different environments within the sarcomere. The nebulin acidic N-terminal region is found at the distal ends of the thin filaments. Nebulette, however, is predicted to extend 150 nm from the center of the Z-line. To dissect out the functions of the N-terminal domain of nebulette, we have performed a yeast two-hybrid screen using nebulette residues 1-86 as bait. We have identified filamin-C, ZASP-1, and tropomyosin-1 as binding partners. Characterization of the nebulette-filamin interaction indicates that filamin-C predominantly interacts with the modules. These data suggest that filamin-C, a known component of striated muscle Z-lines, interacts with nebulette modules. Copyright 2007 Wiley-Liss, Inc.

The immune-neuro-endocrine interactions.

PubMed

Tomaszewska, D; Przekop, F

1997-06-01

This article reviews data concerning the interactions between immune, endocrine and neural systems in physiological, pathophysiological and stress conditions in animals and humans. Numerous studies have provided evidence that these systems interact with each other in maintaining homeostasis. This interaction may be classified as follows: immune, endocrine and neural cell products coexist in lymphoid, endocrine and neural tissue. Endocrine and neural mediators modulate immune system activity. Immune, endocrine and neural cells express receptors for cytokines, hormones, neuropeptides and transmitters.

On the interaction between sad mood and cognitive control: the effect of induced sadness on electrophysiological modulations underlying Stroop conflict processing.

PubMed

Nixon, Elena; Liddle, Peter F; Nixon, Neil L; Liotti, Mario

2013-03-01

The present study employed high-density ERPs to examine the effect of induced sad mood on the spatiotemporal correlates of conflict monitoring and resolution in a colour-word Stroop interference task. Neuroimaging evidence and dipole modelling implicates the involvement of the anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) regions in conflict-laden interference control. On the basis that these structures have been found to mediate emotion-cognition interactions in negative mood states, it was predicted that Stroop-related cognitive control, which relies heavily on anterior neural sources, would be affected by effective sad mood provocation. Healthy participants (N=14) were induced into transient sadness via use of autobiographical sad scripts, a well-validated mood induction technique (Liotti et al., 2000a, 2002). In accord with previous research, interference effects were shown at both baseline and sad states while Stroop conflict was associated with early (N450) and late (Late Positive Component; LPC) electrophysiological modulations at both states. Sad mood induction attenuated the N450 effect in line with our expectation that it would be susceptible to modulation by mood, given its purported anterior limbic source. The LPC effect was displayed at the typical posterior lateral sites but, as predicted, was not affected by sad mood. However, frontocentral LPC activity-presumably generated from an additional anterior limbic source-was affected at sad state, hinting a role in conflict monitoring. Although the neurophysiological underpinnings of interference control are yet to be clarified, this study provided further insight into emotion-cognition interactions as indexed by Stroop conflict-laden processing. Copyright © 2012 Elsevier B.V. All rights reserved.

Interactive Learning for Graphic Design Foundations

ERIC Educational Resources Information Center

Chu, Sauman; Ramirez, German Mauricio Mejia

2012-01-01

One of the biggest problems for students majoring in pre-graphic design is students' inability to apply their knowledge to different design solutions. The purpose of this study is to examine the effectiveness of interactive learning modules in facilitating knowledge acquisition during the learning process and to create interactive learning modules…

Stochastic nanoroughness modulates neuron-astrocyte interactions and function via mechanosensing cation channels.

PubMed

Blumenthal, Nils R; Hermanson, Ola; Heimrich, Bernd; Shastri, V Prasad

2014-11-11

Extracellular soluble signals are known to play a critical role in maintaining neuronal function and homeostasis in the CNS. However, the CNS is also composed of extracellular matrix macromolecules and glia support cells, and the contribution of the physical attributes of these components in maintenance and regulation of neuronal function is not well understood. Because these components possess well-defined topography, we theorize a role for topography in neuronal development and we demonstrate that survival and function of hippocampal neurons and differentiation of telencephalic neural stem cells is modulated by nanoroughness. At roughnesses corresponding to that of healthy astrocytes, hippocampal neurons dissociated and survived independent from astrocytes and showed superior functional traits (increased polarity and calcium flux). Furthermore, telencephalic neural stem cells differentiated into neurons even under exogenous signals that favor astrocytic differentiation. The decoupling of neurons from astrocytes seemed to be triggered by changes to astrocyte apical-surface topography in response to nanoroughness. Blocking signaling through mechanosensing cation channels using GsMTx4 negated the ability of neurons to sense the nanoroughness and promoted decoupling of neurons from astrocytes, thus providing direct evidence for the role of nanotopography in neuron-astrocyte interactions. We extrapolate the role of topography to neurodegenerative conditions and show that regions of amyloid plaque buildup in brain tissue of Alzheimer's patients are accompanied by detrimental changes in tissue roughness. These findings suggest a role for astrocyte and ECM-induced topographical changes in neuronal pathologies and provide new insights for developing therapeutic targets and engineering of neural biomaterials.

Receptor-interacting protein kinases modulate noise-induced sensory hair cell death

PubMed Central

Zheng, H-W; Chen, J; Sha, S-H

2014-01-01

Receptor-interacting protein (RIP) kinases promote the induction of necrotic cell death pathways. Here we investigated signaling pathways in outer hair cells (OHCs) of adult male CBA/J mice exposed to noise that causes permanent threshold shifts, with a particular focus on RIP kinase-regulated necroptosis. One hour after noise exposure, nuclei of OHCs in the basal region of the cochlea displayed both apoptotic and necrotic features. RIP1 and RIP3 protein levels increased and caspase-8 was activated. Treatment with pan-caspase inhibitor ZVAD blocked the activation of caspase-8 and reduced the number of apoptotic nuclei, while increasing levels of RIP1, RIP3, and necrotic OHCs. Conversely, treatment with necrosis inhibitor necrostatin-1 (Nec-1) or RIP3 siRNA (siRIP3) diminished noise-induced increases in RIP1 and RIP3, and decreased necrotic OHC nuclei. This treatment also increased the number of apoptotic nuclei without increasing activation of caspase-8. Consistent with the elevation of levels of RIP1 and RIP3, noise-induced active AMPKα levels increased with ZVAD treatment, but decreased with Nec-1 and siRIP3 treatment. Furthermore, treatment with siRIP3 did not alter the activation of caspase-8, but instead increased activation of caspase-9 and promoted endonuclease G translocation into OHC nuclei. Finally, auditory brainstem response functional measurements and morphological assessment of OHCs showed that ZVAD treatment reduces noise-induced deficits. This protective function is potentiated when combined with siRIP3 treatment. In conclusion, noise-induced OHC apoptosis and necrosis are modulated by caspases and RIP kinases, respectively. Inhibition of either pathway shifts the prevalence of OHC death to the alternative pathway. PMID:24874734

High frequency modulation and injection locking of terahertz quantum cascade lasers

NASA Astrophysics Data System (ADS)

Gu, L.; Wan, W. J.; Zhu, Y. H.; Fu, Z. L.; Li, H.; Cao, J. C.

2017-06-01

Due to intersubband transitions, the quantum cascade laser (QCL) is free of relaxations and able to work under fast modulations. In this work, the authors investigate the fast modulation properties of a continuous wave (cw) terahertz QCL emitting around 3 THz (˜100 μm). Both simulation and experimental results show that the 3 dB modulation bandwidth for the device can reach 11.5 GHz and the modulation response curve is relatively flat upto ˜16 GHz. The radio frequency (RF) injection measurements verify that around the laser threshold the inter-mode beat note interacts strongly with the RF signal and the laser can be modulated at the round trip frequency of 15.5 GHz.

A strategy for early-risk predictions of clinical drug-drug interactions involving the GastroPlusTM DDI module for time-dependent CYP inhibitors.

PubMed

Sohlenius-Sternbeck, Anna-Karin; Meyerson, Gabrielle; Hagbjörk, Ann-Louise; Juric, Sanja; Terelius, Ylva

2018-04-01

1. A set of reference compounds for time-dependent inhibition (TDI) of cytochrome P450 with available literature data for k inact and K I was used to predict clinical implications using the GastroPlus TM software. Comparisons were made to in vivo literature interaction data. 2. The predicted AUC ratios (AUC +inhibitor /AUC control ) could be compared with the observed ratios from literature for all compounds with detailed information about in vivo administration, pharmacokinetics and in vivo interactions (N = 21). For this dataset, the difference between predicted and observed AUC ratios for interactions with midazolam was within twofold for all compounds except one (telaprevir, for which non-CYP-mediated metabolism likely plays a role after multiple dosing). 3. The sensitivity, specificity and accuracy of the GastroPlus TM predictions using a binary classification as no-to-weak interaction versus moderate-to-strong interaction for all compounds with available in vivo interaction data, were 80%, 82% and 81%, respectively (N = 31). 4. As a result of our evaluations of the DDI module in GastroPlus TM , we have implemented an early TDI risk assessment decision tree for our drug discovery projects involving in vitro screening and early GastroPlus TM predictions. Shifted IC 50 values are determined and k inact /K I estimated (by using a regression line established with in house-shifted IC 50 values and literature k inact /K I ratios), followed by GastroPlus TM predictions.

Development of a Web-Based 3D Module for Enhanced Neuroanatomy Education.

PubMed

Allen, Lauren K; Ren, He Zhen; Eagleson, Roy; de Ribaupierre, Sandrine

2016-01-01

Neuroanatomy is a challenging subject, with novice medical students often experiencing difficulty grasping the intricate 3D spatial relationships. Most of the anatomical teaching in undergraduate medicine utilizes conventional 2D resources. E-learning technologies facilitate the development of learner-centered educational tools that can be tailored to meet each student's educational needs, and may foster improved learning in neuroanatomy, however this has yet to be examined fully in the literature. An interactive 3D e-learning module was developed to complement gross anatomy laboratory instruction. Incorporating such 3D modules may provide additional support for students in areas of anatomy that are spatially challenging, such as neuroanatomy. Specific anatomical structures and their relative spatial positions to other structures can be clearly defined in the 3D virtual environment from viewpoints that may not readily be available using cadaveric or 2D image modalities. Providing an interactive user interface for the 3D module in which the student controls many factors may enable the student to develop an improved understanding of the spatial relationships. This work outlines the process for the development of a 3D interactive module of the cerebral structures included in the anatomy curriculum for undergraduate medical students in their second year of study.

Effectiveness of a comprehensive integrated module using interactive lectures and workshops in understanding and knowledge retention about infant feeding practice in fifth year medical students: a quasi-experimental study.

PubMed

Sjarif, Damayanti Rusli; Yuliarti, Klara; Wahyuni, Luh Karunia; Wiguna, Tjhin; Prawitasari, Titis; Devaera, Yoga; Triyuniati, Henni Wahyu; Afriansyah, Andika

2016-08-18

Sixty percent of the 10.9 million under-5 deaths every year are related to malnutrition. More than two thirds of malnutrition is caused by inappropriate infant feeding practice. Only 35 % of mothers worldwide provide 4 months of exclusive breast-feeding, while complementary feeding is often untimely, nutritionally inadequate, hygienically poor, and improperly delivered. The existing pediatric nutrition module in our institution does not include proper delivery of food that involves oral-motor skills and feeding behavior. To scale up the knowledge and skill of medical students regarding evidence-based infant feeding practice, we designed a new module composed of comprehensive and integrated lectures with additional multidisciplinary lectures on oral-motor skill development and feeding behavior. A quasi-experimental study was conducted to evaluate the efficacy of the new module compared to the previous module. Fifth year medical students of Universitas Indonesia were divided into intervention and control groups. The control group received lectures and a paper-based workshop. The intervention group received comprehensive and integrated interactive lectures with additional multidisciplinary lectures on oral-motor skill development and behavioral approaches to feeding problems. A hands-on workshop using real cases shown on recorded video and role-play sessions was also presented to the intervention group. A pre-/post-test, 3-month retention test, and Observed Structured Clinical Examination (OSCE) were performed to evaluate understanding, knowledge retention, and counseling skills. A linear mixed effect model with a random intercept analysis for pre-test, post-test, and retention test scores showed significant higher result for intervention group compared to control group (p < 0.001). Comprehensive knowledge and counselling skills were better in the intervention group than in the control group as shown by the OSCE score (68.6 vs 59.3, p < 0.001). Our

MEMORY MODULATION

PubMed Central

Roozendaal, Benno; McGaugh, James L.

2011-01-01

Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evidence from both animal and human research indicates that emotionally significant experiences activate hormonal and brain systems that regulate the consolidation of newly acquired memories. These effects are integrated through noradrenergic activation of the basolateral amygdala which regulates memory consolidation via interactions with many other brain regions involved in consolidating memories of recent experiences. Modulatory systems not only influence neurobiological processes underlying the consolidation of new information, but also affect other mnemonic processes, including memory extinction, memory recall and working memory. In contrast to their enhancing effects on consolidation, adrenal stress hormones impair memory retrieval and working memory. Such effects, as with memory consolidation, require noradrenergic activation of the basolateral amygdala and interactions with other brain regions. PMID:22122145

Star Power: Providing for the Gifted & Talented. Module 6. Underachievers Among the Gifted/Talented.

ERIC Educational Resources Information Center

Heinemann, Alison

The document presents Module 6, underachievers among the gifted/talented, of the Star Power modules developed for school personnel who have an interest in or a need to explore the area of gifted and talented education. It is explained in an introductory section that the modules can be used for independent study, for small group interaction, or for…

Star Power: Providing for the Gifted & Talented. Module 1. Characteristics of the Gifted/Talented.

ERIC Educational Resources Information Center

Heinemann, Alison

The document presents Module 1, characteristics of the gifted/talented student, of the Star Power modules, developed for school personnel who have an interest in or a need to explore the area of gifted and talented education. It is explained in an introductory section that the modules can be used for independent study, for small group interaction,…

LHX3 interacts with inhibitor of histone acetyltransferase complex subunits LANP and TAF-1β to modulate pituitary gene regulation.

PubMed

Hunter, Chad S; Malik, Raleigh E; Witzmann, Frank A; Rhodes, Simon J

2013-01-01

LIM-homeodomain 3 (LHX3) is a transcription factor required for mammalian pituitary gland and nervous system development. Human patients and animal models with LHX3 gene mutations present with severe pediatric syndromes that feature hormone deficiencies and symptoms associated with nervous system dysfunction. The carboxyl terminus of the LHX3 protein is required for pituitary gene regulation, but the mechanism by which this domain operates is unknown. In order to better understand LHX3-dependent pituitary hormone gene transcription, we used biochemical and mass spectrometry approaches to identify and characterize proteins that interact with the LHX3 carboxyl terminus. This approach identified the LANP/pp32 and TAF-1β/SET proteins, which are components of the inhibitor of histone acetyltransferase (INHAT) multi-subunit complex that serves as a multifunctional repressor to inhibit histone acetylation and modulate chromatin structure. The protein domains of LANP and TAF-1β that interact with LHX3 were mapped using biochemical techniques. Chromatin immunoprecipitation experiments demonstrated that LANP and TAF-1β are associated with LHX3 target genes in pituitary cells, and experimental alterations of LANP and TAF-1β levels affected LHX3-mediated pituitary gene regulation. Together, these data suggest that transcriptional regulation of pituitary genes by LHX3 involves regulated interactions with the INHAT complex.

LHX3 Interacts with Inhibitor of Histone Acetyltransferase Complex Subunits LANP and TAF-1β to Modulate Pituitary Gene Regulation

PubMed Central

Witzmann, Frank A.; Rhodes, Simon J.

2013-01-01

LIM-homeodomain 3 (LHX3) is a transcription factor required for mammalian pituitary gland and nervous system development. Human patients and animal models with LHX3 gene mutations present with severe pediatric syndromes that feature hormone deficiencies and symptoms associated with nervous system dysfunction. The carboxyl terminus of the LHX3 protein is required for pituitary gene regulation, but the mechanism by which this domain operates is unknown. In order to better understand LHX3-dependent pituitary hormone gene transcription, we used biochemical and mass spectrometry approaches to identify and characterize proteins that interact with the LHX3 carboxyl terminus. This approach identified the LANP/pp32 and TAF-1β/SET proteins, which are components of the inhibitor of histone acetyltransferase (INHAT) multi-subunit complex that serves as a multifunctional repressor to inhibit histone acetylation and modulate chromatin structure. The protein domains of LANP and TAF-1β that interact with LHX3 were mapped using biochemical techniques. Chromatin immunoprecipitation experiments demonstrated that LANP and TAF-1β are associated with LHX3 target genes in pituitary cells, and experimental alterations of LANP and TAF-1β levels affected LHX3-mediated pituitary gene regulation. Together, these data suggest that transcriptional regulation of pituitary genes by LHX3 involves regulated interactions with the INHAT complex. PMID:23861948

Electronic Module Design with Scientifically Character-Charged Approach on Kinematics Material Learning to Improve Holistic Competence of High School Students in 10th Grade

NASA Astrophysics Data System (ADS)

Anggraini, R.; Darvina, Y.; Amir, H.; Murtiani, M.; Yulkifli, Y.

2018-04-01

The availability of modules in schools is currently lacking. Learners have not used the module as a source in the learning process. In accordance with the demands of the 2013 curriculum, that learning should be conducted using a scientific approach and loaded with character values as well as learning using interactive learning resources. The solution of this problem is to create an interactive module with a scientifically charged character approach. This interactive module can be used by learners outside the classroom or in the classroom. This interactive module contains straight motion material, parabolic motion and circular motion of high school physics class X semester 1. The purpose of this research is to produce an interactive module with a scientific approach charged with character and determine the validity and practicality. The research is Research and Development. This study was conducted only until the validity test and practice test. The validity test was conducted by three lecturers of Physics of FMIPA UNP as experts. The instruments used in this research are validation sheet and worksheet sheet. Data analysis technique used is product validity analysis. The object of this research is electronic module, while the subject of this research is three validator.

Mediator kinase module and human tumorigenesis.

PubMed

Clark, Alison D; Oldenbroek, Marieke; Boyer, Thomas G

2015-01-01

Mediator is a conserved multi-subunit signal processor through which regulatory informatiosn conveyed by gene-specific transcription factors is transduced to RNA Polymerase II (Pol II). In humans, MED13, MED12, CDK8 and Cyclin C (CycC) comprise a four-subunit "kinase" module that exists in variable association with a 26-subunit Mediator core. Genetic and biochemical studies have established the Mediator kinase module as a major ingress of developmental and oncogenic signaling through Mediator, and much of its function in signal-dependent gene regulation derives from its resident CDK8 kinase activity. For example, CDK8-targeted substrate phosphorylation impacts transcription factor half-life, Pol II activity and chromatin chemistry and functional status. Recent structural and biochemical studies have revealed a precise network of physical and functional subunit interactions required for proper kinase module activity. Accordingly, pathologic change in this activity through altered expression or mutation of constituent kinase module subunits can have profound consequences for altered signaling and tumor formation. Herein, we review the structural organization, biological function and oncogenic potential of the Mediator kinase module. We focus principally on tumor-associated alterations in kinase module subunits for which mechanistic relationships as opposed to strictly correlative associations are established. These considerations point to an emerging picture of the Mediator kinase module as an oncogenic unit, one in which pathogenic activation/deactivation through component change drives tumor formation through perturbation of signal-dependent gene regulation. It follows that therapeutic strategies to combat CDK8-driven tumors will involve targeted modulation of CDK8 activity or pharmacologic manipulation of dysregulated CDK8-dependent signaling pathways.

Mediator kinase module and human tumorigenesis

PubMed Central

Clark, Alison D.; Oldenbroek, Marieke; Boyer, Thomas G.

2016-01-01

Mediator is a conserved multi-subunit signal processor through which regulatory informatiosn conveyed by gene-specific transcription factors is transduced to RNA Polymerase II (Pol II). In humans, MED13, MED12, CDK8 and Cyclin C (CycC) comprise a four-subunit “kinase” module that exists in variable association with a 26-subunit Mediator core. Genetic and biochemical studies have established the Mediator kinase module as a major ingress of developmental and oncogenic signaling through Mediator, and much of its function in signal-dependent gene regulation derives from its resident CDK8 kinase activity. For example, CDK8-targeted substrate phosphorylation impacts transcription factor half-life, Pol II activity and chromatin chemistry and functional status. Recent structural and biochemical studies have revealed a precise network of physical and functional subunit interactions required for proper kinase module activity. Accordingly, pathologic change in this activity through altered expression or mutation of constituent kinase module subunits can have profound consequences for altered signaling and tumor formation. Herein, we review the structural organization, biological function and oncogenic potential of the Mediator kinase module. We focus principally on tumor-associated alterations in kinase module subunits for which mechanistic relationships as opposed to strictly correlative associations are established. These considerations point to an emerging picture of the Mediator kinase module as an oncogenic unit, one in which pathogenic activation/deactivation through component change drives tumor formation through perturbation of signal-dependent gene regulation. It follows that therapeutic strategies to combat CDK8-driven tumors will involve targeted modulation of CDK8 activity or pharmacologic manipulation of dysregulated CDK8-dependent signaling pathways. PMID:26182352

Probiotics as an Immune Modulator.

PubMed

Kang, Hye-Ji; Im, Sin-Hyeog

2015-01-01

Probiotics are nonpathogenic live microorganism that can provide a diverse health benefits on the host when consumed in adequate amounts. Probiotics are consumed in diverse ways including dairy product, food supplements and functional foods with specific health claims. Recently, many reports suggest that certain probiotic strains or multi strain mixture have potent immunomodulatory activity in diverse disorders including allergic asthma, atopic dermatitis and rheumatoid arthritis. However, underlying mechanism of action is still unclear and efficacy of probiotic administration is quite different depending on the type of strains and the amounts of doses. We and others have suggested that live probiotics or their metabolites could interact with diverse immune cells (antigen presenting cells and T cells) and confer them to have immunoregulatory functions. Through this interaction, probiotics could contribute to maintaining immune homeostasis by balancing pro-inflammatory and anti-inflammatory immune responses. However, the effect of probiotics in prevention or modulation of ongoing disease is quite diverse even within a same species. Therefore, identification of functional probiotics with specific immune regulatory property is a certainly important issue. Herein, we briefly review selection methods for immunomodulatory probiotic strains and the mechanism of action of probiotics in immune modulation.

Miniaturized sensor module for a mechatronic bearing

NASA Astrophysics Data System (ADS)

Gao, Robert X.; Sahay, Priyaranjan

1998-12-01

To assess the working condition of a rolling element bearing, the condition monitoring system should be located as close as possible to the bearing to take advantage of shorter signal transmission path, increased signal-to-noise ratio, and reduced complexity of the signal processing electronics. The advantages of integrated sensing are presented in this paper, with a focus on the design and analysis of a miniaturized sensor module. Mechatronic principles have been applied to treat the various subjects in a synergistic way. To complement analytical studies, experiments have been conducted on a scaled-up version of the sensor module to analyze the system dynamic response. The result obtained provided insight into the electromechanical interaction within the module as well as input for the system implementation using miniaturization technologies.

All-optical liquid crystal spatial light modulators

NASA Astrophysics Data System (ADS)

Tabiryan, Nelson; Grozhik, Vladimir; Khoo, Iam Choon; Nersisyan, Sarik R.; Serak, Svetlana

2003-12-01

Nonlinear optical processes in liquid crystals (LC) can be used for construction of all-optical spatial light modulators (SLM) where the photosensitivity and phase modulating functions are integrated into a single layer of an LC-material. Such spatial light integrated modulators (SLIMs) cost only a fraction of the conventional LC-SLM and can be used with high power laser radiation due to high transparency of LC materials and absence of light absorbing electrodes on the substrates of the LC-cell constituting the SLIM. Recent development of LC materials the photosensitivity of which is comparable to that of semiconductors has led to using SLIM in schemes of optical anti-jamming, sensor protection, and image processing. All-optical processes add remarkable versatility to the operation of SLIM harnessing the wealth inherent to light-matter interaction phenomena.

Target-object integration, attention distribution, and object orientation interactively modulate object-based selection.

PubMed

Al-Janabi, Shahd; Greenberg, Adam S

2016-10-01

The representational basis of attentional selection can be object-based. Various studies have suggested, however, that object-based selection is less robust than spatial selection across experimental paradigms. We sought to examine the manner by which the following factors might explain this variation: Target-Object Integration (targets 'on' vs. part 'of' an object), Attention Distribution (narrow vs. wide), and Object Orientation (horizontal vs. vertical). In Experiment 1, participants discriminated between two targets presented 'on' an object in one session, or presented as a change 'of' an object in another session. There was no spatial cue-thus, attention was initially focused widely-and the objects were horizontal or vertical. We found evidence of object-based selection only when targets constituted a change 'of' an object. Additionally, object orientation modulated the sign of object-based selection: We observed a same-object advantage for horizontal objects, but a same-object cost for vertical objects. In Experiment 2, an informative cue preceded a single target presented 'on' an object or as a change 'of' an object (thus, attention was initially focused narrowly). Unlike in Experiment 1, we found evidence of object-based selection independent of target-object integration. We again found that the sign of selection was modulated by the objects' orientation. This result may reflect a meridian effect, which emerged due to anisotropies in the cortical representations when attention is oriented endogenously. Experiment 3 revealed that object orientation did not modulate object-based selection when attention was oriented exogenously. Our findings suggest that target-object integration, attention distribution, and object orientation modulate object-based selection, but only in combination.

A Protein Interaction Map of the Kalimantacin Biosynthesis Assembly Line

PubMed Central

Uytterhoeven, Birgit; Lathouwers, Thomas; Voet, Marleen; Michiels, Chris W.; Lavigne, Rob

2016-01-01

The antimicrobial secondary metabolite kalimantacin (also called batumin) is produced by a hybrid polyketide/non-ribosomal peptide system in Pseudomonas fluorescens BCCM_ID9359. In this study, the kalimantacin biosynthesis gene cluster is analyzed by yeast two-hybrid analysis, creating a protein–protein interaction map of the entire assembly line. In total, 28 potential interactions were identified, of which 13 could be confirmed further. These interactions include the dimerization of ketosynthase domains, a link between assembly line modules 9 and 10, and a specific interaction between the trans-acting enoyl reductase BatK and the carrier proteins of modules 8 and 10. These interactions reveal fundamental insight into the biosynthesis of secondary metabolites. This study is the first to reveal interactions in a complete biosynthetic pathway. Similar future studies could build a strong basis for engineering strategies in such clusters. PMID:27853452

Positive Affect Modulates Flexibility and Evaluative Control

ERIC Educational Resources Information Center

van Wouwe, Nelleke C.; Band, Guido P. H.; Ridderinkhof, K. Richard

2011-01-01

The ability to interact with a constantly changing environment requires a balance between maintaining the currently relevant working memory content and being sensitive to potentially relevant new information that should be given priority access to working memory. Mesocortical dopamine projections to frontal brain areas modulate working memory…

Amplitudes of solar modulation of low energy cosmic rays

NASA Technical Reports Server (NTRS)

Von Rosenvinge, T. T.; Paizis, C.

1982-01-01

There have been differences of opinion regarding the origin and behavior of the solar modulation of galactic cosmic rays. It has been shown that the return to solar maximum intensity levels beginning in early 1978 was dominated by Forbush decreases. These Forbush decreases were caused by radially moving interplanetary shocks resulting from large solar flares. The present investigation is concerned with solar modulation effects which were observed during the previous solar minimum. The effects were associated with high-speed streams in the solar wind. These streams caused the formation of corotating interaction regions with both forward and reverse shocks. The modulation effects seen near earth are intimately connected with these shocks.

Amino Acid Side Chain Interactions in the Presence of Salts

PubMed Central

Hassan, Sergio A.

2005-01-01

The effects of salt on the intermolecular interactions between polar/charged amino acids are investigated through molecular dynamics simulations. The mean forces and associated potentials are calculated for NaCl salt in the 0–2 M concentration range at 298 K. It is found that the addition of salt may stabilize or destabilize the interactions, depending on the nature of the interacting molecules. The degree of (de)stabilization is quantified, and the origin of the salt-dependent modulation is discussed based upon an analysis of solvent density profiles. To gain insight into the molecular origin of the salt modulation, spatial distribution functions (sdf’s) are calculated, revealing a high degree of solvent structuredness in all cases. The peaks in the sdf’s are consistent with long-range hydrogen-bonding networks connecting the solute hydrophilic groups, and that contribute to their intermolecular solvent-induced forces. The restructuring of water around the solutes as they dissociate from close contact is analyzed. This analysis offers clues on how the solvent structure modulates the effective intermolecular interactions in complex solutes. This modulation results from a critical balance between bulk electrostatic forces and those exerted by (i) the water molecules in the structured region between the monomers, which is disrupted by ions that transiently enter the hydration shells, and (ii) the ions in the hydration shells in direct interactions with the solutes. The implications of these findings in protein/ligand (noncovalent) association/dissociation mechanisms are briefly discussed. PMID:16479276

Selective chemical detection by energy modulation of sensors

DOEpatents

Stetter, Joseph R.; Otagawa, Takaaki

1991-01-01

A portable instrument for use in the field in detecting, identifying, and quantifying a component of a sampled fluid includes a sensor which chemically reacts with the component of interest or a derivative thereof, an electrical heating filament for heating the sample before it is applied to the sensor, and modulator for continuously varying the temperature of the filament (and hence the reaction rate) between two values sufficient to produce the chemical reaction. In response to this thermal modulation, the sensor produces a modulated output signal, the modulation of which is a function of the activation energy of the chemical reaction, which activation energy is specific to the particular component of interest and its concentration. Microprocessor which compares the modulated output signal with standard responses for a plurality of components to identify and quantify the particular component of interest. In particular, the concentration of the component of interest is proportional to the amplitude of the modulated output signal, while the identifying activation output energy of the chemical interaction indicative of that component is proportional to a normalized parameter equal to the peak-to-peak amplitude divided by the height of the upper peaks above a base line signal level.

Bifidobacterial surface-exopolysaccharide facilitates commensal-host interaction through immune modulation and pathogen protection

PubMed Central

Fanning, Saranna; Hall, Lindsay J.; Cronin, Michelle; Zomer, Aldert; MacSharry, John; Goulding, David; O'Connell Motherway, Mary; Shanahan, Fergus; Nally, Kenneth; Dougan, Gordon; van Sinderen, Douwe

2012-01-01

Bifidobacteria comprise a significant proportion of the human gut microbiota. Several bifidobacterial strains are currently used as therapeutic interventions, claiming various health benefits by acting as probiotics. However, the precise mechanisms by which they maintain habitation within their host and consequently provide these benefits are not fully understood. Here we show that Bifidobacterium breve UCC2003 produces a cell surface-associated exopolysaccharide (EPS), the biosynthesis of which is directed by either half of a bidirectional gene cluster, thus leading to production of one of two possible EPSs. Alternate transcription of the two opposing halves of this cluster appears to be the result of promoter reorientation. Surface EPS provided stress tolerance and promoted in vivo persistence, but not initial colonization. Marked differences were observed in host immune response: strains producing surface EPS (EPS+) failed to elicit a strong immune response compared with EPS-deficient variants. Specifically, EPS production was shown to be linked to the evasion of adaptive B-cell responses. Furthermore, presence of EPS+ B. breve reduced colonization levels of the gut pathogen Citrobacter rodentium. Our data thus assigns a pivotal and beneficial role for EPS in modulating various aspects of bifidobacterial–host interaction, including the ability of commensal bacteria to remain immunologically silent and in turn provide pathogen protection. This finding enforces the probiotic concept and provides mechanistic insights into health-promoting benefits for both animal and human hosts. PMID:22308390

Star Power: Providing for the Gifted & Talented. Module 9. Programs for the Gifted/Talented.

ERIC Educational Resources Information Center

Mallis, Jackie; Heinemann, Alison

The document presents Module 9, programs for the gifted/talented, of the Star Power modules developed for school personnel who have an interest in or a need to explore the area of gifted and talented education. It is explained in an introductory section that the modules can be used for independent study, for small group interaction, or for a large…

A Modularity-Based Method Reveals Mixed Modules from Chemical-Gene Heterogeneous Network

PubMed Central

Song, Jianglong; Tang, Shihuan; Liu, Xi; Gao, Yibo; Yang, Hongjun; Lu, Peng

2015-01-01

For a multicomponent therapy, molecular network is essential to uncover its specific mode of action from a holistic perspective. The molecular system of a Traditional Chinese Medicine (TCM) formula can be represented by a 2-class heterogeneous network (2-HN), which typically includes chemical similarities, chemical-target interactions and gene interactions. An important premise of uncovering the molecular mechanism is to identify mixed modules from complex chemical-gene heterogeneous network of a TCM formula. We thus proposed a novel method (MixMod) based on mixed modularity to detect accurate mixed modules from 2-HNs. At first, we compared MixMod with Clauset-Newman-Moore algorithm (CNM), Markov Cluster algorithm (MCL), Infomap and Louvain on benchmark 2-HNs with known module structure. Results showed that MixMod was superior to other methods when 2-HNs had promiscuous module structure. Then these methods were tested on a real drug-target network, in which 88 disease clusters were regarded as real modules. MixMod could identify the most accurate mixed modules from the drug-target 2-HN (normalized mutual information 0.62 and classification accuracy 0.4524). In the end, MixMod was applied to the 2-HN of Buchang naoxintong capsule (BNC) and detected 49 mixed modules. By using enrichment analysis, we investigated five mixed modules that contained primary constituents of BNC intestinal absorption liquid. As a matter of fact, the findings of in vitro experiments using BNC intestinal absorption liquid were found to highly accord with previous analysis. Therefore, MixMod is an effective method to detect accurate mixed modules from chemical-gene heterogeneous networks and further uncover the molecular mechanism of multicomponent therapies, especially TCM formulae. PMID:25927435

Very-low-power and footprint integrated photonic modulators and switches for ICT

NASA Astrophysics Data System (ADS)

Thylén, Lars; Holmström, Petter; Wosinski, Lech

2013-03-01

The current development in photonics for communications and interconnects pose increasing requirements on reduction of footprint, power dissipation and cost, as well as increased bandwidth. Integrated nanophotonics has been viewed as one solution to this, capitalizing on development in nanotechnology as such as well as on increased insights into light matter interaction on the nanoscale. The latter can be exemplified by plasmonics and low-dimensional semiconductors such as quantum dots (QDs). In this scenario the development of better electrooptic materials is also of great importance, the electrooptic polymers being an example, since they potentially offer improved properties for optical phase modulators in terms of power and probably cost and general flexibility. Phase modulators are essential for e.g. the rapidly developing advanced modulation formats for telecom, since phase modulation basically can generate any type of modulation. The electrooptic polymers, e.g. in combination with plasmonics nanoparticle array waveguides or nanostructured hybrid plasmonic media can theoretically give extremely compact and low power dissipation modulators, still to be demonstrated. The low-dimensional semiconductors, e.g. in the shape of QDs, can be employed for modulation or switching functions, offering possibilities in the future for scaling to 2 or 3 dimensions for advanced switching functions. In both the plasmonics and QD cases, nanosizing and low power dissipation are generally due to near-field interactions, albeit being of different physical origin in the two cases. A comparison of all-optical and electronically controlled switching is given.

Protein-protein recognition control by modulating electrostatic interactions.

PubMed

Han, Song; Yin, Shijin; Yi, Hong; Mouhat, Stéphanie; Qiu, Su; Cao, Zhijian; Sabatier, Jean-Marc; Wu, Yingliang; Li, Wenxin

2010-06-04

Protein-protein control recognition remains a huge challenge, and its development depends on understanding the chemical and biological mechanisms by which these interactions occur. Here we describe a protein-protein control recognition technique based on the dominant electrostatic interactions occurring between the proteins. We designed a potassium channel inhibitor, BmP05-T, that was 90.32% identical to wild-type BmP05. Negatively charged residues were translocated from the nonbinding interface to the binding interface of BmP05 inhibitor, such that BmP05-T now used BmP05 nonbinding interface as the binding interface. This switch demonstrated that nonbinding interfaces were able to control the orientation of protein binding interfaces in the process of protein-protein recognition. The novel function findings of BmP05-T peptide suggested that the control recognition technique described here had the potential for use in designing and utilizing functional proteins in many biological scenarios.

Energy Balance Modulates Colon Tumor Growth: Interactive Roles of Insulin and Estrogen

PubMed Central

Rondini, Elizabeth A.; Harvey, Alison E.; Steibel, Juan Pedro; Hursting, Stephen D.; Fenton, Jenifer I.

2011-01-01

Obesity increases colorectal cancer (CRC) risk and progression. However, the impact of obesity on CRC in women is dependent on ovarian hormone status. The purpose of this study was to determine the interactive roles of obesity and ovarian hormones on serum markers of inflammation, cell signaling and transplanted colon tumor growth. Female C57BL/6 mice (6 weeks) were either ovariectomized (OVX) or ovaries left intact (NOVX) and randomized to receive a 1) control, 2) 30% calorie-restricted (CR), or 3) diet-induced obese (DIO) diet regimen for 20 weeks to induce differing levels of adiposity. Serum was collected and inflammatory and metabolic markers were measured using an antibody array (62 proteins) and ELISAs. Mice were subcutaneously injected with syngeneic MC38 colon cancer cells after 20 weeks and sacrificed 4 weeks later. CR mice had the smallest tumors irrespective of hormone status, whereas the largest tumors were observed in DIO-OVX mice. Glucose tolerance was impaired in ovariectomized mice, being most severe in the DIO-OVX group. Cytokine arrays suggested that in CR animals, inhibition of tumor growth paralleled insulin sensitivity and associated changes in leptin, adiponectin, and IGF-BPs. Conversely, in DIO-OVX animals, tumor growth was associated with insulin and leptin resistance as well as higher levels of pro-inflammatory proteins. In vitro, leptin and adiponectin had no effect, whereas insulin induced MC38 cell proliferation and MAPK activation. Co-treatment with estrogen blocked the stimulatory effects of insulin. Thus, our in vitro and in vivo data indicate female reproductive hormones have a modulating effect on obesity-induced insulin resistance and inflammation, which may directly or indirectly influence CRC progression. PMID:21480390

Endocannabinoid/GABA interactions in the entopeduncular nucleus modulates alcohol intake in rats.

PubMed

Méndez-Díaz, Mónica; Caynas Rojas, Seraid; Gómez Armas, David; Ruiz-Contreras, Alejandra E; Aguilar-Roblero, Raúl; Prospéro-García, Oscar

2013-02-01

Alcohol use disorder is a compulsive behavior driven by motivational systems and by a poor control of consummatory behavior. The entopeduncular nucleus (EP) seems to be involved in the regulation of executive mechanisms, hence, in the expression of behavior. Endocannabinoids (eCB) are involved in alcohol intake mechanisms. The eCB receptor name cannabinoid receptor 1 (CB1R) is expressed in the EP in GABAergic terminals. The role of the eCB system (eCBs) of the EP in the modulation of alcohol seeking and intake behavior is unknown. Therefore, we decided to investigate the role of the eCBs and its interaction with GABA transmission in rat EP, in the regulation of alcohol intake behavior. Rats were submitted to a 10-day period of moderate alcohol (10% in tap water) ingestion. No tap water was available. On day 11, either anandamide (AEA, CB1 receptor agonist), AM251 (CB1R inverse agonist), baclofen (BAC, GABAB receptor agonist), or CGP35348 (GABAB receptor antagonist) was administered into the EP. One bottle of water and one of alcohol (10% in water) were available ad libitum for the following 24 h, and consumption was quantified at the end of this period. Results show that administration of AEA into the EP decreased alcohol consumption while AM251 and BAC administered independently increased alcohol consumption. AEA prevented the increase induced by AM251 or BAC. Likewise, CGP35348 prevented alcohol ingestion induced by AM251. These data suggest that eCBs dysfunction in the EP may be playing a crucial role in the abuse and dependence of alcohol and other drugs. Copyright © 2013 Elsevier Inc. All rights reserved.

NFI-Ski interactions mediate transforming growth factor beta modulation of human papillomavirus type 16 early gene expression.

PubMed

Baldwin, Amy; Pirisi, Lucia; Creek, Kim E

2004-04-01

Human papillomaviruses (HPVs) are present in virtually all cervical cancers. An important step in the development of malignant disease, including cervical cancer, involves a loss of sensitivity to transforming growth factor beta (TGF-beta). HPV type 16 (HPV16) early gene expression, including that of the E6 and E7 oncoprotein genes, is under the control of the upstream regulatory region (URR), and E6 and E7 expression in HPV16-immortalized human epithelial cells is inhibited at the transcriptional level by TGF-beta. While the URR contains a myriad of transcription factor binding sites, including seven binding sites for nuclear factor I (NFI), the specific sequences within the URR or the transcription factors responsible for TGF-beta modulation of the URR remain unknown. To identify potential transcription factors and binding sites involved in TGF-beta modulation of the URR, we performed DNase I footprint analysis on the HPV16 URR using nuclear extracts from TGF-beta-sensitive HPV16-immortalized human keratinocytes (HKc/HPV16) treated with and without TGF-beta. Differentially protected regions were found to be located around NFI binding sites. Electrophoretic mobility shift assays, using the NFI binding sites as probes, showed decreased binding upon TGF-beta treatment. This decrease in binding was not due to reduced NFI protein or NFI mRNA levels. Mutational analysis of individual and multiple NFI binding sites in the URR defined their role in TGF-beta sensitivity of the promoter. Overexpression of the NFI family members in HKc/HPV16 decreased the ability of TGF-beta to inhibit the URR. Since the oncoprotein Ski has been shown to interact with and increase the transcriptional activity of NFI and since cellular Ski levels are decreased by TGF-beta treatment, we explored the possibility that Ski may provide a link between TGF-beta signaling and NFI activity. Anti-NFI antibodies coimmunoprecipitated endogenous Ski in nuclear extracts from HKc/HPV16, confirming that NFI

Detection of a Novel Mechanism of Acousto-Optic Modulation of Incoherent Light

PubMed Central

Jarrett, Christopher W.; Caskey, Charles F.; Gore, John C.

2014-01-01

A novel form of acoustic modulation of light from an incoherent source has been detected in water as well as in turbid media. We demonstrate that patterns of modulated light intensity appear to propagate as the optical shadow of the density variations caused by ultrasound within an illuminated ultrasonic focal zone. This pattern differs from previous reports of acousto-optical interactions that produce diffraction effects that rely on phase shifts and changes in light directions caused by the acoustic modulation. Moreover, previous studies of acousto-optic interactions have mainly reported the effects of sound on coherent light sources via photon tagging, and/or the production of diffraction phenomena from phase effects that give rise to discrete sidebands. We aimed to assess whether the effects of ultrasound modulation of the intensity of light from an incoherent light source could be detected directly, and how the acoustically modulated (AOM) light signal depended on experimental parameters. Our observations suggest that ultrasound at moderate intensities can induce sufficiently large density variations within a uniform medium to cause measurable modulation of the intensity of an incoherent light source by absorption. Light passing through a region of high intensity ultrasound then produces a pattern that is the projection of the density variations within the region of their interaction. The patterns exhibit distinct maxima and minima that are observed at locations much different from those predicted by Raman-Nath, Bragg, or other diffraction theory. The observed patterns scaled appropriately with the geometrical magnification and sound wavelength. We conclude that these observed patterns are simple projections of the ultrasound induced density changes which cause spatial and temporal variations of the optical absorption within the illuminated sound field. These effects potentially provide a novel method for visualizing sound fields and may assist the

Effect of Career Education Module on Career Development of Community College Students

ERIC Educational Resources Information Center

Talib, Jasmi A.; Salleh, Amla; Amat, Salleh; Ghavifekr, Simin; Ariff, Azlinda M.

2015-01-01

Using a pre-post and control group design, we examined the effect of a career education module on career development among a group of 122 community college students in Malaysia. The effect of gender and the interaction effect of gender and career education module on career development were also investigated. MANOVA analyses showed significant…

Star Power: Providing for the Gifted & Talented. Module 5. Enrichment Activities for the Gifted/Talented.

ERIC Educational Resources Information Center

Mallis, Jackie; Gilman, Sharlene

The document presents Module 5, enrichment activities for the gifted/talented, of the Star Power modules developed for school personnel who have an interest in or a need to explore the area of gifted and talented education. It is explained in an introductory section that the modules can be used for independent study, for small group interaction,…

Creating a Bridge between Industry and Higher Education through an Operations Consultancy Module

ERIC Educational Resources Information Center

Bak, Ozlem

2011-01-01

This paper explores the challenges and use of a postgraduate consultancy module in teaching operations management. The consultancy module extends the traditional learning boundaries between students and lecturers to a tripartite grouping of students, university and industry. The interaction within this group may be influenced by students' skills…

Explicit authenticity and stimulus features interact to modulate BOLD response induced by emotional speech.

PubMed

Drolet, Matthis; Schubotz, Ricarda I; Fischer, Julia

2013-06-01

Context has been found to have a profound effect on the recognition of social stimuli and correlated brain activation. The present study was designed to determine whether knowledge about emotional authenticity influences emotion recognition expressed through speech intonation. Participants classified emotionally expressive speech in an fMRI experimental design as sad, happy, angry, or fearful. For some trials, stimuli were cued as either authentic or play-acted in order to manipulate participant top-down belief about authenticity, and these labels were presented both congruently and incongruently to the emotional authenticity of the stimulus. Contrasting authentic versus play-acted stimuli during uncued trials indicated that play-acted stimuli spontaneously up-regulate activity in the auditory cortex and regions associated with emotional speech processing. In addition, a clear interaction effect of cue and stimulus authenticity showed up-regulation in the posterior superior temporal sulcus and the anterior cingulate cortex, indicating that cueing had an impact on the perception of authenticity. In particular, when a cue indicating an authentic stimulus was followed by a play-acted stimulus, additional activation occurred in the temporoparietal junction, probably pointing to increased load on perspective taking in such trials. While actual authenticity has a significant impact on brain activation, individual belief about stimulus authenticity can additionally modulate the brain response to differences in emotionally expressive speech.

Modulation of interaction of mutant TP53 and wild type BRCA1 by alkaloids: a computational approach towards targeting protein-protein interaction as a futuristic therapeutic intervention strategy for breast cancer impediment.

PubMed

Tiwari, Sameeksha; Awasthi, Manika; Singh, Swati; Pandey, Veda P; Dwivedi, Upendra N

2017-10-23

Protein-protein interactions (PPI) are a new emerging class of novel therapeutic targets. In order to probe these interactions, computational tools provide a convenient and quick method towards the development of therapeutics. Keeping this in view the present study was initiated to analyse interaction of tumour suppressor protein p53 (TP53) and breast cancer associated protein (BRCA1) as promising target against breast cancer. Using computational approaches such as protein-protein docking, hot spot analyses, molecular docking and molecular dynamics simulation (MDS), stepwise analyses of the interactions of the wild type and mutant TP53 with that of wild type BRCA1 and their modulation by alkaloids were done. Protein-protein docking method was used to generate both wild type and mutant complexes of TP53-BRCA1. Subsequently, the complexes were docked using sixteen different alkaloids, fulfilling ADMET and Lipinski's rule of five criteria, and were compared with that of a well-known inhibitor of PPI, namely nutlin. The alkaloid dicentrine was found to be the best docked alkaloid among all the docked alklaloids as well as that of nutlin. Furthermore, MDS analyses of both wild type and mutant complexes with the best docked alkaloid i.e. dicentrine, revealed higher stability of mutant complex than that of the wild one, in terms of average RMSD, RMSF and binding free energy, corroborating the results of docking. Results suggested more pronounced interaction of BRCA1 with mutant TP53 leading to increased expression of mutated TP53 thus showing a dominant negative gain of function and hampering wild type TP53 function leading to tumour progression.

Annual modulation experiments, galactic models and WIMPs

NASA Astrophysics Data System (ADS)

Hudson, Robert G.

Our task in the paper is to examine some recent experiments (in the period 1996-2002) bearing on the issue of whether there is dark matter in the universe in the form of neutralino WIMPs (weakly interacting massive particles). Our main focus is an experiment performed by the DAMA group that claims to have found an 'annual modulation signature' for the WIMP. DAMA's result has been hotly contested by two other groups, EDELWEISS and CDMS, and we study the details of the experiments performed by all three groups. Our goal is to investigate the philosophic and sociological implications of this controversy. Particularly, using an innovative theoretical strategy suggested by (Copi, C. and L. M. Krauss (2003). Comparing interaction rate detectors for weakly interacting massive particles with annual modulation detectors. Physical Review D, 67, 103 507), we suggest a new way of resolving discordant experimental data (extending a previous analysis by (Franklin, A. (2002). Selectivity and discord. Pittsburgh: University of Pittsburgh Press). In addition, we are in a position to contribute substantively to the debate between realists and constructive empiricists. Finally, from a sociological standpoint, we remark that DAMA's work has been valuable in mobilizing other research teams and providing them with a critical focus.

Brain gut microbiome interactions and functional bowel disorders

USDA-ARS?s Scientific Manuscript database

Alterations in the bidirectional interactions between the intestine and the nervous system have important roles in the pathogenesis of irritable bowel syndrome (IBS). A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. A small and poorly defined r...

Designing Templates for Interactive Tasks in CALL Tutorials.

ERIC Educational Resources Information Center

Ruhlmann, Felicitas

The development of templates for computer-assisted language learning (CALL) is discussed, based on experiences with primarily linear multimedia tutorial programs. Design of templates for multiple-choice questions and interactive tasks in a prototype module is described. Possibilities of enhancing interactivity by introducing problem-oriented…

Face age modulates gaze following in young adults.

PubMed

Ciardo, Francesca; Marino, Barbara F M; Actis-Grosso, Rossana; Rossetti, Angela; Ricciardelli, Paola

2014-04-22

Gaze-following behaviour is considered crucial for social interactions which are influenced by social similarity. We investigated whether the degree of similarity, as indicated by the perceived age of another person, can modulate gaze following. Participants of three different age-groups (18-25; 35-45; over 65) performed an eye movement (a saccade) towards an instructed target while ignoring the gaze-shift of distracters of different age-ranges (6-10; 18-25; 35-45; over 70). The results show that gaze following was modulated by the distracter face age only for young adults. Particularly, the over 70 year-old distracters exerted the least interference effect. The distracters of a similar age-range as the young adults (18-25; 35-45) had the most effect, indicating a blurred own-age bias (OAB) only for the young age group. These findings suggest that face age can modulate gaze following, but this modulation could be due to factors other than just OAB (e.g., familiarity).

Electrically tunable terahertz wave modulator based on complementary metamaterial and graphene

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

He, Xun-jun, E-mail: hexunjun@hrbust.edu.cn; Li, Teng-yue; Wang, Lei

2014-05-07

In this paper, we design and numerically demonstrate an electrically controllable light-matter interaction in a hybrid material/metamaterial system consisting of an artificially constructed cross cut-wire complementary metamaterial and an atomically thin graphene layer to realize terahertz (THz) wave modulator. By applying a bias voltage between the metamaterial and the graphene layer, this modulator can dynamically control the amplitude and phase of the transmitted wave near 1.43 THz. Moreover, the distributions of current density show that this large modulation depth can be attributed to the resonant electric field parallel to the graphene sheet. Therefore, the modulator performance indicates the enormous potentialmore » of graphene for developing sophisticated THz communication systems.« less

First and second generation γ-secretase modulators (GSMs) modulate amyloid-β (Aβ) peptide production through different mechanisms.

PubMed

Borgegard, Tomas; Juréus, Anders; Olsson, Fredrik; Rosqvist, Susanne; Sabirsh, Alan; Rotticci, Didier; Paulsen, Kim; Klintenberg, Rebecka; Yan, Hongmei; Waldman, Magnus; Stromberg, Kia; Nord, Johan; Johansson, Jonas; Regner, Anna; Parpal, Santiago; Malinowsky, David; Radesater, Ann-Cathrin; Li, Tingsheng; Singh, Rajeshwar; Eriksson, Hakan; Lundkvist, Johan

2012-04-06

γ-Secretase-mediated cleavage of amyloid precursor protein (APP) results in the production of Alzheimer disease-related amyloid-β (Aβ) peptides. The Aβ42 peptide in particular plays a pivotal role in Alzheimer disease pathogenesis and represents a major drug target. Several γ-secretase modulators (GSMs), such as the nonsteroidal anti-inflammatory drugs (R)-flurbiprofen and sulindac sulfide, have been suggested to modulate the Alzheimer-related Aβ production by targeting the APP. Here, we describe novel GSMs that are selective for Aβ modulation and do not impair processing of Notch, EphB2, or EphA4. The GSMs modulate Aβ both in cell and cell-free systems as well as lower amyloidogenic Aβ42 levels in the mouse brain. Both radioligand binding and cellular cross-competition experiments reveal a competitive relationship between the AstraZeneca (AZ) GSMs and the established second generation GSM, E2012, but a noncompetitive interaction between AZ GSMs and the first generation GSMs (R)-flurbiprofen and sulindac sulfide. The binding of a (3)H-labeled AZ GSM analog does not co-localize with APP but overlaps anatomically with a γ-secretase targeting inhibitor in rodent brains. Combined, these data provide compelling evidence of a growing class of in vivo active GSMs, which are selective for Aβ modulation and have a different mechanism of action compared with the original class of GSMs described.

Cophylogenetic signal is detectable in pollination interactions across ecological scales.

PubMed

Hutchinson, Matthew C; Cagua, Edgar Fernando; Stouffer, Daniel B

2017-10-01

That evolutionary history can influence the way that species interact is a basic tenet of evolutionary ecology. However, when the role of evolution in determining ecological interactions is investigated, focus typically centers on just one side of the interaction. A cophylogenetic signal, the congruence of evolutionary history across both sides of an ecological interaction, extends these previous explorations and provides a more complete picture of how evolutionary patterns influence the way species interact. To date, cophylogenetic signal has most typically been studied in interactions that occur between fine taxonomic clades that show high intimacy. In this study, we took an alternative approach and made an exhaustive assessment of cophylogeny in pollination interactions. To do so, we assessed the strength of cophylogenetic signal at four distinct scales of pollination interaction: (1) across plant-pollinator associations globally, (2) in local pollination communities, (3) within the modular structure of those communities, and (4) in individual modules. We did so using a globally distributed dataset comprised of 54 pollination networks, over 4000 species, and over 12,000 interactions. Within these data, we detected cophylogenetic signal at all four scales. Cophylogenetic signal was found at the level of plant-pollinator interactions on a global scale and in the majority of pollination communities. At the scale defined by the modular structure within those communities, however, we observed a much weaker cophylogenetic signal. Cophylogenetic signal was detectable in a significant proportion of individual modules and most typically when within-module phylogenetic diversity was low. In sum, the detection of cophylogenetic signal in pollination interactions across scales provides a new dimension to the story of how past evolution shapes extant pollinator-angiosperm interactions. © 2017 by the Ecological Society of America.

Palmitoylethanolamide Modulates GPR55 Receptor Signaling in the Ventral Hippocampus to Regulate Mesolimbic Dopamine Activity, Social Interaction, and Memory Processing.

PubMed

Kramar, Cecilia; Loureiro, Michael; Renard, Justine; Laviolette, Steven R

2017-01-01

Introduction: The GPR55 receptor has been identified as an atypical cannabinoid receptor and is implicated in various physiological processes. However, its functional role in the central nervous system is not currently understood. The presence of GPR55 receptor in neural regions such as the ventral hippocampus (vHipp), which is critical for cognition, recognition memory, and affective processing, led us to hypothesize that intra-vHipp GPR55 transmission may modulate mesolimbic activity states and related behavioral phenomena. The vHipp is involved in contextual memory and affective regulation through functional interactions with the mesolimbic dopamine system. Materials and Methods: Using a combination of in vivo electrophysiology and behavioral pharmacological assays in rats, we tested whether intra-vHipp activation of GPR55 receptor transmission with the fatty acid amide, palmitoylethanolamide (PEA), a lipid neuromodulator with agonist actions at the GPR55 receptor, may modulate mesolimbic dopaminergic activity states. We further examined the potential effects of intra-vHipp PEA in affective, cognitive and contextual memory tasks. Discussion: We report that intra-vHipp PEA produces a hyper-dopaminergic state in the mesolimbic system characterized by increased firing and bursting activity of ventral tegmental area dopaminergic neuron populations. Furthermore, while PEA-induced activation of GPR55 transmission had no effects on opiate-related reward-related memory formation, we observed strong disruptions in social interaction and recognition memory, spatial location memory, and context-independent associative fear memory formation. Finally, the effects of intra-vHipp PEA were blocked by a selective GPR55 receptor antagonist, CID160 and were dependent upon NMDA receptor transmission, directly in the vHipp. Conclusions: The present results add to a growing body of evidence demonstrating important functional roles for GPR55 signaling in cannabinoid-related neuronal

Function, dynamics and evolution of network motif modules in integrated gene regulatory networks of worm and plant.

PubMed

Defoort, Jonas; Van de Peer, Yves; Vermeirssen, Vanessa

2018-06-05

Gene regulatory networks (GRNs) consist of different molecular interactions that closely work together to establish proper gene expression in time and space. Especially in higher eukaryotes, many questions remain on how these interactions collectively coordinate gene regulation. We study high quality GRNs consisting of undirected protein-protein, genetic and homologous interactions, and directed protein-DNA, regulatory and miRNA-mRNA interactions in the worm Caenorhabditis elegans and the plant Arabidopsis thaliana. Our data-integration framework integrates interactions in composite network motifs, clusters these in biologically relevant, higher-order topological network motif modules, overlays these with gene expression profiles and discovers novel connections between modules and regulators. Similar modules exist in the integrated GRNs of worm and plant. We show how experimental or computational methodologies underlying a certain data type impact network topology. Through phylogenetic decomposition, we found that proteins of worm and plant tend to functionally interact with proteins of a similar age, while at the regulatory level TFs favor same age, but also older target genes. Despite some influence of the duplication mode difference, we also observe at the motif and module level for both species a preference for age homogeneity for undirected and age heterogeneity for directed interactions. This leads to a model where novel genes are added together to the GRNs in a specific biological functional context, regulated by one or more TFs that also target older genes in the GRNs. Overall, we detected topological, functional and evolutionary properties of GRNs that are potentially universal in all species.

The neuronal Ca(2+) -binding protein 2 (NECAB2) interacts with the adenosine A(2A) receptor and modulates the cell surface expression and function of the receptor.

PubMed

Canela, Laia; Luján, Rafael; Lluís, Carme; Burgueño, Javier; Mallol, Josefa; Canela, Enric I; Franco, Rafael; Ciruela, Francisco

2007-09-01

Heptaspanning membrane also known as G protein-coupled receptors (GPCR) do interact with a variety of intracellular proteins whose function is regulate receptor traffic and/or signaling. Using a yeast two-hybrid screen, NECAB2, a neuronal calcium binding protein, was identified as a binding partner for the adenosine A(2A) receptor (A(2A)R) interacting with its C-terminal domain. Co-localization, co-immunoprecipitation and pull-down experiments showed a close and specific interaction between A(2A)R and NECAB2 in both transfected HEK-293 cells and also in rat striatum. Immunoelectron microscopy detection of NECAB2 and A(2A)R in the rat striatopallidal structures indicated that both proteins are co-distributed in the same glutamatergic nerve terminals. The interaction of NECAB2 with A(2A)R modulated the cell surface expression, the ligand-dependent internalization and the receptor-mediated activation of the MAPK pathway. Overall, these results show that A(2A)R interacts with NECAB2 in striatal neurones co-expressing the two proteins and that the interaction is relevant for A(2A)R function.

Fear conditioning is associated with dynamic directed functional interactions between and within the human amygdala, hippocampus, and frontal lobe.

PubMed

Liu, C C; Crone, N E; Franaszczuk, P J; Cheng, D T; Schretlen, D S; Lenz, F A

2011-08-25

The current model of fear conditioning suggests that it is mediated through modules involving the amygdala (AMY), hippocampus (HIP), and frontal lobe (FL). We now test the hypothesis that habituation and acquisition stages of a fear conditioning protocol are characterized by different event-related causal interactions (ERCs) within and between these modules. The protocol used the painful cutaneous laser as the unconditioned stimulus and ERC was estimated by analysis of local field potentials recorded through electrodes implanted for investigation of epilepsy. During the prestimulus interval of the habituation stage FL>AMY ERC interactions were common. For comparison, in the poststimulus interval of the habituation stage, only a subdivision of the FL (dorsolateral prefrontal cortex, dlPFC) still exerted the FL>AMY ERC interaction (dlFC>AMY). For a further comparison, during the poststimulus interval of the acquisition stage, the dlPFC>AMY interaction persisted and an AMY>FL interaction appeared. In addition to these ERC interactions between modules, the results also show ERC interactions within modules. During the poststimulus interval, HIP>HIP ERC interactions were more common during acquisition, and deep hippocampal contacts exerted causal interactions on superficial contacts, possibly explained by connectivity between the perihippocampal gyrus and the HIP. During the prestimulus interval of the habituation stage, AMY>AMY ERC interactions were commonly found, while interactions between the deep and superficial AMY (indirect pathway) were independent of intervals and stages. These results suggest that the network subserving fear includes distributed or widespread modules, some of which are themselves "local networks." ERC interactions between and within modules can be either static or change dynamically across intervals or stages of fear conditioning. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Selective chemical detection by energy modulation of sensors

DOEpatents

Stetter, J.R.; Otagawa, T.

1991-09-10

A portable instrument for use in the field in detecting, identifying, and quantifying a component of a sampled fluid includes a sensor which chemically reacts with the component of interest or a derivative thereof, an electrical heating filament for heating the sample before it is applied to the sensor, and modulator for continuously varying the temperature of the filament (and hence the reaction rate) between two values sufficient to produce the chemical reaction. In response to this thermal modulation, the sensor produces a modulated output signal, the modulation of which is a function of the activation energy of the chemical reaction, which activation energy is specific to the particular component of interest and its concentration. Microprocessor which compares the modulated output signal with standard responses for a plurality of components to identify and quantify the particular component of interest. In particular, the concentration of the component of interest is proportional to the amplitude of the modulated output signal, while the identifying activation output energy of the chemical interaction indicative of that component is proportional to a normalized parameter equal to the peak-to-peak amplitude divided by the height of the upper peaks above a base line signal level. 5 figures.

Equivalent Circuit Modeling for Carbon Nanotube Schottky Barrier Modulation in Polarized Gases

NASA Technical Reports Server (NTRS)

Yamada, Toshishige

2005-01-01

We study the carbon nanotube Schottky barrier at the metallic electrode interface in polarized gases using an equivalent circuit model. The gas-nanotube interaction is often weak and very little charge transfer is expected [l]. This is the case with'oxygen, but the gas-electrode interaction is appreciable and makes the oxygen molecules negatively charged. In the closed circuit condition, screening positive charges appear in the nanotube as well as in the electrode, and the Schottky barrier is modulated due to the resultant electrostatic effects [2]. In the case of ammonia, both the gas-nanotube and gas-electrode interactions are weak, but the Schottky barrier can still be modulated since the molecules are polarized and align in the preferred orientation within the gap between the electrode and nanotube in the open circuit condition (dipole layer formation). In the closed circuit condition, an electric field appears in the gap and strengthens or weakens the preferred dipole alignment reflecting the nanotube Fermi level. The modulation is visible when the nanotube depletion mode is involved, and the required dipole density is as low as 2 x 10(exp 13) dipoles/sq cm, which is quite feasible experimentally,

Design and Development of High Voltage Direct Current (DC) Sources for the Solar Array Module Plasma Interaction Experiment

NASA Technical Reports Server (NTRS)

Bibyk, Irene K.; Wald, Lawrence W.

1995-01-01

Two programmable, high voltage DC power supplies were developed as part of the flight electronics for the Solar Array Module Plasma Interaction Experiment (SAMPIE). SAMPIE's primary objectives were to study and characterize the high voltage arcing and parasitic current losses of various solar cells and metal samples within the space plasma of low earth orbit (LEO). High voltage arcing can cause large discontinuous changes in spacecraft potential which lead to damage of the power system materials and significant Electromagnetic Interference (EMI). Parasitic currents cause a change in floating potential which lead to reduced power efficiency. These primary SAMPIE objectives were accomplished by applying artificial biases across test samples over a voltage range from -600 VDC to +300 VDC. This paper chronicles the design, final development, and test of the two programmable high voltage sources for SAMPIE. The technical challenges to the design for these power supplies included vacuum, space plasma effects, thermal protection, Shuttle vibrations and accelerations.

Meteorological Instrumentation and Measurements Open Resource Training Modules for Undergraduate and Graduate Education

NASA Astrophysics Data System (ADS)

Rockwell, A.; Clark, R. D.; Stevermer, A.

2017-12-01

The National Center for Atmospheric Research Earth Observing Laboratory, Millersville University and The COMET Program are collaborating to produce a series of nine online modules on the the topic of meteorological instrumentation and measurements. These interactive, multimedia educational modules can be integrated into undergraduate and graduate meteorology courses on instrumentation, measurement science, and observing systems to supplement traditional pedagogies and enhance blended instruction. These freely available and open-source training tools are designed to supplement traditional pedagogies and enhance blended instruction. Three of the modules are now available and address the theory and application of Instrument Performance Characteristics, Meteorological Temperature Instrumentation and Measurements, and Meteorological Pressure Instrumentation and Measurements. The content of these modules is of the highest caliber as it has been developed by scientists and engineers who are at the forefront of the field of observational science. Communicating the availability of these unique and influential educational resources with the community is of high priority. These modules will have a profound effect on the atmospheric observational sciences community by fulfilling a need for contemporary, interactive, multimedia guided education and training modules integrating the latest instructional design and assessment tools in observational science. Thousands of undergraduate and graduate students will benefit, while course instructors will value a set of high quality modules to use as supplements to their courses. The modules can serve as an alternative to observational research training and fill the void between field projects or assist those schools that lack the resources to stage a field- or laboratory-based instrumentation experience.

Ballasted photovoltaic module and module arrays

DOEpatents

Botkin, Jonathan [El Cerrito, CA; Graves, Simon [Berkeley, CA; Danning, Matt [Oakland, CA

2011-11-29

A photovoltaic (PV) module assembly including a PV module and a ballast tray. The PV module includes a PV device and a frame. A PV laminate is assembled to the frame, and the frame includes an arm. The ballast tray is adapted for containing ballast and is removably associated with the PV module in a ballasting state where the tray is vertically under the PV laminate and vertically over the arm to impede overt displacement of the PV module. The PV module assembly can be installed to a flat commercial rooftop, with the PV module and the ballast tray both resting upon the rooftop. In some embodiments, the ballasting state includes corresponding surfaces of the arm and the tray being spaced from one another under normal (low or no wind) conditions, such that the frame is not continuously subjected to a weight of the tray.

Interactive computer graphics system for structural sizing and analysis of aircraft structures

NASA Technical Reports Server (NTRS)

Bendavid, D.; Pipano, A.; Raibstein, A.; Somekh, E.

1975-01-01

A computerized system for preliminary sizing and analysis of aircraft wing and fuselage structures was described. The system is based upon repeated application of analytical program modules, which are interactively interfaced and sequence-controlled during the iterative design process with the aid of design-oriented graphics software modules. The entire process is initiated and controlled via low-cost interactive graphics terminals driven by a remote computer in a time-sharing mode.

Solution conformation of a cohesin module and its scaffoldin linker from a prototypical cellulosome.

PubMed

Galera-Prat, Albert; Pantoja-Uceda, David; Laurents, Douglas V; Carrión-Vázquez, Mariano

2018-04-15

Bacterial cellulases are drawing increased attention as a means to obtain plentiful chemical feedstocks and fuels from renewable lignocellulosic biomass sources. Certain bacteria deploy a large extracellular multi-protein complex, called the cellulosome, to degrade cellulose. Scaffoldin, a key non-catalytic cellulosome component, is a large protein containing a cellulose-specific carbohydrate-binding module and several cohesin modules which bind and organize the hydrolytic enzymes. Despite the importance of the structure and protein/protein interactions of the cohesin module in the cellulosome, its structure in solution has remained unknown to date. Here, we report the backbone 1 H, 13 C and 15 N NMR assignments of the Cohesin module 5 from the highly stable and active cellulosome from Clostridium thermocellum. These data reveal that this module adopts a tightly packed, well folded and rigid structure in solution. Furthermore, since in scaffoldin, the cohesin modules are connected by linkers we have also characterized the conformation of a representative linker segment using NMR spectroscopy. Analysis of its chemical shift values revealed that this linker is rather stiff and tends to adopt extended conformations. This suggests that the scaffoldin linkers act to minimize interactions between cohesin modules. These results pave the way towards solution studies on cohesin/dockerin's fascinating dual-binding mode. Copyright © 2018 Elsevier Inc. All rights reserved.

Tracking the Reorganization of Module Structure in Time-Varying Weighted Brain Functional Connectivity Networks.

PubMed

Schmidt, Christoph; Piper, Diana; Pester, Britta; Mierau, Andreas; Witte, Herbert

2018-05-01

Identification of module structure in brain functional networks is a promising way to obtain novel insights into neural information processing, as modules correspond to delineated brain regions in which interactions are strongly increased. Tracking of network modules in time-varying brain functional networks is not yet commonly considered in neuroscience despite its potential for gaining an understanding of the time evolution of functional interaction patterns and associated changing degrees of functional segregation and integration. We introduce a general computational framework for extracting consensus partitions from defined time windows in sequences of weighted directed edge-complete networks and show how the temporal reorganization of the module structure can be tracked and visualized. Part of the framework is a new approach for computing edge weight thresholds for individual networks based on multiobjective optimization of module structure quality criteria as well as an approach for matching modules across time steps. By testing our framework using synthetic network sequences and applying it to brain functional networks computed from electroencephalographic recordings of healthy subjects that were exposed to a major balance perturbation, we demonstrate the framework's potential for gaining meaningful insights into dynamic brain function in the form of evolving network modules. The precise chronology of the neural processing inferred with our framework and its interpretation helps to improve the currently incomplete understanding of the cortical contribution for the compensation of such balance perturbations.

Star Power: Providing for the Gifted & Talented. Module 10. Guidance and Counseling for the Gifted/Talented.

ERIC Educational Resources Information Center

Heinemann, Alison; Mallis, Jackie

The document presents Module 10, guidance and counseling for the gifted/talented, of the Star Power modules developed for school personnel who have an interest in or a need to explore the area of gifted and talented education. It is explained in an introductory section that the module can be used for independent study, for small group interaction,…

Assessment of a novel module for training dental students in child abuse recognition and reporting.

PubMed

Shapiro, Michael C; Anderson, O Roger; Lal, Shantanu

2014-08-01

This study assessed the merits of introducing a novel, online interactive training module designed to positively engage dental students and teach them to recognize and report signs of child abuse and neglect. The study aimed to determine if the online training module educated the students equivalently or better than a lecture presentation of the same content. Seventy-two students from Columbia University College of Dental Medicine's class of 2015 (90 percent of the class) agreed to participate and were randomly assigned to either a traditional lecture-based presentation or the online training module. Study participants were given a twenty-question multiple-choice pretest on their knowledge of child abuse recognition and reporting prior to the start of the study. The same instrument was administered as a posttest. At the end of the training, questionnaires were also given to both groups to assess students' perceptions of the two educational methodologies. The results showed that the interactive online training module was more effective than the lecture-based method. Results of the posttest comparison of the two groups were statistically significant (p<0.05) in favor of the online training group. Additionally, the students reported that the interactive online training module was engaging and a helpful resource, but on average they did not prefer it as a total replacement for the lecture-based approach.

Aging effects in sequential modulations of poorer-strategy effects during execution of memory strategies.

PubMed

Hinault, Thomas; Lemaire, Patrick; Touron, Dayna

2017-02-01

In this study, we asked young adults and older adults to encode pairs of words. For each item, they were told which strategy to use, interactive imagery or rote repetition. Data revealed poorer-strategy effects in both young adults and older adults: Participants obtained better performance when executing better strategies (i.e., interactive-imagery strategy to encode pairs of concrete words; rote-repetition strategy on pairs of abstract words) than with poorer strategies (i.e., interactive-imagery strategy on pairs of abstract words; rote-repetition strategy on pairs of concrete words). Crucially, we showed that sequential modulations of poorer-strategy effects (i.e., poorer-strategy effects being larger when previous items were encoded with better relative to poorer strategies), previously demonstrated in arithmetic, generalise to memory strategies. We also found reduced sequential modulations of poorer-strategy effects in older adults relative to young adults. Finally, sequential modulations of poorer-strategy effects correlated with measures of cognitive control processes, suggesting that these processes underlie efficient trial-to-trial modulations during strategy execution. Differences in correlations with cognitive control processes were also found between older adults and young adults. These findings have important implications regarding mechanisms underlying memory strategy execution and age differences in memory performance.

Bioluminescence of beetle luciferases with 6'-amino-D-luciferin analogues reveals excited keto-oxyluciferin as the emitter and phenolate/luciferin binding site interactions modulate bioluminescence colors.

PubMed

Viviani, Vadim R; Neves, Deimison Rodrigues; Amaral, Danilo Trabuco; Prado, Rogilene A; Matsuhashi, Takuto; Hirano, Takashi

2014-08-19

Beetle luciferases produce different bioluminescence colors from green to red using the same d-luciferin substrate. Despite many studies of the mechanisms and structural determinants of bioluminescence colors with firefly luciferases, the identity of the emitters and the specific active site interactions responsible for bioluminescence color modulation remain elusive. To address these questions, we analyzed the bioluminescence spectra with 6'-amino-D-luciferin (aminoluciferin) and its 5,5-dimethyl analogue using a set of recombinant beetle luciferases that naturally elicit different colors and different pH sensitivities (pH-sensitive, Amydetes vivianii λmax=538 nm, Macrolampis sp2 λmax=564 nm; pH-insensitive, Phrixotrix hirtus λmax=623 nm, Phrixotrix vivianii λmax=546 nm, and Pyrearinus termitilluminans λmax=534 nm), a luciferase-like enzyme (Tenebrionidae, Zophobas morio λmax=613 nm), and mutants of C311 (S314). The green-yellow-emitting luciferases display red-shifted bioluminescence spectra with aminoluciferin in relation to those with D-luciferin, whereas the red-emitting luciferases displayed blue-shifted spectra. Bioluminescence spectra with 5,5-dimethylaminoluciferin, in which enolization is blocked, were almost identical to those of aminoluciferin. Fluorescence probing using 2-(4-toluidino)naphthalene-6-sulfonate and inference with aminoluciferin confirm that the luciferin binding site of the red-shifted luciferases is more polar than in the case of the green-yellow-emitting luciferases. Altogether, the results show that the keto form of excited oxyluciferin is the emitter in beetle bioluminescence and that bioluminescence colors are essentially modulated by interactions of the 6'-hydroxy group of oxyluciferin and basic moieties under the influence of the microenvironment polarity of the active site: a strong interaction between a base moiety and oxyluciferin phenol in a hydrophobic microenvironment promotes green-yellow emission, whereas a more polar

Smelling directions: Olfaction modulates ambiguous visual motion perception

PubMed Central

Kuang, Shenbing; Zhang, Tao

2014-01-01

Senses of smells are often accompanied by simultaneous visual sensations. Previous studies have documented enhanced olfactory performance with concurrent presence of congruent color- or shape- related visual cues, and facilitated visual object perception when congruent smells are simultaneously present. These visual object-olfaction interactions suggest the existences of couplings between the olfactory pathway and the visual ventral processing stream. However, it is not known if olfaction can modulate visual motion perception, a function that is related to the visual dorsal stream. We tested this possibility by examining the influence of olfactory cues on the perceptions of ambiguous visual motion signals. We showed that, after introducing an association between motion directions and olfactory cues, olfaction could indeed bias ambiguous visual motion perceptions. Our result that olfaction modulates visual motion processing adds to the current knowledge of cross-modal interactions and implies a possible functional linkage between the olfactory system and the visual dorsal pathway. PMID:25052162

Photovoltaic module and interlocked stack of photovoltaic modules

DOEpatents

Wares, Brian S.

2014-09-02

One embodiment relates to an arrangement of photovoltaic modules configured for transportation. The arrangement includes a plurality of photovoltaic modules, each photovoltaic module including a frame. A plurality of individual male alignment features and a plurality of individual female alignment features are included on each frame. Adjacent photovoltaic modules are interlocked by multiple individual male alignment features on a first module of the adjacent photovoltaic modules fitting into and being surrounded by corresponding individual female alignment features on a second module of the adjacent photovoltaic modules. Other embodiments, features and aspects are also disclosed.

Enhancement of collective atomic recoil lasing due to pump phase modulation

NASA Astrophysics Data System (ADS)

Robb, G. R. M.; Burgess, R. T. L.; Firth, W. J.

2008-10-01

We investigate the effect of a phase-modulated pump beam on collective backscattering [also termed collective atomic recoil lasing (CARL)] by a cold, collisionless atomic gas. We show using a numerical analysis that different regimes can be identified in which the atomic dynamics evolves in a qualitatively different manner during the light-atom interaction, depending on the magnitude of the pump modulation frequency. Our results also demonstrate that phase-modulating the pump field can substantially enhance the backscattered field intensity relative to the case of a monochromatic pump which has been used in CARL experiments to date.

Basic avionics module design for general aviation aircraft

NASA Technical Reports Server (NTRS)

Smyth, R. K.; Smyth, D. E.

1978-01-01

The design of an advanced digital avionics system (basic avionics module) for general aviation aircraft operated with a single pilot under IFR conditions is described. The microprocessor based system provided all avionic functions, including flight management, navigation, and lateral flight control. The mode selection was interactive with the pilot. The system used a navigation map data base to provide operation in the current and planned air traffic control environment. The system design included software design listings for some of the required modules. The distributed microcomputer uses the IEEE 488 bus for interconnecting the microcomputer and sensors.

Disgust selectively modulates reciprocal fairness in economic interactions.

PubMed

Moretti, Laura; di Pellegrino, Giuseppe

2010-04-01

We report two studies aimed at investigating the effects of distinct negative emotions on pairwise economic interactions. In the ultimatum game, a proposer offers a division of a sum of money to a responder who decides whether to accept the split, or reject and leave both players with nothing. In Experiment 1, we investigated whether induced disgust, as compared to sadness and neutral emotion, specifically influences responders' decisions to reject unfair proposals. In Experiment 2, we assessed whether the effects of disgust were selectively related to social contexts by contrasting interactions with a human partner with those involving a computer. Results showed that relative to being in a sad or neutral mood, induced feelings of disgust significantly increased rejection rates of unfair offers. Moreover, we found that when the partner was not responsible for the fairness violation, such as in the computer-offer condition, the disgust induction failed to affect participants' choices. We conclude by focusing on the hypothesis that disgust and social norm violations may share common computational components, both at a psychological and a neural level. Copyright 2010 APA, all rights reserved.

A "Do-It-Yourself" Interactive Bone Structure Module: Development and Evaluation of an Online Teaching Resource

ERIC Educational Resources Information Center

Rich, Peter; Guy, Richard

2013-01-01

A stand-alone online teaching module was developed to cover an area of musculoskeletal anatomy (structure of bone) found to be difficult by students. The material presented in the module was not formally presented in any other way, thus providing additional time for other curriculum components, but it was assessed in the final examination. The…

Identification and functional analysis of a core gene module associated with hepatitis C virus-induced human hepatocellular carcinoma progression.

PubMed

Bai, Gaobo; Zheng, Wenling; Ma, Wenli

2018-05-01

Hepatitis C virus (HCV)-induced human hepatocellular carcinoma (HCC) progression may be due to a complex multi-step processes. The developmental mechanism of these processes is worth investigating for the prevention, diagnosis and therapy of HCC. The aim of the present study was to investigate the molecular mechanism underlying the progression of HCV-induced hepatocarcinogenesis. First, the dynamic gene module, consisting of key genes associated with progression between the normal stage and HCC, was identified using the Weighted Gene Co-expression Network Analysis tool from R language. By defining those genes in the module as seeds, the change of co-expression in differentially expressed gene sets in two consecutive stages of pathological progression was examined. Finally, interaction pairs of HCV viral proteins and their directly targeted proteins in the identified module were extracted from the literature and a comprehensive interaction dataset from yeast two-hybrid experiments. By combining the interactions between HCV and their targets, and protein-protein interactions in the Search Tool for the Retrieval of Interacting Genes database (STRING), the HCV-key genes interaction network was constructed and visualized using Cytoscape software 3.2. As a result, a module containing 44 key genes was identified to be associated with HCC progression, due to the dynamic features and functions of those genes in the module. Several important differentially co-expressed gene pairs were identified between non-HCC and HCC stages. In the key genes, cyclin dependent kinase 1 (CDK1), NDC80, cyclin A2 (CCNA2) and rac GTPase activating protein 1 (RACGAP1) were shown to be targeted by the HCV nonstructural proteins NS5A, NS3 and NS5B, respectively. The four genes perform an intermediary role between the HCV viral proteins and the dysfunctional module in the HCV key genes interaction network. These findings provided valuable information for understanding the mechanism of HCV

Developing effective web-based regional anesthesia education: a randomized study evaluating case-based versus non-case-based module design.

PubMed

Kopp, Sandra L; Smith, Hugh M

2011-01-01

Little is known about the use of Web-based education in regional anesthesia training. Benefits of Web-based education include the ability to standardize learning material quality and content, build appropriate learning progressions, use interactive multimedia technologies, and individualize delivery of course materials. The goals of this investigation were (1) to determine whether module design influences regional anesthesia knowledge acquisition, (2) to characterize learner preference patterns among anesthesia residents, and (3) to determine whether learner preferences play a role in knowledge acquisition. Direct comparison of knowledge assessments, learning styles, and learner preferences will be made between an interactive case-based and a traditional textbook-style module design. Forty-three Mayo Clinic anesthesiology residents completed 2 online modules, a knowledge pretest, posttest, an Index of Learning Styles assessment, and a participant satisfaction survey. Interscalene and lumbar plexus regional techniques were selected as the learning content for 4 Web modules constructed using the Blackboard Vista coursework application. One traditional textbook-style module and 1 interactive case-based module were designed for each of the interscalene and lumbar plexus techniques. Participants scored higher on the postmodule knowledge assessment for both of the interscalene and lumbar plexus modules. Postmodule knowledge performance scores were independent of both module design (interactive case-based versus traditional textbook style) and learning style preferences. However, nearly all participants reported a preference for Web-based learning and believe that it should be used in anesthesia resident education. Participants did not feel that Web-base learning should replace the current lecture-based curriculum. All residents scored higher on the postmodule knowledge assessment, but this improvement was independent of the module design and individual learning styles

Commensal bacteria modulate the tumor microenvironment.

PubMed

Poutahidis, Theofilos; Erdman, Susan E

2016-09-28

It has been recently shown that gut microbes modulate whole host immune and hormonal factors impacting the fate of distant preneoplastic lesions toward malignancy or regression. This raises the possibility that the tumor microenvironment interacts with broader systemic microbial-immune networks. These accumulated findings suggest novel therapeutic opportunities for holobiont engineering in emerging tumor microenvironments. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Selective attention modulates early human evoked potentials during emotional face-voice processing.

PubMed

Ho, Hao Tam; Schröger, Erich; Kotz, Sonja A

2015-04-01

Recent findings on multisensory integration suggest that selective attention influences cross-sensory interactions from an early processing stage. Yet, in the field of emotional face-voice integration, the hypothesis prevails that facial and vocal emotional information interacts preattentively. Using ERPs, we investigated the influence of selective attention on the perception of congruent versus incongruent combinations of neutral and angry facial and vocal expressions. Attention was manipulated via four tasks that directed participants to (i) the facial expression, (ii) the vocal expression, (iii) the emotional congruence between the face and the voice, and (iv) the synchrony between lip movement and speech onset. Our results revealed early interactions between facial and vocal emotional expressions, manifested as modulations of the auditory N1 and P2 amplitude by incongruent emotional face-voice combinations. Although audiovisual emotional interactions within the N1 time window were affected by the attentional manipulations, interactions within the P2 modulation showed no such attentional influence. Thus, we propose that the N1 and P2 are functionally dissociated in terms of emotional face-voice processing and discuss evidence in support of the notion that the N1 is associated with cross-sensory prediction, whereas the P2 relates to the derivation of an emotional percept. Essentially, our findings put the integration of facial and vocal emotional expressions into a new perspective-one that regards the integration process as a composite of multiple, possibly independent subprocesses, some of which are susceptible to attentional modulation, whereas others may be influenced by additional factors.

Allosteric Modulation of Metabotropic Glutamate Receptors

PubMed Central

Sheffler, Douglas J.; Gregory, Karen J.; Rook, Jerri M.; Conn, P. Jeffrey

2013-01-01

The development of receptor subtype-selective ligands by targeting allosteric sites of G protein-coupled receptors (GPCRs) has proven highly successful in recent years. One GPCR family that has greatly benefited from this approach is the metabotropic glutamate receptors (mGlus). These family C GPCRs participate in the neuromodulatory actions of glutamate throughout the CNS, where they play a number of key roles in regulating synaptic transmission and neuronal excitability. A large number of mGlu subtype-selective allosteric modulators have been identified, the majority of which are thought to bind within the transmembrane regions of the receptor. These modulators can either enhance or inhibit mGlu functional responses and, together with mGlu knockout mice, have furthered the establishment of the physiologic roles of many mGlu subtypes. Numerous pharmacological and receptor mutagenesis studies have been aimed at providing a greater mechanistic understanding of the interaction of mGlu allosteric modulators with the receptor, which have revealed evidence for common allosteric binding sites across multiple mGlu subtypes and the presence for multiple allosteric sites within a single mGlu subtype. Recent data have also revealed that mGlu allosteric modulators can display functional selectivity toward particular signal transduction cascades downstream of an individual mGlu subtype. Studies continue to validate the therapeutic utility of mGlu allosteric modulators as a potential therapeutic approach for a number of disorders including anxiety, schizophrenia, Parkinson’s disease, and Fragile X syndrome. PMID:21907906

Searching for statistically significant regulatory modules.

PubMed

Bailey, Timothy L; Noble, William Stafford

2003-10-01

The regulatory machinery controlling gene expression is complex, frequently requiring multiple, simultaneous DNA-protein interactions. The rate at which a gene is transcribed may depend upon the presence or absence of a collection of transcription factors bound to the DNA near the gene. Locating transcription factor binding sites in genomic DNA is difficult because the individual sites are small and tend to occur frequently by chance. True binding sites may be identified by their tendency to occur in clusters, sometimes known as regulatory modules. We describe an algorithm for detecting occurrences of regulatory modules in genomic DNA. The algorithm, called mcast, takes as input a DNA database and a collection of binding site motifs that are known to operate in concert. mcast uses a motif-based hidden Markov model with several novel features. The model incorporates motif-specific p-values, thereby allowing scores from motifs of different widths and specificities to be compared directly. The p-value scoring also allows mcast to only accept motif occurrences with significance below a user-specified threshold, while still assigning better scores to motif occurrences with lower p-values. mcast can search long DNA sequences, modeling length distributions between motifs within a regulatory module, but ignoring length distributions between modules. The algorithm produces a list of predicted regulatory modules, ranked by E-value. We validate the algorithm using simulated data as well as real data sets from fruitfly and human. http://meme.sdsc.edu/MCAST/paper

Interaction between protein kinase C and protein kinase A can modulate transmitter release at the rat neuromuscular synapse.

PubMed