Brain regions associated with the acquisition of conditioned place preference for cocaine vs. social interaction

PubMed Central

El Rawas, Rana; Klement, Sabine; Kummer, Kai K.; Fritz, Michael; Dechant, Georg; Saria, Alois; Zernig, Gerald

2012-01-01

Positive social interaction could play an essential role in switching the preference of the substance dependent individual away from drug related activities. We have previously shown that conditioned place preference (CPP) for cocaine at the dose of 15 mg/kg and CPP for four 15-min episodes of social interaction were equally strong when rats were concurrently conditioned for place preference by pairing cocaine with one compartment and social interaction with the other. The aim of the present study was to investigate the differential activation of brain regions related to the reward circuitry after acquisition/expression of cocaine CPP or social interaction CPP. Our findings indicate that cocaine CPP and social interaction CPP activated almost the same brain regions. However, the granular insular cortex and the dorsal part of the agranular insular cortex were more activated after cocaine CPP, whereas the prelimbic cortex and the core subregion of the nucleus accumbens were more activated after social interaction CPP. These results suggest that the insular cortex appears to be potently activated after drug conditioning learning while activation of the prelimbic cortex—nucleus accumbens core projection seems to be preferentially involved in the conditioning to non-drug stimuli such as social interaction. PMID:23015784

ALG-2 activates the MVB sorting function of ALIX through relieving its intramolecular interaction

PubMed Central

Sun, Sheng; Zhou, Xi; Corvera, Joe; Gallick, Gary E; Lin, Sue-Hwa; Kuang, Jian

2015-01-01

The modular adaptor protein ALIX is critically involved in endosomal sorting complexes required for transport (ESCRT)-mediated multivesicular body (MVB) sorting of activated epidermal growth factor receptor (EGFR); however, ALIX contains a default intramolecular interaction that renders ALIX unable to perform this ESCRT function. The ALIX partner protein ALG-2 is a calcium-binding protein that belongs to the calmodulin superfamily. Prompted by a defined biological function of calmodulin, we determined the role of ALG-2 in regulating ALIX involvement in MVB sorting of activated EGFR. Our results show that calcium-dependent ALG-2 interaction with ALIX completely relieves the intramolecular interaction of ALIX and promotes CHMP4-dependent ALIX association with the membrane. EGFR activation induces increased ALG-2 interaction with ALIX, and this increased interaction is responsible for increased ALIX association with the membrane. Functionally, inhibition of ALIX activation by ALG-2 inhibits MVB sorting of activated EGFR as effectively as inhibition of ALIX interaction with CHMP4 does; however, inhibition of ALIX activation by ALG-2 does not affect cytokinetic abscission or equine infectious anemia virus (EIAV) budding. These findings indicate that calcium-dependent ALG-2 interaction with ALIX is specifically responsible for generating functional ALIX that supports MVB sorting of ubiquitinated membrane receptors. PMID:27462417

Why we interact: on the functional role of the striatum in the subjective experience of social interaction.

PubMed

Pfeiffer, Ulrich J; Schilbach, Leonhard; Timmermans, Bert; Kuzmanovic, Bojana; Georgescu, Alexandra L; Bente, Gary; Vogeley, Kai

2014-11-01

There is ample evidence that human primates strive for social contact and experience interactions with conspecifics as intrinsically rewarding. Focusing on gaze behavior as a crucial means of human interaction, this study employed a unique combination of neuroimaging, eye-tracking, and computer-animated virtual agents to assess the neural mechanisms underlying this component of behavior. In the interaction task, participants believed that during each interaction the agent's gaze behavior could either be controlled by another participant or by a computer program. Their task was to indicate whether they experienced a given interaction as an interaction with another human participant or the computer program based on the agent's reaction. Unbeknownst to them, the agent was always controlled by a computer to enable a systematic manipulation of gaze reactions by varying the degree to which the agent engaged in joint attention. This allowed creating a tool to distinguish neural activity underlying the subjective experience of being engaged in social and non-social interaction. In contrast to previous research, this allows measuring neural activity while participants experience active engagement in real-time social interactions. Results demonstrate that gaze-based interactions with a perceived human partner are associated with activity in the ventral striatum, a core component of reward-related neurocircuitry. In contrast, interactions with a computer-driven agent activate attention networks. Comparisons of neural activity during interaction with behaviorally naïve and explicitly cooperative partners demonstrate different temporal dynamics of the reward system and indicate that the mere experience of engagement in social interaction is sufficient to recruit this system. Copyright © 2014 Elsevier Inc. All rights reserved.

Patterns of Communicative Interaction between a Child with Severe Speech and Physical Impairments and Her Caregiver during a Mealtime Activity

ERIC Educational Resources Information Center

Ferm, Ulrika; Ahlsen, Elisabeth; Bjorck-Akesson, Eva

2012-01-01

Background: Interaction between caregivers and children with severe impairments is closely related to the demands of daily activities. This study examines the relationship between interaction and the routine mealtime activity at home. Method: Patterns of interaction between a child (aged 6 years and 6 months) with severe speech and physical…

The influence of interactions among phenolic compounds on the antiradical activity of chokeberries (Aronia melanocarpa).

PubMed

Jakobek, Lidija; Seruga, Marijan; Krivak, Petra

2011-06-01

In the present work, interactions between phenolic compounds from chokeberries and their influence on the antiradical activity was studied. Three fractions were isolated from chokeberries containing different classes of phenolic compounds. The first fraction contained a major part of phenolic acids and flavonols, the second anthocyanins, and the third insoluble phenols and proanthocyanidins. The phenolic compound content was determined using high-performance liquid chromatography, and the antiradical activity using the DPPH test. In order to evaluate the effects of interactions between phenolic compounds on the antiradical activity, the antiradical activity of individual phenolic fractions was compared with that obtained by mixing phenolic fractions. Phenolic mixtures showed the decrease in the antiradical activity in comparison with the individual phenolic fractions. These results suggest the existence of complex interactions among phenolic compounds that caused the decrease of the antiradical activity. Interactions among chokeberry phenols promoted a negative synergism.

Influence of the interactions between tea (Camellia sinensis) extracts and ascorbic acid on their antioxidant activity: analysis with interaction indexes and isobolograms.

PubMed

Enko, Jolanta; Gliszczyńska-Świgło, Anna

2015-01-01

Products containing natural additives, including antioxidants, are usually perceived by consumers as safer than those with synthetic ones. Natural antioxidants, besides having a preservative activity, may exert beneficial health effects. Interactions between antioxidants may significantly change their antioxidant activity, thus in designing functional foods or food/cosmetic ingredients knowledge about the type of interactions could be useful. In the present study, the interactions between ascorbic acid (AA; vitamin C) and different black and green tea extracts and the influence on their antioxidant activities were investigated. The antioxidant activities of tea extracts and their mixtures with AA prepared in several different weight ratios were measured using the trolox equivalent antioxidant capacity (TEAC), 1,1-diphenyl-2-picrylhydrazyl (DPPH), and ferric-reducing antioxidant power (FRAP) methods. The type of interaction was determined by interaction indexes and isobolograms. It was found that the weight ratio of extracts to AA significantly influenced the antioxidant activity of a mixture and the type of interaction between these components. The weight ratio of tea extract to AA can cause the change of interaction, e.g. from antagonism to additivism or from additivism to synergism. The observed differences in the type of interactions were probably also a result of different extracts' polyphenol composition and content. The type of interaction may also be affected by the medium in which extracts and AA interact, especially its pH and the solvent used. To obtain the best antioxidant effect, all these factors should be taken into account during the design of a tea extract-AA mixture.

Learning from instructional explanations: effects of prompts based on the active-constructive-interactive framework.

PubMed

Roelle, Julian; Müller, Claudia; Roelle, Detlev; Berthold, Kirsten

2015-01-01

Although instructional explanations are commonly provided when learners are introduced to new content, they often fail because they are not integrated into effective learning activities. The recently introduced active-constructive-interactive framework posits an effectiveness hierarchy in which interactive learning activities are at the top; these are then followed by constructive and active learning activities, respectively. Against this background, we combined instructional explanations with different types of prompts that were designed to elicit these learning activities and tested the central predictions of the active-constructive-interactive framework. In Experiment 1, N = 83 students were randomly assigned to one of four combinations of instructional explanations and prompts. To test the active < constructive learning hypothesis, the learners received either (1) complete explanations and engaging prompts designed to elicit active activities or (2) explanations that were reduced by inferences and inference prompts designed to engage learners in constructing the withheld information. Furthermore, in order to explore how interactive learning activities can be elicited, we gave the learners who had difficulties in constructing the prompted inferences adapted remedial explanations with either (3) unspecific engaging prompts or (4) revision prompts. In support of the active < constructive learning hypothesis, we found that the learners who received reduced explanations and inference prompts outperformed the learners who received complete explanations and engaging prompts. Moreover, revision prompts were more effective in eliciting interactive learning activities than engaging prompts. In Experiment 2, N = 40 students were randomly assigned to either (1) a reduced explanations and inference prompts or (2) a reduced explanations and inference prompts plus adapted remedial explanations and revision prompts condition. In support of the constructive < interactive learning hypothesis, the learners who received adapted remedial explanations and revision prompts as add-ons to reduced explanations and inference prompts acquired more conceptual knowledge.

Learning from Instructional Explanations: Effects of Prompts Based on the Active-Constructive-Interactive Framework

PubMed Central

Roelle, Julian; Müller, Claudia; Roelle, Detlev; Berthold, Kirsten

2015-01-01

Although instructional explanations are commonly provided when learners are introduced to new content, they often fail because they are not integrated into effective learning activities. The recently introduced active-constructive-interactive framework posits an effectiveness hierarchy in which interactive learning activities are at the top; these are then followed by constructive and active learning activities, respectively. Against this background, we combined instructional explanations with different types of prompts that were designed to elicit these learning activities and tested the central predictions of the active-constructive-interactive framework. In Experiment 1, N = 83 students were randomly assigned to one of four combinations of instructional explanations and prompts. To test the active < constructive learning hypothesis, the learners received either (1) complete explanations and engaging prompts designed to elicit active activities or (2) explanations that were reduced by inferences and inference prompts designed to engage learners in constructing the withheld information. Furthermore, in order to explore how interactive learning activities can be elicited, we gave the learners who had difficulties in constructing the prompted inferences adapted remedial explanations with either (3) unspecific engaging prompts or (4) revision prompts. In support of the active < constructive learning hypothesis, we found that the learners who received reduced explanations and inference prompts outperformed the learners who received complete explanations and engaging prompts. Moreover, revision prompts were more effective in eliciting interactive learning activities than engaging prompts. In Experiment 2, N = 40 students were randomly assigned to either (1) a reduced explanations and inference prompts or (2) a reduced explanations and inference prompts plus adapted remedial explanations and revision prompts condition. In support of the constructive < interactive learning hypothesis, the learners who received adapted remedial explanations and revision prompts as add-ons to reduced explanations and inference prompts acquired more conceptual knowledge. PMID:25853629

Interactivity and reward-related neural activation during a serious videogame.

PubMed

Cole, Steven W; Yoo, Daniel J; Knutson, Brian

2012-01-01

This study sought to determine whether playing a "serious" interactive digital game (IDG)--the Re-Mission videogame for cancer patients--activates mesolimbic neural circuits associated with incentive motivation, and if so, whether such effects stem from the participatory aspects of interactive gameplay, or from the complex sensory/perceptual engagement generated by its dynamic event-stream. Healthy undergraduates were randomized to groups in which they were scanned with functional magnetic resonance imaging (FMRI) as they either actively played Re-Mission or as they passively observed a gameplay audio-visual stream generated by a yoked active group subject. Onset of interactive game play robustly activated mesolimbic projection regions including the caudate nucleus and nucleus accumbens, as well as a subregion of the parahippocampal gyrus. During interactive gameplay, subjects showed extended activation of the thalamus, anterior insula, putamen, and motor-related regions, accompanied by decreased activation in parietal and medial prefrontal cortex. Offset of interactive gameplay activated the anterior insula and anterior cingulate. Between-group comparisons of within-subject contrasts confirmed that mesolimbic activation was significantly more pronounced in the active playgroup than in the passive exposure control group. Individual difference analyses also found the magnitude of parahippocampal activation following gameplay onset to correlate with positive attitudes toward chemotherapy assessed both at the end of the scanning session and at an unannounced one-month follow-up. These findings suggest that IDG-induced activation of reward-related mesolimbic neural circuits stems primarily from participatory engagement in gameplay (interactivity), rather than from the effects of vivid and dynamic sensory stimulation.

Interactivity and Reward-Related Neural Activation during a Serious Videogame

PubMed Central

Cole, Steven W.; Yoo, Daniel J.; Knutson, Brian

2012-01-01

This study sought to determine whether playing a “serious” interactive digital game (IDG) – the Re-Mission videogame for cancer patients – activates mesolimbic neural circuits associated with incentive motivation, and if so, whether such effects stem from the participatory aspects of interactive gameplay, or from the complex sensory/perceptual engagement generated by its dynamic event-stream. Healthy undergraduates were randomized to groups in which they were scanned with functional magnetic resonance imaging (FMRI) as they either actively played Re-Mission or as they passively observed a gameplay audio-visual stream generated by a yoked active group subject. Onset of interactive game play robustly activated mesolimbic projection regions including the caudate nucleus and nucleus accumbens, as well as a subregion of the parahippocampal gyrus. During interactive gameplay, subjects showed extended activation of the thalamus, anterior insula, putamen, and motor-related regions, accompanied by decreased activation in parietal and medial prefrontal cortex. Offset of interactive gameplay activated the anterior insula and anterior cingulate. Between-group comparisons of within-subject contrasts confirmed that mesolimbic activation was significantly more pronounced in the active playgroup than in the passive exposure control group. Individual difference analyses also found the magnitude of parahippocampal activation following gameplay onset to correlate with positive attitudes toward chemotherapy assessed both at the end of the scanning session and at an unannounced one-month follow-up. These findings suggest that IDG-induced activation of reward-related mesolimbic neural circuits stems primarily from participatory engagement in gameplay (interactivity), rather than from the effects of vivid and dynamic sensory stimulation. PMID:22442733

Ferromagnetic interaction model of activity level in workplace communication

NASA Astrophysics Data System (ADS)

Akitomi, Tomoaki; Ara, Koji; Watanabe, Jun-ichiro; Yano, Kazuo

2013-03-01

The nature of human-human interaction, specifically, how people synchronize with each other in multiple-participant conversations, is described by a ferromagnetic interaction model of people’s activity levels. We found two microscopic human interaction characteristics from a real-environment face-to-face conversation. The first characteristic is that people quite regularly synchronize their activity level with that of the other participants in a conversation. The second characteristic is that the degree of synchronization increases as the number of participants increases. Based on these microscopic ferromagnetic characteristics, a “conversation activity level” was modeled according to the Ising model. The results of a simulation of activity level based on this model well reproduce macroscopic experimental measurements of activity level. This model will give a new insight into how people interact with each other in a conversation.

Reliability of a Novel Social Activity Questionnaire: Perceived Social Support and Verbal Interaction in the Wisconsin Registry for Alzheimer's Prevention.

PubMed

Zuelsdorff, Megan L; Koscik, Rebecca L; Okonkwo, Ozioma C; Peppard, Paul E; Hermann, Bruce P; Sager, Mark A; Johnson, Sterling C; Engelman, Corinne D

2018-02-01

Social activity is associated with healthy aging and preserved cognition. Such activity includes a confluence of social support and verbal interaction, each influencing cognition through rarely parsed, mechanistically distinct pathways. We created a novel verbal interaction measure for the Wisconsin Registry for Alzheimer's Prevention (WRAP) and assessed reliability of resultant data, a first step toward mechanism-driven examination of social activity as a modifiable predictor of cognitive health. Two WRAP subsamples completed a test-retest study to determine 8-week stability ( n = 107) and 2-year stability ( n = 136) of verbal interaction, and 2-year stability of perceived social support. Reliability was determined using quadratic-weighted kappa, percent agreement, or correlation coefficients. Reliability was fair to almost perfect. The association between social support and interaction quantity decreased with age. Social activity data demonstrate moderate to excellent temporal stability. Moreover, in older individuals, social support and verbal interaction represent two distinct dimensions of social activity.

Chemical-controlled Activation of Antiviral Myxovirus Resistance Protein 1.

PubMed

Verhelst, Judith; Van Hoecke, Lien; Spitaels, Jan; De Vlieger, Dorien; Kolpe, Annasaheb; Saelens, Xavier

2017-02-10

The antiviral myxovirus resistance protein 1 (MX1) is an interferon-induced GTPase that plays an important role in the defense of mammalian cells against influenza A viruses. Mouse MX1 interacts with the influenza ribonucleoprotein complexes (vRNPs) and can prevent the interaction between polymerase basic 2 (PB2) and the nucleoprotein (NP) of influenza A viruses. However, it is unclear whether mouse MX1 disrupts the PB2-NP interaction in the context of pre-existing vRNPs or prevents the assembly of new vRNP components. Here, we describe a conditionally active mouse MX1 variant that only exerts antiviral activity in the presence of a small molecule drug. Once activated, this MX1 construct phenocopies the antiviral and NP binding activity of wild type MX1. The interaction between PB2 and NP is disrupted within minutes after the addition of the small molecule activator. These findings support a model in which mouse MX1 interacts with the incoming influenza A vRNPs and inhibits their activity by disrupting the PB2-NP interaction. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical-controlled Activation of Antiviral Myxovirus Resistance Protein 1*

PubMed Central

Verhelst, Judith; Van Hoecke, Lien; Spitaels, Jan; De Vlieger, Dorien; Kolpe, Annasaheb

2017-01-01

The antiviral myxovirus resistance protein 1 (MX1) is an interferon-induced GTPase that plays an important role in the defense of mammalian cells against influenza A viruses. Mouse MX1 interacts with the influenza ribonucleoprotein complexes (vRNPs) and can prevent the interaction between polymerase basic 2 (PB2) and the nucleoprotein (NP) of influenza A viruses. However, it is unclear whether mouse MX1 disrupts the PB2-NP interaction in the context of pre-existing vRNPs or prevents the assembly of new vRNP components. Here, we describe a conditionally active mouse MX1 variant that only exerts antiviral activity in the presence of a small molecule drug. Once activated, this MX1 construct phenocopies the antiviral and NP binding activity of wild type MX1. The interaction between PB2 and NP is disrupted within minutes after the addition of the small molecule activator. These findings support a model in which mouse MX1 interacts with the incoming influenza A vRNPs and inhibits their activity by disrupting the PB2-NP interaction. PMID:28011636

Beyond Lecture and Non-Lecture Classrooms: LA-student interactions in Active Learning Classrooms

NASA Astrophysics Data System (ADS)

Gonzalez, Dayana; Kornreich, Hagit; Rodriguez, Idaykis; Monslave, Camila; Pena-Flores, Norma

Our expanded multi-site study on active learning classrooms supported by Learning Assistants (LAs) aims to understand the connections between three classroom elements: the activity, student learning, and how LAs support the learning process in the classroom. At FIU, LAs are used in a variety of active learning settings, from large auditorium settings to studio classroom with movable tables. Our study uses the COPUS observation protocol as a way to characterize LAs behaviors in these classrooms. With a focus on LA-student interactions, our analysis of how LAs interact with students during a 'learning session' generated new observational codes for specific new categories of LA roles. Preliminary results show that LAs spend more time interacting with students in some classes, regardless of the classroom setting, while in other classrooms, LA-student interactions are mostly brief. We discuss how LA-student interactions contribute to the dynamics and mechanism of the socially shared learning activity.

Playing Goffman's Information Game: A Classroom Activity Involving Student Interactions

ERIC Educational Resources Information Center

McCoy, Charles Allan

2017-01-01

Goffman's dramaturgical approach is frequently used to introduce undergraduate students to the sociological understanding of human interaction. While a number of scholars have designed engaging student activities that highlight Goffman's approach, most of these activities tend to involve atypical embarrassing interactions or norm-breaking…

Space environmental interactions with spacecraft surfaces

NASA Technical Reports Server (NTRS)

Stevens, J. N.

1979-01-01

Environmental interactions are defined as the response of spacecraft surfaces to the charged-particle environment. These interactions are divided into two broad categories: spacecraft passive, in which the environment acts on the surfaces and spacecraft active, in which the spacecraft or a system on the spacecraft causes the interaction. The principal spacecraft passive interaction of concern is the spacecraft charging phenomenon. The spacecraft active category introduces the concept of interactions with the thermal plasma environment and Earth's magnetic fields, which are important at all altitudes and must be considered the designs of proposed large space structures and space power systems. The status of the spacecraft charging investigations is reviewed along with the spacecraft active interactions.

Analysis of Stability in Verbal Interaction Types of Science-Gifted Students

ERIC Educational Resources Information Center

Kim, Youngshin; Kim, Myunghee; Ha, Minsu; Lim, Soo-Min

2017-01-01

Science inquiry activities carried out in a small group are learner-centered activities operating under the premise of collaborative interaction between members through various types of communication and consultation in the process of resolving issues. The changes in the types of interactions in the three exploratory activities targeting…

Characterizing Interactive Engagement Activities in a Flipped Introductory Physics Class

ERIC Educational Resources Information Center

Wood, Anna K.; Galloway, Ross K.; Donnelly, Robyn; Hardy, Judy

2016-01-01

Interactive engagement activities are increasingly common in undergraduate physics teaching. As research efforts move beyond simply showing that interactive engagement pedagogies work towards developing an understanding of "how" they lead to improved learning outcomes, a detailed analysis of the way in which these activities are used in…

CASPASE-9 CARD:CORE DOMAIN INTERACTIONS REQUIRE A PROPERLY-FORMED ACTIVE SITE

PubMed Central

Huber, Kristen L.; Serrano, Banyuhay P.; Hardy, Jeanne A.

2018-01-01

Caspase-9 is a critical factor in the initiation of apoptosis, and as a result is tightly regulated by a number of mechanisms. Caspase-9 contains a Caspase Activation and Recruitment Domain (CARD), which enables caspase-9 to form a tight interaction with the apoptosome, a heptameric activating platform. The caspase-9 CARD has been thought to be principally involved in recruitment to the apoptosome, but its roles outside this interaction have yet to be uncovered. In this work we show that the CARD is involved in physical interactions with the catalytic core of caspase-9 in the absence of the apoptosome; this interaction requires a properly formed caspase-9 active site. The active sites of caspases are composed of four extremely mobile loops. When the active-site loops are not properly ordered, the CARD and core domains of caspase-9 do not interact and behave independently, like loosely tethered beads. When the active-site loop bundle is properly ordered, the CARD domain interacts with the catalytic core, forming a single folding unit. Together these findings provide mechanistic insight into a new level of caspase-9 regulation, prompting speculation that the CARD may also play a role in the recruitment or recognition of substrate. PMID:29500231

Active subnetwork recovery with a mechanism-dependent scoring function; with application to angiogenesis and organogenesis studies

PubMed Central

2013-01-01

Background The learning active subnetworks problem involves finding subnetworks of a bio-molecular network that are active in a particular condition. Many approaches integrate observation data (e.g., gene expression) with the network topology to find candidate subnetworks. Increasingly, pathway databases contain additional annotation information that can be mined to improve prediction accuracy, e.g., interaction mechanism (e.g., transcription, microRNA, cleavage) annotations. We introduce a mechanism-based approach to active subnetwork recovery which exploits such annotations. We suggest that neighboring interactions in a network tend to be co-activated in a way that depends on the “correlation” of their mechanism annotations. e.g., neighboring phosphorylation and de-phosphorylation interactions may be more likely to be co-activated than neighboring phosphorylation and covalent bonding interactions. Results Our method iteratively learns the mechanism correlations and finds the most likely active subnetwork. We use a probabilistic graphical model with a Markov Random Field component which creates dependencies between the states (active or non-active) of neighboring interactions, that incorporates a mechanism-based component to the function. We apply a heuristic-based EM-based algorithm suitable for the problem. We validated our method’s performance using simulated data in networks downloaded from GeneGO against the same approach without the mechanism-based component, and two other existing methods. We validated our methods performance in correctly recovering (1) the true interaction states, and (2) global network properties of the original network against these other methods. We applied our method to networks generated from time-course gene expression studies in angiogenesis and lung organogenesis and validated the findings from a biological perspective against current literature. Conclusions The advantage of our mechanism-based approach is best seen in networks composed of connected regions with a large number of interactions annotated with a subset of mechanisms, e.g., a regulatory region of transcription interactions, or a cleavage cascade region. When applied to real datasets, our method recovered novel and biologically meaningful putative interactions, e.g., interactions from an integrin signaling pathway using the angiogenesis dataset, and a group of regulatory microRNA interactions in an organogenesis network. PMID:23432934

Mechanism of Mediator recruitment by tandem Gcn4 activation domains and three Gal11 activator-binding domains.

PubMed

Herbig, Eric; Warfield, Linda; Fish, Lisa; Fishburn, James; Knutson, Bruce A; Moorefield, Beth; Pacheco, Derek; Hahn, Steven

2010-05-01

Targets of the tandem Gcn4 acidic activation domains in transcription preinitiation complexes were identified by site-specific cross-linking. The individual Gcn4 activation domains cross-link to three common targets, Gal11/Med15, Taf12, and Tra1, which are subunits of four conserved coactivator complexes, Mediator, SAGA, TFIID, and NuA4. The Gcn4 N-terminal activation domain also cross-links to the Mediator subunit Sin4/Med16. The contribution of the two Gcn4 activation domains to transcription was gene specific and varied from synergistic to less than additive. Gcn4-dependent genes had a requirement for Gal11 ranging from 10-fold dependence to complete Gal11 independence, while the Gcn4-Taf12 interaction did not significantly contribute to the expression of any gene studied. Complementary methods identified three conserved Gal11 activator-binding domains that bind each Gcn4 activation domain with micromolar affinity. These Gal11 activator-binding domains contribute additively to transcription activation and Mediator recruitment at Gcn4- and Gal11-dependent genes. Although we found that the conserved Gal11 KIX domain contributes to Gal11 function, we found no evidence of specific Gcn4-KIX interaction and conclude that the Gal11 KIX domain does not function by specific interaction with Gcn4. Our combined results show gene-specific coactivator requirements, a surprising redundancy in activator-target interactions, and an activator-coactivator interaction mediated by multiple low-affinity protein-protein interactions.

Staff interactive style during multisensory storytelling with persons with profound intellectual and multiple disabilities.

PubMed

Penne, A; Ten Brug, A; Munde, V; van der Putten, A; Vlaskamp, C; Maes, B

2012-02-01

Multisensory storytelling (MSST) is an individualised activity for people with profound intellectual and multiple disabilities (PIMD) in which a story is being told with an emphasis on sensory experiences and social interaction. MSST is a promising approach, but needs more empirical research evidence. In general, there is a lack of research about staff interaction during specific activities with people with PIMD. In the present study, we explored the possibility to describe staff interactive style during MSST making use of a global coding instrument. Twenty dyads of a person with PIMD and a professional caregiver participated in an observation study. The caregivers received training in MSST and told a multisensory story to their client once a week, for a period of 10 weeks. The first, fifth and last session were recorded on video. Staff interactive style was coded using an adapted version of the Maternal Behavior Rating Scale, with a consensus rating procedure. Professional caregivers scored moderately on the Maternal Behavior Rating Scale. Repeated measures analyses showed no change in time. We did not find a relationship between staff interactive style and client or staff characteristics. The Maternal Behavior Rating Scale contributes to our understanding of staff interactive style during activities with people with PIMD. Specifically for MSST, the moderate scores on the interactive style dimensions were unexpected, because the individualised MSST activity created an optimal situation for high-quality interaction with people with PIMD. Because the interactive style did not improve through the repetition of the activity either, these results might point to a need for staff training in achieving high-quality interaction during activities like MSST. © 2011 The Authors. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.

The next step in health behavior research: the need for ecological moderation analyses - an application to diet and physical activity at childcare.

PubMed

Gubbels, Jessica S; Van Kann, Dave Hh; de Vries, Nanne K; Thijs, Carel; Kremers, Stef Pj

2014-04-17

The ecological perspective holds that human behavior depends on the interaction of different environmental factors and personal characteristics, but it lacks validation and operationalization. In the current paper, an ecological view was adopted to examine the interactive impact of several ecological systems on children's dietary intake and physical activity at childcare or similar facilities. The ecological view was operationalized into three types of interaction: 1) interaction between types of childcare environment (physical, social, political, economic); 2) interaction between micro-systems (the childcare and home environment) in meso-systems; and 3) interaction between childcare environment and child characteristics. The predictive value of each of these interactions was tested based on a systematic review of the literature. Several studies support the hypothesis that the influence of the childcare environment on children's physical activity and diet is moderated by child characteristics (age, gender), but interaction between environmental types as well as between micro-systems is hardly examined in the field of behavioral nutrition and physical activity. Qualitative studies and general child development research provide some valuable insights, but we advocate quantitative research adopting an ecological perspective on environmental influences. Empirical studies operationalizing a true ecological view on diet and physical activity are scarce. Theorizing and assessment of interaction is advocated to become common practice rather than an exception in behavioral nutrition and physical activity research, in order to move the field forward.

The next step in health behavior research: the need for ecological moderation analyses - an application to diet and physical activity at childcare

PubMed Central

2014-01-01

Background The ecological perspective holds that human behavior depends on the interaction of different environmental factors and personal characteristics, but it lacks validation and operationalization. In the current paper, an ecological view was adopted to examine the interactive impact of several ecological systems on children’s dietary intake and physical activity at childcare or similar facilities. The ecological view was operationalized into three types of interaction: 1) interaction between types of childcare environment (physical, social, political, economic); 2) interaction between micro-systems (the childcare and home environment) in meso-systems; and 3) interaction between childcare environment and child characteristics. The predictive value of each of these interactions was tested based on a systematic review of the literature. Discussion Several studies support the hypothesis that the influence of the childcare environment on children’s physical activity and diet is moderated by child characteristics (age, gender), but interaction between environmental types as well as between micro-systems is hardly examined in the field of behavioral nutrition and physical activity. Qualitative studies and general child development research provide some valuable insights, but we advocate quantitative research adopting an ecological perspective on environmental influences. Summary Empirical studies operationalizing a true ecological view on diet and physical activity are scarce. Theorizing and assessment of interaction is advocated to become common practice rather than an exception in behavioral nutrition and physical activity research, in order to move the field forward. PMID:24742167

Structural properties of the promiscuous VP16 activation domain.

PubMed

Jonker, Hendrik R A; Wechselberger, Rainer W; Boelens, Rolf; Folkers, Gert E; Kaptein, Rob

2005-01-25

Herpes simplex virion protein 16 (VP16) contains two strong activation regions that can independently and cooperatively activate transcription in vivo. We have identified the regions and residues involved in the interaction with the human transcriptional coactivator positive cofactor 4 (PC4) and the general transcription factor TFIIB. NMR and biochemical experiments revealed that both VP16 activation regions are required for the interaction and undergo a conformational transition from random coil to alpha-helix upon binding to its target PC4. The interaction is strongly electrostatically driven and the binding to PC4 is enhanced by the presence of its amino-terminal domain. We propose models for binding of VP16 to the core domains of PC4 and TFIIB that are based on two independent docking approaches using NMR chemical shift changes observed in titration experiments. The models are consistent with results from site-directed mutagenesis and provide an explanation for the contribution of both acidic and hydrophobic residues for transcriptional activation by VP16. Both intrinsically unstructured activation domains are attracted to their interaction partner by electrostatic interactions, and adopt an alpha-helical conformation around the important hydrophobic residues. The models showed multiple distinct binding surfaces upon interaction with various partners, providing an explanation for the promiscuous properties, cooperativity, and the high activity of this activation domain.

Randomized trial of a question prompt list to increase patient active participation during interactions with black patients and their oncologists.

PubMed

Eggly, Susan; Hamel, Lauren M; Foster, Tanina S; Albrecht, Terrance L; Chapman, Robert; Harper, Felicity W K; Thompson, Hayley; Griggs, Jennifer J; Gonzalez, Richard; Berry-Bobovski, Lisa; Tkatch, Rifky; Simon, Michael; Shields, Anthony; Gadgeel, Shirish; Loutfi, Randa; Ali, Haythem; Wollner, Ira; Penner, Louis A

2017-05-01

Communication during racially-discordant interactions is often of poor quality and may contribute to racial treatment disparities. We evaluated an intervention designed to increase patient active participation and other communication-related outcomes during interactions between Black patients and non-Black oncologists. Participants were 18 non-Black medical oncologists and 114 Black patients at two cancer hospitals in Detroit, Michigan, USA. Before a clinic visit to discuss treatment, patients were randomly assigned to usual care or to one of two question prompt list (QPL) formats: booklet (QPL-Only), or booklet and communication coach (QPL-plus-Coach). Patient-oncologist interactions were video recorded. Patients reported perceptions of the intervention, oncologist communication, role in treatment decisions, and trust in the oncologist. Observers assessed interaction length, patient active participation, and oncologist communication. The intervention was viewed positively and did not increase interaction length. The QPL-only format increased patient active participation; the QPL-plus-Coach format decreased patient perceptions of oncologist communication. No other significant effects were found. This QPL booklet is acceptable and increases patient active participation in racially-discordant oncology interactions. Future research should investigate whether adding physician-focused interventions might improve other outcomes. This QPL booklet is acceptable and can improve patient active participation in racially-discordant oncology interactions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Interactive flare sites within an active region complex

NASA Technical Reports Server (NTRS)

Poletto, G.; Gary, G. A.; Machado, M. E.

1993-01-01

We examine here a set of images of an active region complex, acquired on June 24-25, 1980, by the Hard X-ray Imaging Spectrometer on SMM, with the purpose of establishing whether there was any interplay between the frequent activity observed at different sites in the activity center and, in such a case, how the interaction was established. By analyzing both quiet and active orbits we show that, as a rule, activity originating in one region triggers the other region's activity. However, we find little unambiguous evidence for the presence of large-scale interconnecting loops. A comparison of X-ray images with magnetic field observations suggested that we interpret the active region behavior in terms of the interaction between different loop systems, in a scenario quite analogous to the interacting bipole representation of individual flares. We conclude that active region interplay provides an easily observable case to study the time-dependent topology and the mechanisms for the spreading of activity in transient events over all energy scales.

Adenovirus E1A functions as a cofactor for retinoic acid receptor beta (RAR beta) through direct interaction with RAR beta.

PubMed

Folkers, G E; van der Saag, P T

1995-11-01

Transcription regulation by DNA-bound activators is thought to be mediated by a direct interaction between these proteins and TATA-binding protein (TBP), TFIIB, or TBP-associated factors, although occasionally cofactors or adapters are required. For ligand-induced activation by the retinoic acid receptor-retinoid X receptor (RAR-RXR) heterodimer, the RAR beta 2 promoter is dependent on the presence of E1A or E1A-like activity, since this promoter is activated by retinoic acid only in cells expressing such proteins. The mechanism underlying this E1A requirement is largely unknown. We now show that direct interaction between RAR and E1A is a requirement for retinoic acid-induced RAR beta 2 activation. The activity of the hormone-dependent activation function 2 (AF-2) of RAR beta is upregulated by E1A, and an interaction between this region and E1A was observed, but not with AF-1 or AF-2 of RXR alpha. This interaction is dependent on conserved region III (CRIII), the 13S mRNA-specific region of E1A. Deletion analysis within this region indicated that the complete CRIII is needed for activation. The putative zinc finger region is crucial, probably as a consequence of interaction with TBP. Furthermore, the region surrounding amino acid 178, partially overlapping with the TBP binding region, is involved in both binding to and activation by AF-2. We propose that E1A functions as a cofactor by interacting with both TBP and RAR, thereby stabilizing the preinitiation complex.

Interactions between psychosocial and built environment factors in explaining older adults' physical activity.

PubMed

Carlson, Jordan A; Sallis, James F; Conway, Terry L; Saelens, Brian E; Frank, Lawrence D; Kerr, Jacqueline; Cain, Kelli L; King, Abby C

2012-01-01

To evaluate ecological model predictions of cross-level interactions among psychosocial and environmental correlates of physical activity in 719 community-dwelling older adults in the Baltimore, Maryland and Seattle, Washington areas during 2005-2008. Walkability, access to parks and recreation facilities and moderate-to-vigorous physical activity (MVPA) minutes per week (min/week) were measured objectively. Neighborhood aesthetics, walking facilities, social support, self-efficacy, barriers and transportation and leisure walking min/week were self-reported. Walkability interacted with social support in explaining total MVPA (B=13.71) and with social support (B=7.90), self-efficacy (B=7.66) and barriers (B=-8.26) in explaining walking for transportation. Aesthetics interacted with barriers in explaining total MVPA (B=-12.20) and walking facilities interacted with self-efficacy in explaining walking for leisure (B=-10.88; Ps<.05). Summarizing across the interactions, living in a supportive environment (vs. unsupportive) was related to 30-59 more min/week of physical activity for participants with more positive psychosocial attributes, but only 0-28 more min/week for participants with less positive psychosocial attributes. Results supported synergistic interactions between built environment and psychosocial factors in explaining physical activity among older adults. Findings suggest multilevel interventions may be most effective in increasing physical activity. Copyright © 2011 Elsevier Inc. All rights reserved.

Hospital's activity-based financing system and manager-physician [corrected] interaction.

PubMed

Crainich, David; Leleu, Hervé; Mauleon, Ana

2011-10-01

This paper examines the consequences of the introduction of an activity-based reimbursement system on the behavior of physicians and hospital's managers. We consider a private for-profit sector where both hospitals and physicians are initially paid on a fee-for-service basis. We show that the benefit of the introduction of an activity-based system depends on the type of interaction between managers and physicians (simultaneous or sequential decision-making games). It is shown that, under the activity-based system, a sequential interaction with physician leader could be beneficial for both agents in the private sector. We further model an endogenous timing game à la Hamilton and Slutsky (Games Econ Behav 2: 29-46, 1990) in which the type of interaction is determined endogenously. We show that, under the activity-based system, the sequential interaction with physician leader is the unique subgame perfect equilibrium.

Direct observation of children's preferences and activity levels during interactive and online electronic games.

PubMed

Sit, Cindy H P; Lam, Jessica W K; McKenzie, Thomas L

2010-07-01

Interactive electronic games have recently been popularized and are believed to help promote children's physical activity (PA). The purpose of the study was to examine preferences and PA levels during interactive and online electronic games among overweight and nonoverweight boys and girls. Using a modification of the SOFIT, we systematically observed 70 Hong Kong Chinese children (35 boys, 35 girls; 50 nonoverweight, 20 overweight), age 9 to 12 years, during 2 60-minute recreation sessions and recorded their game mode choices and PA levels. During Session One children could play either an interactive or an online electronic bowling game and during Session Two they could play an interactive or an online electronic running game. Children chose to play the games during 94% of session time and split this time between interactive (52%) and online (48%) versions. They engaged in significantly more moderate-to-vigorous physical activity (MVPA) during interactive games than their online electronic versions (70% vs. 2% of game time). Boys and nonoverweight children expended relatively more energy during the interactive games than girls and overweight children, respectively. New-generation interactive games can facilitate physical activity in children, and given the opportunity children may select them over sedentary versions.

Genetic Susceptibility, Change in Physical Activity, and Long-term Weight Gain.

PubMed

Wang, Tiange; Huang, Tao; Heianza, Yoriko; Sun, Dianjianyi; Zheng, Yan; Ma, Wenjie; Jensen, Majken K; Kang, Jae H; Wiggs, Janey L; Pasquale, Louis R; Rimm, Eric B; Manson, JoAnn E; Hu, Frank B; Willett, Walter C; Qi, Lu

2017-10-01

Whether change in physical activity over time modifies the genetic susceptibility to long-term weight gain is unknown. We calculated a BMI-genetic risk score (GRS) based on 77 BMI-associated single nucleotide polymorphisms (SNPs) and a body fat percentage (BF%)-GRS based on 12 BF%-associated SNPs in 9,390 women from the Nurses' Health Study (NHS) and 5,291 men from the Health Professionals Follow-Up Study (HPFS). We analyzed the interactions between each GRS and change in physical activity on BMI/body weight change within five 4-year intervals from 1986 to 2006 using multivariable generalized linear models with repeated-measures analyses. Both the BMI-GRS and the BF%-GRS were associated with long-term increases in BMI/weight, and change in physical activity consistently interacted with the BF%-GRS on BMI change in the NHS ( P for interaction = 0.025) and HPFS ( P for interaction = 0.001). In the combined cohorts, 4-year BMI change per 10-risk allele increment was -0.02 kg/m 2 among participants with greatest increase in physical activity and 0.24 kg/m 2 among those with greatest decrease in physical activity ( P for interaction < 0.001), corresponding to 0.01 kg versus 0.63 kg weight changes every 4 years ( P for interaction = 0.001). Similar but marginal interactions were observed for the BMI-GRS ( P for interaction = 0.045). Our data indicate that the genetic susceptibility to weight gain may be diminished by increasing physical activity. © 2017 by the American Diabetes Association.

Nonlinear Directed Interactions Between HRV and EEG Activity in Children With TLE.

PubMed

Schiecke, Karin; Pester, Britta; Piper, Diana; Benninger, Franz; Feucht, Martha; Leistritz, Lutz; Witte, Herbert

2016-12-01

Epileptic seizure activity influences the autonomic nervous system (ANS) in different ways. Heart rate variability (HRV) is used as indicator for alterations of the ANS. It was shown that linear, nondirected interactions between HRV and EEG activity before, during, and after epileptic seizure occur. Accordingly, investigations of directed nonlinear interactions are logical steps to provide, e.g., deeper insight into the development of seizure onsets. Convergent cross mapping (CCM) investigates nonlinear, directed interactions between time series by using nonlinear state space reconstruction. CCM is applied to simulated and clinically relevant data, i.e., interactions between HRV and specific EEG components of children with temporal lobe epilepsy (TLE). In addition, time-variant multivariate Autoregressive model (AR)-based estimation of partial directed coherence (PDC) was performed for the same data. Influence of estimation parameters and time-varying behavior of CCM estimation could be demonstrated by means of simulated data. AR-based estimation of PDC failed for the investigation of our clinical data. Time-varying interval-based application of CCM on these data revealed directed interactions between HRV and delta-related EEG activity. Interactions between HRV and alpha-related EEG activity were visible but less pronounced. EEG components mainly drive HRV. The interaction pattern and directionality clearly changed with onset of seizure. Statistical relevant interactions were quantified by bootstrapping and surrogate data approach. In contrast to AR-based estimation of PDC CCM was able to reveal time-courses and frequency-selective views of nonlinear interactions for the further understanding of complex interactions between the epileptic network and the ANS in children with TLE.

Web-Based Assessment Tool for Communication and Active Listening Skill Development

ERIC Educational Resources Information Center

Cheon, Jongpil; Grant, Michael

2009-01-01

The website "Active Listening" was developed within a larger project--"Interactive Web-based training in the subtleties of communication and active listening skill development." The Active Listening site aims to provide beginning counseling psychology students with didactic and experimental learning activities and interactive tests so that…

The solar magnetic activity band interaction and instabilities that shape quasi-periodic variability

NASA Astrophysics Data System (ADS)

McIntosh, Scott W.; Leamon, Robert J.; Krista, Larisza D.; Title, Alan M.; Hudson, Hugh S.; Riley, Pete; Harder, Jerald W.; Kopp, Greg; Snow, Martin; Woods, Thomas N.; Kasper, Justin C.; Stevens, Michael L.; Ulrich, Roger K.

2015-04-01

Solar magnetism displays a host of variational timescales of which the enigmatic 11-year sunspot cycle is most prominent. Recent work has demonstrated that the sunspot cycle can be explained in terms of the intra- and extra-hemispheric interaction between the overlapping activity bands of the 22-year magnetic polarity cycle. Those activity bands appear to be driven by the rotation of the Sun's deep interior. Here we deduce that activity band interaction can qualitatively explain the `Gnevyshev Gap'--a well-established feature of flare and sunspot occurrence. Strong quasi-annual variability in the number of flares, coronal mass ejections, the radiative and particulate environment of the heliosphere is also observed. We infer that this secondary variability is driven by surges of magnetism from the activity bands. Understanding the formation, interaction and instability of these activity bands will considerably improve forecast capability in space weather and solar activity over a range of timescales.

Understanding Active and Passive Users: The Effects of an Active User Using Normal, Hard and Unreliable Technologies on User Assessment of Trust in Technology and Co-User

PubMed Central

Montague, Enid; JieXu

2011-01-01

The aim of this study was to understand how passive users perceive the trustworthiness of active users and technologies under varying technological conditions. An experimental study was designed to vary the functioning of technologies that active users interacted with, while passive users observed these interactions. Active and passive user ratings of technology and partner were collected. Exploratory data analysis suggests that passive users developed perceptions of technologies based on the functioning of the technology and how the active user interacted with the technologies. Findings from this research have implications for the design of technologies in environments where active and passive users interact with technologies in different ways. Future work in this area should explore interventions that lead to enhanced affective engagement and trust calibration. PMID:22192788

Using Music To Develop Peer Interaction: An Examination of the Response of Two Subjects with a Learning Disability.

ERIC Educational Resources Information Center

Hooper, Jeff

2002-01-01

A study examined the response of two adults who attended a music activity therapy program in which music activities encouraged peer interaction. Music activity therapy was compared with a control condition (i.e., ball and target games). Both conditions increased the level of positive interaction, however, music therapy was least effective.…

Genetical Analysis of Chromosomal Interaction Effects on the Activities of the Glucose 6-Phosphate and 6-Phosphogluconate Dehydrogenases in DROSOPHILA MELANOGASTER

PubMed Central

Miyashita, Naohiko; Laurie-Ahlberg, C. C.

1984-01-01

By combining ten second and ten third chromosomes, we investigated chromosomal interaction with respect to the action of the modifier factors on G6PD and 6PGD activities in Drosophila melanogaster. Analysis of variance revealed that highly significant chromosomal interaction exists for both enzyme activities. From the estimated variance components, it was concluded that the variation in enzyme activity attributed to the interaction is as great as the variation attributed to the second chromosome but less than attributed to the third chromosome. The interaction is not explained by the variation of body size (live weight). The interaction is generated from both the lack of correlation of second chromosomes for third chromosome backgrounds and the heterogeneous variance of second chromosomes for different third chromosome backgrounds. Large and constant correlation between G6PD and 6PGD activities were found for third chromosomes with any second chromosome background, whereas the correlations for second chromosomes were much smaller and varied considerably with the third chromosome background. This result suggests that the activity modifiers on the second chromosome are under the influence of third chromosome factors. PMID:6425115

Confirmation of high-throughput screening data and novel mechanistic insights into VDR-xenobiotic interactions by orthogonal assays.

PubMed

Mahapatra, Debabrata; Franzosa, Jill A; Roell, Kyle; Kuenemann, Melaine Agnes; Houck, Keith A; Reif, David M; Fourches, Denis; Kullman, Seth W

2018-06-11

High throughput screening (HTS) programs have demonstrated that the Vitamin D receptor (VDR) is activated and/or antagonized by a wide range of structurally diverse chemicals. In this study, we examined the Tox21 qHTS data set generated against VDR for reproducibility and concordance and elucidated functional insights into VDR-xenobiotic interactions. Twenty-one potential VDR agonists and 19 VDR antagonists were identified from a subset of >400 compounds with putative VDR activity and examined for VDR functionality utilizing select orthogonal assays. Transient transactivation assay (TT) using a human VDR plasmid and Cyp24 luciferase reporter construct revealed 20/21 active VDR agonists and 18/19 active VDR antagonists. Mammalian-2-hybrid assay (M2H) was then used to evaluate VDR interactions with co-activators and co-regulators. With the exception of a select few compounds, VDR agonists exhibited significant recruitment of co-regulators and co-activators whereas antagonists exhibited considerable attenuation of recruitment by VDR. A unique set of compounds exhibiting synergistic activity in antagonist mode and no activity in agonist mode was identified. Cheminformatics modeling of VDR-ligand interactions were conducted and revealed selective ligand VDR interaction. Overall, data emphasizes the molecular complexity of ligand-mediated interactions with VDR and suggest that VDR transactivation may be a target site of action for diverse xenobiotics.

Quantitative functional characterization of conserved molecular interactions in the active site of mannitol 2-dehydrogenase

PubMed Central

Lucas, James E; Siegel, Justin B

2015-01-01

Enzyme active site residues are often highly conserved, indicating a significant role in function. In this study we quantitate the functional contribution for all conserved molecular interactions occurring within a Michaelis complex for mannitol 2-dehydrogenase derived from Pseudomonas fluorescens (pfMDH). Through systematic mutagenesis of active site residues, we reveal that the molecular interactions in pfMDH mediated by highly conserved residues not directly involved in reaction chemistry can be as important to catalysis as those directly involved in the reaction chemistry. This quantitative analysis of the molecular interactions within the pfMDH active site provides direct insight into the functional role of each molecular interaction, several of which were unexpected based on canonical sequence conservation and structural analyses. PMID:25752240

Noncovalent Ubiquitin Interactions Regulate the Catalytic Activity of Ubiquitin Writers.

PubMed

Wright, Joshua D; Mace, Peter D; Day, Catherine L

2016-11-01

Covalent modification of substrate proteins with ubiquitin is the end result of an intricate network of protein-protein interactions. The inherent ability of the E1, E2, and E3 proteins of the ubiquitylation cascade (the ubiquitin writers) to interact with ubiquitin facilitates this process. Importantly, contact between ubiquitin and the E2/E3 writers is required for catalysis and the assembly of chains of a given linkage. However, ubiquitin is also an activator of ubiquitin-writing enzymes, with many recent studies highlighting the ability of ubiquitin to regulate activity and substrate modification. Here, we review the interactions between ubiquitin-writing enzymes and regulatory ubiquitin molecules that promote activity, and highlight the potential of these interactions to promote processive ubiquitin transfer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of a Novel LXXLL Motif in α-Actinin 4-spliced Isoform That Is Critical for Its Interaction with Estrogen Receptor α and Co-activators*

PubMed Central

Khurana, Simran; Chakraborty, Sharmistha; Zhao, Xuan; Liu, Yu; Guan, Dongyin; Lam, Minh; Huang, Wei; Yang, Sichun; Kao, Hung-Ying

2012-01-01

α-Actinins (ACTNs) are a family of proteins cross-linking actin filaments that maintain cytoskeletal organization and cell motility. Recently, it has also become clear that ACTN4 can function in the nucleus. In this report, we found that ACTN4 (full length) and its spliced isoform ACTN4 (Iso) possess an unusual LXXLL nuclear receptor interacting motif. Both ACTN4 (full length) and ACTN4 (Iso) potentiate basal transcription activity and directly interact with estrogen receptor α, although ACTN4 (Iso) binds ERα more strongly. We have also found that both ACTN4 (full length) and ACTN4 (Iso) interact with the ligand-independent and the ligand-dependent activation domains of estrogen receptor α. Although ACTN4 (Iso) interacts efficiently with transcriptional co-activators such as p300/CBP-associated factor (PCAF) and steroid receptor co-activator 1 (SRC-1), the full length ACTN4 protein either does not or does so weakly. More importantly, the flanking sequences of the LXXLL motif are important not only for interacting with nuclear receptors but also for the association with co-activators. Taken together, we have identified a novel extended LXXLL motif that is critical for interactions with both receptors and co-activators. This motif functions more efficiently in a spliced isoform of ACTN4 than it does in the full-length protein. PMID:22908231

Columnar interactions determine horizontal propagation of recurrent network activity in neocortex

PubMed Central

Wester, Jason C.; Contreras, Diego

2012-01-01

The cortex is organized in vertical and horizontal circuits that determine the spatiotemporal properties of distributed cortical activity. Despite detailed knowledge of synaptic interactions among individual cells in the neocortex, little is known about the rules governing interactions among local populations. Here we used self-sustained recurrent activity generated in cortex, also known as up-states, in rat thalamocortical slices in vitro to understand interactions among laminar and horizontal circuits. By means of intracellular recordings and fast optical imaging with voltage sensitive dyes, we show that single thalamic inputs activate the cortical column in a preferential L4→L2/3→L5 sequence, followed by horizontal propagation with a leading front in supra and infragranular layers. To understand the laminar and columnar interactions, we used focal injections of TTX to block activity in small local populations, while preserving functional connectivity in the rest of the network. We show that L2/3 alone, without underlying L5, does not generate self-sustained activity and is inefficient propagating activity horizontally. In contrast, L5 sustains activity in the absence of L2/3 and is necessary and sufficient to propagate activity horizontally. However, loss of L2/3 delays horizontal propagation via L5. Finally, L5 amplifies activity in L2/3. Our results show for the first time that columnar interactions between supra and infragranular layers are required for the normal propagation of activity in the neocortex. Our data suggest that supra and infragranular circuits with their specific and complex set of inputs and outputs, work in tandem to determine the patterns of cortical activation observed in vivo. PMID:22514308

MOLECULAR INTERACTION POTENTIALS FOR THE DEVELOPMENT OF STRUCTURE-ACTIVITY RELATIONSHIPS

EPA Science Inventory

Abstract
One reasonable approach to the analysis of the relationships between molecular structure and toxic activity is through the investigation of the forces and intermolecular interactions responsible for chemical toxicity. The interaction between the xenobiotic and the bio...

[Molecular Dynamics of N- and C-terminal Interactions during Autoinhibition and Activation of Formin mDial].

PubMed

Orshanskiy, I A; Popinako, A V; Volokh, O I; Shaitan, K V; Sokolova, O S

2015-01-01

With the method of molecular dynamics, pairs of amino acid residues have been identified on the surface of the interacting formin mDial domains: DID-DAD, which are responsible for the autoinhibition of formin, and the GTPase Rho-DID domain, and control activation. It was found that the most stable interactions are ionic interactions between Glu178 residue and Arg248 residue, as well as hydrophobic interactions between Thr175 and Phe247. The strongest interactions proved to be between the DID domain with Rho-GTPase. These interactions are mediated by specific triple ionic interactions between positively charged amino acid in Rho, and a triplet of amino acids in DID, consisting of two negatively charged amino acids, separated by one uncharged. Binding sites for Rho-GTPase and DAD partially overlap, but various amino acids on the DID participate in interactions with different domains. We discuss the possible conformational changes in formin domains during activation and inactivation.

Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation.

PubMed

Filippakopoulos, Panagis; Kofler, Michael; Hantschel, Oliver; Gish, Gerald D; Grebien, Florian; Salah, Eidarus; Neudecker, Philipp; Kay, Lewis E; Turk, Benjamin E; Superti-Furga, Giulio; Pawson, Tony; Knapp, Stefan

2008-09-05

The SH2 domain of cytoplasmic tyrosine kinases can enhance catalytic activity and substrate recognition, but the molecular mechanisms by which this is achieved are poorly understood. We have solved the structure of the prototypic SH2-kinase unit of the human Fes tyrosine kinase, which appears specialized for positive signaling. In its active conformation, the SH2 domain tightly interacts with the kinase N-terminal lobe and positions the kinase alphaC helix in an active configuration through essential packing and electrostatic interactions. This interaction is stabilized by ligand binding to the SH2 domain. Our data indicate that Fes kinase activation is closely coupled to substrate recognition through cooperative SH2-kinase-substrate interactions. Similarly, we find that the SH2 domain of the active Abl kinase stimulates catalytic activity and substrate phosphorylation through a distinct SH2-kinase interface. Thus, the SH2 and catalytic domains of active Fes and Abl pro-oncogenic kinases form integrated structures essential for effective tyrosine kinase signaling.

Therapeutic Strategies Against Cyclin E1 Amplified Ovarian Cancers

DTIC Science & Technology

2017-10-01

interaction will lead to enhancement of RB/E2F interaction and suppression of E2F- dependent oncogenic activity resulting in activity against CCNE1-amplified...relevant for CCNE1-amplified ovarian tumors which are dependent on hyperactive HR and are sensitive to suppression of BRCA1. 15. SUBJECT TERMS Ovarian...enhancement of RB/E2F interaction and suppression of E2F- dependent oncogenic activity resulting in activity against CCNE1-amplified cells. In the third

Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats

PubMed Central

Salti, Ahmad; Kummer, Kai K.; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

2016-01-01

We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. PMID:26300300

Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats.

PubMed

Salti, Ahmad; Kummer, Kai K; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

2015-12-01

We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

"Prey Play": Learning about Predators and Prey through an Interactive, Role-Play Game

ERIC Educational Resources Information Center

Deaton, Cynthia C. M.; Dodd, Kristen; Drennon, Katherine; Nagle, Jack

2012-01-01

"Prey Play" is an interactive role-play activity that provides fifth-grade students with opportunities to examine predator-prey interactions. This four-part, role-play activity allows students to take on the role of a predator and prey as they reflect on the behaviors animals exhibit as they collect food and interact with one another, as well as…

Interaction with Single-stranded DNA-binding Protein Stimulates Escherichia coli Ribonuclease HI Enzymatic Activity*

PubMed Central

Petzold, Christine; Marceau, Aimee H.; Miller, Katherine H.; Marqusee, Susan; Keck, James L.

2015-01-01

Single-stranded (ss) DNA-binding proteins (SSBs) bind and protect ssDNA intermediates formed during replication, recombination, and repair reactions. SSBs also directly interact with many different genome maintenance proteins to stimulate their enzymatic activities and/or mediate their proper cellular localization. We have identified an interaction formed between Escherichia coli SSB and ribonuclease HI (RNase HI), an enzyme that hydrolyzes RNA in RNA/DNA hybrids. The RNase HI·SSB complex forms by RNase HI binding the intrinsically disordered C terminus of SSB (SSB-Ct), a mode of interaction that is shared among all SSB interaction partners examined to date. Residues that comprise the SSB-Ct binding site are conserved among bacterial RNase HI enzymes, suggesting that RNase HI·SSB complexes are present in many bacterial species and that retaining the interaction is important for its cellular function. A steady-state kinetic analysis shows that interaction with SSB stimulates RNase HI activity by lowering the reaction Km. SSB or RNase HI protein variants that disrupt complex formation nullify this effect. Collectively our findings identify a direct RNase HI/SSB interaction that could play a role in targeting RNase HI activity to RNA/DNA hybrid substrates within the genome. PMID:25903123

Choice of Interactive Dance and Bicycle Games in Overweight and Nonoverweight Youth

PubMed Central

Epstein, Leonard H.; Beecher, Meghan D.; Graf, Jennifer L.; Roemmich, James N.

2008-01-01

Background: Interactive video games are a popular alternative to physical activity in youth. One advancement in computer games are interactive games that use physical activity as a game playing controller, combining exercise and entertainment, or exertainment. Purpose: This study tested the reinforcing value and activity levels of interactive dance and bicycle race games in 18 overweight and 17 nonoverweight 8- to 12-year-old youth. Methods: Reinforcing value was studied using a behavioral choice paradigm that provided children the opportunity to respond on progressive ratio schedules of reinforcement for a choice of either playing the video dance or bicycle game using a handheld video game controller or one of three options: dancing or bicycling alone, dancing or bicycling while watching a video, or playing the interactive dance or bicycle game. Reinforcing value was defined in relationship to the amount of responding children engaged in for either choice. Results: Results showed the interactive dance game was more reinforcing than dancing alone or dancing while watching the video (p = .003), but there was no difference across bicycling conditions. Nonoverweight youth were more active when given the opportunity to play the interactive dance game than overweight children (p = .05). Conclusions: These results suggest that children may be motivated to be active when given the opportunity to play an interactive dance game. PMID:17447864

The Individual, Joint, and Additive Interaction Associations of Aerobic-Based Physical Activity and Muscle Strengthening Activities on Metabolic Syndrome.

PubMed

Dankel, Scott J; Loenneke, Jeremy P; Loprinzi, Paul D

2016-12-01

Previous research has demonstrated that physical activity and muscle strengthening activities are independently and inversely associated with metabolic syndrome. Despite a number of studies examining the individual associations, only a few studies have examined the joint associations, and to our knowledge, no previous studies have examined the potential additive interaction of performing muscle strengthening activities and aerobic-based physical activity and their association with metabolic syndrome. Using data from the 2003 to 2006 National Health and Nutrition Examination Survey (NHANES), we computed three separate multivariable logistic regression models to examine the individual, combined, and additive interaction of meeting guidelines for accelerometer-assessed physical activity and self-reported muscle strengthening activities, and their association with metabolic syndrome. We found that individuals meeting physical activity and muscle strengthening activity guidelines, respectively, were at 61 and 25 % lower odds of having metabolic syndrome. Furthermore, individuals meeting both guidelines had the lowest odds of having metabolic syndrome (70 %), in part due to the additive interaction of performing both modes of exercise. In this national sample, accelerometer-assessed physical activity and muscle strengthening activities were synergistically associated with metabolic syndrome.

Interactions of psychosocial factors with built environments in explaining adolescents' active transportation.

PubMed

Wang, Xiaobo; Conway, Terry L; Cain, Kelli L; Frank, Lawrence D; Saelens, Brian E; Geremia, Carrie; Kerr, Jacqueline; Glanz, Karen; Carlson, Jordan A; Sallis, James F

2017-07-01

The present study examined independent and interacting associations of psychosocial and neighborhood built environment variables with adolescents' reported active transportation. Moderating effects of adolescent sex were explored. Mixed-effects regression models were conducted on data from the Teen Environment and Neighborhood observational study (N=928) in the Seattle, WA and Baltimore regions 2009-2011. Frequency index of active transportation to neighborhood destinations (dependent variable) and 7 psychosocial measures were reported by adolescents. Built environment measures included home walkability and count of nearby parks and recreation facilities using GIS procedures and streetscape quality from environmental audits. Results indicated all 3 environmental variables and 3 psychosocial variables (self-efficacy, social support from peers, and enjoyment of physical activity) had significant positive main effects with active transportation (Ps<0.05). Three of 21 two-way interactions were significant in explaining active transportation (Ps<0.1): self-efficacy×GIS-based walkability index, barriers to activity in neighborhood×MAPS streetscape scores, and self-efficacy×GIS-based counts of parks and recreation facilities. In each two-way interaction the highest active transportation was found among adolescents with the combination of activity-supportive built environment and positive psychosocial characteristics. Three-way interactions with sex indicated similar associations for girls and boys, with one exception. Results provided modest support for the ecological model principle of interactions across levels, highlight the importance of both built environment and psychosocial factors in shaping adolescents' active transportation, demonstrated the possibility of sex-specific findings, and suggested strategies for improving adolescents' active transportation may be most effective when targeting multiple levels of influence. Copyright © 2017 Elsevier Inc. All rights reserved.

[Effects of functional interactions between nonhomologous insulators Wari and Su(Hw)].

PubMed

Erokhin, M M; Georgiev, P G; Chetverina, D A

2010-01-01

Insulators are regulatory DNA elements restricting gene activation by enhancers. Interactions between insulators can lead to both insulation and activation of promoters by enhancers. In this work, we analyzed the effects of interaction of two Drosophila insulators, Wari and Su(Hw). The functional interaction between these insulators was found to enhance the activity of the Su(Hw) insulator only, but not of the Wari insulator. This suggests that the formation of a chromatin loop between interacting insulators is not a key factor for enhancement of insulation, which is in disagreement with the main idea of structural models. In addition, the effect of interaction between Wari and Su(Hw) depends on a distance between them and on the position in the system relative to other regulatory elements.

Edible bioactive fatty acid-cellulosic derivative composites used in food-packaging applications.

PubMed

Sebti, Issam; Ham-Pichavant, Frédérique; Coma, Véronique

2002-07-17

To develop biodegradable packaging that both acts as a moisture barrier and as antimicrobial activity, nisin and stearic acid were incorporated into a hydroxy propyl methyl cellulose (HPMC) based film. Fifteen percent (w/w HPMC) of stearic acid improved film moisture barrier. However, film mechanical resistance and film antimicrobial activity on Listeria monocytogenes and Staphylococcus aureus pathogenic strains were both reduced. This lower film inhibitory activity was due to interactions between nisin and stearic acid. The molecular interaction was modeled, and an equation was developed to calculate the nisin concentration needed to be incorporated into the film matrix to obtain a desired residual antimicrobial activity. Because the molecular interactions were pH dependent, the impact of the pH of the film-forming solution on film inhibitory activity was investigated. Adjusting the pH to 3 totally avoided stearic acid and nisin interaction, inducing a high film inhibitory activity.

The hydroxyflavone, fisetin, suppresses mast cell activation induced by interaction with activated T cell membranes

PubMed Central

Nagai, K; Takahashi, Y; Mikami, I; Fukusima, T; Oike, H; Kobori, M

2009-01-01

Background and purpose: Cell-to-cell interactions between mast cells and activated T cells are increasingly recognized as a possible mechanism in the aetiology of allergic or non-allergic inflammatory disorders. To determine the anti-allergic effect of fisetin, we examined the ability of fisetin to suppress activation of the human mast cell line, HMC-1, induced by activated Jurkat T cell membranes. Experimental approach: HMC-1 cells were incubated with or without fisetin for 15 min and then co-cultured with Jurkat T cell membranes activated by phorbol-12-myristate 13-acetate for 16 h. We determined gene expression in activated HMC-1 cells by DNA microarray and quantitative reverse transcription (RT)-PCR analysis. We also examined activation of the transcription factor NF-κB and MAP kinases (MAPKs) in activated HMC-1 cells. Key results: Fisetin suppresses cell spreading and gene expression in HMC-1 cells stimulated by activated T cell membranes. Additionally, we show that these stimulated HMC-1 cells expressed granzyme B. The stimulatory interaction also induced activation of NF-κB and MAPKs; these activations were suppressed by fisetin. Fisetin also reduced the amount of cell surface antigen CD40 and intercellular adhesion molecule-1 (ICAM-1) on activated HMC-1 cells. Conclusions and implications: Fisetin suppressed activation of HMC-1 cells by activated T cell membranes by interfering with cell-to-cell interaction and inhibiting the activity of NF-κB and MAPKs and thereby suppressing gene expression. Fisetin may protect against the progression of inflammatory diseases by limiting interactions between mast cells and activated T cells. PMID:19702784

Physical interaction of the activator protein-1 factors c-Fos and c-Jun with Cbfa1 for collagenase-3 promoter activation

NASA Technical Reports Server (NTRS)

D'Alonzo, Richard C.; Selvamurugan, Nagarajan; Karsenty, Gerard; Partridge, Nicola C.

2002-01-01

Previously, we determined that the activator protein-1 (AP-1)-binding site and the runt domain (RD)-binding site and their binding proteins, c-Fos.c-Jun and Cbfa, regulate the collagenase-3 promoter in parathyroid hormone-treated and differentiating osteoblasts. Here we show that Cbfa1 and c-Fos.c-Jun appear to cooperatively bind the RD- and AP-1-binding sites and form ternary structures in vitro. Both in vitro and in vivo co-immunoprecipitation and yeast two-hybrid studies further demonstrate interaction between Cbfa1 with c-Fos and c-Jun in the absence of phosphorylation and without binding to DNA. Additionally, only the runt domain of Cbfa1 was required for interaction with c-Jun and c-Fos. In mammalian cells, overexpression of Cbfa1 enhanced c-Jun activation of AP-1-binding site promoter activity, demonstrating functional interaction. Finally, insertion of base pairs that disrupted the helical phasing between the AP-1- and RD-binding sites also inhibited collagenase-3 promoter activation. Thus, we provide direct evidence that Cbfa1 and c-Fos.c-Jun physically interact and cooperatively bind the AP-1- and RD-binding sites in the collagenase-3 promoter. Moreover, the AP-1- and RD-binding sites appear to be organized in a specific required helical arrangement that facilitates transcription factor interaction and enables promoter activation.

Active Learning in PhysicsTechnology and Research-based Techniques Emphasizing Interactive Lecture Demonstrations

NASA Astrophysics Data System (ADS)

Thornton, Ronald

2010-10-01

Physics education research has shown that learning environments that engage students and allow them to take an active part in their learning can lead to large conceptual gains compared to traditional instruction. Examples of successful curricula and methods include Peer Instruction, Just in Time Teaching, RealTime Physics, Workshop Physics, Scale-Up, and Interactive Lecture Demonstrations (ILDs). An active learning environment is often difficult to achieve in lecture sessions. This presentation will demonstrate the use of sequences of Interactive Lecture Demonstrations (ILDs) that use real experiments often involving real-time data collection and display combined with student interaction to create an active learning environment in large or small lecture classes. Interactive lecture demonstrations will be done in the area of mechanics using real-time motion probes and the Visualizer. A video tape of students involved in interactive lecture demonstrations will be shown. The results of a number of research studies at various institutions (including international) to measure the effectiveness of ILDs and guided inquiry conceptual laboratories will be presented.

Social motor coordination during adult-child interactions.

PubMed

Pfeiffer, Rita; Wallace, Mark; Lense, Miriam

2018-05-04

Social motor coordination (SMC) pertains to the timing of contingent movements during social interactions and is of high relevance for successful social and musical interactions. Semi-automated, objective methods are increasingly being used to analyze SMC, though it is unclear if these methods are feasible in naturalistic settings with young children. The purpose of the current preliminary study was to explore SMC in adult-child dyads during semi-structured social interactions. Thirteen dyads (mean age of children = 36 months) participated in a predictable turn-taking task from a social communication assessment, and a semi-automated frame-difference approach was used to capture movement activity. Relative timing and activity approaches revealed that, while there is some evidence of co-occurring movement, the dyad predominantly exhibited patterns of responsive movement activity (e.g., turn taking or alternating movement) consistent with the activity's structure. Future work may extend these approaches to social musical interactions in order to examine movement coordination and prosocial behavior during joint music-making activities with young children. © 2018 New York Academy of Sciences.

Do infants perceive the social robot Keepon as a communicative partner?

PubMed

Peca, Andreea; Simut, Ramona; Cao, Hoang-Long; Vanderborght, Bram

2016-02-01

This study investigates if infants perceive an unfamiliar agent, such as the robot Keepon, as a social agent after observing an interaction between the robot and a human adult. 23 infants, aged 9-17 month, were exposed, in a first phase, to either a contingent interaction between the active robot and an active human adult, or to an interaction between an active human adult and the non-active robot, followed by a second phase, in which infants were offered the opportunity to initiate a turn-taking interaction with Keepon. The measured variables were: (1) the number of social initiations the infant directed toward the robot, and (2) the number of anticipatory orientations of attention to the agent that follows in the conversation. The results indicate a significant higher level of initiations in the interactive robot condition compared to the non-active robot condition, while the difference between the frequencies of anticipations of turn-taking behaviors was not significant. Copyright © 2015 Elsevier Inc. All rights reserved.

Activity-Based Introductory Physics Reform *

NASA Astrophysics Data System (ADS)

Thornton, Ronald

2004-05-01

Physics education research has shown that learning environments that engage students and allow them to take an active part in their learning can lead to large conceptual gains compared to those of good traditional instruction. Examples of successful curricula and methods include Peer Instruction, Just in Time Teaching, RealTime Physics, Workshop Physics, Scale-Up, and Interactive Lecture Demonstrations (ILDs). RealTime Physics promotes interaction among students in a laboratory setting and makes use of powerful real-time data logging tools to teach concepts as well as quantitative relationships. An active learning environment is often difficult to achieve in large lecture sessions and Workshop Physics and Scale-Up largely eliminate lectures in favor of collaborative student activities. Peer Instruction, Just in Time Teaching, and Interactive Lecture Demonstrations (ILDs) make lectures more interactive in complementary ways. This presentation will introduce these reforms and use Interactive Lecture Demonstrations (ILDs) with the audience to illustrate the types of curricula and tools used in the curricula above. ILDs make use real experiments, real-time data logging tools and student interaction to create an active learning environment in large lecture classes. A short video of students involved in interactive lecture demonstrations will be shown. The results of research studies at various institutions to measure the effectiveness of these methods will be presented.

Nervous kidney. Interaction between renal sympathetic nerves and the renin-angiotensin system in the control of renal function.

PubMed

DiBona, G F

2000-12-01

Increases in renal sympathetic nerve activity regulate the functions of the nephron, the vasculature, and the renin-containing juxtaglomerular granular cells. Because increased activity of the renin-angiotensin system can also influence nephron and vascular function, it is important to understand the interactions between the renal sympathetic nerves and the renin-angiotensin system in the control of renal function. These interactions can be intrarenal, for example, the direct (by specific innervation) and indirect (by angiotensin II) contributions of increased renal sympathetic nerve activity to the regulation of renal function. The effects of increased renal sympathetic nerve activity on renal function are attenuated when the activity of the renin-angiotensin system is suppressed or antagonized with ACE inhibitors or angiotensin II-type AT(1)-receptor antagonists. The effects of intrarenal administration of angiotensin II are attenuated after renal denervation. These interactions can also be extrarenal, for example, in the central nervous system, wherein renal sympathetic nerve activity and its arterial baroreflex control are modulated by changes in activity of the renin-angiotensin system. In addition to the circumventricular organs, whose permeable blood-brain barrier permits interactions with circulating angiotensin II, there are interactions at sites behind the blood-brain barrier that depend on the influence of local angiotensin II. The responses to central administration of angiotensin II-type AT(1)-receptor antagonists into the ventricular system or microinjected into the rostral ventrolateral medulla are modulated by changes in activity of the renin-angiotensin system produced by physiological changes in dietary sodium intake. Similar modulation is observed in pathophysiological models wherein activity of both the renin-angiotensin and sympathetic nervous systems is increased (eg, congestive heart failure). Thus, both renal and extrarenal sites of interaction between the renin-angiotensin system and renal sympathetic nerve activity are involved in influencing the neural control of renal function.

Ratchet Effects in Active Matter Systems

NASA Astrophysics Data System (ADS)

Reichhardt, C. J. Olson; Reichhardt, C.

2017-03-01

Ratchet effects can arise for single or collectively interacting Brownian particles on an asymmetric substrate when a net dc transport is produced by an externally applied ac driving force or by periodically flashing the substrate. Recently, a new class of active ratchet systems that do not require the application of external driving has been realized through the use of active matter; they are self-propelled units that can be biological or nonbiological in nature. When active materials such as swimming bacteria interact with an asymmetric substrate, a net dc directed motion can arise even without external driving, opening a wealth of possibilities such as sorting, cargo transport, or micromachine construction. We review the current status of active matter ratchets for swimming bacteria, cells, active colloids, and swarming models, focusing on the role of particle-substrate interactions. We describe ratchet reversals produced by collective effects and the use of active ratchets to transport passive particles. We discuss future directions including deformable substrates or particles, the role of different swimming modes, varied particle-particle interactions, and nondissipative effects.

The solar magnetic activity band interaction and instabilities that shape quasi-periodic variability

PubMed Central

McIntosh, Scott W.; Leamon, Robert J.; Krista, Larisza D.; Title, Alan M.; Hudson, Hugh S.; Riley, Pete; Harder, Jerald W.; Kopp, Greg; Snow, Martin; Woods, Thomas N.; Kasper, Justin C.; Stevens, Michael L.; Ulrich, Roger K.

2015-01-01

Solar magnetism displays a host of variational timescales of which the enigmatic 11-year sunspot cycle is most prominent. Recent work has demonstrated that the sunspot cycle can be explained in terms of the intra- and extra-hemispheric interaction between the overlapping activity bands of the 22-year magnetic polarity cycle. Those activity bands appear to be driven by the rotation of the Sun's deep interior. Here we deduce that activity band interaction can qualitatively explain the ‘Gnevyshev Gap'—a well-established feature of flare and sunspot occurrence. Strong quasi-annual variability in the number of flares, coronal mass ejections, the radiative and particulate environment of the heliosphere is also observed. We infer that this secondary variability is driven by surges of magnetism from the activity bands. Understanding the formation, interaction and instability of these activity bands will considerably improve forecast capability in space weather and solar activity over a range of timescales. PMID:25849045

Metal-chelating active packaging film enhances lysozyme inhibition of Listeria monocytogenes.

PubMed

Roman, Maxine J; Decker, Eric A; Goddard, Julie M

2014-07-01

Several studies have demonstrated that metal chelators enhance the antimicrobial activity of lysozyme. This study examined the effect of metal-chelating active packaging film on the antimicrobial activity of lysozyme against Listeria monocytogenes. Polypropylene films were surface modified by photoinitiated graft polymerization of acrylic acid (PP-g-PAA) from the food contact surface of the films to impart chelating activity based on electrostatic interactions. PP-g-PAA exhibited a carboxylic acid density of 113 ± 5.4 nmol cm(-2) and an iron chelating activity of 53.7 ± 9.8 nmol cm(-2). The antimicrobial interaction of lysozyme and PP-g-PAA depended on growth media composition. PP-g-PAA hindered lysozyme activity at low ionic strength (2.48-log increase at 64.4 mM total ionic strength) and enhanced lysozyme activity at moderate ionic strength (5.22-log reduction at 120 mM total ionic strength). These data support the hypothesis that at neutral pH, synergy between carboxylate metal-chelating films (pKa(bulk) 6.45) and lysozyme (pI 11.35) is optimal in solutions of moderate to high ionic strength to minimize undesirable charge interactions, such as lysozyme absorption onto film. These findings suggest that active packaging, which chelates metal ions based on ligand-specific interactions, in contrast to electrostatic interactions, may improve antimicrobial synergy. This work demonstrates the potential application of metal-chelating active packaging films to enhance the antimicrobial activity of membrane-disrupting antimicrobials, such as lysozyme.

Reduction of Helicopter Blade-Vortex Interaction Noise by Active Rotor Control Technology

NASA Technical Reports Server (NTRS)

Yu, Yung H.; Gmelin, Bernd; Splettstoesser, Wolf; Brooks, Thomas F.; Philippe, Jean J.; Prieur, Jean

1997-01-01

Helicopter blade-vortex interaction noise is one of the most severe noise sources and is very important both in community annoyance and military detection. Research over the decades has substantially improved basic physical understanding of the mechanisms generating rotor blade-vortex interaction noise and also of controlling techniques, particularly using active rotor control technology. This paper reviews active rotor control techniques currently available for rotor blade vortex interaction noise reduction, including higher harmonic pitch control, individual blade control, and on-blade control technologies. Basic physical mechanisms of each active control technique are reviewed in terms of noise reduction mechanism and controlling aerodynamic or structural parameters of a blade. Active rotor control techniques using smart structures/materials are discussed, including distributed smart actuators to induce local torsional or flapping deformations, Published by Elsevier Science Ltd.

Reading Aloud: Discrete Stage(s) Redux

PubMed Central

Robidoux, Serje; Besner, Derek

2017-01-01

Interactive activation accounts of processing have had a broad and deep influence on cognitive psychology, particularly so in the context of computational accounts of reading aloud at the single word level. Here we address the issue of whether such a framework can simulate the joint effects of stimulus quality and word frequency (which have been shown to produce both additive and interactive effects depending on the context). We extend previous work on this question by considering an alternative implementation of a stimulus quality manipulation, and the role of interactive activation. Simulations with a version of the Dual Route Cascaded model (a model with interactive activation dynamics along the lexical route) demonstrate that the model is unable to simulate the entire pattern seen in human performance. We discuss how a hybrid interactive activation model that includes some context dependent staged processing could accommodate these data. PMID:28289395

Shared Activity Coordination

NASA Technical Reports Server (NTRS)

Clement, Bradley J.; Barrett, Anthony C.

2003-01-01

Interacting agents that interleave planning and execution must reach consensus on their commitments to each other. In domains where agents have varying degrees of interaction and different constraints on communication and computation, agents will require different coordination protocols in order to efficiently reach consensus in real time. We briefly describe a largely unexplored class of real-time, distributed planning problems (inspired by interacting spacecraft missions), new challenges they pose, and a general approach to solving the problems. These problems involve self-interested agents that have infrequent communication but collaborate on joint activities. We describe a Shared Activity Coordination (SHAC) framework that provides a decentralized algorithm for negotiating the scheduling of shared activities in a dynamic environment, a soft, real-time approach to reaching consensus during execution with limited communication, and a foundation for customizing protocols for negotiating planner interactions. We apply SHAC to a realistic simulation of interacting Mars missions and illustrate the simplicity of protocol development.

Continual coordination through shared activities

NASA Technical Reports Server (NTRS)

Clement, Bradley J.; Barrett, Anthony C.

2003-01-01

Interacting agents that interleave planning and execution must reach consensus on their commitments to each other. In domains where agents have varying degrees of interaction and different constraints on communication and computation, agents will require different coordination protocols in order to efficiently reach consensus in real time. We briefly describe a largely unexplored class of realtime, distributed planning problems (inspired by interacting spacecraft missions), new challenges they pose, and a general approach to solving the problems. These problems involve self-interested agents that have infrequent communication but collaborate on joint activities. We describe a Shared Activity Coordination (SHAC) framework that provides a decentralized algorithm for negotiating the scheduling of shared activities over the lifetimes of separate missions, a soft, real-time approach to reaching consensus during execution with limited communication, and a foundation for customizing protocols for negotiating planner interactions. We apply SHAC to a realistic simulation of interacting Mars missions and illustrate the simplicity of protocol development.

EHV-1 EICP22 protein sequences that mediate its physical interaction with the immediate-early protein are not sufficient to enhance the trans-activation activity of the IE protein.

PubMed

Derbigny, Wilbert A; Kim, Seong K; Jang, Hyung K; O'Callaghan, Dennis J

2002-03-20

The early 293 amino acid EICP22 protein (EICP22P) of equine herpesvirus 1 localizes within the nucleus and functions as an accessory regulatory protein (J. Virol. 68 (1994) 4329). Transient transfection assays indicated that although the EICP22P by itself only minimally trans-activates EHV-1 promoters, the EICP22P functions synergistically with the immediate-early protein (IEP) to enhance expression of EHV-1 early genes (J. Virol. 71 (1997) 1004). We previously showed that the EICP22 protein enhances the DNA-binding activity of the EHV-1 IEP and that it also physically interacts with the IEP (J. Virol. 74 (2000) 1425). In this communication, we employed transient trans-activation assays utilizing EICP22P deletion mutants to address whether the sequences required for EICP22P-IEP physical interactions are essential for EICP22P's ability to interact synergistically with the IEP. Assays employing various classes of the EHV-1 promoters fused to the chloramphenicol acetyl-transferase (CAT) reporter gene indicated that: (1) neither full length nor any of the EICP22P mutants tested was able to overcome repression of the IE promoter elicited by the IEP, (2) the full-length EICP22P interacted synergistically with the IEP to trans-activate the early and late promoters tested, and (3) all of the EICP22P mutants, including those that were able to physically interact with IEP and itself, failed to function synergistically with the IEP to trans-activate representative EHV-1 early and late promoters. The results suggest that EICP22P sequences required for its interaction with the IE protein are not sufficient to mediate its synergistic effect on the trans-activation function of the IEP. The possible explanations as to why sequences in addition to those that mediate EICP22P-IEP interaction and EICP22P self-interactions are essential for the synergistic function of EICP22P are discussed.

Secondhand Smoke Enhances Lung Cancer Risk in Male Smokers: An Interaction.

PubMed

Li, Wentao; Tse, Lap Ah; Au, Joseph S K; Wang, Feng; Qiu, Hong; Yu, Ignatius Tak-Sun

2016-11-01

Previous studies revealed that some indoor air pollutants and fine particle matter can interact with active smoking, enhancing lung cancer risk in smokers. Secondhand smoke (SHS), with remarkable differences from active smoking, contributes significantly to indoor air pollution and generates a considerable amount of fine particle matter, may cause a similar interaction with active smoking. Information on lifetime SHS along with active smoking and other confirmed or suspected risk factors for lung cancer was collected in this case-referent study. Odds ratios and the 95% confidence intervals (95% CIs) of smoking status in different levels of SHS were evaluated. Potential multiplicative and additive interactions were explored. Compared with never-smokers without SHS, current smokers who were exposed to a high level of SHS demonstrated the highest odds ratio (15.13, 95% CI: 8.60, 26.65), almost doubles the effect in the current smokers without SHS. Significant additive interactions between current smoking and high level of SHS were observed for all lung cancers (synergy index = 1.80, 95% CI: 1.02, 3.24) and the squamous carcinoma subgroup. High level of SHS exposure greatly enhanced lung cancer risk among current smokers, consistent with an additive interaction; while this interaction was predominant for the squamous carcinoma. The results provide new evidence to the rationale of promoting global smoking cessation. Some indoor air pollutants can interact with active smoking, yielding a synergistic effect on inducing lung cancer. SHS, with noticeable differences from active smoking, is a major source of indoor air pollution. However, little has been known about the effect of SHS in smokers and whether there is a similar interaction between SHS and active smoking. In this study, we evaluated their separate and joint effects and indeed found a more than additive interaction between them. This finding suggests a potential problem of gathering smoking aggravating by venue restriction policies and re-advocates policy efforts on smoking cessation. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Interactive Whiteboards and All That Jazz: Analysing Classroom Activity with Interactive Technologies

ERIC Educational Resources Information Center

Tanner, Howard; Beauchamp, Gary; Jones, Sonia; Kennewell, Steve

2010-01-01

The term "orchestration", has been used to describe the teacher's role in activity settings incorporating interactive technologies. This musical analogy suggests pre-planned manipulation of events to generate "performance" leading to learning. However, in two recent projects we have observed how effective teaching and learning…

How Guidance Affects Student Engagement with an Interactive Simulation

ERIC Educational Resources Information Center

Chamberlain, Julia M.; Lancaster, Kelly; Parson, Robert; Perkins, Katherine K.

2014-01-01

We studied how students engaged with an interactive simulation in a classroom setting and how that engagement was affected by the design of a guiding activity. Students (n = 210) completed a written activity using an interactive simulation in second semester undergraduate general chemistry recitations. The same simulation--PhET Interactive…

Improving the EFL Learners' Speaking Ability through Interactive Storytelling

ERIC Educational Resources Information Center

Marzuki; Prayogo, Johannes Ananto; Wahyudi, Arwijati

2016-01-01

This present research was aimed to improve the EFL learners' speaking ability and their classroom activities through the implementation of Interactive Storytelling Strategy. Therefore, this study was directed to explore the beneficial of Interactive Storytelling that closely related to the EFL learners' everyday activities at their home and…

Interactional Feedback in Naturalistic Interaction between L2 English Learners

ERIC Educational Resources Information Center

Ranaweera, Mahishi

2015-01-01

Theoretical and empirical data support that the feedback given in small group activities promote second language acquisition. There are many studies that have examined the impact of interaction on second language acquisition in controlled language situations. This study examines the small group activity "conversation partner" in order to…

The Interaction-Activity Connection

NASA Technical Reports Server (NTRS)

Borne, Kirk D.

1996-01-01

A review is presented of the numerous studies that have been undertaken to investigate the likely interaction-activity connection among galaxies. Both observational evidence and theoretical supporting models are reviewed. Some specific examples of "interactive" galaxies from the author's own research are presented: (a) the collision-induced AGN (Active Galactic Nuclei) activity in the radio jet source 3C278; and (b) the collision-induced starburst activity in the spectacular "Cartwheel" ring galaxy. Some comments are offered concerning some of the more promising theoretical investigations that are now taking place. A few words of warning are also offered about the possible misinterpretation of putative collision-induced morphologies among some galaxy samples.

Interaction with Single-stranded DNA-binding Protein Stimulates Escherichia coli Ribonuclease HI Enzymatic Activity

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

Petzold, Christine; Marceau, Aimee H.; Miller, Katherine H.

Single-stranded (ss) DNA-binding proteins (SSBs) bind and protect ssDNA intermediates formed during replication, recombination, and repair reactions. SSBs also directly interact with many different genome maintenance proteins to stimulate their enzymatic activities and/or mediate their proper cellular localization. We have identified an interaction formed between Escherichia coli SSB and ribonuclease HI (RNase HI), an enzyme that hydrolyzes RNA in RNA/DNA hybrids. The RNase HI·SSB complex forms by RNase HI binding the intrinsically disordered C terminus of SSB (SSB-Ct), a mode of interaction that is shared among all SSB interaction partners examined to date. Residues that comprise the SSB-Ct binding sitemore » are conserved among bacterial RNase HI enzymes, suggesting that RNase HI·SSB complexes are present in many bacterial species and that retaining the interaction is important for its cellular function. A steady-state kinetic analysis shows that interaction with SSB stimulates RNase HI activity by lowering the reaction Km. SSB or RNase HI protein variants that disrupt complex formation nullify this effect. Collectively our findings identify a direct RNase HI/SSB interaction that could play a role in targeting RNase HI activity to RNA/DNA hybrid substrates within the genome.« less

Increased frequency of social interaction is associated with enjoyment enhancement and reward system activation

PubMed Central

Kawamichi, Hiroaki; Sugawara, Sho K.; Hamano, Yuki H.; Makita, Kai; Kochiyama, Takanori; Sadato, Norihiro

2016-01-01

Positive social interactions contribute to the sense that one’s life has meaning. Enjoyment of feelings associated through social interaction motivates humans to build social connections according to their personal preferences. Therefore, we hypothesized that social interaction itself activates the reward system in a manner that depends upon individual interaction preferences. To test this hypothesis, we conducted a functional magnetic resonance imaging (fMRI) study in which 38 participants played a virtual ball-toss game in which the number of ball tosses to the participant was either similar to (normal-frequency condition) or higher than (high-frequency condition) the number of tosses to the other players. Participants reported greater-than-anticipated enjoyment during the high-frequency condition, suggesting that receiving a social reward led to unexpected positive feelings. Consistent with this, the high-frequency condition produced stronger activation in the ventral striatum, which is part of the reward system, and the precuneus, representing positive self-image, which might be translated to social reward. Furthermore, ventral striatal activation covaried with individual participants’ preference for interactions with others. These findings suggest that an elevated frequency of social interaction is represented as a social reward, which might motivate individuals to promote social interaction in a manner that is modulated by personal preference. PMID:27090501

Increased frequency of social interaction is associated with enjoyment enhancement and reward system activation.

PubMed

Kawamichi, Hiroaki; Sugawara, Sho K; Hamano, Yuki H; Makita, Kai; Kochiyama, Takanori; Sadato, Norihiro

2016-04-19

Positive social interactions contribute to the sense that one's life has meaning. Enjoyment of feelings associated through social interaction motivates humans to build social connections according to their personal preferences. Therefore, we hypothesized that social interaction itself activates the reward system in a manner that depends upon individual interaction preferences. To test this hypothesis, we conducted a functional magnetic resonance imaging (fMRI) study in which 38 participants played a virtual ball-toss game in which the number of ball tosses to the participant was either similar to (normal-frequency condition) or higher than (high-frequency condition) the number of tosses to the other players. Participants reported greater-than-anticipated enjoyment during the high-frequency condition, suggesting that receiving a social reward led to unexpected positive feelings. Consistent with this, the high-frequency condition produced stronger activation in the ventral striatum, which is part of the reward system, and the precuneus, representing positive self-image, which might be translated to social reward. Furthermore, ventral striatal activation covaried with individual participants' preference for interactions with others. These findings suggest that an elevated frequency of social interaction is represented as a social reward, which might motivate individuals to promote social interaction in a manner that is modulated by personal preference.

Interaction with Single-stranded DNA-binding Protein Stimulates Escherichia coli Ribonuclease HI Enzymatic Activity.

PubMed

Petzold, Christine; Marceau, Aimee H; Miller, Katherine H; Marqusee, Susan; Keck, James L

2015-06-05

Single-stranded (ss) DNA-binding proteins (SSBs) bind and protect ssDNA intermediates formed during replication, recombination, and repair reactions. SSBs also directly interact with many different genome maintenance proteins to stimulate their enzymatic activities and/or mediate their proper cellular localization. We have identified an interaction formed between Escherichia coli SSB and ribonuclease HI (RNase HI), an enzyme that hydrolyzes RNA in RNA/DNA hybrids. The RNase HI·SSB complex forms by RNase HI binding the intrinsically disordered C terminus of SSB (SSB-Ct), a mode of interaction that is shared among all SSB interaction partners examined to date. Residues that comprise the SSB-Ct binding site are conserved among bacterial RNase HI enzymes, suggesting that RNase HI·SSB complexes are present in many bacterial species and that retaining the interaction is important for its cellular function. A steady-state kinetic analysis shows that interaction with SSB stimulates RNase HI activity by lowering the reaction Km. SSB or RNase HI protein variants that disrupt complex formation nullify this effect. Collectively our findings identify a direct RNase HI/SSB interaction that could play a role in targeting RNase HI activity to RNA/DNA hybrid substrates within the genome. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Pestivirus Npro Directly Interacts with Interferon Regulatory Factor 3 Monomer and Dimer

PubMed Central

Holthauzen, Luis Marcelo F.; Ruggli, Nicolas

2016-01-01

ABSTRACT Interferon regulatory factor 3 (IRF3) is a transcription factor involved in the activation of type I alpha/beta interferon (IFN-α/β) in response to viral infection. Upon viral infection, the IRF3 monomer is activated into a phosphorylated dimer, which induces the transcription of interferon genes in the nucleus. Viruses have evolved several ways to target IRF3 in order to subvert the innate immune response. Pestiviruses, such as classical swine fever virus (CSFV), target IRF3 for ubiquitination and subsequent proteasomal degradation. This is mediated by the viral protein Npro that interacts with IRF3, but the molecular details for this interaction are largely unknown. We used recombinant Npro and IRF3 proteins and show that Npro interacts with IRF3 directly without additional proteins and forms a soluble 1:1 complex. The full-length IRF3 but not merely either of the individual domains is required for this interaction. The interaction between Npro and IRF3 is not dependent on the activation state of IRF3, since Npro binds to a constitutively active form of IRF3 in the presence of its transcriptional coactivator, CREB-binding protein (CBP). The results indicate that the Npro-binding site on IRF3 encompasses a region that is unperturbed by the phosphorylation and subsequent activation of IRF3 and thus excludes the dimer interface and CBP-binding site. IMPORTANCE The pestivirus N-terminal protease, Npro, is essential for evading the host's immune system by facilitating the degradation of interferon regulatory factor 3 (IRF3). However, the nature of the Npro interaction with IRF3, including the IRF3 species (inactive monomer versus activated dimer) that Npro targets for degradation, is largely unknown. We show that classical swine fever virus Npro and porcine IRF3 directly interact in solution and that full-length IRF3 is required for interaction with Npro. Additionally, Npro interacts with a constitutively active form of IRF3 bound to its transcriptional cofactor, the CREB-binding protein. This is the first study to demonstrate that Npro is able to bind both inactive IRF3 monomer and activated IRF3 dimer and thus likely targets both IRF3 species for ubiquitination and proteasomal degradation. PMID:27334592

Supporting self-efficacy through interactive discussion in online communities of weight loss.

PubMed

Wang, Ye; Willis, Erin

2016-06-01

By conducting a content analysis of online communities connected by the Weight Watchers' online message boards, this study examined the relationship between conversational interactivity and consumer-generated content about consumer health information, self-efficacious content, and experiences with dieting and physical activities. The results showed that discussion about successful experiences with weight loss tended to be more interactive. Discussion about consumer health information tended to be non-interactive. The findings suggest that online communities generate social support through interactive discussion about successful experiences, and the interactive discussion, in return, sustains active participation in the community.

Interactive Diet and Activity Tracking in AARP (IDATA) Study Data | Division of Cancer Prevention

Cancer.gov

The Interactive Diet and Activity Tracking in AARP (IDATA) Study is a methodologic study of device-based, internet-based, and conventional self-report instrum | Device-based and intensive self-report physical activity and diet data with biomarkers

Molecular docking and molecular dynamics studies on the interactions of hydroxylated polybrominated diphenyl ethers to estrogen receptor alpha.

PubMed

Lu, Qun; Cai, Zhengqing; Fu, Jie; Luo, Siyi; Liu, Chunsheng; Li, Xiaolin; Zhao, Dongye

2014-03-01

Environmental estrogens have attracted great concerns. Recent studies have indicated that some hydroxylated polybrominated diphenyl ethers (HO-PBDEs) can interact with estrogen receptor (ER), and exhibit estrogenic activity. However, interactions between HO-PBDEs and ER are not well understood. In this work, molecular docking and molecular dynamics (MD) simulations were performed to characterize interactions of two HO-PBDEs (4'-HO-BDE30 and 4'-HO-BDE121) with ERα. Surflex-Dock was employed to reveal the probable binding conformations of the compounds at the active site of ERα; MD simulation was used to determine the detailed binding process. The driving forces of the binding between HO-PBDEs and ERα were van der Waals and electrostatic interactions. The decomposition of the binding free energy indicated that the hydrogen bonds between the residues Glu353, Gly521 and ligands were crucial for anchoring the ligands into the active site of ERα and stabilizing their conformations. The results showed that different interaction modes and different specific interactions with some residues were responsible for the different estrogenic activities of the two HO-PBDEs. Copyright © 2013 Elsevier Inc. All rights reserved.

A study of the antibacterial activity of L-phenylalanine and L-tyrosine esters in relation to their CMCs and their interactions with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC as model membrane.

PubMed

Joondan, Nausheen; Jhaumeer-Laulloo, Sabina; Caumul, Prakashanand

2014-01-01

Cationic amino acid-based surfactants are known to interact with the lipid bilayer of cell membranes resulting in depolarization, lysis and cell death through a disruption of the membrane topology. A range of cationic surfactant analogues derived from L-Phenylalanine (C1-C20) and L-Tyrosine (C8-C14) esters have been synthesized and screened for their antibacterial activity. The esters were more active against gram positive than gram negative bacteria. The activity increased with increasing chain length, exhibiting a cut-off effect at C12 for gram positive and C8/C10 for gram negative bacteria. The cut-off effect for gram negative bacteria was observed at a lower alkyl chain length. The CMC was correlated with the MIC, inferring that micellar activity contribute to the cut-off effect in antibacterial activity. The interaction of the cationic surfactants with the phospholipid vesicles (1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC) in the presence of 1-anilino-8-naphthalene sulfonate (ANS) and 1,6-diphenyl-1,3,5-hexatriene (DPH) as fluorescence probes showed that an increase in ionic interaction causes an increase in antibacterial activity. Increase in hydrophobic interaction increases the antibacterial activity only to a certain chain length, attributing to the cut-off effect. Therefore, both electrostatic and hydrophobic interactions, involving the polar and nonpolar moieties are of paramount importance for the bactericidal properties. Copyright © 2014 Elsevier GmbH. All rights reserved.

New insights into the interaction between pyrrolyl diketoacids and HIV-1 integrase active site and comparison with RNase H.

PubMed

Corona, Angela; di Leva, Francesco Saverio; Rigogliuso, Giuseppe; Pescatori, Luca; Madia, Valentina Noemi; Subra, Frederic; Delelis, Olivier; Esposito, Francesca; Cadeddu, Marta; Costi, Roberta; Cosconati, Sandro; Novellino, Ettore; di Santo, Roberto; Tramontano, Enzo

2016-10-01

HIV-1 integrase (IN) inhibitors are one of the most recent innovations in the treatment of HIV infection. The selection of drug resistance viral strains is however a still open issue requiring constant efforts to identify new anti-HIV-1 drugs. Pyrrolyl diketo acid (DKA) derivatives inhibit HIV-1 replication by interacting with the Mg 2+ cofactors within the HIV-1 IN active site or within the HIV-1 reverse-transcriptase associated ribonuclease H (RNase H) active site. While the interaction mode of pyrrolyl DKAs with the RNase H active site has been recently reported and substantiated by mutagenesis experiments, their interaction within the IN active site still lacks a detailed understanding. In this study, we investigated the binding mode of four pyrrolyl DKAs to the HIV-1 IN active site by molecular modeling coupled with site-directed mutagenesis studies showing that the DKA pyrrolyl scaffold primarily interacts with the IN amino residues P145, Q146 and Q148. Importantly, the tested DKAs demonstrated good effectiveness against HIV-1 Raltegravir resistant Y143A and N155H INs, thus showing an interaction pattern with relevant differences if compared with the first generation IN inhibitors. These data provide precious insights for the design of new HIV inhibitors active on clinically selected Raltegravir resistant variants. Furthermore, this study provides new structural information to modulate IN and RNase H inhibitory activities for development of dual-acting anti-HIV agents. Copyright © 2016 Elsevier B.V. All rights reserved.

Interactions between Lactobacillus sakei and CNC (Staphylococcus xylosus and Kocuria varians) and their influence on proteolytic activity.

PubMed

Tremonte, P; Reale, A; Di Renzo, T; Tipaldi, L; Di Luccia, A; Coppola, R; Sorrentino, E; Succi, M

2010-11-01

To evaluate interactions between Lactobacillus sakei and coagulase negative cocci (CNC) (Staphylococcus xylosus and Kocuria varians) and to investigate the influence of these interactions on their own proteolytic activity. Interactions occurring between strains of Lact. sakei and CNC were assessed by spectrophotometric analysis. The growth of 35 strains of Lact. sakei, used as indicators, was compared to that obtained combining the same strains with growing cells or cell-free supernatants of 20 CNC (18 Staph. xylosus and 2 K. varians). The proteolytic activity expressed by single strains or by their combinations was assessed on sarcoplasmic protein extracts by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results evidenced that interactions are able to affect not only the growth but also the in vitro proteolytic activity of Lact. sakei and CNC used in combination. A relationship between the presence of interactions among useful strains and the strength of technological characteristics, such as proteolysis, was defined. The study highlighted that CNC are able to stimulate the growth of some Lact. sakei strains. At the same time, this interaction positively influences the proteolytic activity of strains used in combination. Given the importance of proteolysis during the ripening of fermented meats, this phenomenon should be taken into account to select meat starter cultures. © 2010 The Authors. © 2010 The Society for Applied Microbiology.

Site-specific Interaction Mapping of Phosphorylated Ubiquitin to Uncover Parkin Activation*♦

PubMed Central

Yamano, Koji; Queliconi, Bruno B.; Koyano, Fumika; Saeki, Yasushi; Hirokawa, Takatsugu; Tanaka, Keiji; Matsuda, Noriyuki

2015-01-01

Damaged mitochondria are eliminated through autophagy machinery. A cytosolic E3 ubiquitin ligase Parkin, a gene product mutated in familial Parkinsonism, is essential for this pathway. Recent progress has revealed that phosphorylation of both Parkin and ubiquitin at Ser65 by PINK1 are crucial for activation and recruitment of Parkin to the damaged mitochondria. However, the mechanism by which phosphorylated ubiquitin associates with and activates phosphorylated Parkin E3 ligase activity remains largely unknown. Here, we analyze interactions between phosphorylated forms of both Parkin and ubiquitin at a spatial resolution of the amino acid residue by site-specific photo-crosslinking. We reveal that the in-between-RING (IBR) domain along with RING1 domain of Parkin preferentially binds to ubiquitin in a phosphorylation-dependent manner. Furthermore, another approach, the Fluoppi (fluorescent-based technology detecting protein-protein interaction) assay, also showed that pathogenic mutations in these domains blocked interactions with phosphomimetic ubiquitin in mammalian cells. Molecular modeling based on the site-specific photo-crosslinking interaction map combined with mass spectrometry strongly suggests that a novel binding mechanism between Parkin and ubiquitin leads to a Parkin conformational change with subsequent activation of Parkin E3 ligase activity. PMID:26260794

Discriminative latent models for recognizing contextual group activities.

PubMed

Lan, Tian; Wang, Yang; Yang, Weilong; Robinovitch, Stephen N; Mori, Greg

2012-08-01

In this paper, we go beyond recognizing the actions of individuals and focus on group activities. This is motivated from the observation that human actions are rarely performed in isolation; the contextual information of what other people in the scene are doing provides a useful cue for understanding high-level activities. We propose a novel framework for recognizing group activities which jointly captures the group activity, the individual person actions, and the interactions among them. Two types of contextual information, group-person interaction and person-person interaction, are explored in a latent variable framework. In particular, we propose three different approaches to model the person-person interaction. One approach is to explore the structures of person-person interaction. Differently from most of the previous latent structured models, which assume a predefined structure for the hidden layer, e.g., a tree structure, we treat the structure of the hidden layer as a latent variable and implicitly infer it during learning and inference. The second approach explores person-person interaction in the feature level. We introduce a new feature representation called the action context (AC) descriptor. The AC descriptor encodes information about not only the action of an individual person in the video, but also the behavior of other people nearby. The third approach combines the above two. Our experimental results demonstrate the benefit of using contextual information for disambiguating group activities.

Discriminative Latent Models for Recognizing Contextual Group Activities

PubMed Central

Lan, Tian; Wang, Yang; Yang, Weilong; Robinovitch, Stephen N.; Mori, Greg

2012-01-01

In this paper, we go beyond recognizing the actions of individuals and focus on group activities. This is motivated from the observation that human actions are rarely performed in isolation; the contextual information of what other people in the scene are doing provides a useful cue for understanding high-level activities. We propose a novel framework for recognizing group activities which jointly captures the group activity, the individual person actions, and the interactions among them. Two types of contextual information, group-person interaction and person-person interaction, are explored in a latent variable framework. In particular, we propose three different approaches to model the person-person interaction. One approach is to explore the structures of person-person interaction. Differently from most of the previous latent structured models, which assume a predefined structure for the hidden layer, e.g., a tree structure, we treat the structure of the hidden layer as a latent variable and implicitly infer it during learning and inference. The second approach explores person-person interaction in the feature level. We introduce a new feature representation called the action context (AC) descriptor. The AC descriptor encodes information about not only the action of an individual person in the video, but also the behavior of other people nearby. The third approach combines the above two. Our experimental results demonstrate the benefit of using contextual information for disambiguating group activities. PMID:22144516

Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds

NASA Astrophysics Data System (ADS)

Harada, Shusaku; Hiromori, Youhei; Nakamura, Shota; Kawahara, Kazuki; Fukakusa, Shunsuke; Maruno, Takahiro; Noda, Masanori; Uchiyama, Susumu; Fukui, Kiichi; Nishikawa, Jun-Ichi; Nagase, Hisamitsu; Kobayashi, Yuji; Yoshida, Takuya; Ohkubo, Tadayasu; Nakanishi, Tsuyoshi

2015-02-01

Organotin compounds such as triphenyltin (TPT) and tributyltin (TBT) act as endocrine disruptors through the peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway. We recently found that TPT is a particularly strong agonist of PPARγ. To elucidate the mechanism underlying organotin-dependent PPARγ activation, we here analyzed the interactions of PPARγ ligand-binding domain (LBD) with TPT and TBT by using X-ray crystallography and mass spectroscopy in conjunction with cell-based activity assays. Crystal structures of PPARγ-LBD/TBT and PPARγ-LBD/TPT complexes were determined at 1.95 Å and 1.89 Å, respectively. Specific binding of organotins is achieved through non-covalent ionic interactions between the sulfur atom of Cys285 and the tin atom. Comparisons of the determined structures suggest that the strong activity of TPT arises through interactions with helix 12 of LBD primarily via π-π interactions. Our findings elucidate the structural basis of PPARγ activation by TPT.

Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds

PubMed Central

Harada, Shusaku; Hiromori, Youhei; Nakamura, Shota; Kawahara, Kazuki; Fukakusa, Shunsuke; Maruno, Takahiro; Noda, Masanori; Uchiyama, Susumu; Fukui, Kiichi; Nishikawa, Jun-ichi; Nagase, Hisamitsu; Kobayashi, Yuji; Yoshida, Takuya; Ohkubo, Tadayasu; Nakanishi, Tsuyoshi

2015-01-01

Organotin compounds such as triphenyltin (TPT) and tributyltin (TBT) act as endocrine disruptors through the peroxisome proliferator–activated receptor γ (PPARγ) signaling pathway. We recently found that TPT is a particularly strong agonist of PPARγ. To elucidate the mechanism underlying organotin-dependent PPARγ activation, we here analyzed the interactions of PPARγ ligand-binding domain (LBD) with TPT and TBT by using X-ray crystallography and mass spectroscopy in conjunction with cell-based activity assays. Crystal structures of PPARγ-LBD/TBT and PPARγ-LBD/TPT complexes were determined at 1.95 Å and 1.89 Å, respectively. Specific binding of organotins is achieved through non-covalent ionic interactions between the sulfur atom of Cys285 and the tin atom. Comparisons of the determined structures suggest that the strong activity of TPT arises through interactions with helix 12 of LBD primarily via π-π interactions. Our findings elucidate the structural basis of PPARγ activation by TPT. PMID:25687586

The Inositol Phosphatase SHIP-1 Inhibits NOD2-Induced NF-κB Activation by Disturbing the Interaction of XIAP with RIP2

PubMed Central

Condé, Claude; Rambout, Xavier; Lebrun, Marielle; Lecat, Aurore; Di Valentin, Emmanuel; Dequiedt, Franck; Piette, Jacques

2012-01-01

SHIP-1 is an inositol phosphatase predominantly expressed in hematopoietic cells. Over the ten past years, SHIP-1 has been described as an important regulator of immune functions. Here, we characterize a new inhibitory function for SHIP-1 in NOD2 signaling. NOD2 is a crucial cytoplasmic bacterial sensor that activates proinflammatory and antimicrobial responses upon bacterial invasion. We observed that SHIP-1 decreases NOD2-induced NF-κB activation in macrophages. This negative regulation relies on its interaction with XIAP. Indeed, we observed that XIAP is an essential mediator of the NOD2 signaling pathway that enables proper NF-κB activation in macrophages. Upon NOD2 activation, SHIP-1 C-terminal proline rich domain (PRD) interacts with XIAP, thereby disturbing the interaction between XIAP and RIP2 in order to decrease NF-κB signaling. PMID:22815893

Interaction of perceived neighborhood walkability and self-efficacy on physical activity.

PubMed

Kaczynski, Andrew T; Robertson-Wilson, Jennifer; Decloe, Melissa

2012-02-01

Few social ecological studies have considered the joint effects of intrapersonal and environmental influences on physical activity. This study investigated the interaction of self-efficacy and perceived neighborhood walkability in predicting neighborhood-based physical activity and how this relationship varied by gender and body mass index. Data were derived from a cross-sectional investigation of environmental and psychosocial correlates of physical activity among adults (n = 585). Participants completed a detailed 7-day physical activity log booklet, along with a questionnaire that included measures of neighborhood walkability, self-efficacy, and several sociodemographic items. Factorial analysis of variance tests were used to examine the main effects of and interaction between walkability and self-efficacy. In predicting neighborhood-based physical activity, significant interactions were observed between self-efficacy and neighborhood walkability for females (but not for males) and for overweight/obese participants (but not for healthy weight individuals). Women and overweight/obese individuals with low self-efficacy demonstrated substantially greater physical activity when living in a high walkable neighborhood. Physical activity research and promotion efforts should take into account both environmental and personal factors and the interrelationships between them that influence active living.

Interactive Video Training and Development Activity.

ERIC Educational Resources Information Center

Troy State Univ., AL.

The Interactive Video Training and Development Activity of Troy State University (Troy, Alabama) is described in this report. The project has trained more than 30 people in the production of interactive video programs since its inception in 1983. Since 1985, training programs have been offered twice a year to individuals within and outside the…

[Regulation on EGFR function via its interacting proteins and its potential application].

PubMed

Zheng, Jun-Fang; Chen, Hui-Min; He, Jun-Qi

2013-12-01

Epidermal growth factor receptor (EGFR) is imptortant for cell activities, oncogenesis and cell migration, and EGFR inhibitor can treat cancer efficiently, but its side effects, for example, in skin, limited its usage. On the other hand, EGFR interacting proteins may also lead to oncogenesis and its interacting protein as drug targets can avoid cutaneous side effect, which implies possibly a better outcome and life quality of cancer patients. For the multiple EGFR interaction proteins, B1R enhances Erk/MAPK signaling, while PTPN12, Kek1, CEACAM1 and NHERF repress Erk/MAPK signaling. CaM may alter charge of EGFR juxamembrane domain and regulate activation of PI3K/Akt and PLC-gamma/PKC. STAT1, STAT5b are widely thought to be activated by EGFR, while there is unexpectedly inhibiting sequence within EGFR to repress the activity of STATs. LRIG1 and ACK1 enhance the internalization and degration of EGFR, while NHERF and HIP1 repress it. In this article, proteins interacting with EGFR, their interacting sites and their regulation on EGFR signal transduction will be reviewed.

Environmental Education Activities & Programs 1998-1999.

ERIC Educational Resources Information Center

Bureau of Reclamation (Dept. of Interior), Denver, CO.

This document features descriptions of interactive learning models and presentations in environmental education concerning groundwater, geology, the environment, weather, water activities, and interactive games. Activities include: (1) GW-Standard; (2) GW-w/no Leaky Underground Storage Tank (No UST); (3) GW-Karst; (4) GW-Landfill Models--Standard…

Physical and functional interactions between Drosophila TRAF2 and Pelle kinase contribute to Dorsal activation.

PubMed

Shen, B; Liu, H; Skolnik, E Y; Manley, J L

2001-07-17

Signaling through the Toll receptor is required for dorsal/ventral polarity in Drosophila embryos, and also plays an evolutionarily conserved role in the immune response. Upon ligand binding, Toll appears to multimerize and activate the associated kinase, Pelle. However, the immediate downstream targets of Pelle have not been identified. Here we show that Drosophila tumor necrosis factor receptor-associated factor 2 (dTRAF2), a homologue of human TRAF6, physically and functionally interacts with Pelle, and is phosphorylated by Pelle in vitro. Importantly, dTRAF2 and Pelle cooperate to activate Dorsal synergistically in cotransfected Schneider cells. Deletion of the C-terminal TRAF domain of dTRAF2 enhances Dorsal activation, perhaps reflecting the much stronger interaction of the mutant protein with phosphorylated, active Pelle. Taken together, our results indicate that Pelle and dTRAF2 physically and functionally interact, and that the TRAF domain acts as a regulator of this interaction. dTRAF2 thus appears to be a downstream target of Pelle. We discuss these results in the context of Toll signaling in flies and mammals.

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

Reichhardt, Cynthia Jane; Reichhardt, Charles

Ratchet effects can arise for single or collectively interacting Brownian particles on an asymmetric substrate when a net dc transport is produced by an externally applied ac driving force or by periodically flashing the substrate. Recently, a new class of active ratchet systems that do not require the application of external driving has been realized through the use of active matter; they are self-propelled units that can be biological or nonbiological in nature. When active materials such as swimming bacteria interact with an asymmetric substrate, a net dc directed motion can arise even without external driving, opening a wealth ofmore » possibilities such as sorting, cargo transport, or micromachine construction. We review the current status of active matter ratchets for swimming bacteria, cells, active colloids, and swarming models, focusing on the role of particle-substrate interactions. Here, we describe ratchet reversals produced by collective effects and the use of active ratchets to transport passive particles. We discuss future directions including deformable substrates or particles, the role of different swimming modes, varied particle–particle interactions, and nondissipative effects.« less

Cannibalism by damselflies increases with rising temperature

PubMed Central

Kirk, Devin; Shea, Dylan

2017-01-01

Trophic interactions are likely to change under climate warming. These interactions can be altered directly by changing consumption rates, or indirectly by altering growth rates and size asymmetries among individuals that in turn affect feeding. Understanding these processes is particularly important for intraspecific interactions, as direct and indirect changes may exacerbate antagonistic interactions. We examined the effect of temperature on activity rate, growth and intraspecific size asymmetries, and how these temperature dependencies affected cannibalism in Lestes congener, a damselfly with marked intraspecific variation in size. Temperature increased activity rates and exacerbated differences in body size by increasing growth rates. Increased activity and changes in body size interacted to increase cannibalism at higher temperatures. We argue that our results are likely to be general to species with life-history stages that vary in their temperature dependencies, and that the effects of climate change on communities may depend on the temperature dependencies of intraspecific interactions. PMID:28515331

Cannibalism by damselflies increases with rising temperature.

PubMed

Start, Denon; Kirk, Devin; Shea, Dylan; Gilbert, Benjamin

2017-05-01

Trophic interactions are likely to change under climate warming. These interactions can be altered directly by changing consumption rates, or indirectly by altering growth rates and size asymmetries among individuals that in turn affect feeding. Understanding these processes is particularly important for intraspecific interactions, as direct and indirect changes may exacerbate antagonistic interactions. We examined the effect of temperature on activity rate, growth and intraspecific size asymmetries, and how these temperature dependencies affected cannibalism in Lestes congener , a damselfly with marked intraspecific variation in size. Temperature increased activity rates and exacerbated differences in body size by increasing growth rates. Increased activity and changes in body size interacted to increase cannibalism at higher temperatures. We argue that our results are likely to be general to species with life-history stages that vary in their temperature dependencies, and that the effects of climate change on communities may depend on the temperature dependencies of intraspecific interactions. © 2017 The Author(s).

Long-range tertiary interactions in single hammerhead ribozymes bias motional sampling toward catalytically active conformations

PubMed Central

McDowell, S. Elizabeth; Jun, Jesse M.; Walter, Nils G.

2010-01-01

Enzymes generally are thought to derive their functional activity from conformational motions. The limited chemical variation in RNA suggests that such structural dynamics may play a particularly important role in RNA function. Minimal hammerhead ribozymes are known to cleave efficiently only in ∼10-fold higher than physiologic concentrations of Mg2+ ions. Extended versions containing native loop–loop interactions, however, show greatly enhanced catalytic activity at physiologically relevant Mg2+ concentrations, for reasons that are still ill-understood. Here, we use Mg2+ titrations, activity assays, ensemble, and single molecule fluorescence resonance energy transfer (FRET) approaches, combined with molecular dynamics (MD) simulations, to ask what influence the spatially distant tertiary loop–loop interactions of an extended hammerhead ribozyme have on its structural dynamics. By comparing hammerhead variants with wild-type, partially disrupted, and fully disrupted loop–loop interaction sequences we find that the tertiary interactions lead to a dynamic motional sampling that increasingly populates catalytically active conformations. At the global level the wild-type tertiary interactions lead to more frequent, if transient, encounters of the loop-carrying stems, whereas at the local level they lead to an enrichment in favorable in-line attack angles at the cleavage site. These results invoke a linkage between RNA structural dynamics and function and suggest that loop–loop interactions in extended hammerhead ribozymes—and Mg2+ ions that bind to minimal ribozymes—may generally allow more frequent access to a catalytically relevant conformation(s), rather than simply locking the ribozyme into a single active state. PMID:20921269

The influence of the interactions between anthropogenic activities and multiple ecological factors on land surface temperatures of urban forests

NASA Astrophysics Data System (ADS)

Ren, Y.

2017-12-01

Context Land surface temperatures (LSTs) spatio-temporal distribution pattern of urban forests are influenced by many ecological factors; the identification of interaction between these factors can improve simulations and predictions of spatial patterns of urban cold islands. This quantitative research requires an integrated method that combines multiple sources data with spatial statistical analysis. Objectives The purpose of this study was to clarify urban forest LST influence interaction between anthropogenic activities and multiple ecological factors using cluster analysis of hot and cold spots and Geogdetector model. We introduced the hypothesis that anthropogenic activity interacts with certain ecological factors, and their combination influences urban forests LST. We also assumed that spatio-temporal distributions of urban forest LST should be similar to those of ecological factors and can be represented quantitatively. Methods We used Jinjiang as a representative city in China as a case study. Population density was employed to represent anthropogenic activity. We built up a multi-source data (forest inventory, digital elevation models (DEM), population, and remote sensing imagery) on a unified urban scale to support urban forest LST influence interaction research. Through a combination of spatial statistical analysis results, multi-source spatial data, and Geogdetector model, the interaction mechanisms of urban forest LST were revealed. Results Although different ecological factors have different influences on forest LST, in two periods with different hot spots and cold spots, the patch area and dominant tree species were the main factors contributing to LST clustering in urban forests. The interaction between anthropogenic activity and multiple ecological factors increased LST in urban forest stands, linearly and nonlinearly. Strong interactions between elevation and dominant species were generally observed and were prevalent in either hot or cold spots areas in different years. Conclusions In conclusion, a combination of spatial statistics and GeogDetector models should be effective for quantitatively evaluating interactive relationships among ecological factors, anthropogenic activity and LST.

Ratchet Effects in Active Matter Systems

DOE PAGES

Reichhardt, Cynthia Jane; Reichhardt, Charles

2016-12-21

Ratchet effects can arise for single or collectively interacting Brownian particles on an asymmetric substrate when a net dc transport is produced by an externally applied ac driving force or by periodically flashing the substrate. Recently, a new class of active ratchet systems that do not require the application of external driving has been realized through the use of active matter; they are self-propelled units that can be biological or nonbiological in nature. When active materials such as swimming bacteria interact with an asymmetric substrate, a net dc directed motion can arise even without external driving, opening a wealth ofmore » possibilities such as sorting, cargo transport, or micromachine construction. We review the current status of active matter ratchets for swimming bacteria, cells, active colloids, and swarming models, focusing on the role of particle-substrate interactions. Here, we describe ratchet reversals produced by collective effects and the use of active ratchets to transport passive particles. We discuss future directions including deformable substrates or particles, the role of different swimming modes, varied particle–particle interactions, and nondissipative effects.« less

An Interactive Classroom Activity Demonstrating Reaction Mechanisms and Rate-Determining Steps

ERIC Educational Resources Information Center

Jennings, Laura D.; Keller, Steven W.

2005-01-01

An interactive classroom activity that includes two-step reaction of unwrapping and eating chocolate candies is described which brings not only the reaction intermediate, but also the reactants and products into macroscopic view. The qualitative activation barriers of both steps can be adjusted independently.

The Effects of Structured Physical Activity Program on Social Interaction and Communication for Children with Autism.

PubMed

Zhao, Mengxian; Chen, Shihui

2018-01-01

The purpose of this study was to investigate the effects of structured physical activity program on social interaction and communication of children with autism spectrum disorder (ASD). Fifty children with ASD from a special school were randomly divided into experimental and control groups. 25 children with ASD were placed in the experimental group, and the other 25 children as the control group participated in regular physical activity. A total of forty-one participants completed the study. A 12-week structured physical activity program was implemented with a total of 24 exercise sessions targeting social interaction and communication of children with ASD, and a quasi-experimental design was used for this study. Data were collected using quantitative and qualitative instruments. SSIS and ABLLS-R results showed that an overall improvement in social skills and social interaction for the experimental group across interim and posttests, F = 8.425, p = 0.001 ( p < 0.005), and significant improvements appeared in communication, cooperation, social interaction, and self-control subdomains ( p < 0.005). Conversely, no statistically significant differences were found in the control group ( p > 0.005). The study concluded that the special structured physical activity program positively influenced social interaction and communication skills of children with ASD, especially in social skills, communication, prompt response, and frequency of expression.

c-Abl interacts with the WAVE2 signaling complex to induce membrane ruffling and cell spreading.

PubMed

Stuart, Jeremy R; Gonzalez, Francis H; Kawai, Hidehiko; Yuan, Zhi-Min

2006-10-20

The Wiskott-Aldrich syndrome-related protein WAVE2 promotes Arp2/3-dependent actin polymerization downstream of Rho-GTPase activation. The Abelson-interacting protein-1 (Abi-1) forms the core of the WAVE2 complex and is necessary for proper stimulation of WAVE2 activity. Here we have shown that the Abl-tyrosine kinase interacts with the WAVE2 complex and that Abl kinase activity facilitates interaction between Abl and WAVE2 complex members. We have characterized various interactions between Abl and members of the WAVE2 complex and revealed that Abi-1 promotes interaction between Abl and WAVE2 members. We have demonstrated that Abl-dependent phosphorylation of WAVE2 is necessary for its activation in vivo, which is highlighted by the findings that RNA interference of WAVE2 expression in Abl/Arg-/- cells has no additive effect on the amount of membrane ruffling. Furthermore, Abl phosphorylates WAVE2 on tyrosine 150, and WAVE2-deficient cells rescued with a Y150F mutant fail to regain their ability to ruffle and form microspikes, unlike cells rescued with wild-type WAVE2. Together, these data show that c-Abl activates WAVE2 via tyrosine phosphorylation to promote actin remodeling in vivo and that Abi-1 forms the crucial link between these two factors.

Intelligent nanomedicine integrating diagnosis and therapy

NASA Technical Reports Server (NTRS)

Li, Na (Inventor); Tan, Winny (Inventor)

2012-01-01

A method of controlling the activity of a biologically active compound. The method concerns an oligonucleotide-based compound, comprising a hairpin-forming oligonucleotide, an effector moiety physically associated with the oligonucleotide, where the effector moiety possesses a biological activity, and a regulating moiety physically associated with the oligonucleotide, where the regulating moiety controls the biological activity of the effector moiety by interacting with the effector moiety. The oligonucleotide can assume a hairpin configuration, where the effector and regulating moieties interact, or an open configuration, where the effector and regulating moieties fail to interact. Depending on the nature of the effector and regulating moieties, either configuration can result in the expression of the biological activity of the effector moiety.

Structural investigation of protein kinase C inhibitors

NASA Technical Reports Server (NTRS)

Barak, D.; Shibata, M.; Rein, R.

1991-01-01

The phospholipid and Ca2+ dependent protein kinase (PKC) plays an essential role in a variety of cellular events. Inhibition of PKC was shown to arrest growth in tumor cell cultures making it a target for possible antitumor therapy. Calphostins are potent inhibitors of PKC with high affinity for the enzyme regulatory site. Structural characteristics of calphostins, which confer the inhibitory activity, are investigated by comparing their optimized structures with the existing models for PKC activation. The resulting model of inhibitory activity assumes interaction with two out of the three electrostatic interaction sites postulated for activators. The model shows two sites of hydrophobic interaction and enables the inhibitory activity of gossypol to be accounted for.

PIAS1 interacts with FLASH and enhances its co-activation of c-Myb

PubMed Central

2011-01-01

Background FLASH is a huge nuclear protein involved in various cellular functions such as apoptosis signalling, NF-κB activation, S-phase regulation, processing of histone pre-mRNAs, and co-regulation of transcription. Recently, we identified FLASH as a co-activator of the transcription factor c-Myb and found FLASH to be tightly associated with active transcription foci. As a huge multifunctional protein, FLASH is expected to have many interaction partners, some which may shed light on its function as a transcriptional regulator. Results To find additional FLASH-associated proteins, we performed a yeast two-hybrid (Y2H) screening with FLASH as bait and identified the SUMO E3 ligase PIAS1 as an interaction partner. The association appears to involve two distinct interaction surfaces in FLASH. We verified the interaction by Y2H-mating, GST pulldowns, co-IP and ChIP. FLASH and PIAS1 were found to co-localize in nuclear speckles. Functional assays revealed that PIAS1 enhances the intrinsic transcriptional activity of FLASH in a RING finger-dependent manner. Furthermore, PIAS1 also augments the specific activity of c-Myb, and cooperates with FLASH to further co-activate c-Myb. The three proteins, FLASH, PIAS1, and c-Myb, are all co-localized with active RNA polymerase II foci, resembling transcription factories. Conclusions We conclude that PIAS1 is a common partner for two cancer-related nuclear factors, c-Myb and FLASH. Our results point to a functional cooperation between FLASH and PIAS1 in the enhancement of c-Myb activity in active nuclear foci. PMID:21338522

The role of strong electrostatic interactions at the dimer interface of human glutathione synthetase.

PubMed

De Jesus, Margarita C; Ingle, Brandall L; Barakat, Khaldoon A; Shrestha, Bisesh; Slavens, Kerri D; Cundari, Thomas R; Anderson, Mary E

2014-10-01

The obligate homodimer human glutathione synthetase (hGS) provides an ideal system for exploring the role of protein-protein interactions in the structural stability, activity and allostery of enzymes. The two active sites of hGS, which are 40 Å apart, display allosteric modulation by the substrate γ-glutamylcysteine (γ-GC) during the synthesis of glutathione, a key cellular antioxidant. The two subunits interact at a relatively small dimer interface dominated by electrostatic interactions between S42, R221, and D24. Alanine scans of these sites result in enzymes with decreased activity, altered γ-GC affinity, and decreased thermal stability. Molecular dynamics simulations indicate these mutations disrupt interchain bonding and impact the tertiary structure of hGS. While the ionic hydrogen bonds and salt bridges between S42, R221, and D24 do not mediate allosteric communication in hGS, these interactions have a dramatic impact on the activity and structural stability of the enzyme.

Hot particles attract in a cold bath

NASA Astrophysics Data System (ADS)

Tanaka, Hidenori; Lee, Alpha A.; Brenner, Michael P.

2017-04-01

Controlling interactions out of thermodynamic equilibrium is crucial for designing addressable and functional self-organizing structures. These active interactions also underpin collective behavior in biological systems. Here we study a general setting of active particles in a bath of passive particles and demonstrate a mechanism for long-range attraction between active particles. The mechanism operates when the translational persistence length of the active particle motion is smaller than the particle diameter. In this limit, the system reduces to particles of higher diffusivity ("hot" particles) in a bath of particles with lower diffusivity ("cold" particles). This attractive interaction arises as a hot particle pushes cold particles away to create a large hole around itself, and the holes interact via a depletion-like attraction. Strikingly, the interaction range is more than an order of magnitude larger than the particle radius, well beyond the range of the conventional depletion force. Although the mechanism occurs outside the parameter regime of typical biological swimmers, the mechanism could be realized in the laboratory.

Metal-Metal Interactions in Heterobimetallic Complexes with Dinucleating Redox-Active Ligands.

PubMed

Broere, Daniël L J; Modder, Dieuwertje K; Blokker, Eva; Siegler, Maxime A; van der Vlugt, Jarl Ivar

2016-02-12

The tuning of metal-metal interactions in multinuclear assemblies is a challenge. Selective P coordination of a redox-active PNO ligand to Au(I) followed by homoleptic metalation of the NO pocket with Ni(II) affords a unique trinuclear Au-Ni-Au complex. This species features two antiferromagnetically coupled ligand-centered radicals and a double intramolecular d(8)-d(10) interaction, as supported by spectroscopic, single-crystal X-ray diffraction, and computational data. A corresponding cationic dinuclear Au-Ni analogue with a stronger d(8)-d(10) interaction is also reported. Although both heterobimetallic structures display rich electrochemistry, only the trinuclear Au-Ni-Au complex facilitates electrocatalytic C-X bond activation of alkyl halides in its doubly reduced state. Hence, the presence of a redox-active ligand framework, an available coordination site at gold, and the nature of the nickel-gold interaction appear to be essential for this reactivity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A first principle study on the interaction between acetylcholinesterase and acetylcholine, and also rivastigmine in alzheimer's disease case

NASA Astrophysics Data System (ADS)

Khoirunisa, V.; Rusydi, F.; Kasai, H.; Gandaryus, A. G.; Dipojono, H. K.

2016-08-01

The catalytic activity of acetylcholinesterase enzyme (AChE) relates to the symptom progress in Alzheimer's disease. Interaction of AChE with rivastigmine (from the medicine) can reduce its catalytic activity toward acetylcholine to decelerate the progression of Alzheimer's disease. This research attempts to study the interaction between AChE and rivastigmine, and also acetylcholine (without the presence of rivastigmine) using density functional theory by simplifying the reaction occurs in the active site, which is assumed to be C2H5OH, C3N2H3(Ch3), and CH3COO-. The results suggest that AChE interacts easier with acetylcholine than with rivastigmine, which implies that the medicine does not effectively reduce the catalytic activity of AChE. At this stage, no experimental data is available to be compared with the calculation results. Nonetheless, this study has shown a good prospect to understand the AChE-substrate interaction using a first-principles calculation.

Wildland fire emissions, carbon, and climate: Wildfire–climate interactions

Treesearch

Yongqiang Liu; Scott Goodrick; Warren Heilman

2014-01-01

Increasing wildfire activity in recent decades, partially related to extended droughts, along with concern over potential impacts of future climate change on fire activity has resulted in increased attention on fire–climate interactions. Findings from studies published in recent years have remarkably increased our understanding of fire–climate interactions and improved...

An Activity Theoretical Approach to Social Interaction during Study Abroad

ERIC Educational Resources Information Center

Shively, Rachel L.

2016-01-01

This case study examines how one study abroad student oriented to social interaction during a semester in Spain. Using an activity theoretical approach, the findings indicate that the student not only viewed social interaction with his Spanish host family and an expert-Spanish-speaking age peer as an opportunity for second language (L2) learning,…

Preschool Peer Interactions and Readiness To Learn: Relationships between Classroom Peer Play and Learning Behaviors and Conduct.

ERIC Educational Resources Information Center

Coolahan, Kathleen; Fantuzzo, John; Mendez, Julia; McDermott, Paul

2000-01-01

Examines whether low-income preschool children's peer play interactions relate to learning behaviors and problem behaviors, and differ according to age and gender. Positive interactive play behavior was associated with active engagement in classroom learning activities, whereas disconnection in play related to inattention, passivity, and lack of…

Dynamics of Student Interactions: An Empirical Study of Orienteering Lessons in Physical Education

ERIC Educational Resources Information Center

Jourand, Clément; Adé, David; Sève, Carole; Komar, John; Thouvarecq, Régis

2018-01-01

Introduction: Many studies in physical education (PE) have sought to identify and categorize the modes of student interaction in order to gain greater insight into the nature of cooperative activity. More others recent studies have examined how modes of interaction evolve on the basis of the modes of collective activity that they generate. These…

Creative Multimodal Learning Environments and Blended Interaction for Problem-Based Activity in HCI Education

ERIC Educational Resources Information Center

Ioannou, Andri; Vasiliou, Christina; Zaphiris, Panayiotis; Arh, Tanja; Klobucar, Tomaž; Pipan, Matija

2015-01-01

This exploratory case study aims to examine how students benefit from a multimodal learning environment while they engage in collaborative problem-based activity in a Human Computer Interaction (HCI) university course. For 12 weeks, 30 students, in groups of 5-7 each, participated in weekly face-to-face meetings and online interactions.…

A theoretical study on the characteristics of the intermolecular interactions in the active site of human androsterone sulphotransferase: DFT calculations of NQR and NMR parameters and QTAIM analysis.

PubMed

Astani, Elahe K; Heshmati, Emran; Chen, Chun-Jung; Hadipour, Nasser L

2016-07-01

A theoretical study at the level of density functional theory (DFT) was performed to characterize noncovalent intermolecular interactions, especially hydrogen bond interactions, in the active site of enzyme human androsterone sulphotransferase (SULT2A1/ADT). Geometry optimization, interaction energy, (2)H, (14)N, and (17)O electric field gradient (EFG) tensors, (1)H, (13)C, (17)O, and (15)N chemical shielding (CS) tensors, Natural Bonding Orbital (NBO) analysis, and quantum theory of atoms in molecules (QTAIM) analysis of this active site were investigated. It was found that androsterone (ADT) is able to form hydrogen bonds with residues Ser80, Ile82, and His99 of the active site. The interaction energy calculations and NBO analysis revealed that the ADT molecule forms the strongest hydrogen bond with Ser80. Results revealed that ADT interacts with the other residues through electrostatic and Van der Waals interactions. Results showed that these hydrogen bonds influence on the calculated (2)H, (14)N, and (17)O quadrupole coupling constants (QCCs), as well as (1)H, (13)C, (17)O, and (15)N CS tensors. The magnitude of the QCC and CS changes at each nucleus depends directly on its amount of contribution to the hydrogen bond interaction. Copyright © 2016 Elsevier Inc. All rights reserved.

Neural correlate of human reciprocity in social interactions

PubMed Central

Sakaiya, Shiro; Shiraito, Yuki; Kato, Junko; Ide, Hiroko; Okada, Kensuke; Takano, Kouji; Kansaku, Kenji

2013-01-01

Reciprocity plays a key role maintaining cooperation in society. However, little is known about the neural process that underpins human reciprocity during social interactions. Our neuroimaging study manipulated partner identity (computer, human) and strategy (random, tit-for-tat) in repeated prisoner's dilemma games and investigated the neural correlate of reciprocal interaction with humans. Reciprocal cooperation with humans but exploitation of computers by defection was associated with activation in the left amygdala. Amygdala activation was also positively and negatively correlated with a preference change for human partners following tit-for-tat and random strategies, respectively. The correlated activation represented the intensity of positive feeling toward reciprocal and negative feeling toward non-reciprocal partners, and so reflected reciprocity in social interaction. Reciprocity in social interaction, however, might plausibly be misinterpreted and so we also examined the neural coding of insight into the reciprocity of partners. Those with and without insight revealed differential brain activation across the reward-related circuitry (i.e., the right middle dorsolateral prefrontal cortex and dorsal caudate) and theory of mind (ToM) regions [i.e., ventromedial prefrontal cortex (VMPFC) and precuneus]. Among differential activations, activation in the precuneus, which accompanied deactivation of the VMPFC, was specific to those without insight into human partners who were engaged in a tit-for-tat strategy. This asymmetric (de)activation might involve specific contributions of ToM regions to the human search for reciprocity. Consequently, the intensity of emotion attached to human reciprocity was represented in the amygdala, whereas insight into the reciprocity of others was reflected in activation across the reward-related and ToM regions. This suggests the critical role of mentalizing, which was not equated with reward expectation during social interactions. PMID:24381534

Neural correlate of human reciprocity in social interactions.

PubMed

Sakaiya, Shiro; Shiraito, Yuki; Kato, Junko; Ide, Hiroko; Okada, Kensuke; Takano, Kouji; Kansaku, Kenji

2013-01-01

Reciprocity plays a key role maintaining cooperation in society. However, little is known about the neural process that underpins human reciprocity during social interactions. Our neuroimaging study manipulated partner identity (computer, human) and strategy (random, tit-for-tat) in repeated prisoner's dilemma games and investigated the neural correlate of reciprocal interaction with humans. Reciprocal cooperation with humans but exploitation of computers by defection was associated with activation in the left amygdala. Amygdala activation was also positively and negatively correlated with a preference change for human partners following tit-for-tat and random strategies, respectively. The correlated activation represented the intensity of positive feeling toward reciprocal and negative feeling toward non-reciprocal partners, and so reflected reciprocity in social interaction. Reciprocity in social interaction, however, might plausibly be misinterpreted and so we also examined the neural coding of insight into the reciprocity of partners. Those with and without insight revealed differential brain activation across the reward-related circuitry (i.e., the right middle dorsolateral prefrontal cortex and dorsal caudate) and theory of mind (ToM) regions [i.e., ventromedial prefrontal cortex (VMPFC) and precuneus]. Among differential activations, activation in the precuneus, which accompanied deactivation of the VMPFC, was specific to those without insight into human partners who were engaged in a tit-for-tat strategy. This asymmetric (de)activation might involve specific contributions of ToM regions to the human search for reciprocity. Consequently, the intensity of emotion attached to human reciprocity was represented in the amygdala, whereas insight into the reciprocity of others was reflected in activation across the reward-related and ToM regions. This suggests the critical role of mentalizing, which was not equated with reward expectation during social interactions.

Activities Contributing a Great Deal to the Students' Interactive Skills in Foreign Language Classes

ERIC Educational Resources Information Center

Asatryan, Susanna

2016-01-01

While teaching speaking it is desired to provide a rich environment in class for meaningful communication to take place. With this aim, various speaking activities can contribute a great deal to students in developing their interactive skills necessary for life. These activities make students active in the learning process and at the same time…

Role of Interaction in Enhancing the Epistemic Utility of 3D Mathematical Visualizations

ERIC Educational Resources Information Center

Liang, Hai-Ning; Sedig, Kamran

2010-01-01

Many epistemic activities, such as spatial reasoning, sense-making, problem solving, and learning, are information-based. In the context of epistemic activities involving mathematical information, learners often use interactive 3D mathematical visualizations (MVs). However, performing such activities is not always easy. Although it is generally…

ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1.

PubMed

You, Zhongsheng; Chahwan, Charly; Bailis, Julie; Hunter, Tony; Russell, Paul

2005-07-01

ATM has a central role in controlling the cellular responses to DNA damage. It and other phosphoinositide 3-kinase-related kinases (PIKKs) have giant helical HEAT repeat domains in their amino-terminal regions. The functions of these domains in PIKKs are not well understood. ATM activation in response to DNA damage appears to be regulated by the Mre11-Rad50-Nbs1 (MRN) complex, although the exact functional relationship between the MRN complex and ATM is uncertain. Here we show that two pairs of HEAT repeats in fission yeast ATM (Tel1) interact with an FXF/Y motif at the C terminus of Nbs1. This interaction resembles nucleoporin FXFG motif binding to HEAT repeats in importin-beta. Budding yeast Nbs1 (Xrs2) appears to have two FXF/Y motifs that interact with Tel1 (ATM). In Xenopus egg extracts, the C terminus of Nbs1 recruits ATM to damaged DNA, where it is subsequently autophosphorylated. This interaction is essential for ATM activation. A C-terminal 147-amino-acid fragment of Nbs1 that has the Mre11- and ATM-binding domains can restore ATM activation in an Nbs1-depleted extract. We conclude that an interaction between specific HEAT repeats in ATM and the C-terminal FXF/Y domain of Nbs1 is essential for ATM activation. We propose that conformational changes in the MRN complex that occur upon binding to damaged DNA are transmitted through the FXF/Y-HEAT interface to activate ATM. This interaction also retains active ATM at sites of DNA damage.

Robot-assisted therapy for improving social interactions and activity participation among institutionalized older adults: a pilot study.

PubMed

Sung, Huei-Chuan; Chang, Shu-Min; Chin, Mau-Yu; Lee, Wen-Li

2015-03-01

Animal-assisted therapy is gaining popularity as part of therapeutic activities for older adults in many long-term care facilities. However, concerns about dog bites, allergic responses to pets, disease, and insufficient available resources to care for a real pet have led to many residential care facilities to ban this therapy. There are situations where a substitute artificial companion, such as robotic pet, may serve as a better alternative. This pilot study used a one-group pre- and posttest design to evaluate the effect of a robot-assisted therapy for older adults. Sixteen eligible participants participated in the study and received a group robot-assisted therapy using a seal-like robot pet for 30 minutes twice a week for 4 weeks. All participants received assessments of their communication and interaction skills using the Assessment of Communication and Interaction Skills (ACIS-C) and activity participation using the Activity Participation Scale at baseline and at week 4. A total of 12 participants completed the study. Wilcoxon signed rank test showed that participants' communication and interaction skills (z = -2.94, P = 0.003) and activity participation (z = -2.66, P = 0.008) were significantly improved after receiving 4-week robot-assisted therapy. By interacting with a robot pet, such as Paro, the communication, interaction skills, and activity participation of the older adults can be improved. The robot-assisted therapy can be provided as a routine activity program and has the potential to improve social health of older adults in residential care facilities. Copyright © 2014 Wiley Publishing Asia Pty Ltd.

A novel actin binding site of myosin required for effective muscle contraction.

PubMed

Várkuti, Boglárka H; Yang, Zhenhui; Kintses, Bálint; Erdélyi, Péter; Bárdos-Nagy, Irén; Kovács, Attila L; Hári, Péter; Kellermayer, Miklós; Vellai, Tibor; Málnási-Csizmadia, András

2012-02-12

F-actin serves as a track for myosin's motor functions and activates its ATPase activity by several orders of magnitude, enabling actomyosin to produce effective force against load. Although actin activation is a ubiquitous property of all myosin isoforms, the molecular mechanism and physiological role of this activation are unclear. Here we describe a conserved actin-binding region of myosin named the 'activation loop', which interacts with the N-terminal segment of actin. We demonstrate by biochemical, biophysical and in vivo approaches using transgenic Caenorhabditis elegans strains that the interaction between the activation loop and actin accelerates the movement of the relay, stimulating myosin's ATPase activity. This interaction results in efficient force generation, but it is not essential for the unloaded motility. We conclude that the binding of actin to myosin's activation loop specifically increases the ratio of mechanically productive to futile myosin heads, leading to efficient muscle contraction.

Analyzing Reaction Rates with the Distortion/Interaction‐Activation Strain Model

PubMed Central

2017-01-01

Abstract The activation strain or distortion/interaction model is a tool to analyze activation barriers that determine reaction rates. For bimolecular reactions, the activation energies are the sum of the energies to distort the reactants into geometries they have in transition states plus the interaction energies between the two distorted molecules. The energy required to distort the molecules is called the activation strain or distortion energy. This energy is the principal contributor to the activation barrier. The transition state occurs when this activation strain is overcome by the stabilizing interaction energy. Following the changes in these energies along the reaction coordinate gives insights into the factors controlling reactivity. This model has been applied to reactions of all types in both organic and inorganic chemistry, including substitutions and eliminations, cycloadditions, and several types of organometallic reactions. PMID:28447369

Social interaction recruits mentalizing and reward systems in middle childhood.

PubMed

Alkire, Diana; Levitas, Daniel; Warnell, Katherine Rice; Redcay, Elizabeth

2018-06-08

Social cognition develops in the context of reciprocal social interaction. However, most neuroimaging studies of mentalizing have used noninteractive tasks that may fail to capture important aspects of real-world mentalizing. In adults, social-interactive context modulates activity in regions linked to social cognition and reward, but few interactive studies have been done with children. The current fMRI study examines children aged 8-12 using a novel paradigm in which children believed they were interacting online with a peer. We compared mental and non-mental state reasoning about a live partner (Peer) versus a story character (Character), testing the effects of mentalizing and social interaction in a 2 × 2 design. Mental versus Non-Mental reasoning engaged regions identified in prior mentalizing studies, including the temporoparietal junction, superior temporal sulcus, and dorsomedial prefrontal cortex. Moreover, peer interaction, even in conditions without explicit mentalizing demands, activated many of the same mentalizing regions. Peer interaction also activated areas outside the traditional mentalizing network, including the reward system. Our results demonstrate that social interaction engages multiple neural systems during middle childhood and contribute further evidence that social-interactive paradigms are needed to fully capture how the brain supports social processing in the real world. © 2018 Wiley Periodicals, Inc.

Interactions Increase Forager Availability and Activity in Harvester Ants.

PubMed

Pless, Evlyn; Queirolo, Jovel; Pinter-Wollman, Noa; Crow, Sam; Allen, Kelsey; Mathur, Maya B; Gordon, Deborah M

2015-01-01

Social insect colonies use interactions among workers to regulate collective behavior. Harvester ant foragers interact in a chamber just inside the nest entrance, here called the 'entrance chamber'. Previous studies of the activation of foragers in red harvester ants show that an outgoing forager inside the nest experiences an increase in brief antennal contacts before it leaves the nest to forage. Here we compare the interaction rate experienced by foragers that left the nest and ants that did not. We found that ants in the entrance chamber that leave the nest to forage experienced more interactions than ants that descend to the deeper nest without foraging. Additionally, we found that the availability of foragers in the entrance chamber is associated with the rate of forager return. An increase in the rate of forager return leads to an increase in the rate at which ants descend to the deeper nest, which then stimulates more ants to ascend into the entrance chamber. Thus a higher rate of forager return leads to more available foragers in the entrance chamber. The highest density of interactions occurs near the nest entrance and the entrances of the tunnels from the entrance chamber to the deeper nest. Local interactions with returning foragers regulate both the activation of waiting foragers and the number of foragers available to be activated.

A Novel Interaction between the SH2 Domain of Signaling Adaptor Protein Nck-1 and the Upstream Regulator of the Rho Family GTPase Rac1 Engulfment and Cell Motility 1 (ELMO1) Promotes Rac1 Activation and Cell Motility*

PubMed Central

Zhang, Guo; Chen, Xia; Qiu, Fanghua; Zhu, Fengxin; Lei, Wenjing; Nie, Jing

2014-01-01

Nck family proteins function as adaptors to couple tyrosine phosphorylation signals to actin cytoskeleton reorganization. Several lines of evidence indicate that Nck family proteins involve in regulating the activity of Rho family GTPases. In the present study, we characterized a novel interaction between Nck-1 with engulfment and cell motility 1 (ELMO1). GST pull-down and co-immunoprecipitation assay demonstrated that the Nck-1-ELMO1 interaction is mediated by the SH2 domain of Nck-1 and the phosphotyrosine residues at position 18, 216, 395, and 511 of ELMO1. A R308K mutant of Nck-1 (in which the SH2 domain was inactive), or a 4YF mutant of ELMO1 lacking these four phosphotyrosine residues, diminished Nck-1-ELMO1 interaction. Conversely, tyrosine phosphatase inhibitor treatment and overexpression of Src family kinase Hck significantly enhanced Nck-1-ELMO1 interaction. Moreover, wild type Nck-1, but not R308K mutant, significantly augmented the interaction between ELMO1 and constitutively active RhoG (RhoGV12A), thus promoted Rac1 activation and cell motility. Taken together, the present study characterized a novel Nck-1-ELMO1 interaction and defined a new role for Nck-1 in regulating Rac1 activity. PMID:24928514

The transcriptional co-activator p/CIP (NCoA-3) is up-regulated by STAT6 and serves as a positive regulator of transcriptional activation by STAT6.

PubMed

Arimura, Akinori; vn Peer, Maartje; Schröder, Andreas J; Rothman, Paul B

2004-07-23

Transcriptional activation by signal transducer and activator of transcription 6 (STAT6) has been shown to require the direct interaction not only with co-activators such as p300 and cAMP-responsive element-binding protein-binding protein (CBP) but also with nuclear co-activator 1, a member of the p160/steroid receptor co-activator family. Among the p160/steroid receptor co-activators, only p/CIP (nuclear co-activator 3) has been shown to be up-regulated by interleukin (IL)-4 in B cells through a STAT-6-dependent mechanism using Gene-Chip analysis. In this study, we have investigated the function of p/CIP in the transcriptional activation by STAT6. We found that p/CIP indirectly interacted with STAT6 via p300, and overexpression of the CBP-interacting domain of p/CIP (p/CIP(947-1084)) prevented the interaction of p/CIP with STAT6 by blocking the binding of p/CIP to p300. Whereas expression of p/CIP(947-1084) resulted in a marked reduction of STAT6-mediated transactivation, overexpression of wild type p/CIP resulted in significant enhancement of it. In addition, p/CIP(947-1084) markedly reduced CD23 expression on B cells stimulated with IL-4, whereas overexpression of wild type p/CIP enhanced it. Chromatin immunoprecipitations demonstrate that IL-4 increases the interaction of p/CIP with the murine immunoglobulin heavy chain germ line epsilon promoter in B cells. These results suggest that p/CIP positively regulates STAT6 transcriptional activation through formation of a STAT6, p300/CBP, and p/CIP complex.

Effect of ethyleneoxide groups of anionic surfactants on lipase activity.

PubMed

Magalhães, Solange S; Alves, Luís; Sebastião, Marco; Medronho, Bruno; Almeida, Zaida L; Faria, Tiago Q; Brito, Rui M M; Moreno, Maria J; Antunes, Filipe E

2016-09-01

The use of enzymes in laundry and dish detergent products is growing. Such tendency implies dedicated studies to understand surfactant-enzyme interactions. The interactions between surfactants and enzymes and their impact on the catalytic efficiency represent a central problem and were here evaluated using circular dichroism, dynamic light scattering, and enzyme activity determinations. This work focuses on this key issue by evaluating the role of the ethyleneoxide (EO) groups of anionic surfactants on the structure and activity of a commercial lipase, and by focusing on the protein/surfactant interactions at a molecular level. The conformational changes and enzymatic activity of the protein were evaluated in the presence of sodium dodecyl sulfate (SDS also denoted as SLE 0 S) and of sodium lauryl ether sulfate with two EO units (SLE 2 S). The results strongly suggest that the presence of EO units in the surfactant polar headgroup determines the stability and the activity of the enzyme. While SDS promotes enzyme denaturation and consequent loss of activity, SLE 2 S preserves the enzyme structure and activity. The data further highlights that the electrostatic interactions among the protein groups are changed by the presence of the adsorbed anionic surfactants being such absorption mainly driven by hydrophobic interactions. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1276-1282, 2016. © 2016 American Institute of Chemical Engineers.

Tyrosine dephosphorylation enhances the therapeutic target activity of epidermal growth factor receptor (EGFR) by disrupting its interaction with estrogen receptor (ER).

PubMed

Ma, Shao; Yin, Ning; Qi, Xiaomei; Pfister, Sandra L; Zhang, Mei-Jie; Ma, Rong; Chen, Guan

2015-05-30

Protein-protein interactions can increase or decrease its therapeutic target activity and the determining factors involved, however, are largely unknown. Here, we report that tyrosine-dephosphorylation of epidermal growth factor receptor (EGFR) increases its therapeutic target activity by disrupting its interaction with estrogen receptor (ER). Protein tyrosine phosphatase H1 (PTPH1) dephosphorylates the tyrosine kinase EGFR, disrupts its interaction with the nuclear receptor ER, and increases breast cancer sensitivity to small molecule tyrosine kinase inhibitors (TKIs). These effects require PTPH1 catalytic activity and its interaction with EGFR, suggesting that the phosphatase may increase the sensitivity by dephosphorylating EGFR leading to its dissociation with ER. Consistent with this notion, a nuclear-localization defective ER has a higher EGFR-binding activity and confers the resistance to TKI-induced growth inhibition. Additional analysis show that PTPH1 stabilizes EGFR, stimulates the membranous EGFR accumulation, and enhances the growth-inhibitory activity of a combination therapy of TKIs with an anti-estrogen. Since EGFR and ER both are substrates for PTPH1 in vitro and in intact cells, these results indicate that an inhibitory EGFR-ER protein complex can be switched off through a competitive enzyme-substrate binding. Our results would have important implications for the treatment of breast cancer with targeted therapeutics.

Latent myostatin has significant activity and this activity is controlled more efficiently by WFIKKN1 than by WFIKKN2

PubMed Central

Szláma, György; Trexler, Mária; Patthy, László

2013-01-01

Myostatin, a negative regulator of skeletal muscle growth, is produced from myostatin precursor by multiple steps of proteolytic processing. After cleavage by a furin-type protease, the propeptide and growth factor domains remain associated, forming a noncovalent complex, the latent myostatin complex. Mature myostatin is liberated from latent myostatin by bone morphogenetic protein 1/tolloid proteases. Here, we show that, in reporter assays, latent myostatin preparations have significant myostatin activity, as the noncovalent complex dissociates at an appreciable rate, and both mature and semilatent myostatin (a complex in which the dimeric growth factor domain interacts with only one molecule of myostatin propeptide) bind to myostatin receptor. The interaction of myostatin receptor with semilatent myostatin is efficiently blocked by WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 1 or growth and differentiation factor-associated serum protein 2 (WFIKKN1), a large extracellular multidomain protein that binds both mature myostatin and myostatin propeptide [Kondás et al. (2008) J Biol Chem 283, 23677–23684]. Interestingly, the paralogous protein WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 2 or growth and differentiation factor-associated serum protein 1 (WFIKKN2) was less efficient than WFIKKN1 as an antagonist of the interactions of myostatin receptor with semilatent myostatin. Our studies have shown that this difference is attributable to the fact that only WFIKKN1 has affinity for the propeptide domain, and this interaction increases its potency in suppressing the receptor-binding activity of semilatent myostatin. As the interaction of WFIKKN1 with various forms of myostatin permits tighter control of myostatin activity until myostatin is liberated from latent myostatin by bone morphogenetic protein 1/tolloid proteases, WFIKKN1 may have greater potential as an antimyostatic agent than WFIKKN2. Structured digital abstract Furin cleaves Promyostatin by protease assay (View interaction) myostatin binds to PRO by surface plasmon resonance (View interaction) BMP-1 cleaves Promyostatin by protease assay (View interaction) ACR IIB physically interacts with Latent Myostatin by surface plasmon resonance (View interaction) Promyostatin and Promyostatin bind by comigration in gel electrophoresis (View interaction) WFIKKN1 binds to Latent Myostatin by pull down (View interaction) ACR IIB binds to Mature Myostatin by surface plasmon resonance (View Interaction: 1, 2, 3) WFIKKN1 binds to Myostatin Prodomain by surface plasmon resonance (View Interaction: 1, 2, 3) PMID:23829672

An active site rearrangement within the Tetrahymena group I ribozyme releases nonproductive interactions and allows formation of catalytic interactions

PubMed Central

Sengupta, Raghuvir N.; Van Schie, Sabine N.S.; Giambaşu, George; Dai, Qing; Yesselman, Joseph D.; York, Darrin; Piccirilli, Joseph A.; Herschlag, Daniel

2016-01-01

Biological catalysis hinges on the precise structural integrity of an active site that binds and transforms its substrates and meeting this requirement presents a unique challenge for RNA enzymes. Functional RNAs, including ribozymes, fold into their active conformations within rugged energy landscapes that often contain misfolded conformers. Here we uncover and characterize one such “off-pathway” species within an active site after overall folding of the ribozyme is complete. The Tetrahymena group I ribozyme (E) catalyzes cleavage of an oligonucleotide substrate (S) by an exogenous guanosine (G) cofactor. We tested whether specific catalytic interactions with G are present in the preceding E•S•G and E•G ground-state complexes. We monitored interactions with G via the effects of 2′- and 3′-deoxy (–H) and −amino (–NH2) substitutions on G binding. These and prior results reveal that G is bound in an inactive configuration within E•G, with the nucleophilic 3′-OH making a nonproductive interaction with an active site metal ion termed MA and with the adjacent 2′-OH making no interaction. Upon S binding, a rearrangement occurs that allows both –OH groups to contact a different active site metal ion, termed MC, to make what are likely to be their catalytic interactions. The reactive phosphoryl group on S promotes this change, presumably by repositioning the metal ions with respect to G. This conformational transition demonstrates local rearrangements within an otherwise folded RNA, underscoring RNA's difficulty in specifying a unique conformation and highlighting Nature's potential to use local transitions of RNA in complex function. PMID:26567314

An active site rearrangement within the Tetrahymena group I ribozyme releases nonproductive interactions and allows formation of catalytic interactions.

PubMed

Sengupta, Raghuvir N; Van Schie, Sabine N S; Giambaşu, George; Dai, Qing; Yesselman, Joseph D; York, Darrin; Piccirilli, Joseph A; Herschlag, Daniel

2016-01-01

Biological catalysis hinges on the precise structural integrity of an active site that binds and transforms its substrates and meeting this requirement presents a unique challenge for RNA enzymes. Functional RNAs, including ribozymes, fold into their active conformations within rugged energy landscapes that often contain misfolded conformers. Here we uncover and characterize one such "off-pathway" species within an active site after overall folding of the ribozyme is complete. The Tetrahymena group I ribozyme (E) catalyzes cleavage of an oligonucleotide substrate (S) by an exogenous guanosine (G) cofactor. We tested whether specific catalytic interactions with G are present in the preceding E•S•G and E•G ground-state complexes. We monitored interactions with G via the effects of 2'- and 3'-deoxy (-H) and -amino (-NH(2)) substitutions on G binding. These and prior results reveal that G is bound in an inactive configuration within E•G, with the nucleophilic 3'-OH making a nonproductive interaction with an active site metal ion termed MA and with the adjacent 2'-OH making no interaction. Upon S binding, a rearrangement occurs that allows both -OH groups to contact a different active site metal ion, termed M(C), to make what are likely to be their catalytic interactions. The reactive phosphoryl group on S promotes this change, presumably by repositioning the metal ions with respect to G. This conformational transition demonstrates local rearrangements within an otherwise folded RNA, underscoring RNA's difficulty in specifying a unique conformation and highlighting Nature's potential to use local transitions of RNA in complex function. © 2015 Sengupta et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Alterations of social interaction through genetic and environmental manipulation of the 22q11.2 gene Sept5 in the mouse brain.

PubMed

Harper, Kathryn M; Hiramoto, Takeshi; Tanigaki, Kenji; Kang, Gina; Suzuki, Go; Trimble, William; Hiroi, Noboru

2012-08-01

Social behavior dysfunction is a symptomatic element of schizophrenia and autism spectrum disorder (ASD). Although altered activities in numerous brain regions are associated with defective social cognition and perception, the causative relationship between these altered activities and social cognition and perception-and their genetic underpinnings-are not known in humans. To address these issues, we took advantage of the link between hemizygous deletion of human chromosome 22q11.2 and high rates of social behavior dysfunction, schizophrenia and ASD. We genetically manipulated Sept5, a 22q11.2 gene, and evaluated its role in social interaction in mice. Sept5 deficiency, against a high degree of homogeneity in a congenic genetic background, selectively impaired active affiliative social interaction in mice. Conversely, virally guided overexpression of Sept5 in the hippocampus or, to a lesser extent, the amygdala elevated levels of active affiliative social interaction in C57BL/6J mice. Congenic knockout mice and mice overexpressing Sept5 in the hippocampus or amygdala were indistinguishable from control mice in novelty and olfactory responses, anxiety or motor activity. Moreover, post-weaning individual housing, an environmental condition designed to reduce stress in male mice, selectively raised levels of Sept5 protein in the amygdala and increased active affiliative social interaction in C57BL/6J mice. These findings identify this 22q11.2 gene in the hippocampus and amygdala as a determinant of social interaction and suggest that defective social interaction seen in 22q11.2-associated schizophrenia and ASD can be genetically and environmentally modified by altering this 22q11.2 gene.

Multiple Taf subunits of TFIID interact with Ino2 activation domains and contribute to expression of genes required for yeast phospholipid biosynthesis.

PubMed

Hintze, Stefan; Engelhardt, Maike; van Diepen, Laura; Witt, Eric; Schüller, Hans-Joachim

2017-12-01

Expression of phospholipid biosynthetic genes in yeast requires activator protein Ino2 which can bind to the UAS element inositol/choline-responsive element (ICRE) and trigger activation of target genes, using two separate transcriptional activation domains, TAD1 and TAD2. However, it is still unknown which cofactors mediate activation by TADs of Ino2. Here, we show that multiple subunits of basal transcription factor TFIID (TBP-associated factors Taf1, Taf4, Taf6, Taf10 and Taf12) are able to interact in vitro with activation domains of Ino2. Interaction was no longer observed with activation-defective variants of TAD1. We were able to identify two nonoverlapping regions in the N-terminus of Taf1 (aa 1-100 and aa 182-250) each of which could interact with TAD1 of Ino2 as well as with TAD4 of activator Adr1. Specific missense mutations within Taf1 domain aa 182-250 affecting basic and hydrophobic residues prevented interaction with wild-type TAD1 and caused reduced expression of INO1. Using chromatin immunoprecipitation we demonstrated Ino2-dependent recruitment of Taf1 and Taf6 to ICRE-containing promoters INO1 and CHO2. Transcriptional derepression of INO1 was no longer possible with temperature-sensitive taf1 and taf6 mutants cultivated under nonpermissive conditions. This result supports the hypothesis of Taf-dependent expression of structural genes activated by Ino2. © 2017 John Wiley & Sons Ltd.

Understanding Task-in-Process through the Lens of Laughter: Activity Designs, Instructional Materials, Learner Orientations, and Interpersonal Relationships

ERIC Educational Resources Information Center

Hasegawa, Atsushi

2018-01-01

Using the framework of conversation analysis, this study investigated the interactional workings of laughter in task-based interactions. The analysis was drawn from 160 cases of pair work interactions, collected in 2nd-semester Japanese-as-a-foreign-language classrooms. The pair work activities examined in this study are mostly grammar-focused,…

Cholinesterases: structure of the active site and mechanism of the effect of cholinergic receptor blockers on the rate of interaction with ligands

NASA Astrophysics Data System (ADS)

Antokhin, A. M.; Gainullina, E. T.; Taranchenko, V. F.; Ryzhikov, S. B.; Yavaeva, D. K.

2010-10-01

Modern views on the structure of cholinesterase active sites and the mechanism of their interaction with organophosphorus inhibitors are considered. The attention is focused on the mechanism of the effect of cholinergic receptor blockers, acetylcholine antagonists, on the rate of interaction of acetylcholine esterase with organophosphorus inhibitors.

Dealing with Emergence, Diversity and Multiplicity of Grammar and Interaction: The Japanese Clause-Ending Form TE

ERIC Educational Resources Information Center

Hashimoto, Yuria

2011-01-01

Grammar in natural interaction is an emergent, dynamic and adaptive system that is consistently subject to change. It is understood as a collection of open multiple subsystems, each of which is activated as the language users recurrently participate in a particular linguistic, interactional and social activity. When a certain linguistic form or…

Interaction of fucoidan with proteases and inhibitors of coagulation and fibrinolysis.

PubMed

Minix, R; Doctor, V M

1997-09-01

The interactions of fucoidan with glutamic plasminogen (Glu-Plg), two-chain tissue plasminogen activator (t-PA), LMwt-urokinase, thrombin, and antithrombin III (AT-III) were investigated using fucoidan-sepharose affinity chromatography. The results showed 1) a high degree of affinity between fucoidan-sepharose and Glu-Plg; Lmwt-urokinase and thrombin while t-Pa and AT-III did not bind with fucoidan-sepharose. 2) The double reciprocal plot for the LMwt-urokinase activation of Glu-Plg showed that plasminogen activator inhibitor (PAI-1) inhibited this reaction in a noncompetitive manner and that the presence of fucoidan decreased Km for this interaction by 50% and increased Kcat by 30-fold, 3) The double reciprocal plot for the t-PA activation of Glu-Plg showed that PAI-1 inhibited this reaction in a competitive manner and that fucoidan in conjunction with 6-aminohexanoic acid (6-AH) increased Kcat for this interaction by 5-fold without affecting Km. 4) Fucoidan enhanced the interaction of thrombin with both AT-III and heparin cofactor II (HC-II) and it was more effective than unfractionated heparin of LMwt-heparin in enhancing the interaction of HC-II with thrombin.

Ligand-Dependent Interaction of PPARδ With T-Cell Protein Tyrosine Phosphatase 45 Enhances Insulin Signaling.

PubMed

Yoo, Taesik; Ham, Sun Ah; Lee, Won Jin; Hwang, Seon In; Park, Jin-A; Hwang, Jung Seok; Hur, Jinwoo; Shin, Ho-Chul; Han, Sung Gu; Lee, Chi-Ho; Han, Dong Wook; Paek, Kyung Shin; Seo, Han Geuk

2018-03-01

Peroxisome proliferator-activated receptor (PPAR) δ plays a pivotal role in metabolic homeostasis through its effect on insulin signaling. Although diverse genomic actions of PPARδ are postulated, the specific molecular mechanisms whereby PPARδ controls insulin signaling have not been fully elucidated. We demonstrate here that short-term activation of PPARδ results in the formation of a stable complex with nuclear T-cell protein tyrosine phosphatase 45 (TCPTP45) isoform. This interaction of PPARδ with TCPTP45 blocked translocation of TCPTP45 into the cytoplasm, thereby preventing its interaction with the insulin receptor, which inhibits insulin signaling. Interaction of PPARδ with TCPTP45 blunted interleukin 6-induced insulin resistance, leading to retention of TCPTP45 in the nucleus, thereby facilitating deactivation of the signal transducer and activator of transcription 3 (STAT3)-suppressor of cytokine signaling 3 (SOCS3) signal. Finally, GW501516-activated PPARδ improved insulin signaling and glucose intolerance in mice fed a high-fat diet through its interaction with TCPTP45. This novel interaction of PPARδ constitutes the most upstream component identified of the mechanism downregulating insulin signaling. © 2017 by the American Diabetes Association.

Negotiating substance use stigma: the role of cultural health capital in provider–patient interactions

PubMed Central

Chang, Jamie; Dubbin, Leslie; Shim, Janet

2016-01-01

Diverse aspects of life and lifestyles, including stigmatised attributes and behaviors are revealed as providers and patients discuss health. In this article, we examine how the stigma associated with substance use issues shapes clinical interactions. We use the theoretical framework of cultural health capital (CHC) to explain how substance use stigma is created, reinforced and sometimes negotiated as providers and patients engage in health interactions. We present two main findings using examples. First, two theoretical concepts – habitus and field – set the social position and expectations of providers and patients in ways that facilitate the stigmatisation of substance use. Second, we found both providers and patients actively exchanged CHC as a key strategy to reduce the negative effects of stigma. In some clinical encounters, patients possessed and activated CHC, providers acknowledged patient’s CHC and CHC was successfully exchanged. These interactions were productive and mutually satisfying, even when patients were actively using substances. However, when CHC was not activated, acknowledged and exchanged, stigma was unchallenged and dominated the interaction. The CHC theoretical framework allows us to examine how the stigma process is operationalized and potentially even counteracted in clinical interactions. PMID:26382837

Plant-Derived Polyphenols Interact with Staphylococcal Enterotoxin A and Inhibit Toxin Activity

PubMed Central

Shimamura, Yuko; Aoki, Natsumi; Sugiyama, Yuka; Tanaka, Takashi; Murata, Masatsune; Masuda, Shuichi

2016-01-01

This study was performed to investigate the inhibitory effects of 16 different plant-derived polyphenols on the toxicity of staphylococcal enterotoxin A (SEA). Plant-derived polyphenols were incubated with the cultured Staphylococcus aureus C-29 to investigate the effects of these samples on SEA produced from C-29 using Western blot analysis. Twelve polyphenols (0.1–0.5 mg/mL) inhibited the interaction between the anti-SEA antibody and SEA. We examined whether the polyphenols could directly interact with SEA after incubation of these test samples with SEA. As a result, 8 polyphenols (0.25 mg/mL) significantly decreased SEA protein levels. In addition, the polyphenols that interacted with SEA inactivated the toxin activity of splenocyte proliferation induced by SEA. Polyphenols that exerted inhibitory effects on SEA toxic activity had a tendency to interact with SEA. In particular, polyphenol compounds with 1 or 2 hexahydroxydiphenoyl groups and/or a galloyl group, such as eugeniin, castalagin, punicalagin, pedunculagin, corilagin and geraniin, strongly interacted with SEA and inhibited toxin activity at a low concentration. These polyphenols may be used to prevent S. aureus infection and staphylococcal food poisoning. PMID:27272505

Plant-Derived Polyphenols Interact with Staphylococcal Enterotoxin A and Inhibit Toxin Activity.

PubMed

Shimamura, Yuko; Aoki, Natsumi; Sugiyama, Yuka; Tanaka, Takashi; Murata, Masatsune; Masuda, Shuichi

2016-01-01

This study was performed to investigate the inhibitory effects of 16 different plant-derived polyphenols on the toxicity of staphylococcal enterotoxin A (SEA). Plant-derived polyphenols were incubated with the cultured Staphylococcus aureus C-29 to investigate the effects of these samples on SEA produced from C-29 using Western blot analysis. Twelve polyphenols (0.1-0.5 mg/mL) inhibited the interaction between the anti-SEA antibody and SEA. We examined whether the polyphenols could directly interact with SEA after incubation of these test samples with SEA. As a result, 8 polyphenols (0.25 mg/mL) significantly decreased SEA protein levels. In addition, the polyphenols that interacted with SEA inactivated the toxin activity of splenocyte proliferation induced by SEA. Polyphenols that exerted inhibitory effects on SEA toxic activity had a tendency to interact with SEA. In particular, polyphenol compounds with 1 or 2 hexahydroxydiphenoyl groups and/or a galloyl group, such as eugeniin, castalagin, punicalagin, pedunculagin, corilagin and geraniin, strongly interacted with SEA and inhibited toxin activity at a low concentration. These polyphenols may be used to prevent S. aureus infection and staphylococcal food poisoning.

Negotiating substance use stigma: the role of cultural health capital in provider-patient interactions.

PubMed

Chang, Jamie; Dubbin, Leslie; Shim, Janet

2016-01-01

Diverse aspects of life and lifestyles, including stigmatised attributes and behaviors are revealed as providers and patients discuss health. In this article, we examine how the stigma associated with substance use issues shapes clinical interactions. We use the theoretical framework of cultural health capital (CHC) to explain how substance use stigma is created, reinforced and sometimes negotiated as providers and patients engage in health interactions. We present two main findings using examples. First, two theoretical concepts--habitus and field--set the social position and expectations of providers and patients in ways that facilitate the stigmatisation of substance use. Second, we found both providers and patients actively exchanged CHC as a key strategy to reduce the negative effects of stigma. In some clinical encounters, patients possessed and activated CHC, providers acknowledged patient's CHC and CHC was successfully exchanged. These interactions were productive and mutually satisfying, even when patients were actively using substances. However, when CHC was not activated, acknowledged and exchanged, stigma was unchallenged and dominated the interaction. The CHC theoretical framework allows us to examine how the stigma process is operationalized and potentially even counteracted in clinical interactions. © 2015 Foundation for the Sociology of Health & Illness.

Design of copper DNA intercalators with leishmanicidal activity.

PubMed

Navarro, Maribel; Cisneros-Fajardo, Efrén José; Sierralta, Aníbal; Fernández-Mestre, Mercedes; Silva, Pedro; Arrieche, Dwight; Marchán, Edgar

2003-04-01

The complexes [Cu(dppz)(NO(3))]NO(3) (1), [Cu(dppz)(2)(NO(3))]NO(3) (2), [Cu(dpq)(NO(3))]NO(3) (3), and [Cu(dpq)(2)(NO(3))]NO(3) (4) were synthesized and characterized by elemental analysis, FAB-mass spectrometry, EPR, UV, and IR spectroscopies, and molar conductivity. DNA interaction studies showed that intercalation is an important way of interacting with DNA for these complexes. The biological activity of these copper complexes was evaluated on Leishmania braziliensis promastigotes, and the results showed leishmanicidal activity. Preliminary ultrastructural studies with the most active complex (2) at 1 h revealed parasite swelling and binucleated cells. This finding suggests that the leishmanicidal activity of the copper complexes could be associated with their interaction with the parasitic DNA.

Cross-sectional interactions between quality of the physical and social environment and self-reported physical activity in adults living in income-deprived communities.

PubMed

Sawyer, Alexia D M; Jones, Russell; Ucci, Marcella; Smith, Lee; Kearns, Ade; Fisher, Abi

2017-01-01

Understanding the environmental determinants of physical activity in populations at high risk of inactivity could contribute to the development of effective interventions. Socioecological models of activity propose that environmental factors have independent and interactive effects of physical activity but there is a lack of research into interactive effects. This study aimed to explore independent and interactive effects of social and physical environmental factors on self-reported physical activity in income-deprived communities. Participants were 5,923 adults in Glasgow, United Kingdom. Features of the social environment were self-reported. Quality of the physical environment was objectively-measured. Neighbourhood walking and participation in moderate physical activity [MPA] on ≥5 days/week was self-reported. Multilevel multivariate logistic regression models tested independent and interactive effects of environmental factors on activity. 'Social support' (walking: OR:1.22,95%CI = 1.06-1.41,p<0.01; MPA: OR:0.79,95%CI = 0.67-0.94,p<0.01), 'social interaction' (walking: OR:1.25,95%CI = 1.10-1.42,p<0.01; MPA: OR:6.16,95%CI = 5.14-7.37,p<0.001) and 'cohesion and safety' (walking: OR:1.78,95%CI = 1.56-2.03,p<0.001; MPA: OR:1.93,95%CI = 1.65-2.27,p<0.001), but not 'trust and empowerment', had independent effects on physical activity. 'Aesthetics of built form' (OR:1.47,95%CI = 1.22-1.77,p<0.001) and 'aesthetics and maintenance of open space' (OR:1.32, 95%CI = 1.13-1.54,p<0.01) were related to walking. 'Physical disorder' (OR:1.63,95%CI = 1.31-2.03,p<0.001) had an independent effect on MPA. Interactive effects of social and physical factors on walking and MPA were revealed. Findings suggest that intervening to create activity-supportive environments in deprived communities may be most effective when simultaneously targeting the social and physical neighbourhood environment.

The Effect of Activity Type on the Engagement and Interaction of Young Children with Disabilities in Inclusive Childcare Settings

ERIC Educational Resources Information Center

Kemp, Coral; Kishida, Yuriko; Carter, Mark; Sweller, Naomi

2013-01-01

The engagement and adult and peer interaction of 37 young children with a range of disabilities was measured in free play, group, and meal-routine activities in inclusive childcare settings. A significant effect for activity type was found for total engagement, active engagement, and passive engagement, with the children being more engaged in…

Study of the functional hyperconnectivity between couples of pilots during flight simulation: an EEG hyperscanning study.

PubMed

Astolfi, L; Toppi, J; Borghini, G; Vecchiato, G; Isabella, R; De Vico Fallani, F; Cincotti, F; Salinari, S; Mattia, D; He, B; Caltagirone, C; Babiloni, F

2011-01-01

Brain Hyperscanning, i.e. the simultaneous recording of the cerebral activity of different human subjects involved in interaction tasks, is a very recent field of Neuroscience aiming at understanding the cerebral processes generating and generated by social interactions. This approach allows the observation and modeling of the neural signature specifically dependent on the interaction between subjects, and, even more interestingly, of the functional links existing between the activities in the brains of the subjects interacting together. In this EEG hyperscanning study we explored the functional hyperconnectivity between the activity in different scalp sites of couples of Civil Aviation Pilots during different phases of a flight reproduced in a flight simulator. Results shown a dense network of connections between the two brains in the takeoff and landing phases, when the cooperation between them is maximal, in contrast with phases during which the activity of the two pilots was independent, when no or quite few links were shown. These results confirms that the study of the brain connectivity between the activity simultaneously acquired in human brains during interaction tasks can provide important information about the neural basis of the "spirit of the group".

Activity-induced clustering in model dumbbell swimmers: the role of hydrodynamic interactions.

PubMed

Furukawa, Akira; Marenduzzo, Davide; Cates, Michael E

2014-08-01

Using a fluid-particle dynamics approach, we numerically study the effects of hydrodynamic interactions on the collective dynamics of active suspensions within a simple model for bacterial motility: each microorganism is modeled as a stroke-averaged dumbbell swimmer with prescribed dipolar force pairs. Using both simulations and qualitative arguments, we show that, when the separation between swimmers is comparable to their size, the swimmers' motions are strongly affected by activity-induced hydrodynamic forces. To further understand these effects, we investigate semidilute suspensions of swimmers in the presence of thermal fluctuations. A direct comparison between simulations with and without hydrodynamic interactions shows these to enhance the dynamic clustering at a relatively small volume fraction; with our chosen model the key ingredient for this clustering behavior is hydrodynamic trapping of one swimmer by another, induced by the active forces. Furthermore, the density dependence of the motility (of both the translational and rotational motions) exhibits distinctly different behaviors with and without hydrodynamic interactions; we argue that this is linked to the clustering tendency. Our study illustrates the fact that hydrodynamic interactions not only affect kinetic pathways in active suspensions, but also cause major changes in their steady state properties.

Glucagon gene polymorphism modifies the effects of smoking and physical activity on risk of type 2 diabetes mellitus in Han Chinese.

PubMed

Li, Linlin; Gao, Kaiping; Zhao, Jingzhi; Feng, Tianping; Yin, Lei; Wang, Jinjin; Wang, Chongjian; Li, Chunyang; Wang, Yan; Wang, Qian; Zhai, Yujia; You, Haifei; Ren, Yongcheng; Wang, Bingyuan; Hu, Dongsheng

2014-01-25

Few genome-wide association studies have considered interactions between multiple genetic variants and environmental factors associated with disease. The interaction was examined between a glucagon gene (GCG) polymorphism and smoking, alcohol consumption and physical activity and the association with risk of type 2 diabetes mellitus (T2DM) in a case-control study of Chinese Han subjects. The rs12104705 polymorphism of GCG and interactions with environmental variables were analyzed for 9619 participants by binary multiple logistic regression. Smoking with the C-C haplotype of rs12104705 was associated with increased risk of T2DM (OR=1.174, 95% CI=1.013-1.361). Moderate and high physical activity with the C-C genotype was associated with decreased risk of T2DM as compared with low physical activity with the genotype (OR=0.251, 95% CI=0.206-0.306 and OR=0.190, 95% CI=0.164-0.220). However, the interaction of drinking and genotype was not associated with risk of T2DM. Genetic polymorphism in rs12104705 of GCG may interact with smoking and physical activity to modify the risk of T2DM. © 2013.

Activity-induced clustering in model dumbbell swimmers: The role of hydrodynamic interactions

NASA Astrophysics Data System (ADS)

Furukawa, Akira; Marenduzzo, Davide; Cates, Michael E.

2014-08-01

Using a fluid-particle dynamics approach, we numerically study the effects of hydrodynamic interactions on the collective dynamics of active suspensions within a simple model for bacterial motility: each microorganism is modeled as a stroke-averaged dumbbell swimmer with prescribed dipolar force pairs. Using both simulations and qualitative arguments, we show that, when the separation between swimmers is comparable to their size, the swimmers' motions are strongly affected by activity-induced hydrodynamic forces. To further understand these effects, we investigate semidilute suspensions of swimmers in the presence of thermal fluctuations. A direct comparison between simulations with and without hydrodynamic interactions shows these to enhance the dynamic clustering at a relatively small volume fraction; with our chosen model the key ingredient for this clustering behavior is hydrodynamic trapping of one swimmer by another, induced by the active forces. Furthermore, the density dependence of the motility (of both the translational and rotational motions) exhibits distinctly different behaviors with and without hydrodynamic interactions; we argue that this is linked to the clustering tendency. Our study illustrates the fact that hydrodynamic interactions not only affect kinetic pathways in active suspensions, but also cause major changes in their steady state properties.

Marital Conflict and Children's Externalizing Behavior: Interactions between Parasympathetic and Sympathetic Nervous System Activity

ERIC Educational Resources Information Center

El-Sheikh, Mona; Kouros, Chrystyna D.; Erath, Stephen; Cummings, E. Mark; Keller, Peggy; Staton, Lori

2009-01-01

Toward greater specificity in the prediction of externalizing problems in the context of interparental conflict, interactions between children's parasympathetic and sympathetic nervous system (PNS and SNS) activity were examined as moderators. PNS activity was indexed by respiratory sinus arrhythmia (RSA) and RSA reactivity (RSA-R) to lab…

Affection Activities: Procedures for Encouraging Young Children with Handicaps to Interact with Their Peers.

ERIC Educational Resources Information Center

McEvoy, Mary A.; And Others

1990-01-01

Affection activities (such as hugging, smiling, and saying positive things) can be added to typical preschool games and songs to encourage interaction between handicapped children and nonhandicapped peers. The intervention can be adapted for use with children with diverse handicapping conditions. Typical activities, modified directions for…

Primary Numberplay: "InterActivities" for the Discovery of Mathematics Concepts. User's Guide.

ERIC Educational Resources Information Center

Sullivan, W. Edward

This document plus diskette product provides nine interactive puzzles and games that both teach and provide practice with simple addition and subtraction concepts. The activities address these skills through carrying in addition and regrouping in subtraction. The activities address cognitive skills such as problem solving, planning, visual pattern…

Gene–Physical Activity Interactions: Overview of Human Studies

PubMed Central

Rankinen, Tuomo; Bouchard, Claude

2009-01-01

Physical activity level is an important component of the total daily energy expenditure and as such contributes to body weight regulation. A body of data indicates that the level of physical activity plays a role in the risk of excessive weight gain, in weight loss programs, and particularly in the prevention of weight regain. Most studies dealing with potential gene–physical activity interaction effects use an exercise and fitness or performance paradigm as opposed to an obesity-driven model. From these studies, it is clear that there are considerable individual differences in the response to an exercise regimen and that there is a substantial familial aggregation component to the observed heterogeneity. Few studies have focused on the role of specific genes in accounting for the highly prevalent gene–exercise interaction effects. Results for specific genes have been inconsistent with few exceptions. Progress is likely to come when studies will be designed to truly address gene–exercise or physical activity interaction issues and with sample sizes that will provide adequate statistical power. PMID:19037212

Trans-synaptic zinc mobilization improves social interaction in two mouse models of autism through NMDAR activation.

PubMed

Lee, Eun-Jae; Lee, Hyejin; Huang, Tzyy-Nan; Chung, Changuk; Shin, Wangyong; Kim, Kyungdeok; Koh, Jae-Young; Hsueh, Yi-Ping; Kim, Eunjoon

2015-05-18

Genetic aspects of autism spectrum disorders (ASDs) have recently been extensively explored, but environmental influences that affect ASDs have received considerably less attention. Zinc (Zn) is a nutritional factor implicated in ASDs, but evidence for a strong association and linking mechanism is largely lacking. Here we report that trans-synaptic Zn mobilization rapidly rescues social interaction in two independent mouse models of ASD. In mice lacking Shank2, an excitatory postsynaptic scaffolding protein, postsynaptic Zn elevation induced by clioquinol (a Zn chelator and ionophore) improves social interaction. Postsynaptic Zn is mainly derived from presynaptic pools and activates NMDA receptors (NMDARs) through postsynaptic activation of the tyrosine kinase Src. Clioquinol also improves social interaction in mice haploinsufficient for the transcription factor Tbr1, which accompanies NMDAR activation in the amygdala. These results suggest that trans-synaptic Zn mobilization induced by clioquinol rescues social deficits in mouse models of ASD through postsynaptic Src and NMDAR activation.

N(epsilon)-carboxymethyllysine-modified proteins are unable to bind to RAGE and activate an inflammatory response.

PubMed

Buetler, Timo M; Leclerc, Estelle; Baumeyer, Alexandra; Latado, Helia; Newell, John; Adolfsson, Oskar; Parisod, Véronique; Richoz, Janique; Maurer, Sarah; Foata, Francis; Piguet, Dominique; Junod, Sylviane; Heizmann, Claus W; Delatour, Thierry

2008-03-01

Advanced glycation endproducts (AGEs) containing carboxymethyllysine (CML) modifications are generally thought to be ligands of the receptor for AGEs, RAGEs. It has been argued that this results in the activation of pro-inflammatory pathways and diseases. However, it has not been shown conclusively that a CML-modified protein can interact directly with RAGE. Here, we have analyzed whether beta-lactoglobulin (bLG) or human serum albumin (HSA) modified chemically to contain only CML (10-40% lysine modification) can (i) interact with RAGE in vitro and (ii) interact with and activate RAGE in lung epithelial cells. Our results show that CML-modified bLG or HSA are unable to bind to RAGE in a cell-free assay system (Biacore). Furthermore, they are unable to activate pro-inflammatory signaling in the cellular system. Thus, CML probably does not form the necessary structure(s) to interact with RAGE and activate an inflammatory signaling cascade in RAGE-expressing cells.

Contact processes with competitive dynamics in bipartite lattices: effects of distinct interactions

NASA Astrophysics Data System (ADS)

Pianegonda, Salete; Fiore, Carlos E.

2014-05-01

The two-dimensional contact process (CP) with a competitive dynamics proposed by Martins et al (2011 Phys. Rev. E 84 011125) leads to the appearance of an unusual active-asymmetric phase, in which the system sublattices are unequally populated. It differs from the usual CP only by the fact that particles also interact with their next-nearest neighbor sites via a distinct strength creation rate, and for the inclusion of an inhibition effect, proportional to the local density. Aimed at investigating the robustness of such an asymmetric phase, in this paper we study the influence of distinct interactions for two bidimensional CPs. In the first model, the interaction between first neighbors requires a minimal neighborhood of adjacent particles for creating new offspring, whereas second neighbors interact as usual (e.g. at least one neighboring particle is required). The second model takes the opposite situation, in which the restrictive dynamics is in the interaction between next-nearest neighbor sites. Both models are investigated under mean field theory (MFT) and Monte Carlo simulations. In similarity with results by Martins et al, the inclusion of distinct sublattice interactions maintains the occurrence of an asymmetric active phase and re-entrant transition lines. In contrast, remarkable differences are presented, such as discontinuous phase transitions (even between the active phases), the appearance of tricritical points and the stabilization of active phases under larger values of control parameters. Finally, we have shown that the critical behaviors are not altered due to the change of interactions, in which the absorbing transitions belong to the directed percolation (DP) universality class, whereas second-order active phase transitions belong to the Ising universality class.

Cortical activity and functional hyperconnectivity by simultaneous EEG recordings from interacting couples of professional pilots.

PubMed

Astolfi, L; Toppi, J; Borghini, G; Vecchiato, G; He, E J; Roy, A; Cincotti, F; Salinari, S; Mattia, D; He, B; Babiloni, F

2012-01-01

Controlling an aircraft during a flight is a compelling condition, which requires a strict and well coded interaction between the crew. The interaction level between the Captain and the First Officer changes during the flight, ranging from a maximum (during takeoff and landing, as well as in case of a failure of the instrumentation or other emergency situations) to a minimum during quiet mid-flight. In this study, our aim is to investigate the neural correlates of different kinds and levels of interaction between couples of professional crew members by means of the innovative technique called brain hyperscanning, i.e. the simultaneous recording of the hemodynamic or neuroelectrical activity of different human subjects involved in interaction tasks. This approach allows the observation and modeling of the neural signature specifically dependent on the interaction between subjects, and, even more interestingly, of the functional links existing between the brain activities of the subjects interacting together. In this EEG hyperscanning study, different phases of a flight were reproduced in a professional flight simulator, which allowed, on one side, to reproduce the ecological setting of a real flight, and, on the other, to keep under control the different levels of interaction induced in the crew by means of systematic and simulated failures of the aircraft instrumentation. Results of the procedure of linear inverse estimation, together with functional hyperconnectivity estimated by means of Partial Directed Coherence, showed a dense network of connections between the activity in the two brains in the takeoff and landing phases, when the cooperation between the crew is maximal, while conversely no significant links were shown during the phases in which the activity of the two pilots was independent.

Interaction with glycosaminoglycans is required for cyclophilin B to trigger integrin-mediated adhesion of peripheral blood T lymphocytes to extracellular matrix

PubMed Central

Allain, Fabrice; Vanpouille, Christophe; Carpentier, Mathieu; Slomianny, Marie-Christine; Durieux, Sandrine; Spik, Geneviève

2002-01-01

Cyclophilins A and B (CyPA and CyPB) are cyclosporin A-binding proteins that are involved in inflammatory events. We have reported that CyPB interacts with two types of cell-surface-binding sites. The first site corresponds to a functional receptor and requires interaction with the central core of CyPB. This region is highly conserved in cyclophilins, suggesting that CyPA and CyPB might share biological activities mediated by interaction with this receptor. The second site is identified with glycosaminoglycans (GAGs), the binding region located in the N terminus of CyPB. The difference in the N-terminal extensions of CyPA and CyPB suggests that a unique interaction with GAGs might account for selective activity of CyPB. To explore this hypothesis, we analyzed the lymphocyte responses triggered by CyPA, CyPB, and CyPBKKK−, a mutant unable to interact with GAGs. The three ligands seemed capable enough to elicit calcium signal and chemotaxis by binding to the same signaling receptor. In contrast, only CyPB enhanced firm adhesion of T cells to the extracellular matrix. This activity depended on the interactions with GAGs and signaling receptor. CyPB-mediated adhesion required CD147 presumably because it was a costimulatory molecule and was related to an activation of α4β1 and α4β7 integrins. Finally, we showed that CyPB was capable mainly to enhance T cell adhesion of the CD4+CD45RO+ subset. The present data indicate that CyPB rather than CyPA is a proinflammatory factor for T lymphocytes and highlight the crucial role of CyPB–GAG interaction in the chemokine-like activity of this protein. PMID:11867726

Interaction with glycosaminoglycans is required for cyclophilin B to trigger integrin-mediated adhesion of peripheral blood T lymphocytes to extracellular matrix.

PubMed

Allain, Fabrice; Vanpouille, Christophe; Carpentier, Mathieu; Slomianny, Marie-Christine; Durieux, Sandrine; Spik, Geneviève

2002-03-05

Cyclophilins A and B (CyPA and CyPB) are cyclosporin A-binding proteins that are involved in inflammatory events. We have reported that CyPB interacts with two types of cell-surface-binding sites. The first site corresponds to a functional receptor and requires interaction with the central core of CyPB. This region is highly conserved in cyclophilins, suggesting that CyPA and CyPB might share biological activities mediated by interaction with this receptor. The second site is identified with glycosaminoglycans (GAGs), the binding region located in the N terminus of CyPB. The difference in the N-terminal extensions of CyPA and CyPB suggests that a unique interaction with GAGs might account for selective activity of CyPB. To explore this hypothesis, we analyzed the lymphocyte responses triggered by CyPA, CyPB, and CyPB(KKK-), a mutant unable to interact with GAGs. The three ligands seemed capable enough to elicit calcium signal and chemotaxis by binding to the same signaling receptor. In contrast, only CyPB enhanced firm adhesion of T cells to the extracellular matrix. This activity depended on the interactions with GAGs and signaling receptor. CyPB-mediated adhesion required CD147 presumably because it was a costimulatory molecule and was related to an activation of alpha4beta1 and alpha4beta7 integrins. Finally, we showed that CyPB was capable mainly to enhance T cell adhesion of the CD4+CD45RO+ subset. The present data indicate that CyPB rather than CyPA is a proinflammatory factor for T lymphocytes and highlight the crucial role of CyPB-GAG interaction in the chemokine-like activity of this protein.

Interactive modeling activities in the classroom—rotational motion and smartphone gyroscopes

NASA Astrophysics Data System (ADS)

Pörn, Ray; Braskén, Mats

2016-11-01

The wide-spread availability of smartphones makes them a valuable addition to the measurement equipment in both the physics classroom and the instructional laboratory, encouraging an active interaction between measurements and modeling activities. In this paper we illustrate this interaction by making use of the internal gyroscope of a smartphone to study and measure the rotational dynamics of objects rotating about a fixed axis. The workflow described in this paper has been tested in a classroom setting and found to encourage an exploratory approach to both data collecting and modeling.

Functional interaction of glutathione S-transferase pi and peroxiredoxin 6 in intact cells.

PubMed

Zhou, Suiping; Lien, Yu-Chin; Shuvaeva, Tea; DeBolt, Kristine; Feinstein, Sheldon I; Fisher, Aron B

2013-02-01

Peroxiredoxin 6 (Prdx6) is a 1-Cys member of the peroxiredoxin superfamily that plays an important role in antioxidant defense. Glutathionylation of recombinant Prdx6 mediated by π glutathione S-transferase (GST) is required for reduction of the oxidized Cys and completion of the peroxidatic catalytic cycle in vitro. This study investigated the requirement for πGST in intact cells. Transfection with a plasmid construct expressing πGST into MCF7, a cell line that lacks endogenous πGST, significantly increased phospholipid peroxidase activity as measured in cell lysates and protected intact cells against a peroxidative stress. siRNA knockdown indicated that this increased peroxidase activity was Prdx6 dependent. Interaction between πGST and Prdx6, evaluated by the Duolink Proximity Ligation Assay, was minimal under basal conditions but increased dramatically following treatment of cells with the oxidant, tert-butyl hydroperoxide. Interaction was abolished by mutation of C47, the active site for Prdx6 peroxidase activity. Depletion of cellular GSH by treatment of cells with buthionine sulfoximine had no effect on the interaction of Prdx6 and πGST. These data are consistent with the hypothesis that oxidation of the catalytic cysteine in Prdx6 is required for its interaction with πGST and that the interaction plays an important role in regenerating the peroxidase activity of Prdx6. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Effects of Structured Physical Activity Program on Social Interaction and Communication for Children with Autism

PubMed Central

Zhao, Mengxian

2018-01-01

The purpose of this study was to investigate the effects of structured physical activity program on social interaction and communication of children with autism spectrum disorder (ASD). Fifty children with ASD from a special school were randomly divided into experimental and control groups. 25 children with ASD were placed in the experimental group, and the other 25 children as the control group participated in regular physical activity. A total of forty-one participants completed the study. A 12-week structured physical activity program was implemented with a total of 24 exercise sessions targeting social interaction and communication of children with ASD, and a quasi-experimental design was used for this study. Data were collected using quantitative and qualitative instruments. SSIS and ABLLS-R results showed that an overall improvement in social skills and social interaction for the experimental group across interim and posttests, F = 8.425, p = 0.001 (p < 0.005), and significant improvements appeared in communication, cooperation, social interaction, and self-control subdomains (p < 0.005). Conversely, no statistically significant differences were found in the control group (p > 0.005). The study concluded that the special structured physical activity program positively influenced social interaction and communication skills of children with ASD, especially in social skills, communication, prompt response, and frequency of expression. PMID:29568743

The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility.

PubMed

Lamontanara, Allan Joaquim; Georgeon, Sandrine; Tria, Giancarlo; Svergun, Dmitri I; Hantschel, Oliver

2014-11-17

The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both conformation and phosphorylation status to determine substrate access. In this study, we use recombinant Abl tyrosine kinases and conformation-specific kinase inhibitors to quantitatively analyse structural changes that occur after Abl activation. Allosteric SH2-kinase domain interactions were previously shown to be essential for the leukemogenesis caused by the Bcr-Abl oncoprotein. We find that these allosteric interactions switch the Abl activation loop from a closed to a fully open conformation. This enables the trans-autophosphorylation of the activation loop and requires prior phosphorylation of the SH2-kinase linker. Disruption of the SH2-kinase interaction abolishes activation loop phosphorylation. Our analysis provides a molecular mechanism for the SH2 domain-dependent activation of Abl that may also regulate other tyrosine kinases.

The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility

NASA Astrophysics Data System (ADS)

Lamontanara, Allan Joaquim; Georgeon, Sandrine; Tria, Giancarlo; Svergun, Dmitri I.; Hantschel, Oliver

2014-11-01

The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both conformation and phosphorylation status to determine substrate access. In this study, we use recombinant Abl tyrosine kinases and conformation-specific kinase inhibitors to quantitatively analyse structural changes that occur after Abl activation. Allosteric SH2-kinase domain interactions were previously shown to be essential for the leukemogenesis caused by the Bcr-Abl oncoprotein. We find that these allosteric interactions switch the Abl activation loop from a closed to a fully open conformation. This enables the trans-autophosphorylation of the activation loop and requires prior phosphorylation of the SH2-kinase linker. Disruption of the SH2-kinase interaction abolishes activation loop phosphorylation. Our analysis provides a molecular mechanism for the SH2 domain-dependent activation of Abl that may also regulate other tyrosine kinases.

Social Interaction Affects Neural Outcomes of Sign Language Learning As a Foreign Language in Adults.

PubMed

Yusa, Noriaki; Kim, Jungho; Koizumi, Masatoshi; Sugiura, Motoaki; Kawashima, Ryuta

2017-01-01

Children naturally acquire a language in social contexts where they interact with their caregivers. Indeed, research shows that social interaction facilitates lexical and phonological development at the early stages of child language acquisition. It is not clear, however, whether the relationship between social interaction and learning applies to adult second language acquisition of syntactic rules. Does learning second language syntactic rules through social interactions with a native speaker or without such interactions impact behavior and the brain? The current study aims to answer this question. Adult Japanese participants learned a new foreign language, Japanese sign language (JSL), either through a native deaf signer or via DVDs. Neural correlates of acquiring new linguistic knowledge were investigated using functional magnetic resonance imaging (fMRI). The participants in each group were indistinguishable in terms of their behavioral data after the instruction. The fMRI data, however, revealed significant differences in the neural activities between two groups. Significant activations in the left inferior frontal gyrus (IFG) were found for the participants who learned JSL through interactions with the native signer. In contrast, no cortical activation change in the left IFG was found for the group who experienced the same visual input for the same duration via the DVD presentation. Given that the left IFG is involved in the syntactic processing of language, spoken or signed, learning through social interactions resulted in an fMRI signature typical of native speakers: activation of the left IFG. Thus, broadly speaking, availability of communicative interaction is necessary for second language acquisition and this results in observed changes in the brain.

Dual Role for Hsc70 in the Biogenesis and Regulation of the Heme-Regulated Kinase of the α Subunit of Eukaryotic Translation Initiation Factor 2

PubMed Central

Uma, Sheri; Thulasiraman, Vanitha; Matts, Robert L.

1999-01-01

The heme-regulated kinase of the α subunit of eukaryotic initiation factor 2 (HRI) is activated in rabbit reticulocyte lysate (RRL) in response to a number of environmental conditions, including heme deficiency, heat shock, and oxidative stress. Activation of HRI causes an arrest of initiation of protein synthesis. Recently, we have demonstrated that the heat shock cognate protein Hsc70 negatively modulates the activation of HRI in RRL in response to these environmental conditions. Hsc70 is also known to be a critical component of the Hsp90 chaperone machinery in RRL, which plays an obligatory role for HRI to acquire and maintain a conformation that is competent to activate. Using de novo-synthesized HRI in synchronized pulse-chase translations, we have examined the role of Hsc70 in the regulation of HRI biogenesis and activation. Like Hsp90, Hsc70 interacted with nascent HRI and HRI that was matured to a state which was competent to undergo stimulus-induced activation (mature-competent HRI). Interaction of HRI with Hsc70 was required for the transformation of HRI, as the Hsc70 antagonist clofibric acid inhibited the folding of HRI into a mature-competent conformation. Unlike Hsp90, Hsc70 also interacted with transformed HRI. Clofibric acid disrupted the interaction of Hsc70 with transformed HRI that had been matured and transformed in the absence of the drug. Disruption of Hsc70 interaction with transformed HRI in heme-deficient RRL resulted in its hyperactivation. Furthermore, activation of HRI in response to heat shock or denatured proteins also resulted in a similar blockage of Hsc70 interaction with transformed HRI. These results indicate that Hsc70 is required for the folding and transformation of HRI into an active kinase but is subsequently required to negatively attenuate the activation of transformed HRI. PMID:10454533

Formation of readiness for future physics teachers by using interactive learning tools

NASA Astrophysics Data System (ADS)

Kulikova, N. U.; Danilchuk, E. V.; Zhidkova, A. V.

2017-01-01

In this article we give the reviewing of approaches to the preparedness of future physics teachers for the usage of interactive means of education as an important part of their professional activity. We discuss the key concepts such as interactivity, an interactive dialogue, and interactive means of education. The conception of interactive means of education as a tool of teachers' professional activity, which provides a way for the students to intensify their learning in class by using interactive tools and electronic educational resources, is validated. Furthermore, it is proved that interactive means of education allow the students to intensify their learning in the course of an interactive dialogue by means of organization different types of feedback in electronic educational resources (the program behavior depending on a user actions in the form of comments, prompts, elements of arrangement of objects, etc, the control and correction of students' actions by the program, providing with recommendations for further learning, carrying out constant access to reference information, etc), involving in different types of educational activity (modeling, investigation, etc), self-selection of time, speed, content of learning, complexity and priority of the usage of educational information on the screen, etc. By training students - future teachers of physics authors consider technological aspects, methodical features and examples of creation of these resources for physics lesson.

InterACTIVE Interpreted Interviews (I3): A multi-lingual, mobile method to examine the neighbourhood environment with older adults.

PubMed

Tong, Catherine; Sims-Gould, Joanie; McKay, Heather

2016-11-01

The global population is aging and older adults overwhelmingly wish to age in place. A positive neighbourhood context is crucial for the wellbeing of older adults. The ability to age in place is predicated on mobility; mobility is the capacity to move oneself around the home and community using a variety of modes. Segments of the population have been entirely overlooked within the mobility and built environment literature; we know surprisingly little about foreign-born older adults (FBOAs). We sought to understand the impact of the neighbourhood environment on the mobility and physical activity of FBOAs. To do so we endeavoured to develop an interview tool that would allow us to interact with the environment alongside, or through the eyes of, our participants. This article outlines lessons learned following design and implementation of an interview approach that we conducted with FBOAs -- "InterACTIVE Interpreted Interviews (I 3 )". We used the interACTIVE interview approach in a large mixed-method study on FBOA mobility in Vancouver, Canada. All aspects of the study were offered in Hindi, Punjabi, Cantonese, Mandarin and English, with the aid of professional interpreters. Twenty FBOAs completed in-depth qualitative interviews. Of these, thirteen completed the mobile, interACTIVE interview. The interACTIVE interview consisted of a neighbourhood walk, guided by the participant. Our approach integrated elements of participant observation, researcher participation, and unstructured interviewing to enrich discussions with participants. The interACTIVE approach deepened our understanding of neighbourhood context and allowed researchers and participants to overcome issues inherent in language interpretation. We were able to overcome concerns of privacy, safety and comfort to successfully implement this observational tool and recommend it as an attractive, alternative approach for those conducting studies with FBOAs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Investigating Catalyst–Support Interactions To Improve the Hydrogen Evolution Reaction Activity of Thiomolybdate [Mo 3 S 13 ] 2– Nanoclusters

DOE PAGES

Hellstern, Thomas R.; Kibsgaard, Jakob; Tsai, Charlie; ...

2017-09-22

Molybdenum sulfides have been identified as promising materials for catalyzing the hydrogen evolution reaction (HER) in acid, with active edge sites that exhibit some of the highest turnover frequencies among nonpreciousmetal catalysts. The thiomolybdate [Mo 3S 13] 2- nanocluster catalyst contains a structural motif that resembles the active site of MoS 2 and has been reported to be among the most active forms of molybdenum sulfide. Herein, we improve the activity of the [Mo 3S 13] 2- catalysts through catalyst-support interactions. We synthesize [Mo 3S 13] 2- on gold, silver, glassy carbon, and copper supports to demonstrate the ability tomore » tune the hydrogen binding energy of [Mo 3S 13] 2- using catalyst-support electronic interactions and optimize HER activity.« less

Investigating Catalyst–Support Interactions To Improve the Hydrogen Evolution Reaction Activity of Thiomolybdate [Mo 3 S 13 ] 2– Nanoclusters

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

Hellstern, Thomas R.; Kibsgaard, Jakob; Tsai, Charlie

Molybdenum sulfides have been identified as promising materials for catalyzing the hydrogen evolution reaction (HER) in acid, with active edge sites that exhibit some of the highest turnover frequencies among nonpreciousmetal catalysts. The thiomolybdate [Mo 3S 13] 2- nanocluster catalyst contains a structural motif that resembles the active site of MoS 2 and has been reported to be among the most active forms of molybdenum sulfide. Herein, we improve the activity of the [Mo 3S 13] 2- catalysts through catalyst-support interactions. We synthesize [Mo 3S 13] 2- on gold, silver, glassy carbon, and copper supports to demonstrate the ability tomore » tune the hydrogen binding energy of [Mo 3S 13] 2- using catalyst-support electronic interactions and optimize HER activity.« less

77 FR 32943 - Takes of Marine Mammals Incidental to Specified Activities; Pile Driving in the Columbia River, WA

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-04

..., (1) social interactions; (2) foraging; (3) orientation; and (4) predator detection. Interference with...-strike, gear interaction, and/or entanglement), the Port shall immediately cease the specified activities...

Unfolding large-scale online collaborative human dynamics

PubMed Central

Zha, Yilong; Zhou, Tao; Zhou, Changsong

2016-01-01

Large-scale interacting human activities underlie all social and economic phenomena, but quantitative understanding of regular patterns and mechanism is very challenging and still rare. Self-organized online collaborative activities with a precise record of event timing provide unprecedented opportunity. Our empirical analysis of the history of millions of updates in Wikipedia shows a universal double–power-law distribution of time intervals between consecutive updates of an article. We then propose a generic model to unfold collaborative human activities into three modules: (i) individual behavior characterized by Poissonian initiation of an action, (ii) human interaction captured by a cascading response to previous actions with a power-law waiting time, and (iii) population growth due to the increasing number of interacting individuals. This unfolding allows us to obtain an analytical formula that is fully supported by the universal patterns in empirical data. Our modeling approaches reveal “simplicity” beyond complex interacting human activities. PMID:27911766

Solution characterization of the extracellular region of CD147 and its interaction with its enzyme ligand cyclophilin-A

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

Schlegel, Jennifer; Redzic, Jasmina S.; Porter, Christopher

2009-08-21

The CD147 receptor plays an integral role in numerous diseases by stimulating the expression of several protein families and serving as the receptor for extracellular cyclophilins, however, neither CD147 nor its interactions with its cyclophilin ligands have been well characterized in solution. CD147 is a unique protein in that it can function both at the cell membrane and after being released from cells where it continues to retain activity. Thus, the CD147 receptor functions through at least two mechanisms that include both cyclophilin-independent and cyclophilin-dependent modes of action. In regard to CD147 cyclophilin-independent activity, CD147 homophilic interactions are thought tomore » underlie its activity. In regard to CD147 cyclophilin-dependent activity, cyclophilin/CD147 interactions may represent a novel means of signaling since cyclophilins are also peptidyl-prolyl isomerases.« less

The two-brain approach: how can mutually interacting brains teach us something about social interaction?

PubMed Central

Konvalinka, Ivana; Roepstorff, Andreas

2012-01-01

Measuring brain activity simultaneously from two people interacting is intuitively appealing if one is interested in putative neural markers of social interaction. However, given the complex nature of interactions, it has proven difficult to carry out two-person brain imaging experiments in a methodologically feasible and conceptually relevant way. Only a small number of recent studies have put this into practice, using fMRI, EEG, or NIRS. Here, we review two main two-brain methodological approaches, each with two conceptual strategies. The first group has employed two-brain fMRI recordings, studying (1) turn-based interactions on the order of seconds, or (2) pseudo-interactive scenarios, where only one person is scanned at a time, investigating the flow of information between brains. The second group of studies has recorded dual EEG/NIRS from two people interacting, in (1) face-to-face turn-based interactions, investigating functional connectivity between theory-of-mind regions of interacting partners, or in (2) continuous mutual interactions on millisecond timescales, to measure coupling between the activity in one person's brain and the activity in the other's brain. We discuss the questions these approaches have addressed, and consider scenarios when simultaneous two-brain recordings are needed. Furthermore, we suggest that (1) quantification of inter-personal neural effects via measures of emergence, and (2) multivariate decoding models that generalize source-specific features of interaction, may provide novel tools to study brains in interaction. This may allow for a better understanding of social cognition as both representation and participation. PMID:22837744

Using PyMOL to Explore the Effects of ph on Noncovalent Interactions between Immunoglobulin G and Protein A: A Guided-Inquiry Biochemistry Activity

ERIC Educational Resources Information Center

Roche Allred, Zahilyn D.; Tai, Heeyoung; Bretz, Stacey Lowery; Page, Richard C.

2017-01-01

Students' understandings of foundational concepts such as noncovalent interactions, pH and pK[subscript a] are crucial for success in undergraduate biochemistry courses. We developed a guided-inquiry activity to aid students in making connections between noncovalent interactions and pH/pK[subscript a]. Students explore these concepts by examining…

Miming the cancer-immune system competition by kinetic Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Bianca, Carlo; Lemarchand, Annie

2016-10-01

In order to mimic the interactions between cancer and the immune system at cell scale, we propose a minimal model of cell interactions that is similar to a chemical mechanism including autocatalytic steps. The cells are supposed to bear a quantity called activity that may increase during the interactions. The fluctuations of cell activity are controlled by a so-called thermostat. We develop a kinetic Monte Carlo algorithm to simulate the cell interactions and thermalization of cell activity. The model is able to reproduce the well-known behavior of tumors treated by immunotherapy: the first apparent elimination of the tumor by the immune system is followed by a long equilibrium period and the final escape of cancer from immunosurveillance.

Investigation on the interaction of catalase with sodium lauryl sulfonate and the underlying mechanisms.

PubMed

Wang, Jing; Jia, Rui; Wang, Jiaxi; Sun, Zhiqiang; Wu, Zitao; Liu, Rutao; Zong, Wansong

2018-02-01

As a classic type of anionic surfactants, sodium lauryl sulfonate (SLS) might change the structure and function of antioxidant enzyme catalase (CAT) through their direct interactions. However, the underlying molecular mechanism is still unknown. This study investigated the direct interaction of SLS with CAT molecule and the underlying mechanisms using multi-spectroscopic methods, isothermal titration calorimetry, and molecular docking studies. No obvious effects were observed on CAT structure and activity under low SLS concentration exposure. The particle size of CAT molecule decreased and CAT activity was slightly inhibited under high SLS concentration exposure. SLS prefers to bind to the interface of CAT mainly via van der Waals' forces and hydrogen bonds. Subsequently, SLS interacts with the amino acid residues around the heme groups of CAT via hydrophobic interactions and might inhibit CAT activity. © 2017 Wiley Periodicals, Inc.

[Social interactions of preschool children with Down syndrome during extracurricular activities].

PubMed

Lucisano, Renata Valdívia; Pfeifer, Luzia Iara; Pinto, Maria Paula Panuncio; Santos, Jair Lício Ferreira; Anhão, Patrícia Páfaro Gomes

2013-01-01

The aim of this research was to identify the process of social interaction of children with Down Syndrome (DS) during extracurricular activities in the regular early childhood education in Ribeirão Preto-SP, Brazil. Six children aged 3-6 years participated in this study. There were two recordings of each child in situations of social interaction during extracurricular activities, and analyzed by 15 behaviors, divided into two categories of social skills: interpersonal and self-expression. The results demonstrate that, in the interpersonal skill category, the higher occurrence was the behavior "occurs interaction with other children". In the self-expression skills category, only the behaviors "smiles" and "imitates other children" have significant occurrence. The behaviors more frequently identified in this study permit to understand that the school environment is a facilitator for the interaction of child with DS with the typical developmental children, allowing him/her to develop the expected social skills.

Complete active space configuration interaction from state-averaged configuration interaction singles natural orbitals: Analytic first derivatives and derivative coupling vectors

NASA Astrophysics Data System (ADS)

Fales, B. Scott; Shu, Yinan; Levine, Benjamin G.; Hohenstein, Edward G.

2017-09-01

A new complete active space configuration interaction (CASCI) method was recently introduced that uses state-averaged natural orbitals from the configuration interaction singles method (configuration interaction singles natural orbital CASCI, CISNO-CASCI). This method has been shown to perform as well or better than state-averaged complete active space self-consistent field for a variety of systems. However, further development and testing of this method have been limited by the lack of available analytic first derivatives of the CISNO-CASCI energy as well as the derivative coupling between electronic states. In the present work, we present a Lagrangian-based formulation of these derivatives as well as a highly efficient implementation of the resulting equations accelerated with graphical processing units. We demonstrate that the CISNO-CASCI method is practical for dynamical simulations of photochemical processes in molecular systems containing hundreds of atoms.

Complete active space configuration interaction from state-averaged configuration interaction singles natural orbitals: Analytic first derivatives and derivative coupling vectors.

PubMed

Fales, B Scott; Shu, Yinan; Levine, Benjamin G; Hohenstein, Edward G

2017-09-07

A new complete active space configuration interaction (CASCI) method was recently introduced that uses state-averaged natural orbitals from the configuration interaction singles method (configuration interaction singles natural orbital CASCI, CISNO-CASCI). This method has been shown to perform as well or better than state-averaged complete active space self-consistent field for a variety of systems. However, further development and testing of this method have been limited by the lack of available analytic first derivatives of the CISNO-CASCI energy as well as the derivative coupling between electronic states. In the present work, we present a Lagrangian-based formulation of these derivatives as well as a highly efficient implementation of the resulting equations accelerated with graphical processing units. We demonstrate that the CISNO-CASCI method is practical for dynamical simulations of photochemical processes in molecular systems containing hundreds of atoms.

Coordinated Interaction between Hippocampal Sharp-Wave Ripples and Anterior Cingulate Unit Activity

PubMed Central

2016-01-01

Hippocampal–cortical interaction during sleep promotes transformation of memory for long-term storage in the cortex. In particular, hippocampal sharp-wave ripple-associated neural activation is important for this transformation during slow-wave sleep. The anterior cingulate cortex (ACC) has been shown to be crucial for expression and likely storage of long-term memory. However, little is known about how ACC activity is influenced by hippocampal ripple activity during sleep. We report here about coordinated interactions between hippocampal ripple activity and ACC neural firings. By recording from the ACC and hippocampal CA1 simultaneously in mice, we found that almost all ACC neurons showed increased activity before hippocampal ripple activity; moreover, a subpopulation (17%) displayed a further activation immediately after ripple activity. This postripple activation of ACC neurons correlated positively with ripple amplitude, and the same neurons were excited upon electrical stimulation of the CA1. Interestingly, the preripple activation of ACC neurons was present during the sleep state, but not during the awake state. These results suggest intimate interactions between hippocampal sharp-wave ripples and ACC neurons in a state-dependent manner. Importantly, sharp-wave ripples and associated activation appear to regulate activity of a small population of ACC neurons, a process that may play a critical role in memory consolidation. SIGNIFICANCE STATEMENT The hippocampus communicates with the cortex for memory transformation. Memories of previous experiences become less dependent on the hippocampus and increasingly dependent on cortical areas, such as the anterior cingulate cortex (ACC). However, little evidence is available to directly support this hippocampus-to-cortex information transduction hypothesis of memory consolidation. Here we show that a subpopulation of ACC neurons becomes active just after hippocampal ripple activity, and that electrical stimulation of the hippocampus excites the same ACC neurons. In addition, the majority of ACC neurons are activated just before ripple activity during the sleep state, but not during the awake state. These results provide evidence supporting the hypothesis of hippocampus-to-cortex information flow for memory consolidation as well as reciprocal interaction between the hippocampus and the cortex. PMID:27733616

[The Ability to Successfully Perform Different Kinds of Cognitive Activity Is Reflected in the Topological Features of Intracortical Interactions (Sex Differences in Boys and Girls Aged 5-6 Years)].

PubMed

Panasevich, E A; Tsitseroshin, M N

2015-01-01

We studied the correlation of intellectual development according to The Wechsler Intelligence Scale for Children (WISC test) with the spatial organization of resting EEG in 52 children aged 5-6 years. It was found that the patterns of interregional interactions of different parts of the cortex which correspond with the best performance in the subtests in boys (n = 23) and girls (n = 29) have significant topological differences. In girls, successful subtest performance positively correlated to a greater extent with interhemispheric interactions; in boys--long longitudinal rostral-caudal interactions between various regions of the cortex. The results showed that there are important gender differences in the spatial organization of brain activity associated with the performance of different cognitive activities in preschool children. The successful performance of various subtests by boys required considerable variability in the organization of spatial patterns of interregional interactions; on the contrary, the spatial structure of these patterns in girls was relatively invariable. Obviously, for the successful performance of various cognitive activities at this age in boys, the cortex need to form highly specialized organization of intracortical interactions, while in girls the brain uses relatively similar reorganization of interactions. The data suggest that 5-6-year-old boys and girls use different cognitive strategies when performing the same subtests of the WISC test.

Interactions Increase Forager Availability and Activity in Harvester Ants

PubMed Central

Pinter-Wollman, Noa; Crow, Sam; Allen, Kelsey; Mathur, Maya B.; Gordon, Deborah M.

2015-01-01

Social insect colonies use interactions among workers to regulate collective behavior. Harvester ant foragers interact in a chamber just inside the nest entrance, here called the 'entrance chamber'. Previous studies of the activation of foragers in red harvester ants show that an outgoing forager inside the nest experiences an increase in brief antennal contacts before it leaves the nest to forage. Here we compare the interaction rate experienced by foragers that left the nest and ants that did not. We found that ants in the entrance chamber that leave the nest to forage experienced more interactions than ants that descend to the deeper nest without foraging. Additionally, we found that the availability of foragers in the entrance chamber is associated with the rate of forager return. An increase in the rate of forager return leads to an increase in the rate at which ants descend to the deeper nest, which then stimulates more ants to ascend into the entrance chamber. Thus a higher rate of forager return leads to more available foragers in the entrance chamber. The highest density of interactions occurs near the nest entrance and the entrances of the tunnels from the entrance chamber to the deeper nest. Local interactions with returning foragers regulate both the activation of waiting foragers and the number of foragers available to be activated. PMID:26539724

Effects of multiple enzyme-substrate interactions in basic units of cellular signal processing

NASA Astrophysics Data System (ADS)

Seaton, D. D.; Krishnan, J.

2012-08-01

Covalent modification cycles are a ubiquitous feature of cellular signalling networks. In these systems, the interaction of an active enzyme with the unmodified form of its substrate is essential for signalling to occur. However, this interaction is not necessarily the only enzyme-substrate interaction possible. In this paper, we analyse the behaviour of a basic model of signalling in which additional, non-essential enzyme-substrate interactions are possible. These interactions include those between the inactive form of an enzyme and its substrate, and between the active form of an enzyme and its product. We find that these additional interactions can result in increased sensitivity and biphasic responses, respectively. The dynamics of the responses are also significantly altered by the presence of additional interactions. Finally, we evaluate the consequences of these interactions in two variations of our basic model, involving double modification of substrate and scaffold-mediated signalling, respectively. We conclude that the molecular details of protein-protein interactions are important in determining the signalling properties of enzymatic signalling pathways.

Construction of CASCI-type wave functions for very large active spaces.

PubMed

Boguslawski, Katharina; Marti, Konrad H; Reiher, Markus

2011-06-14

We present a procedure to construct a configuration-interaction expansion containing arbitrary excitations from an underlying full-configuration-interaction-type wave function defined for a very large active space. Our procedure is based on the density-matrix renormalization group (DMRG) algorithm that provides the necessary information in terms of the eigenstates of the reduced density matrices to calculate the coefficient of any basis state in the many-particle Hilbert space. Since the dimension of the Hilbert space scales binomially with the size of the active space, a sophisticated Monte Carlo sampling routine is employed. This sampling algorithm can also construct such configuration-interaction-type wave functions from any other type of tensor network states. The configuration-interaction information obtained serves several purposes. It yields a qualitatively correct description of the molecule's electronic structure, it allows us to analyze DMRG wave functions converged for the same molecular system but with different parameter sets (e.g., different numbers of active-system (block) states), and it can be considered a balanced reference for the application of a subsequent standard multi-reference configuration-interaction method.

Genetically determined interaction between the dopamine transporter and the D2 receptor on prefronto-striatal activity and volume in humans.

PubMed

Bertolino, Alessandro; Fazio, Leonardo; Di Giorgio, Annabella; Blasi, Giuseppe; Romano, Raffaella; Taurisano, Paolo; Caforio, Grazia; Sinibaldi, Lorenzo; Ursini, Gianluca; Popolizio, Teresa; Tirotta, Emanuele; Papp, Audrey; Dallapiccola, Bruno; Borrelli, Emiliana; Sadee, Wolfgang

2009-01-28

Dopamine modulation of neuronal activity during memory tasks identifies a nonlinear inverted-U shaped function. Both the dopamine transporter (DAT) and dopamine D(2) receptors (encoded by DRD(2)) critically regulate dopamine signaling in the striatum and in prefrontal cortex during memory. Moreover, in vitro studies have demonstrated that DAT and D(2) proteins reciprocally regulate each other presynaptically. Therefore, we have evaluated the genetic interaction between a DRD(2) polymorphism (rs1076560) causing reduced presynaptic D(2) receptor expression and the DAT 3'-VNTR variant (affecting DAT expression) in a large sample of healthy subjects undergoing blood oxygenation level-dependent (BOLD)-functional magnetic resonance imaging (MRI) during memory tasks and structural MRI. Results indicated a significant DRD(2)/DAT interaction in prefrontal cortex and striatum BOLD activity during both working memory and encoding of recognition memory. The differential effect on BOLD activity of the DAT variant was mostly manifest in the context of the DRD(2) allele associated with lower presynaptic expression. Similar results were also evident for gray matter volume in caudate. These interactions describe a nonlinear relationship between compound genotypes and brain activity or gray matter volume. Complementary data from striatal protein extracts from wild-type and D(2) knock-out animals (D2R(-/-)) indicate that DAT and D(2) proteins interact in vivo. Together, our results demonstrate that the interaction between genetic variants in DRD(2) and DAT critically modulates the nonlinear relationship between dopamine and neuronal activity during memory processing.

Interactive computer-assisted instruction in acid-base physiology for mobile computer platforms.

PubMed

Longmuir, Kenneth J

2014-03-01

In this project, the traditional lecture hall presentation of acid-base physiology in the first-year medical school curriculum was replaced by interactive, computer-assisted instruction designed primarily for the iPad and other mobile computer platforms. Three learning modules were developed, each with ∼20 screens of information, on the subjects of the CO2-bicarbonate buffer system, other body buffer systems, and acid-base disorders. Five clinical case modules were also developed. For the learning modules, the interactive, active learning activities were primarily step-by-step learner control of explanations of complex physiological concepts, usually presented graphically. For the clinical cases, the active learning activities were primarily question-and-answer exercises that related clinical findings to the relevant basic science concepts. The student response was remarkably positive, with the interactive, active learning aspect of the instruction cited as the most important feature. Also, students cited the self-paced instruction, extensive use of interactive graphics, and side-by-side presentation of text and graphics as positive features. Most students reported that it took less time to study the subject matter with this online instruction compared with subject matter presented in the lecture hall. However, the approach to learning was highly examination driven, with most students delaying the study of the subject matter until a few days before the scheduled examination. Wider implementation of active learning computer-assisted instruction will require that instructors present subject matter interactively, that students fully embrace the responsibilities of independent learning, and that institutional administrations measure instructional effort by criteria other than scheduled hours of instruction.

Process, Goal and Social Interaction Differences in Recreation: What Makes an Activity Substitutable.

ERIC Educational Resources Information Center

Baumgartner, Robert; Heberlein, Thomas A.

Two recreational activities, deer hunting and goose hunting, both similar in form, are compared. It was hypothesized that the activity for which participants rated the process, the goal, and the social interaction as most important to the experience and for which participants showed the strongest family ties and social support for participation…

Binding of high molecular weight kininogen to human endothelial cells is mediated via a site within domains 2 and 3 of the urokinase receptor.

PubMed Central

Colman, R W; Pixley, R A; Najamunnisa, S; Yan, W; Wang, J; Mazar, A; McCrae, K R

1997-01-01

The urokinase receptor (uPAR) binds urokinase-type plasminogen activator (u-PA) through specific interactions with uPAR domain 1, and vitronectin through interactions with a site within uPAR domains 2 and 3. These interactions promote the expression of cell surface plasminogen activator activity and cellular adhesion to vitronectin, respectively. High molecular weight kininogen (HK) also stimulates the expression of cell surface plasminogen activator activity through its ability to serve as an acquired receptor for prekallikrein, which, after its activation, may directly activate prourokinase. Here, we report that binding of the cleaved form of HK (HKa) to human umbilical vein endothelial cells (HUVEC) is mediated through zinc-dependent interactions with uPAR. These occur through a site within uPAR domains 2 and 3, since the binding of 125I-HKa to HUVEC is inhibited by vitronectin, anti-uPAR domain 2 and 3 antibodies and soluble, recombinant uPAR (suPAR), but not by antibody 7E3, which recognizes the beta chain of the endothelial cell vitronectin receptor (integrin alphavbeta3), or fibrinogen, another alphavbeta3 ligand. We also demonstrate the formation of a zinc-dependent complex between suPAR and HKa. Interactions of HKa with endothelial cell uPAR may underlie its ability to promote kallikrein-dependent cell surface plasmin generation, and also explain, in part, its antiadhesive properties. PMID:9294114

An activity canyon characterization of the pharmacological topography.

PubMed

Kulkarni, Varsha S; Wild, David J

2016-01-01

Highly chemically similar drugs usually possess similar biological activities, but sometimes, small changes in chemistry can result in a large difference in biological effects. Chemically similar drug pairs that show extreme deviations in activity represent distinctive drug interactions having important implications. These associations between chemical and biological similarity are studied as discontinuities in activity landscapes. Particularly, activity cliffs are quantified by the drop in similar activity of chemically similar drugs. In this paper, we construct a landscape using a large drug-target network and consider the rises in similarity and variation in activity along the chemical space. Detailed analysis of structure and activity gives a rigorous quantification of distinctive pairs and the probability of their occurrence. We analyze pairwise similarity (s) and variation (d) in activity of drugs on proteins. Interactions between drugs are quantified by considering pairwise s and d weights jointly with corresponding chemical similarity (c) weights. Similarity and variation in activity are measured as the number of common and uncommon targets of two drugs respectively. Distinctive interactions occur between drugs having high c and above (below) average d (s). Computation of predicted probability of distinctiveness employs joint probability of c, s and of c, d assuming independence of structure and activity. Predictions conform with the observations at different levels of distinctiveness. Results are validated on the data used and another drug ensemble. In the landscape, while s and d decrease as c increases, d maintains value more than s. c ∈ [0.3, 0.64] is the transitional region where rises in d are significantly greater than drops in s. It is fascinating that distinctive interactions filtered with high d and low s are different in nature. It is crucial that high c interactions are more probable of having above average d than s. Identification of distinctive interactions is better with high d than low s. These interactions belong to diverse classes. d is greatest between drugs and analogs prepared for treatment of same class of ailments but with different therapeutic specifications. In contrast, analogs having low s would treat ailments from distinct classes. Intermittent spikes in d along the axis of c represent canyons in the activity landscape. This new representation accounts for distinctiveness through relative rises in s and d. It provides a mathematical basis for predicting the probability of occurrence of distinctiveness. It identifies the drug pairs at varying levels of distinctiveness and non-distinctiveness. The predicted probability formula is validated even if data approximately satisfy the conditions of its construction. Also, the postulated independence of structure and activity is of little significance to the overall assessment. The difference in distinctive interactions obtained by s and d highlights the importance of studying both of them, and reveals how the choice of measurement can affect the interpretation. The methods in this paper can be used to interpret whether or not drug interactions are distinctive and the probability of their occurrence. Practitioners and researchers can rely on this identification for quantitative modeling and assessment.

Self-propulsion and interactions of catalytic particles in a chemically active medium.

PubMed

Banigan, Edward J; Marko, John F

2016-01-01

Enzymatic "machines," such as catalytic rods or colloids, can self-propel and interact by generating gradients of their substrates. We theoretically investigate the behaviors of such machines in a chemically active environment where their catalytic substrates are continuously synthesized and destroyed, as occurs in living cells. We show how the kinetic properties of the medium modulate self-propulsion and pairwise interactions between machines, with the latter controlled by a tunable characteristic interaction range analogous to the Debye screening length in an electrolytic solution. Finally, we discuss the effective force arising between interacting machines and possible biological applications, such as partitioning of bacterial plasmids.

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.

The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation.

PubMed

Malik, Sohail; Roeder, Robert G

2010-11-01

The Mediator is an evolutionarily conserved, multiprotein complex that is a key regulator of protein-coding genes. In metazoan cells, multiple pathways that are responsible for homeostasis, cell growth and differentiation converge on the Mediator through transcriptional activators and repressors that target one or more of the almost 30 subunits of this complex. Besides interacting directly with RNA polymerase II, Mediator has multiple functions and can interact with and coordinate the action of numerous other co-activators and co-repressors, including those acting at the level of chromatin. These interactions ultimately allow the Mediator to deliver outputs that range from maximal activation of genes to modulation of basal transcription to long-term epigenetic silencing.

Increasing Interactive Activity: Using Technology to Enhance Interaction between Teachers, Students and Learning Material.

ERIC Educational Resources Information Center

Bucknall, Ruary

1996-01-01

Overview of the interactive technologies used by the Northern Territory Secondary Correspondence School in Australia: print media utilizing desktop publishing and electronic transfer; telephone or H-F radio; interactive television; and interactive computing. More fully describes its interactive CD-ROM courses. Emphasizes that the programs are…

Interaction between organophosphate pesticide exposure and PON1 activity on thyroid function

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

Lacasana, Marina, E-mail: marina.lacasana.easp@juntadeandalucia.e; CIBER de Epidemiologia y Salud Publica; Lopez-Flores, Inmaculada

Organophosphate pesticides are widely used in agricultural purposes. Recently, a few studies have demonstrated the ability of these chemicals to alter the function of the thyroid gland in human. Moreover, the paraoxonase-1 enzyme (PON1) plays an important role in the toxicity of some organophosphate pesticides, with low PON1 activity being associated with higher pesticide sensitivity. This study evaluates the interaction between exposure to organophosphate compounds and PON1 enzyme activity on serum levels of TSH and thyroid hormones in a population of workers occupationally exposed to pesticides. A longitudinal study was conducted on a population of floriculture workers from Mexico, duringmore » two periods of high and low-intensity levels of pesticide application. A structured questionnaire was completed by workers containing questions on sociodemographic characteristics and other variables of interest. Urine and blood samples were taken, and biomarkers of exposure (dialkylphosphates), susceptibility (PON1 polymorphisms and activity) and effect (thyroid hormone levels) were determined. Interaction between dialkylphosphates and PON1 polymorphisms or PON1 activity on hormone levels was evaluated by generalized estimating equation (GEE) models. A significant interaction was found between serum diazoxonase activity and total dialkylphosphates ({Sigma}DAP) on TSH levels. Thus, when PON1 activity was increased we observed a decrease in the percentage of variation of TSH level for each increment in one logarithmic unit of the {Sigma}DAP levels. This interaction was also observed with the PON1{sub 192}RR genotype. These results suggest a stronger association between organophosphate pesticides and thyroid function in individuals with lower PON1 activity.« less

Talk and community: The place of reporting in a life sciences laboratory

NASA Astrophysics Data System (ADS)

Swieringa, Robert Cecil

This study investigates the routine situated communicative practice within the weekly meetings of a life sciences laboratory. The key, constitutive discourse of "reporting" is examined as an activity in which participants jointly sustain the work community of the laboratory and manage their own work within this community. This study seeks to contribute to studies of small groups by focusing upon the multifunctionality and situated nature of the meeting interactions within this enduring "bona fide" group as participants undertake multiple goals associated with their own progress and with the overlapping contexts of the setting. It also seeks to contribute to investigations of institutional talk and activity by examining "reporting" as interaction with institutional and community consequences for members of the community. This study takes a practice-oriented perspective to investigate the laboratory as a community of practice, focusing upon the "activity" of interaction as the overall unit of analysis. Ethnographic materials (involving observation, interviews, conversations, and activity logs) and discourse analysis techniques (involving audiotaping and transcriptions of meetings) were used to locate and record data within a university entomology laboratory over a two year period. Through triangulation of data, "reporting" is identified as a key discourse activity within the laboratory. As situated communicative practice within the weekly meetings, reporting is found to be compelled discourse through which interactants interactively manage one's ongoing goals and activity while temporally situating that activity within the broader stream of laboratory work. This study provides an example of how engagement in situated discursive activity provides for the coordination of individual lines of progress within the ongoing work of a community.

The Flipped Classroom: An active teaching and learning strategy for making the sessions more interactive and challenging.

PubMed

Sultan, Amber Shamim

2018-04-01

Flipping the classroom is a pedagogical model that employs easy to use, readily accessible technology based resources such as video lectures, reading handouts, and practice problems outside the classroom, whereas interactive group-based, problem-solving activities conducted in the classroom. This strategy permits for an extended range of learning activities during the session. Using class time for active learning provides greater opportunity for mentoring and peer to peer collaboration. Instead of spending too much time on delivering lectures, class time can best be utilized by interacting with students, discussing their concerns related to the particular topic to be taught, providing real life examples relevant to the course content, challenging students to think in a broader aspect about complex process and encouraging different team based learning activities.

HIV Tat/P-TEFb Interaction: A Potential Target for Novel Anti-HIV Therapies.

PubMed

Asamitsu, Kaori; Fujinaga, Koh; Okamoto, Takashi

2018-04-17

Transcription is a crucial step in the life cycle of the human immunodeficiency virus type 1 (HIV 1) and is primarily involved in the maintenance of viral latency. Both viral and cellular transcription factors, including transcriptional activators, suppressor proteins and epigenetic factors, are involved in HIV transcription from the proviral DNA integrated within the host cell genome. Among them, the virus-encoded transcriptional activator Tat is the master regulator of HIV transcription. Interestingly, unlike other known transcriptional activators, Tat primarily activates transcriptional elongation and initiation by interacting with the cellular positive transcriptional elongation factor b (P-TEFb). In this review, we describe the molecular mechanism underlying how Tat activates viral transcription through interaction with P-TEFb. We propose a novel therapeutic strategy against HIV replication through blocking Tat action.

Short peptides derived from the interaction domain of SARS coronavirus nonstructural protein nsp10 can suppress the 2'-O-methyltransferase activity of nsp10/nsp16 complex.

PubMed

Ke, Min; Chen, Yu; Wu, Andong; Sun, Ying; Su, Ceyang; Wu, Hao; Jin, Xu; Tao, Jiali; Wang, Yi; Ma, Xiao; Pan, Ji-An; Guo, Deyin

2012-08-01

Coronaviruses are the etiological agents of respiratory and enteric diseases in humans and livestock, exemplified by the life-threatening severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV). However, effective means for combating coronaviruses are still lacking. The interaction between nonstructural protein (nsp) 10 and nsp16 has been demonstrated and the crystal structure of SARS-CoV nsp16/10 complex has been revealed. As nsp10 acts as an essential trigger to activate the 2'-O-methyltransferase activity of nsp16, short peptides derived from nsp10 may have inhibitory effect on viral 2'-O-methyltransferase activity. In this study, we revealed that the domain of aa 65-107 of nsp10 was sufficient for its interaction with nsp16 and the region of aa 42-120 in nsp10, which is larger than the interaction domain, was needed for stimulating the nsp16 2'-O-methyltransferase activity. We further showed that two short peptides derived from the interaction domain of nsp10 could inhibit the 2'-O-methyltransferase activity of SARS-CoV nsp16/10 complex, thus providing a novel strategy and proof-of-principle study for developing peptide inhibitors against SARS-CoV. Copyright © 2012 Elsevier B.V. All rights reserved.

The physical environment, activity and interaction in residential care facilities for older people: a comparative case study.

PubMed

Nordin, Susanna; McKee, Kevin; Wallinder, Maria; von Koch, Lena; Wijk, Helle; Elf, Marie

2017-12-01

The physical environment is of particular importance for supporting activities and interactions among older people living in residential care facilities (RCFs) who spend most of their time inside the facility. More knowledge is needed regarding the complex relationships between older people and environmental aspects in long-term care. The present study aimed to explore how the physical environment influences resident activities and interactions at two RCFs by using a mixed-method approach. Environmental assessments were conducted via the Swedish version of the Sheffield Care Environment Assessment Matrix (S-SCEAM), and resident activities, interactions and locations were assessed through an adapted version of the Dementia Care Mapping (DCM). The Observed Emotion Rating Scale (OERS) was used to assess residents' affective states. Field notes and walk-along interviews were also used. Findings indicate that the design of the physical environment influenced the residents' activities and interactions. Private apartments and dining areas showed high environmental quality at both RCFs, whereas the overall layout had lower quality. Safety was highly supported. Despite high environmental quality in general, several factors restricted resident activities. To optimise care for older people, the design process must clearly focus on accessible environments that provide options for residents to use the facility independently. © 2016 The Authors. Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College of Caring Science.

What Makes Sports Fans Interactive? Identifying Factors Affecting Chat Interactions in Online Sports Viewing

PubMed Central

Yeo, Jaeryong; Lee, Juyeong

2016-01-01

Sports fans are able to watch games from many locations using TV services while interacting with other fans online. In this paper, we identify the factors that affect sports viewers’ online interactions. Using a large-scale dataset of more than 25 million chat messages from a popular social TV site for baseball, we extract various game-related factors, and investigate the relationships between these factors and fans’ interactions using a series of multiple regression analyses. As a result, we identify several factors that are significantly related to viewer interactions. In addition, we determine that the influence of these factors varies according to the user group; i.e., active vs. less active users, and loyal vs. non-loyal users. PMID:26849568

Effects of high-frequency activity on latent heat flux of MJO

NASA Astrophysics Data System (ADS)

Gao, Yingxia; Hsu, Pang-Chi; Li, Tim

2018-04-01

The effect of high-frequency (HF) variability on latent heat flux (LHF) associated with the Madden-Julian Oscillation (MJO) during the boreal winter is investigated through diagnosis using two reanalysis datasets and numerical experiments of an atmospheric general circulation model (AGCM). The diagnostic results show that the HF activities exert an impact on the variability of MJO LHF mainly through their interactions with the longer than 90-day low-frequency background state (LFBS). The contribution of intraseasonal LHF induced by the interactions between LFBS and HF activities accounts for more than 20% of the total intraseasonal LHF over active MJO regions. The intraseasonal LHF induced by the LFBS-HF interaction is in phase with the MJO convection, while the total intraseasonal LHF appears at and to the west of the MJO convection center. This suggests that the intraseasonal LHF via the feedback of HF activity interacting with LFBS is conducive to the maintenance and eastward propagation of MJO convection. To confirm the role of HF disturbances in MJO convection activity, we carry out a series of experiments using the AGCM of ECHAM4, which captures well the general features of MJO. We select a number of MJO cases with enhanced convective signals and significant eastward propagation from a 30-year climatological simulation. Once the HF components of surface wind and moisture fields in LHF are excluded in model integration for each MJO case, most of the simulated MJO convection shows weakened activity and a slower propagation speed compared to the simulations containing all time-scale components. The outputs of these sensitivity experiments support the diagnostic results that HF activities contribute to the maintenance and propagation of MJO convection through the intraseasonal LHF induced by the scale interaction of HF activities with lower frequency variability.

Simian Virus 40 Large T Antigen Interacts with Human TFIIB-Related Factor and Small Nuclear RNA-Activating Protein Complex for Transcriptional Activation of TATA-Containing Polymerase III Promoters

PubMed Central

Damania, Blossom; Mital, Renu; Alwine, James C.

1998-01-01

The TATA-binding protein (TBP) is common to the basal transcription factors of all three RNA polymerases, being associated with polymerase-specific TBP-associated factors (TAFs). Simian virus 40 large T antigen has previously been shown to interact with the TBP-TAFII complexes, TFIID (B. Damania and J. C. Alwine, Genes Dev. 10:1369–1381, 1996), and the TBP-TAFI complex, SL1 (W. Zhai, J. Tuan, and L. Comai, Genes Dev. 11:1605–1617, 1997), and in both cases these interactions are critical for transcriptional activation. We show a similar mechanism for activation of the class 3 polymerase III (pol III) promoter for the U6 RNA gene. Large T antigen can activate this promoter, which contains a TATA box and an upstream proximal sequence element but cannot activate the TATA-less, intragenic VAI promoter (a class 2, pol III promoter). Mutants of large T antigen that cannot activate pol II promoters also fail to activate the U6 promoter. We provide evidence that large T antigen can interact with the TBP-containing pol III transcription factor human TFIIB-related factor (hBRF), as well as with at least two of the three TAFs in the pol III-specific small nuclear RNA-activating protein complex (SNAPc). In addition, we demonstrate that large T antigen can cofractionate and coimmunoprecipitate with the hBRF-containing complex TFIIIB derived from HeLa cells infected with a recombinant adenovirus which expresses large T antigen. Hence, similar to its function with pol I and pol II promoters, large T antigen interacts with TBP-containing, basal pol III transcription factors and appears to perform a TAF-like function. PMID:9488448

Membrane lipid-protein interactions modify the regulatory role of adenosine-deaminase complexing protein: a phase fluorometry study of a malignancy marker

NASA Astrophysics Data System (ADS)

Parola, Abraham H.; Porat, Nurith; Caiolfa, Valeria R.; Gill, David; Kiesow, Lutz A.; Weisman, Mathew; Nemschitz, S.; Yaron, Dahlia; Singer, Karen; Solomon, Ethel

1990-05-01

The role of membrane lipid-protein interactions in malignant cell transformation was examined with adenosine deaminase (ADA) as a representative membrane protein. ADA's activity changes dramatically in transformed cells and accordingly it is a malignancy marker. Yet, the mechanisms controlling its variable activity are unknown. We undertook the spectroscopic deciphering of its interactions with its lipidic environment in normal and malignant cells. ADA exists in two interconvertible forms, small (45 KD) and large (21OKD). The large form consists of two small catalytic subunits (55-ADA) and a dimeric complexing protein ADCP. The physiological role of ADCP was not known either. Our studies were carried out at three levels.: 1. Solution enzyme kinetics, 2. The interaction of 55-ADA with ADCP reconstituted in liposomes: Effect of cholesterol and 3. Multifrequency phase modulation spectrofluorometry of pyrene-labeled 55-ADA bound to ADCP on the membranes of normal and RSV or RSV Ts68 transformed chick embryo fibroblasts. We found: 1. ADCP has an allosteric regulatory role on 55-ADA, which may be of physiological relevance: It inhibits 55-ADA activity at low physiological adenosine concentrations but accelerates deamination at high substrate concentration. 2. When reconstituted in DMPC liposomes, it retains 55-ADA activity (in its absence the activity is lost) and upon rigidification with cholesterol, a three fold increase in 55-ADA activity is attained, contrary to ADCP's regulatory activity when free of lipids. 3. The reduced ADA activity in transformed chick embryo fibroblasts is associated with increased membrane lipid fluidity (reduced order parameter), reduced accessibility of ADCP and increase rotational dynamics of the complex. We thus obtained spectroscopic deciphering of the vertical motion of ADCP, controlled by lipid-protein interaction, resulting in variable activity of this malignancy marker.

MD-2-mediated Ionic Interactions between Lipid A and TLR4 Are Essential for Receptor Activation*

PubMed Central

Meng, Jianmin; Lien, Egil; Golenbock, Douglas T.

2010-01-01

Lipopolysaccharide (LPS) activates innate immune responses through TLR4·MD-2. LPS binds to the MD-2 hydrophobic pocket and bridges the dimerization of two TLR4·MD-2 complexes to activate intracellular signaling. However, exactly how lipid A, the endotoxic moiety of LPS, activates myeloid lineage cells remains unknown. Lipid IVA, a tetra-acylated lipid A precursor, has been used widely as a model for lipid A activation. For unknown reasons, lipid IVA activates proinflammatory responses in rodent cells but inhibits the activity of LPS in human cells. Using stable TLR4-expressing cell lines and purified monomeric MD-2, as well as MD-2-deficient bone marrow-derived macrophages, we found that both mouse TLR4 and mouse MD-2 are required for lipid IVA activation. Computational studies suggested that unique ionic interactions exist between lipid IVA and TLR4 at the dimerization interface in the mouse complex only. The negatively charged 4′-phosphate on lipid IVA interacts with two positively charged residues on the opposing mouse, but not human, TLR4 (Lys367 and Arg434) at the dimerization interface. When replaced with their negatively charged human counterparts Glu369 and Gln436, mouse TLR4 was no longer responsive to lipid IVA. In contrast, human TLR4 gained lipid IVA responsiveness when ionic interactions were enabled by charge reversal at the dimerization interface, defining the basis of lipid IVA species specificity. Thus, using lipid IVA as a selective lipid A agonist, we successfully decoupled and coupled two sequential events required for intracellular signaling: receptor engagement and dimerization, underscoring the functional role of ionic interactions in receptor activation. PMID:20018893

An evolutionarily conserved motif in the TAB1 C-terminal region is necessary for interaction with and activation of TAK1 MAPKKK.

PubMed

Ono, K; Ohtomo, T; Sato, S; Sugamata, Y; Suzuki, M; Hisamoto, N; Ninomiya-Tsuji, J; Tsuchiya, M; Matsumoto, K

2001-06-29

TAK1, a member of the MAPKKK family, is involved in the intracellular signaling pathways mediated by transforming growth factor beta, interleukin 1, and Wnt. TAK1 kinase activity is specifically activated by the TAK1-binding protein TAB1. The C-terminal 68-amino acid sequence of TAB1 (TAB1-C68) is sufficient for TAK1 interaction and activation. Analysis of various truncated versions of TAB1-C68 defined a C-terminal 30-amino acid sequence (TAB1-C30) necessary for TAK1 binding and activation. NMR studies revealed that the TAB1-C30 region has a unique alpha-helical structure. We identified a conserved sequence motif, PYVDXA/TXF, in the C-terminal domain of mammalian TAB1, Xenopus TAB1, and its Caenorhabditis elegans homolog TAP-1, suggesting that this motif constitutes a specific TAK1 docking site. Alanine substitution mutagenesis showed that TAB1 Phe-484, located in the conserved motif, is crucial for TAK1 binding and activation. The C. elegans homolog of TAB1, TAP-1, was able to interact with and activate the C. elegans homolog of TAK1, MOM-4. However, the site in TAP-1 corresponding to Phe-484 of TAB1 is an alanine residue (Ala-364), and changing this residue to Phe abrogates the ability of TAP-1 to interact with and activate MOM-4. These results suggest that the Phe or Ala residue within the conserved motif of the TAB1-related proteins is important for interaction with and activation of specific TAK1 MAPKKK family members in vivo.

Identification of N-Terminal Lobe Motifs that Determine the Kinase Activity of the Catalytic Domains and Regulatory Strategies of Src and Csk Protein Tyrosine Kinases†

PubMed Central

Huang, Kezhen; Wang, Yue-Hao; Brown, Alex; Sun, Gongqin

2009-01-01

Csk and Src protein tyrosine kinases are structurally homologous, but use opposite regulatory strategies. The isolated catalytic domain of Csk is intrinsically inactive and is activated by interactions with the regulatory SH3 and SH2 domains, while the isolated catalytic domain of Src is intrinsically active and is suppressed by interactions with the regulatory SH3 and SH2 domains. The structural basis for why one isolated catalytic domain is intrinsically active while the other is inactive is not clear. In this current study, we identify the structural elements in the N-terminal lobe of the catalytic domain that render the Src catalytic domain active. These structural elements include the α-helix C region, a β-turn between the β-4 and β-5 strands, and an Arg residue at the beginning of the catalytic domain. These three motifs interact with each other to activate the Src catalytic domain, but the equivalent motifs in Csk directly interact with the regulatory domains that are important for Csk activation. The Src motifs can be grafted to the Csk catalytic domain to obtain an active Csk catalytic domain. These results, together with available Src and Csk tertiary structures, reveal an important structural switch that determines the kinase activity of a catalytic domain and dictates the regulatory strategy of a kinase. PMID:19244618

Effects of BDNF polymorphism and physical activity on episodic memory in the elderly: a cross sectional study.

PubMed

Canivet, Anne; Albinet, Cédric T; André, Nathalie; Pylouster, Jean; Rodríguez-Ballesteros, Montserrat; Kitzis, Alain; Audiffren, Michel

2015-01-01

The brain-derived neurotrophic factor (BDNF) concentration is highest in the hippocampus compared with that in other brain structures and affects episodic memory, a cognitive function that is impaired in older adults. According to the neurotrophic hypothesis, BDNF released during physical activity enhances brain plasticity and consequently brain health. However, even if the physical activity level is involved in the secretion of neurotrophin, this protein is also under the control of a specific gene. The aim of the present study was to examine the effect of the interaction between physical activity and BDNF Val66Met (rs6265), a genetic polymorphism, on episodic memory. Two hundred and five volunteers aged 55 and older with a Mini Mental State Examination score ≥ 24 participated in this study. Four groups of participants were established according to their physical activity level and polymorphism BDNF profile (Active Val homozygous, Inactive Val homozygous, Active Met carriers, Inactive Met carriers). Episodic memory was evaluated based on the delayed recall of the Logical Memory test of the MEM III battery. As expected, the physical activity level interacted with BDNF polymorphism to affect episodic memory performance (p < .05). The active Val homozygous participants significantly outperformed the active Met carriers and inactive Val homozygous participants. This study clearly demonstrates an interaction between physical activity and BDNF Val66Met polymorphism that affects episodic memory in the elderly and confirms that physical activity contributes to the neurotrophic mechanism implicated in cognitive health. The interaction shows that only participants with Val/Val polymorphism benefited from physical activity.

Using Virtual Pets to Promote Physical Activity in Children: An Application of the Youth Physical Activity Promotion Model.

PubMed

Ahn, Sun Joo Grace; Johnsen, Kyle; Robertson, Tom; Moore, James; Brown, Scott; Marable, Amanda; Basu, Aryabrata

2015-01-01

A virtual pet was developed based on the framework of the youth physical activity promotion model and tested as a vehicle for promoting physical activity in children. Children in the treatment group interacted with the virtual pet for three days, setting physical activity goals and teaching tricks to the virtual pet when their goals were met. The virtual pet became more fit and learned more sophisticated tricks as the children achieved activity goals. Children in the control group interacted with a computer system presenting equivalent features but without the virtual pet. Physical activity and goal attainment were evaluated using activity monitors. Results indicated that children in the treatment group engaged in 1.09 more hours of daily physical activity (156% more) than did those in the control group. Physical activity self-efficacy and beliefs served as mediators driving this increase in activity. Children that interacted with the virtual pet also expressed higher intentions than children in the control group to continue physical activity in the future. Theoretical and practical potentials of using a virtual pet to systematically promote physical activity in children are discussed.

Limited communication capacity unveils strategies for human interaction

NASA Astrophysics Data System (ADS)

Miritello, Giovanna; Lara, Rubén; Cebrian, Manuel; Moro, Esteban

2013-06-01

Connectivity is the key process that characterizes the structural and functional properties of social networks. However, the bursty activity of dyadic interactions may hinder the discrimination of inactive ties from large interevent times in active ones. We develop a principled method to detect tie de-activation and apply it to a large longitudinal, cross-sectional communication dataset (~19 months, ~20 million people). Contrary to the perception of ever-growing connectivity, we observe that individuals exhibit a finite communication capacity, which limits the number of ties they can maintain active in time. On average men display higher capacity than women, and this capacity decreases for both genders over their lifespan. Separating communication capacity from activity reveals a diverse range of tie activation strategies, from stable to exploratory. This allows us to draw novel relationships between individual strategies for human interaction and the evolution of social networks at global scale.

Limited communication capacity unveils strategies for human interaction

PubMed Central

Miritello, Giovanna; Lara, Rubén; Cebrian, Manuel; Moro, Esteban

2013-01-01

Connectivity is the key process that characterizes the structural and functional properties of social networks. However, the bursty activity of dyadic interactions may hinder the discrimination of inactive ties from large interevent times in active ones. We develop a principled method to detect tie de-activation and apply it to a large longitudinal, cross-sectional communication dataset (≈19 months, ≈20 million people). Contrary to the perception of ever-growing connectivity, we observe that individuals exhibit a finite communication capacity, which limits the number of ties they can maintain active in time. On average men display higher capacity than women, and this capacity decreases for both genders over their lifespan. Separating communication capacity from activity reveals a diverse range of tie activation strategies, from stable to exploratory. This allows us to draw novel relationships between individual strategies for human interaction and the evolution of social networks at global scale. PMID:23739519

Rupture Forces among Human Blood Platelets at different Degrees of Activation

PubMed Central

Nguyen, Thi-Huong; Palankar, Raghavendra; Bui, Van-Chien; Medvedev, Nikolay; Greinacher, Andreas; Delcea, Mihaela

2016-01-01

Little is known about mechanics underlying the interaction among platelets during activation and aggregation. Although the strength of a blood thrombus has likely major biological importance, no previous study has measured directly the adhesion forces of single platelet-platelet interaction at different activation states. Here, we filled this void first, by minimizing surface mediated platelet-activation and second, by generating a strong adhesion force between a single platelet and an AFM cantilever, preventing early platelet detachment. We applied our setup to measure rupture forces between two platelets using different platelet activation states, and blockade of platelet receptors. The rupture force was found to increase proportionally to the degree of platelet activation, but reduced with blockade of specific platelet receptors. Quantification of single platelet-platelet interaction provides major perspectives for testing and improving biocompatibility of new materials; quantifying the effect of drugs on platelet function; and assessing the mechanical characteristics of acquired/inherited platelet defects. PMID:27146004

Glutathione S-Transferases Interact with AMP-Activated Protein Kinase: Evidence for S-Glutathionylation and Activation In Vitro

PubMed Central

Polge, Cécile; Ramirez, Sacnicte; Michelland, Sylvie; Sève, Michel; Vertommen, Didier; Rider, Mark; Lentze, Nicolas; Auerbach, Daniel; Schlattner, Uwe

2013-01-01

AMP-activated protein kinase (AMPK) is a cellular and whole body energy sensor with manifold functions in regulating energy homeostasis, cell morphology and proliferation in health and disease. Here we apply multiple, complementary in vitro and in vivo interaction assays to identify several isoforms of glutathione S-transferase (GST) as direct AMPK binding partners: Pi-family member rat GSTP1 and Mu-family members rat GSTM1, as well as Schistosoma japonicum GST. GST/AMPK interaction is direct and involves the N-terminal domain of the AMPK β-subunit. Complex formation of the mammalian GSTP1 and -M1 with AMPK leads to their enzymatic activation and in turn facilitates glutathionylation and activation of AMPK in vitro. GST-facilitated S-glutathionylation of AMPK may be involved in rapid, full activation of the kinase under mildly oxidative physiological conditions. PMID:23741294

Brief Introduction to Higher Education Institutions in China.

DTIC Science & Technology

1984-01-12

were sent to foreign countries to study. Through these activities, the friendship and interaction with foreign scholars and experts have been promoted...the interaction between each pair of echoes was presented for the first time. The paper (overall reactance = general theory on opposing end networks...the school for a visit. The number of people reached over 500. These exchange and interaction activities promoted the friendship with foreign scholars

Interaction Activities in the Foreign Classroom, or How to Grow a Tulip-Rose

ERIC Educational Resources Information Center

Paulston, Christina Bratt; Selekman, Howard R.

1976-01-01

A report is made on the use of foreign language for spontaneous communication in an elementary language class. Four correction-free, peer communicative/interaction activities are outlined according to procedures, objectives, and evaluations. (Author/RM)

Interactions of the Algicidal Bacterium Kordia algicida with Diatoms: Regulated Protease Excretion for Specific Algal Lysis

PubMed Central

Paul, Carsten; Pohnert, Georg

2011-01-01

Interactions of planktonic bacteria with primary producers such as diatoms have great impact on plankton population dynamics. Several studies described the detrimental effect of certain bacteria on diatoms but the biochemical nature and the regulation mechanism involved in the production of the active compounds remained often elusive. Here, we investigated the interactions of the algicidal bacterium Kordia algicida with the marine diatoms Skeletonema costatum, Thalassiosira weissflogii, Phaeodactylum tricornutum, and Chaetoceros didymus. Algicidal activity was only observed towards the first three of the tested diatom species while C. didymus proved to be not susceptible. The cell free filtrate and the >30 kDa fraction of stationary K. algicida cultures is fully active, suggesting a secreted algicidal principle. The active supernatant from bacterial cultures exhibited high protease activity and inhibition experiments proved that these enzymes are involved in the observed algicidal action of the bacteria. Protease mediated interactions are not controlled by the presence of the alga but dependent on the cell density of the K. algicida culture. We show that protease release is triggered by cell free bacterial filtrates suggesting a quorum sensing dependent excretion mechanism of the algicidal protein. The K. algicida / algae interactions in the plankton are thus host specific and under the control of previously unidentified factors. PMID:21695044

Interactions of the algicidal bacterium Kordia algicida with diatoms: regulated protease excretion for specific algal lysis.

PubMed

Paul, Carsten; Pohnert, Georg

2011-01-01

Interactions of planktonic bacteria with primary producers such as diatoms have great impact on plankton population dynamics. Several studies described the detrimental effect of certain bacteria on diatoms but the biochemical nature and the regulation mechanism involved in the production of the active compounds remained often elusive. Here, we investigated the interactions of the algicidal bacterium Kordia algicida with the marine diatoms Skeletonema costatum, Thalassiosira weissflogii, Phaeodactylum tricornutum, and Chaetoceros didymus. Algicidal activity was only observed towards the first three of the tested diatom species while C. didymus proved to be not susceptible. The cell free filtrate and the >30 kDa fraction of stationary K. algicida cultures is fully active, suggesting a secreted algicidal principle. The active supernatant from bacterial cultures exhibited high protease activity and inhibition experiments proved that these enzymes are involved in the observed algicidal action of the bacteria. Protease mediated interactions are not controlled by the presence of the alga but dependent on the cell density of the K. algicida culture. We show that protease release is triggered by cell free bacterial filtrates suggesting a quorum sensing dependent excretion mechanism of the algicidal protein. The K. algicida / algae interactions in the plankton are thus host specific and under the control of previously unidentified factors.

Tactile interactions activate mirror system regions in the human brain.

PubMed

McKyton, Ayelet

2011-12-07

Communicating with others is essential for the development of a society. Although types of communications, such as language and visual gestures, were thoroughly investigated in the past, little research has been done to investigate interactions through touch. To study this we used functional magnetic resonance imaging. Twelve participants were scanned with their eyes covered while stroking four kinds of items, representing different somatosensory stimuli: a human hand, a realistic rubber hand, an object, and a simple texture. Although the human and the rubber hands had the same overall shape, in three regions there was significantly more blood oxygen level dependent activation when touching the real hand: the anterior medial prefrontal cortex, the ventral premotor cortex, and the posterior superior temporal cortex. The last two regions are part of the mirror network and are known to be activated through visual interactions such as gestures. Interestingly, in this study, these areas were activated through a somatosensory interaction. A control experiment was performed to eliminate confounds of temperature, texture, and imagery, suggesting that the activation in these areas was correlated with the touch of a human hand. These results reveal the neuronal network working behind human tactile interactions, and highlight the participation of the mirror system in such functions.

Tidal effects on stellar activity

NASA Astrophysics Data System (ADS)

Poppenhaeger, K.

2017-10-01

The architecture of many exoplanetary systems is different from the solar system, with exoplanets being in close orbits around their host stars and having orbital periods of only a few days. We can expect interactions between the star and the exoplanet for such systems that are similar to the tidal interactions observed in close stellar binary systems. For the exoplanet, tidal interaction can lead to circularization of its orbit and the synchronization of its rotational and orbital period. For the host star, it has long been speculated if significant angular momentum transfer can take place between the planetary orbit and the stellar rotation. In the case of the Earth-Moon system, such tidal interaction has led to an increasing distance between Earth and Moon. For stars with Hot Jupiters, where the orbital period of the exoplanet is typically shorter than the stellar rotation period, one expects a decreasing semimajor axis for the planet and enhanced stellar rotation, leading to increased stellar activity. Also excess turbulence in the stellar convective zone due to rising and subsiding tidal bulges may change the magnetic activity we observe for the host star. I will review recent observational results on stellar activity and tidal interaction in the presence of close-in exoplanets, and discuss the effects of enhanced stellar activity on the exoplanets in such systems.

Structural and Functional Analysis of a Novel Interaction Motif within UFM1-activating Enzyme 5 (UBA5) Required for Binding to Ubiquitin-like Proteins and Ufmylation*

PubMed Central

Habisov, Sabrina; Huber, Jessica; Ichimura, Yoshinobu; Akutsu, Masato; Rogova, Natalia; Loehr, Frank; McEwan, David G.; Johansen, Terje; Dikic, Ivan; Doetsch, Volker; Komatsu, Masaaki; Rogov, Vladimir V.; Kirkin, Vladimir

2016-01-01

The covalent conjugation of ubiquitin-fold modifier 1 (UFM1) to proteins generates a signal that regulates transcription, response to cell stress, and differentiation. Ufmylation is initiated by ubiquitin-like modifier activating enzyme 5 (UBA5), which activates and transfers UFM1 to ubiquitin-fold modifier-conjugating enzyme 1 (UFC1). The details of the interaction between UFM1 and UBA5 required for UFM1 activation and its downstream transfer are however unclear. In this study, we described and characterized a combined linear LC3-interacting region/UFM1-interacting motif (LIR/UFIM) within the C terminus of UBA5. This single motif ensures that UBA5 binds both UFM1 and light chain 3/γ-aminobutyric acid receptor-associated proteins (LC3/GABARAP), two ubiquitin (Ub)-like proteins. We demonstrated that LIR/UFIM is required for the full biological activity of UBA5 and for the effective transfer of UFM1 onto UFC1 and a downstream protein substrate both in vitro and in cells. Taken together, our study provides important structural and functional insights into the interaction between UBA5 and Ub-like modifiers, improving the understanding of the biology of the ufmylation pathway. PMID:26929408

Simultaneous recordings from the primary visual cortex and lateral geniculate nucleus reveal rhythmic interactions and a cortical source for γ-band oscillations.

PubMed

Bastos, Andre M; Briggs, Farran; Alitto, Henry J; Mangun, George R; Usrey, W Martin

2014-05-28

Oscillatory synchronization of neuronal activity has been proposed as a mechanism to modulate effective connectivity between interacting neuronal populations. In the visual system, oscillations in the gamma-frequency range (30-100 Hz) are thought to subserve corticocortical communication. To test whether a similar mechanism might influence subcortical-cortical communication, we recorded local field potential activity from retinotopically aligned regions in the lateral geniculate nucleus (LGN) and primary visual cortex (V1) of alert macaque monkeys viewing stimuli known to produce strong cortical gamma-band oscillations. As predicted, we found robust gamma-band power in V1. In contrast, visual stimulation did not evoke gamma-band activity in the LGN. Interestingly, an analysis of oscillatory phase synchronization of LGN and V1 activity identified synchronization in the alpha (8-14 Hz) and beta (15-30 Hz) frequency bands. Further analysis of directed connectivity revealed that alpha-band interactions mediated corticogeniculate feedback processing, whereas beta-band interactions mediated geniculocortical feedforward processing. These results demonstrate that although the LGN and V1 display functional interactions in the lower frequency bands, gamma-band activity in the alert monkey is largely an emergent property of cortex. Copyright © 2014 the authors 0270-6474/14/347639-06$15.00/0.

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

A Small-molecule Inhibitor, 5′-O-Tritylthymidine, targets FAK and Mdm-2 Interaction, and Blocks Breast and Colon Tumorigenesis in vivo

PubMed Central

Golubovskaya, Vita; Palma, Nadia L.; Zheng, Min; Ho, Baotran; Magis, Andrew; Ostrov, David; Cance, William G.

2013-01-01

Focal Adhesion Kinase (FAK) is overexpressed in many types of tumors and plays an important role in survival. We developed a novel approach, targeting FAK-protein interactions by computer modeling and screening of NCI small molecule drug database. In this report we targeted FAK and Mdm-2 protein interaction to decrease tumor growth. By macromolecular modeling we found a model of FAK and Mdm-2 interaction and performed screening of >200,000 small molecule compounds from NCI database with drug-like characteristics, targeting the FAK-Mdm-2 interaction. We identified 5′-O-Tritylthymidine, called M13 compound that significantly decreased viability in different cancer cells. M13 was docked into the pocket of FAK and Mdm-2 interaction and was directly bound to the FAK-N terminal domain by ForteBio Octet assay. In addition, M13 compound affected FAK and Mdm-2 levels and decreased complex of FAK and Mdm-2 proteins in breast and colon cancer cells. M13 re-activated p53 activity inhibited by FAK with Mdm-2 promoter. M13 decreased viability, clonogenicity, increased detachment and apoptosis in a dose-dependent manner in BT474 breast and in HCT116 colon cancer cells in vitro. M13 decreased FAK, activated p53 and caspase-8 in both cell lines. In addition, M13 decreased breast and colon tumor growth in vivo. M13 activated p53 and decreased FAK in tumor samples consistent with decreased tumor growth. The data demonstrate a novel approach for targeting FAK and Mdm-2 protein interaction, provide a model of FAK and Mdm-2 interaction, identify M13 compound targeting this interaction and decreasing tumor growth that is critical for future targeted therapeutics. PMID:22292771

Effect of ultraviolet irradiation on free radical scavenging activity of immunosuppressants used in lung transplantation and comparative electron paramagnetic resonance study of kinetics of their interactions with model free radicals.

PubMed

Stanjek-Cichoracka, A; Żegleń, S; Ramos, P; Pilawa, B; Wojarski, J

2018-06-01

The immunosuppressive drugs used in solid organ transplantation or autoimmunological processes were studied by electron paramagnetic resonance (EPR) spectroscopy to estimate their free radical scavenging activity. The interactions of immunosuppressants with free radicals were examined by an X-band (9.3 GHz) EPR spectroscopy and a model of DPPH free radicals. The EPR spectra of DPPH and DPPH interacting with individual drugs were compared. Kinetic studies were performed, and the effect of ultraviolet (UV) irradiation on the free radical scavenging activity of the tested drugs was determined. The free radical scavenging activity of non-irradiated drugs decreased in the order: rapamycin > mycophenolate mofetil > ciclosporin > tacrolimus. UV irradiation increased the free radical scavenging activity of all the tested immunosuppressive drugs, and the effect was highest for tacrolimus. For the non-irradiated samples, the speed of free radical interactions decreased in the order: ciclosporin > tacrolimus > mycophenolate mofetil > rapamycin. UV irradiation only slightly affected the speed of interactions of the immunosuppressive drugs with the model DPPH free radicals. Electron paramagnetic resonance spectroscopy is useful for obtaining information on interactions of immunosuppressive drugs with free radicals. We hypothesized that the long-term immunosuppressive effects of these drugs after transplantation or during autoimmune disorders may be mediated by anti-inflammatory action in addition to the known receptor/cell cycle inhibition. © 2018 John Wiley & Sons Ltd.

ABA signaling in guard cells entails a dynamic protein-protein interaction relay from the PYL-RCAR family receptors to ion channels.

PubMed

Lee, Sung Chul; Lim, Chae Woo; Lan, Wenzhi; He, Kai; Luan, Sheng

2013-03-01

Plant hormone abscisic acid (ABA) serves as an integrator of environmental stresses such as drought to trigger stomatal closure by regulating specific ion channels in guard cells. We previously reported that SLAC1, an outward anion channel required for stomatal closure, was regulated via reversible protein phosphorylation events involving ABA signaling components, including protein phosphatase 2C members and a SnRK2-type kinase (OST1). In this study, we reconstituted the ABA signaling pathway as a protein-protein interaction relay from the PYL/RCAR-type receptors, to the PP2C-SnRK2 phosphatase-kinase pairs, to the ion channel SLAC1. The ABA receptors interacted with and inhibited PP2C phosphatase activity against the SnRK2-type kinase, releasing active SnRK2 kinase to phosphorylate, and activate the SLAC1 channel, leading to reduced guard cell turgor and stomatal closure. Both yeast two-hybrid and bimolecular fluorescence complementation assays were used to verify the interactions among the components in the pathway. These biochemical assays demonstrated activity modifications of phosphatases and kinases by their interaction partners. The SLAC1 channel activity was used as an endpoint readout for the strength of the signaling pathway, depending on the presence of different combinations of signaling components. Further study using transgenic plants overexpressing one of the ABA receptors demonstrated that changing the relative level of interacting partners would change ABA sensitivity.

Genotype by energy expenditure interaction with metabolic syndrome traits: the Portuguese healthy family study.

PubMed

Santos, Daniel M V; Katzmarzyk, Peter T; Diego, Vincent P; Souza, Michele C; Chaves, Raquel N; Blangero, John; Maia, José A R

2013-01-01

Moderate-to-high levels of physical activity are established as preventive factors in metabolic syndrome development. However, there is variability in the phenotypic expression of metabolic syndrome under distinct physical activity conditions. In the present study we applied a Genotype X Environment interaction method to examine the presence of GxEE interaction in the phenotypic expression of metabolic syndrome. A total of 958 subjects, from 294 families of The Portuguese Healthy Family study, were included in the analysis. Total daily energy expenditure was assessed using a 3 day physical activity diary. Six metabolic syndrome related traits, including waist circumference, systolic blood pressure, glucose, HDL cholesterol, total cholesterol and triglycerides, were measured and adjusted for age and sex. GxEE examination was performed on SOLAR 4.3.1. All metabolic syndrome indicators were significantly heritable. The GxEE interaction model fitted the data better than the polygenic model (p<0.001) for waist circumference, systolic blood pressure, glucose, total cholesterol and triglycerides. For waist circumference, glucose, total cholesterol and triglycerides, the significant GxEE interaction was due to rejection of the variance homogeneity hypothesis. For waist circumference and glucose, GxEE was also significant by the rejection of the genetic correlation hypothesis. The results showed that metabolic syndrome traits expression is significantly influenced by the interaction established between total daily energy expenditure and genotypes. Physical activity may be considered an environmental variable that promotes metabolic differences between individuals that are distinctively active.

p62 regulates CD40-mediated NFκB activation in macrophages through interaction with TRAF6

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

Seibold, Kristina; Ehrenschwender, Martin, E-mail: martin.ehrenschwender@ukr.de

CD40 is a member of the tumor necrosis factor (TNF) receptor family. Activation-induced recruitment of adapter proteins, so-called TNF-receptor-associated factors (TRAFs) to the cytoplasmic tail of CD40 triggers signaling cascades important in the immune system, but has also been associated with excessive inflammation in diseases such as atherosclerosis and rheumatoid arthritis. Especially, pro-inflammatory nuclear factor κB (NFκB) signaling emanating from CD40-associated TRAF6 appears to be a key pathogenic driving force. Consequently, targeting the CD40-TRAF6 interaction is emerging as a promising therapeutic strategy, but the underlying molecular machinery of this signaling axis is to date poorly understood. Here, we identified themore » multifunctional adaptor protein p62 as a critical regulator in CD40-mediated NFκB signaling via TRAF6. CD40 activation triggered formation of a TRAF6-p62 complex. Disturbing this interaction tremendously reduced CD40-mediated NFκB signaling in macrophages, while TRAF6-independent signaling pathways remained unaffected. This highlights p62 as a potential target in hyper-inflammatory, CD40-associated pathologies. - Highlights: • CD40 activation triggers interaction of the adapter protein TRAF6 with p62. • TRAF6-p62 interaction regulates CD40-mediated NFκB signaling in macrophages. • Defective TRAF6-p62 interaction reduces CD40-mediated NFκB activation in macrophages.« less

[CHANGE OF CHARACTER OF INTERSYSTEMIC INTERACTIONS IN NEWBORN RAT PUPS UNDER CONDITIONS OF A DECREASE OF MOTOR ACTIVITY].

PubMed

Sizonov, V A; Dmitrieva, L E; Kuznetsov, S V

2015-01-01

Interaction of slow-wave.rhythmic components of cardiac, respiratory.and motor activity was investigated in newborn rat pups on the first day after birth under normal conditions and after pharmacological depression of spontaneous periodic motor activity (SPMA) produced by injecting myocuran (myanesin) at low (100 mg/pg, i/p) and maximal (235 mg/pg, i/p) dosages. The data obtained allow to infer that in rat pups after birth the intersystemic interactions are realized mainly via slow-wave oscillations of about-one- and many-minute ranges whereas the rhythms of decasecond range do not play a significant role in integrative processes. Injection of miocuran at a dose causing no muscle relaxation and no inhibition of motor activity produces changes of the cardiac and respiratory rhythms as well as a transitory decrease of the magnitude of coordinate relations mediated by the rhythms of about-one- and many-minute ranges. The consequences of muscle relaxant injection were found to be more significant for intersystemic interactions with participation of the respiratory system. An increase of the dosage and, correspondingly, the total inhibition of SPMA is accompanied by reduction of the slow-wave components from the pattern of cardiac and respiratory rhythms. The cardiorespiratory interactions, more expressed in intact rat pups, are reduced in the about-one- and many-minute ranges of modulation whereas in the decasecond range of modulation they are slightly increased. Key words: early ontogenesis, intersystemic interactions, cardiac rhythm, respiration, motor activity, myocuran (myanesin).

Closing the Loop: Integrated Waste Management Activities for School & Home. K-12 Edition. A School-Based Waste Minimization and Education Program.

ERIC Educational Resources Information Center

Institute for Environmental Education, Chagrin Falls, OH.

Increased human population has led to more frequent interactions with the environment. The results of those interactions have affected the Earth's ecosystem. This manual contains hands-on, problem-centered activities to help students develop an environmental ethic and stewardship regarding waste management. The activities are grouped under three…

Do Predators Always Win? Starfish versus Limpets: A Hands-On Activity Examining Predator-Prey Interactions

ERIC Educational Resources Information Center

Faria, Claudia; Boaventura, Diana; Galvao, Cecilia; Chagas, Isabel

2011-01-01

In this article we propose a hands-on experimental activity about predator-prey interactions that can be performed both in a research laboratory and in the classroom. The activity, which engages students in a real scientific experiment, can be explored not only to improve students' understanding about the diversity of anti-predator behaviors but…

"Horrible or Happy--We'll Have a Little Grey Now": Aesthetic Judgements in Children's Narration with an Interactive Whiteboard

ERIC Educational Resources Information Center

Skantz Åberg, Ewa

2017-01-01

This empirical study investigates what activities emerge when six-year olds are instructed to create narratives with an interactive whiteboard (IWB). A detailed analysis is provided of what the participants are oriented towards in the activity, and further what aesthetic judgements are used and their role in the evolving activity. Theoretically,…

Nanostructure and force spectroscopy analysis of human peripheral blood CD4+ T cells using atomic force microscopy.

PubMed

Hu, Mingqian; Wang, Jiongkun; Cai, Jiye; Wu, Yangzhe; Wang, Xiaoping

2008-09-12

To date, nanoscale imaging of the morphological changes and adhesion force of CD4(+) T cells during in vitro activation remains largely unreported. In this study, we used atomic force microscopy (AFM) to study the morphological changes and specific binding forces in resting and activated human peripheral blood CD4(+) T cells. The AFM images revealed that the volume of activated CD4(+) T cells increased and the ultrastructure of these cells also became complex. Using a functionalized AFM tip, the strength of the specific binding force of the CD4 antigen-antibody interaction was found to be approximately three times that of the unspecific force. The adhesion forces were not randomly distributed over the surface of a single activated CD4(+) T cell, indicated that the CD4 molecules concentrated into nanodomains. The magnitude of the adhesion force of the CD4 antigen-antibody interaction did not change markedly with the activation time. Multiple bonds involved in the CD4 antigen-antibody interaction were measured at different activation times. These results suggest that the adhesion force involved in the CD4 antigen-antibody interaction is highly selective and of high affinity.

[Interaction between CYP450 enzymes and metabolism of traditional Chinese medicine as well as enzyme activity assay].

PubMed

Lu, Tu-lin; Su, Lian-lin; Ji, De; Gu, Wei; Mao, Chun-qin

2015-09-01

Drugs are exogenous compounds for human bodies, and will be metabolized by many enzymes after administration. CYP450 enzyme, as a major metabolic enzyme, is an important phase I drug metabolizing enzyme. In human bodies, about 75% of drug metabolism is conducted by CYP450 enzymes, and CYP450 enzymes is the key factor for drug interactions between traditional Chinese medicine( TCM) -TCM, TCM-medicine and other drug combination. In order to make clear the interaction between metabolic enzymes and TCM metabolism, we generally chose the enzymatic activity as an evaluation index. That is to say, the enhancement or reduction of CYP450 enzyme activity was used to infer the inducing or inhibitory effect of active ingredients and extracts of traditional Chinese medicine on enzymes. At present, the common method for measuring metabolic enzyme activity is Cocktail probe drugs, and it is the key to select the suitable probe substrates. This is of great significance for study drug's absorption, distribution, metabolism and excretion (ADME) process in organisms. The study focuses on the interaction between TCMs, active ingredients, herbal extracts, cocktail probe substrates as well as CYP450 enzymes, in order to guide future studies.

Serine proteases activity is important for the interaction of nematophagous fungus Duddingtonia flagrans with infective larvae of trichostrongylides and free-living nematodes Panagrellus spp.

PubMed

Cruz, Daniela G; Costa, Luana M; Rocha, Letícia O; Retamal, Claudio A; Vieira, Ricardo A M; Seabra, Sergio H; Silva, Carlos P; DaMatta, Renato A; Santos, Clóvis P

2015-08-01

The nematode-trapping fungus Duddingtonia flagrans has been studied as a possible control method for gastrointestinal nematodes of livestock animals. These fungi capture and infect the nematode by cuticle penetration, immobilization, and digestion of the internal contents. It has been suggested that this sequence of events occurs by a combination of physical and enzymatical activities. The aim of this study was to investigate the participation of proteolytic enzymatic activity during the interaction of the nematophagous fungus D. flagrans with infective larvae of trichostrongylides and the free-living nematode Panagrellus spp. Protease inhibitors used interfered in the predatory activity of D. flagrans. However, only PMSF significantly reduced the mean number of Panagrellus spp. captured by D. flagrans in comparison with the control. The experiment with fluorogenic substrate showed that maximum urokinase activity during the interaction of the fungus with the infective larvae of trichostrongylides or Panagrellus spp. occurred within 7 or 1 h of incubation, respectively. The protease activity, especially of the serine class, may be important during the interaction between the fungus and nematodes. Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Pharmacokinetic Drug Interactions with Panax ginseng.

PubMed

Ramanathan, Meenakshi R; Penzak, Scott R

2017-08-01

Panax ginseng is widely used as an adaptogen throughout the world. The major active constituents of P. ginseng are ginsenosides. Most naturally occurring ginsenosides are deglycosylated by colonic bacteria to intestinal metabolites. Ginsenosides along with these metabolites are widely accepted as being responsible for the pharmacologic activity and drug interaction potential of ginseng. Numerous preclinical studies have assessed the influence of various ginseng components on cytochrome P450 (CYP), glucuronidation, and drug transport activity. Results from these investigations have been largely inconclusive due to the use of different ginseng products and variations in methodology between studies. Drug interaction studies in humans have been conflicting and have largely yielded negative results or results that suggest only a weak interaction. One study using a midazolam probe found weak CYP3A induction and another using a fexofenadine probe found weak P-gp inhibition. Despite several case reports indicating a drug interaction between warfarin and P. ginseng, pharmacokinetic studies involving these agents in combination have failed to find significant pharmacokinetic or pharmacodynamic interactions. To this end, drug interactions involving P. ginseng appear to be rare; however, close clinical monitoring is still suggested for patients taking warfarin or CYP3A or P-gp substrates with narrow therapeutic indices.

A physiologically required G protein-coupled receptor (GPCR)-regulator of G protein signaling (RGS) interaction that compartmentalizes RGS activity.

PubMed

Croft, Wayne; Hill, Claire; McCann, Eilish; Bond, Michael; Esparza-Franco, Manuel; Bennett, Jeannette; Rand, David; Davey, John; Ladds, Graham

2013-09-20

G protein-coupled receptors (GPCRs) can interact with regulator of G protein signaling (RGS) proteins. However, the effects of such interactions on signal transduction and their physiological relevance have been largely undetermined. Ligand-bound GPCRs initiate by promoting exchange of GDP for GTP on the Gα subunit of heterotrimeric G proteins. Signaling is terminated by hydrolysis of GTP to GDP through intrinsic GTPase activity of the Gα subunit, a reaction catalyzed by RGS proteins. Using yeast as a tool to study GPCR signaling in isolation, we define an interaction between the cognate GPCR (Mam2) and RGS (Rgs1), mapping the interaction domains. This reaction tethers Rgs1 at the plasma membrane and is essential for physiological signaling response. In vivo quantitative data inform the development of a kinetic model of the GTPase cycle, which extends previous attempts by including GPCR-RGS interactions. In vivo and in silico data confirm that GPCR-RGS interactions can impose an additional layer of regulation through mediating RGS subcellular localization to compartmentalize RGS activity within a cell, thus highlighting their importance as potential targets to modulate GPCR signaling pathways.

Discover the pythagorean theorem using interactive multimedia learning

NASA Astrophysics Data System (ADS)

Adhitama, I.; Sujadi, I.; Pramudya, I.

2018-04-01

In learning process students are required to play an active role in learning. They do not just accept the concept directly from teachers, but also build their own knowledge so that the learning process becomes more meaningful. Based on the observation, when learning Pythagorean theorem, students got difficulty on determining hypotenuse. One of the solution to solve this problem is using an interactive multimedia learning. This article aims to discuss the interactive multimedia as learning media for students. This was a Research and Development (R&D) by using ADDIE model of development. The results obtained was multimedia which was developed proper for students as learning media. Besides, on Phytagorian theorem learning activity we also compare Discovery Learning (DL) model with interactive multimedia and DL without interactive multimedia, and obtained that DL with interactive gave positive effect better than DL without interactive multimedia. It was also obtainde that interactive multimedia can attract and increase the interest ot the students on learning math. Therefore, the use of interactive multimedia on DL procees can improve student learning achievement.

Naphthol AS-E Phosphate Inhibits the Activity of the Transcription Factor Myb by Blocking the Interaction with the KIX Domain of the Coactivator p300.

PubMed

Uttarkar, Sagar; Dukare, Sandeep; Bopp, Bertan; Goblirsch, Michael; Jose, Joachim; Klempnauer, Karl-Heinz

2015-06-01

The transcription factor c-Myb is highly expressed in hematopoietic progenitor cells and controls the transcription of genes important for lineage determination, cell proliferation, and differentiation. Deregulation of c-Myb has been implicated in the development of leukemia and certain other types of human cancer. c-Myb activity is highly dependent on the interaction of the c-Myb with the KIX domain of the coactivator p300, making the disruption of this interaction a reasonable strategy for the development of Myb inhibitors. Here, we have used bacterial Autodisplay to develop an in vitro binding assay that mimics the interaction of Myb and the KIX domain of p300. We have used this binding assay to investigate the potential of Naphthol AS-E phosphate, a compound known to bind to the KIX domain, to disrupt the interaction between Myb and p300. Our data show that Naphthol AS-E phosphate interferes with the Myb-KIX interaction in vitro and inhibits Myb activity in vivo. By using several human leukemia cell lines, we demonstrate that Naphthol AS-E phosphate suppresses the expression of Myb target genes and induces myeloid differentiation and apoptosis. Our work identifies Naphthol AS-E phosphate as the first low molecular weight compound that inhibits Myb activity by disrupting its interaction with p300, and suggests that inhibition of the Myb-KIX interaction might be a useful strategy for the treatment of leukemia and other tumors caused by deregulated c-Myb. ©2015 American Association for Cancer Research.

Promoting Physical Activity in Low-Active Adolescents via Facebook: A Pilot Randomized Controlled Trial to Test Feasibility.

PubMed

Wójcicki, Thomas R; Grigsby-Toussaint, Diana; Hillman, Charles H; Huhman, Marian; McAuley, Edward

2014-10-30

The World Wide Web is an effective method for delivering health behavior programs, yet major limitations remain (eg, cost of development, time and resource requirements, limited interactivity). Social media, however, has the potential to deliver highly customizable and socially interactive behavioral interventions with fewer constraints. Thus, the evaluation of social media as a means to influence health behaviors is warranted. The objective of this trial was to examine and demonstrate the feasibility of using an established social networking platform (ie, Facebook) to deliver an 8 week physical activity intervention to a sample of low-active adolescents (N=21; estimated marginal mean age 13.48 years). Participants were randomized to either an experimental (ie, Behavioral) or attentional control (ie, Informational) condition. Both conditions received access to a restricted-access, study-specific Facebook group where the group's administrator made two daily wall posts containing youth-based physical activity information and resources. Primary outcomes included physical activity as assessed by accelerometry and self-report. Interactions and main effects were examined, as well as mean differences in effect sizes. Analyses revealed significant improvements over time on subjectively reported weekly leisure-time physical activity (F1,18=8.426, P=.009, η2 = .319). However, there was no interaction between time and condition (F1,18=0.002, P=.968, η2 = .000). There were no significant time or interaction effects among the objectively measured physical activity variables. Examination of effect sizes revealed moderate-to-large changes in physical activity outcomes. Results provide initial support for the feasibility of delivery of a physical activity intervention to low-active adolescents via social media. Whether by employing behavioral interventions via social media can result in statistically meaningful changes in health-related behaviors and outcomes remains to be determined. ClinicalTrials.gov NCT01870323; http://clinicaltrials.gov/show/NCT01870323 (Archived by WebCite at http://www.webcitation.org/6SUTmSeZZ).

Induced Star Formation

NASA Astrophysics Data System (ADS)

Kennicutt, Robert C., Jr.

Overview: Induced Star Formation and Interactions Introduction Historical Background: First Hints Systematic Studies: Starbursts Interactions and Nuclear activity IRAS and Ultralumious starburst Galaxies The 1990's: HST, Supercomputers, and the Distant Universe Key Questions and Issues Organization of Lectures Star Formation Properties of Normal Galaxies Observational Techniques Results: Star Formation in Normal Galaxies Interpretation: Star Formation Histories Global Star Formation in interacting Galaxies A Gallery of Interactions and Mergers Star Formation Statistics: Guilt By Association Tests SFRs in Interacting vs Noninteracting Galaxies Kinematic Properties and Regulation of SFRs Induced Nuclear Activity and Star Formation Background: Nuclear Spectra and Classification Nuclear Star Formation and Starbursts Nuclear Star Formation and Interactions Induced AGN Activity: Statistics of Seyfert Galaxies Environments of Quasars Kinematic Clues to the Triggering of AGNs Infrared Luminous Galaxies and Starbursts Background: IR Luminous Galaxies and IRAS Infrared Luminosity Function and Spectra Infrared Structure and Morphology Interstellar Gas X-Ray Emission and Superwinds Optical, UV, and Near-Infrared Spectra Radio Continuum Emission Evidence for Interactions and Mergers The Power Source: Starbursts or Dusty AGNs? Spectral Diagnostics of Starbursts Evolutionary Synthesis Models Applications: Integrated Colors of Interacting Galaxies Applications: Hα Emission, Colors, and SFRs Applications: Spectral Modelling of Evolved Starbursts Infrared Starbursts and the IMF in starbursts Triggering and Regulation of Star Formation: The Problem Introduction: Star Formation as a Nonlinear Process The schmidt Law in Normal Galaxies Star Formation Regimes in Interacting Galaxies Summary Triggering and Regulation of Starbusts: Theoretical Ideas Gravitational Star Formation Thresholds Cloud Collision Models Radial Transport of Gas: Clues from Barred Galaxies Simulations of Starbursts in Merging Galaxies The Cosmological Role of Interactions and Starbursts Interactions in Hierarchical Cosmology Interaction-Induced Star Formation Today Interaction-Induced Star Formation in the Past Disk kinematics and the Merger Rate Global Effects of Starbursts and Superwinds Concluding Remarks References

Dynamic control of spin states in interacting magnetic elements

DOEpatents

Jain, Shikha; Novosad, Valentyn

2014-10-07

A method for the control of the magnetic states of interacting magnetic elements comprising providing a magnetic structure with a plurality of interacting magnetic elements. The magnetic structure comprises a plurality of magnetic states based on the state of each interacting magnetic element. The desired magnetic state of the magnetic structure is determined. The active resonance frequency and amplitude curve of the desired magnetic state is determined. Each magnetic element of the magnetic structure is then subjected to an alternating magnetic field or electrical current having a frequency and amplitude below the active resonance frequency and amplitude curve of said desired magnetic state and above the active resonance frequency and amplitude curve of the current state of the magnetic structure until the magnetic state of the magnetic structure is at the desired magnetic state.

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

Direct Interactions with the Integrin β1 Cytoplasmic Tail Activate the Abl2/Arg Kinase*

PubMed Central

Simpson, Mark A.; Bradley, William D.; Harburger, David; Parsons, Maddy; Calderwood, David A.; Koleske, Anthony J.

2015-01-01

Integrins are heterodimeric α/β extracellular matrix adhesion receptors that couple physically to the actin cytoskeleton and regulate kinase signaling pathways to control cytoskeletal remodeling and adhesion complex formation and disassembly. β1 integrins signal through the Abl2/Arg (Abl-related gene) nonreceptor tyrosine kinase to control fibroblast cell motility, neuronal dendrite morphogenesis and stability, and cancer cell invasiveness, but the molecular mechanisms by which integrin β1 activates Arg are unknown. We report here that the Arg kinase domain interacts directly with a lysine-rich membrane-proximal segment in the integrin β1 cytoplasmic tail, that Arg phosphorylates the membrane-proximal Tyr-783 in the β1 tail, and that the Arg Src homology domain then engages this phosphorylated region in the tail. We show that these interactions mediate direct binding between integrin β1 and Arg in vitro and in cells and activate Arg kinase activity. These findings provide a model for understanding how β1-containing integrins interact with and activate Abl family kinases. PMID:25694433

Authoring and Enactment of Mobile Pyramid-Based Collaborative Learning Activities

ERIC Educational Resources Information Center

Manathunga, Kalpani; Hernández-Leo, Davinia

2018-01-01

Collaborative learning flow patterns (CLFPs) formulate best practices for the orchestration of activity sequences and collaboration mechanisms that can elicit fruitful social interactions. Mobile technology features offer opportunities to support interaction mediation and content accessibility. However, existing mobile collaborative learning…

76 FR 49491 - Proposed Information Collection Activity; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Administration for Children and Families Proposed Information Collection Activity; Comment Request Title: Understanding Urban Indians' Interactions with ACF...' Interactions with ACF Programs and Services'' research study, site visits will be conducted to three to five...

Endothelial connexin 32 regulates tissue factor expression induced by inflammatory stimulation and direct cell-cell interaction with activated cells.

PubMed

Okamoto, Takayuki; Akita, Nobuyuki; Hayashi, Tatsuya; Shimaoka, Motomu; Suzuki, Koji

2014-10-01

Endothelial cell (EC) interacts with adjacent EC through gap junction, and abnormal expression or function of Cxs is associated with cardiovascular diseases. In patients with endothelial dysfunction, the up-regulation of tissue factor (TF) expression promotes the pathogenic activation of blood coagulation, however the relationship between gap junctions and TF expression in ECs remains uncharacterized. ECs express the gap junction (GJ) proteins connexin32 (Cx32), Cx37, Cx40 and Cx43. We investigated the role of endothelial gap junctions, particularly Cx32, in modulating TF expression during vascular inflammation. Human umbilical vein endothelial cells (HUVECs) were stimulated with tumor necrosis factor-α (TNF-α) and TF activity was assessed in the presence of GJ blockers and an inhibitory anti-Cx32 monoclonal antibody. Treatment with GJ blockers and anti-Cx32 monoclonal antibody enhanced the TNF-α-induced TF activity and mRNA expression in HUVECs. TNF-α-activated effector HUVECs or mouse MS-1 cells were co-cultured with non-stimulated acceptor HUVECs and TF expression in acceptor HUVECs was detected. Effector EC induced TF expression in adjacent acceptor HUVECs through direct cell-cell interaction. Cell-cell interaction induced TF expression was reduced by anti-intercellular adhesion molecule-1 (ICAM1) monoclonal antibody. Soluble ICAM1-Fc fusion protein promotes TF expression. GJ blockers and anti-Cx32 monoclonal antibody enhanced TF expression induced by cell-cell interaction and ICAM1-Fc treatment. Blockade of endothelial Cx32 increased TF expression induced by TNF-α stimulation and cell-cell interaction which was at least partly dependent upon ICAM1. These results suggest that direct Cx32-mediated interaction modulates TF expression in ECs during vascular inflammation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

ATP and AMP Mutually Influence Their Interaction with the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) at Separate Binding Sites*

PubMed Central

Randak, Christoph O.; Dong, Qian; Ver Heul, Amanda R.; Elcock, Adrian H.; Welsh, Michael J.

2013-01-01

Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel in the ATP-binding cassette (ABC) transporter protein family. In the presence of ATP and physiologically relevant concentrations of AMP, CFTR exhibits adenylate kinase activity (ATP + AMP ⇆ 2 ADP). Previous studies suggested that the interaction of nucleotide triphosphate with CFTR at ATP-binding site 2 is required for this activity. Two other ABC proteins, Rad50 and a structural maintenance of chromosome protein, also have adenylate kinase activity. All three ABC adenylate kinases bind and hydrolyze ATP in the absence of other nucleotides. However, little is known about how an ABC adenylate kinase interacts with ATP and AMP when both are present. Based on data from non-ABC adenylate kinases, we hypothesized that ATP and AMP mutually influence their interaction with CFTR at separate binding sites. We further hypothesized that only one of the two CFTR ATP-binding sites is involved in the adenylate kinase reaction. We found that 8-azidoadenosine 5′-triphosphate (8-N3-ATP) and 8-azidoadenosine 5′-monophosphate (8-N3-AMP) photolabeled separate sites in CFTR. Labeling of the AMP-binding site with 8-N3-AMP required the presence of ATP. Conversely, AMP enhanced photolabeling with 8-N3-ATP at ATP-binding site 2. The adenylate kinase active center probe P1,P5-di(adenosine-5′) pentaphosphate interacted simultaneously with an AMP-binding site and ATP-binding site 2. These results show that ATP and AMP interact with separate binding sites but mutually influence their interaction with the ABC adenylate kinase CFTR. They further indicate that the active center of the adenylate kinase comprises ATP-binding site 2. PMID:23921386

Gain in Transcriptional Activity by Primate-specific Coevolution of Melanoma Antigen-A11 and Its Interaction Site in Androgen Receptor*

PubMed Central

Liu, Qiang; Su, Shifeng; Blackwelder, Amanda J.; Minges, John T.; Wilson, Elizabeth M.

2011-01-01

Male sex development and growth occur in response to high affinity androgen binding to the androgen receptor (AR). In contrast to complete amino acid sequence conservation in the AR DNA and ligand binding domains among mammals, a primate-specific difference in the AR NH2-terminal region that regulates the NH2- and carboxyl-terminal (N/C) interaction enables direct binding to melanoma antigen-A11 (MAGE-11), an AR coregulator that is also primate-specific. Human, mouse, and rat AR share the same NH2-terminal 23FQNLF27 sequence that mediates the androgen-dependent N/C interaction. However, the mouse and rat AR FXXLF motif is flanked by Ala33 that evolved to Val33 in primates. Human AR Val33 was required to interact directly with MAGE-11 and for the inhibitory effect of the AR N/C interaction on activation function 2 that was relieved by MAGE-11. The functional importance of MAGE-11 was indicated by decreased human AR regulation of an androgen-dependent endogenous gene using lentivirus short hairpin RNAs and by the greater transcriptional strength of human compared with mouse AR. MAGE-11 increased progesterone and glucocorticoid receptor activity independently of binding an FXXLF motif by interacting with p300 and p160 coactivators. We conclude that the coevolution of the AR NH2-terminal sequence and MAGE-11 expression among primates provides increased regulatory control over activation domain dominance. Primate-specific expression of MAGE-11 results in greater steroid receptor transcriptional activity through direct interactions with the human AR FXXLF motif region and indirectly through steroid receptor-associated p300 and p160 coactivators. PMID:21730049

The molecular mechanism for interaction of ceruloplasmin and myeloperoxidase

NASA Astrophysics Data System (ADS)

Bakhautdin, Bakytzhan; Bakhautdin, Esen Göksöy

2016-04-01

Ceruloplasmin (Cp) is a copper-containing ferroxidase with potent antioxidant activity. Cp is expressed by hepatocytes and activated macrophages and has been known as physiologic inhibitor of myeloperoxidase (MPO). Enzymatic activity of MPO produces anti-microbial agents and strong prooxidants such as hypochlorous acid and has a potential to damage host tissue at the sites of inflammation and infection. Thus Cp-MPO interaction and inhibition of MPO has previously been suggested as an important control mechanism of excessive MPO activity. Our aim in this study was to identify minimal Cp domain or peptide that interacts with MPO. We first confirmed Cp-MPO interaction by ELISA and surface plasmon resonance (SPR). SPR analysis of the interaction yielded 30 nM affinity between Cp and MPO. We then designed and synthesized 87 overlapping peptides spanning the entire amino acid sequence of Cp. Each of the peptides was tested whether it binds to MPO by direct binding ELISA. Two of the 87 peptides, P18 and P76 strongly interacted with MPO. Amino acid sequence analysis of identified peptides revealed high sequence and structural homology between them. Further structural analysis of Cp's crystal structure by PyMOL software unfolded that both peptides represent surface-exposed sites of Cp and face nearly the same direction. To confirm our finding we raised anti-P18 antisera in rabbit and demonstrated that this antisera disrupts Cp-MPO binding and rescues MPO activity. Collectively, our results confirm Cp-MPO interaction and identify two nearly identical sites on Cp that specifically bind MPO. We propose that inhibition of MPO by Cp requires two nearly identical sites on Cp to bind homodimeric MPO simultaneously and at an angle of at least 120 degrees, which, in turn, exerts tension on MPO and results in conformational change.

Talk-in-Interaction: Multilingual Perspectives

ERIC Educational Resources Information Center

Nguyen, Hanh thi, Ed.; Kasper, Gabriele, Ed.

2009-01-01

"Talk-in-interaction: Multilingual perspectives" offers original studies of interaction in a range of languages and language varieties, including Chinese, English, Japanese, Korean, Spanish, Swahili, Thai, and Vietnamese; monolingual and bilingual interactions; and activities designed for second or foreign language learning. Conducted from the…

Toward a neural basis for peer-interaction: what makes peer-learning tick?

PubMed Central

Clark, Ian; Dumas, Guillaume

2015-01-01

Many of the instructional practices that have been advanced as intrinsically motivating are inherent in socio-constructivist learning environments. There is now emerging scientific evidence to explain why interactive learning environments promote the intrinsic motivation to learn. The “two-body” and “second person” approaches have begun to explore the “dark matter” of social neuroscience: the intra- and inter-individual brain dynamics during social interaction. Moreover, studies indicate that when young learners are given expanded opportunities to actively and equitably participate in collaborative learning activities they experienced feelings of well-being, contentment, or even excitement. Neuroscience starts demonstrating how this naturally rewarding aspect is strongly associated with the implication of the mesolimbic dopaminergic pathway during social interaction. The production of dopamine reinforces the desire to continue the interaction, and heightens feelings of anticipation for future peer-learning activities. Here we review how cooperative learning and problem-solving interactions can bring about the “intrinsic” motivation to learn. Overall, the reported theoretical arguments and neuroscientific results have clear implications for school and organization approaches and support social constructivist perspectives. PMID:25713542

Vocal and visual stimulation, congruence and lateralization affect brain oscillations in interspecies emotional positive and negative interactions.

PubMed

Balconi, Michela; Vanutelli, Maria Elide

2016-01-01

The present research explored the effect of cross-modal integration of emotional cues (auditory and visual (AV)) compared with only visual (V) emotional cues in observing interspecies interactions. The brain activity was monitored when subjects processed AV and V situations, which represented an emotional (positive or negative), interspecies (human-animal) interaction. Congruence (emotionally congruous or incongruous visual and auditory patterns) was also modulated. electroencephalography brain oscillations (from delta to beta) were analyzed and the cortical source localization (by standardized Low Resolution Brain Electromagnetic Tomography) was applied to the data. Frequency band (mainly low-frequency delta and theta) showed a significant brain activity increasing in response to negative compared to positive interactions within the right hemisphere. Moreover, differences were found based on stimulation type, with an increased effect for AV compared with V. Finally, delta band supported a lateralized right dorsolateral prefrontal cortex (DLPFC) activity in response to negative and incongruous interspecies interactions, mainly for AV. The contribution of cross-modality, congruence (incongruous patterns), and lateralization (right DLPFC) in response to interspecies emotional interactions was discussed at light of a "negative lateralized effect."

Reduced spontaneous but relatively normal deliberate vicarious representations in psychopathy

PubMed Central

Meffert, Harma; Gazzola, Valeria; den Boer, Johan A.; Bartels, Arnold A. J.

2013-01-01

Psychopathy is a personality disorder associated with a profound lack of empathy. Neuroscientists have associated empathy and its interindividual variation with how strongly participants activate brain regions involved in their own actions, emotions and sensations while viewing those of others. Here we compared brain activity of 18 psychopathic offenders with 26 control subjects while viewing video clips of emotional hand interactions and while experiencing similar interactions. Brain regions involved in experiencing these interactions were not spontaneously activated as strongly in the patient group while viewing the video clips. However, this group difference was markedly reduced when we specifically instructed participants to feel with the actors in the videos. Our results suggest that psychopathy is not a simple incapacity for vicarious activations but rather reduced spontaneous vicarious activations co-existing with relatively normal deliberate counterparts. PMID:23884812

Compassionate love buffers stress-reactive mothers from fight-or-flight parenting.

PubMed

Miller, Jonas G; Kahle, Sarah; Lopez, Monica; Hastings, Paul D

2015-01-01

The links among mothers' compassionate love for their child, autonomic nervous system activity, and parenting behavior during less and more challenging mother-child interactions were examined. Mothers expressed and reported less negative affect when they exhibited autonomic patterns of increased parasympathetic dominance (high parasympathetic and low sympathetic activation) or autonomic coactivation (high parasympathetic and high sympathetic activation) during the less challenging interaction and autonomic coactivation during the more challenging interaction. Compassionate love predicted less reported and observed negativity in mothers who showed increased sympathetic nervous system dominance (high sympathetic and low parasympathetic activation). Compassionate love appeared to help mothers, and particularly those who experienced strong physiological arousal during difficult parenting situations, establish positive socialization contexts for their children and avoid stress-induced adverse parenting.

Biological Activity Predictions and Hydrogen Bonding Analysis in Quinolines

NASA Astrophysics Data System (ADS)

Gupta, Palvi; Kamni

The paper has been designed to make a comprehensive review of a particular series of organic molecular assembly in the form of compendium. An overview of general description of fifteen quinoline derivatives has been given. The biological activity spectra of quinoline derivatives have been correlated on structure activity relationships base which provides the different Pa (possibility of activity) and Pi (possibility of inactivity) values. Expositions of the role of intermolecular interactions in the identified derivatives have been discussed with the standard distance and angle cut-off criteria criteria as proposed by Desiraju and Steiner (1999) in an International monogram on crystallography. Distance-angle scatter plots for intermolecular interactions are presented for a better understanding of the packing interactions which exist in quinoline derivatives.

Exploring the interaction of patient activation and message design variables: message frame and presentation mode influence on the walking behavior of patients with type 2 diabetes.

PubMed

Ledford, Christy J W

2012-10-01

Examining interpersonal (physician-patient) communication strategies for promoting walking exercise to patients with type 2 diabetes assigned to primary care clinics, the study evaluated two message design variables--frame and presentation mode--as influencers of communication and adoption success. The single-site, four-week, prospective intervention study followed a 2×3 factorial, non-equivalent comparison group quasi-experimental design. Results showed frame was significantly related to steps walked; however, when including patient activation as an interaction, frame was non-significant. The model including patient activation interactions, however, detected significant mode effects on behavior. Results provide evidence that statistics are most effectively used with activated patients.

Identification and Characterization of ART-27, a Novel Coactivator for the Androgen Receptor N Terminus

PubMed Central

Markus, Steven M.; Taneja, Samir S.; Logan, Susan K.; Li, Wenhui; Ha, Susan; Hittelman, Adam B.; Rogatsky, Inez; Garabedian, Michael J.

2002-01-01

The androgen receptor (AR) is a ligand-regulated transcription factor that stimulates cell growth and differentiation in androgen-responsive tissues. The AR N terminus contains two activation functions (AF-1a and AF-1b) that are necessary for maximal transcriptional enhancement by the receptor; however, the mechanisms and components regulating AR transcriptional activation are not fully understood. We sought to identify novel factors that interact with the AR N terminus from an androgen-stimulated human prostate cancer cell library using a yeast two-hybrid approach designed to identify proteins that interact with transcriptional activation domains. A 157-amino acid protein termed ART-27 was cloned and shown to interact predominantly with the AR153–336, containing AF-1a and a part of AF-1b, localize to the nucleus and increase the transcriptional activity of AR when overexpressed in cultured mammalian cells. ART-27 also enhanced the transcriptional activation by AR153–336 fused to the LexA DNA-binding domain but not other AR N-terminal subdomains, suggesting that ART-27 exerts its effect via an interaction with a defined region of the AR N terminus. ART-27 interacts with AR in nuclear extracts from LNCaP cells in a ligand-independent manner. Interestingly, velocity gradient sedimentation of HeLa nuclear extracts suggests that native ART-27 is part of a multiprotein complex. ART-27 is expressed in a variety of human tissues, including sites of androgen action such as prostate and skeletal muscle, and is conserved throughout evolution. Thus, ART-27 is a novel cofactor that interacts with the AR N terminus and plays a role in facilitating receptor-induced transcriptional activation. PMID:11854421

Identification and characterization of ART-27, a novel coactivator for the androgen receptor N terminus.

PubMed

Markus, Steven M; Taneja, Samir S; Logan, Susan K; Li, Wenhui; Ha, Susan; Hittelman, Adam B; Rogatsky, Inez; Garabedian, Michael J

2002-02-01

The androgen receptor (AR) is a ligand-regulated transcription factor that stimulates cell growth and differentiation in androgen-responsive tissues. The AR N terminus contains two activation functions (AF-1a and AF-1b) that are necessary for maximal transcriptional enhancement by the receptor; however, the mechanisms and components regulating AR transcriptional activation are not fully understood. We sought to identify novel factors that interact with the AR N terminus from an androgen-stimulated human prostate cancer cell library using a yeast two-hybrid approach designed to identify proteins that interact with transcriptional activation domains. A 157-amino acid protein termed ART-27 was cloned and shown to interact predominantly with the AR(153-336), containing AF-1a and a part of AF-1b, localize to the nucleus and increase the transcriptional activity of AR when overexpressed in cultured mammalian cells. ART-27 also enhanced the transcriptional activation by AR(153-336) fused to the LexA DNA-binding domain but not other AR N-terminal subdomains, suggesting that ART-27 exerts its effect via an interaction with a defined region of the AR N terminus. ART-27 interacts with AR in nuclear extracts from LNCaP cells in a ligand-independent manner. Interestingly, velocity gradient sedimentation of HeLa nuclear extracts suggests that native ART-27 is part of a multiprotein complex. ART-27 is expressed in a variety of human tissues, including sites of androgen action such as prostate and skeletal muscle, and is conserved throughout evolution. Thus, ART-27 is a novel cofactor that interacts with the AR N terminus and plays a role in facilitating receptor-induced transcriptional activation.

G Protein-regulated inducer of neurite outgrowth (GRIN) modulates Sprouty protein repression of mitogen-activated protein kinase (MAPK) activation by growth factor stimulation.

PubMed

Hwangpo, Tracy Anh; Jordan, J Dedrick; Premsrirut, Prem K; Jayamaran, Gomathi; Licht, Jonathan D; Iyengar, Ravi; Neves, Susana R

2012-04-20

Gα(o/i) interacts directly with GRIN (G protein-regulated inducer of neurite outgrowth). Using the yeast two-hybrid system, we identified Sprouty2 as an interacting partner of GRIN. Gα(o) and Sprouty2 bind to overlapping regions of GRIN, thus competing for GRIN binding. Imaging experiments demonstrated that Gα(o) expression promoted GRIN translocation to the plasma membrane, whereas Sprouty2 expression failed to do so. Given the role of Sprouty2 in the regulation of growth factor-mediated MAPK activation, we examined the contribution of the GRIN-Sprouty2 interaction to CB1 cannabinoid receptor regulation of FGF receptor signaling. In Neuro-2A cells, a system that expresses all of the components endogenously, modulation of GRIN levels led to regulation of MAPK activation. Overexpression of GRIN potentiated FGF activation of MAPK and decreased tyrosine phosphorylation of Sprouty2. Pretreatment with G(o/i)-coupled CB1 receptor agonist attenuated subsequent FGF activation of MAPK. Decreased expression of GRIN both diminished FGF activation of MAPK and blocked CB1R attenuation of MAPK activation. These observations indicate that Gα(o) interacts with GRIN and outcompetes GRIN from bound Sprouty. Free Sprouty then in turn inhibits growth factor signaling. Thus, here we present a novel mechanism of how G(o/i)-coupled receptors can inhibit growth factor signaling to MAPK.

Insights into intermolecular interactions, electrostatic properties and the stability of C646 in the binding pocket of p300 histone acetyltransferase enzyme: a combined molecular dynamics and charge density study.

PubMed

Sivanandam, Magudeeswaran; Saravanan, Kandasamy; Kumaradhas, Poomani

2017-10-30

Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are enzymes that exhibit an important transcription activity. Dysfunction of these enzymes may lead to different diseases including cancer, cardiovascular, and other diseases. Therefore, these enzymes are the potential target for the generation of new therapeutics. C646 is a synthetic p300 HAT inhibitor; its structural and the electrostatic properties are the paradigm to understand its activity in the active site of p300 HAT enzyme. The docked C646 molecule in the active site forms expected key intermolecular interactions with the amino acid residues Trp1436, Tyr1467, and one water molecule (W1861); and these interactions are important for acetylation reaction. When compare the active site structure of C646 with the gas-phase structure, it is confirmed that the electron density distribution of polar bonds are highly altered, when the molecule present in the active site. In the gas-phase structure of C646, a large negative regions of electrostatic potential is found at the vicinity of O(4), O(5), and O(6) atoms; whereas, the negative region of these atoms are reduced in the active site. The molecular dynamics (MD) simulation also performed, it reveals the conformational stability and the intermolecular interactions of C646 molecule in the active site of p300.

Direct molecular interactions between Beclin 1 and the canonical NFκB activation pathway.

PubMed

Niso-Santano, Mireia; Criollo, Alfredo; Malik, Shoaib Ahmad; Michaud, Michael; Morselli, Eugenia; Mariño, Guillermo; Lachkar, Sylvie; Galluzzi, Lorenzo; Maiuri, Maria Chaira; Kroemer, Guido

2012-02-01

General (macro)autophagy and the activation of NFκB constitute prominent responses to a large array of intracellular and extracellular stress conditions. The depletion of any of the three subunits of the inhibitor of NFκB (IκB) kinase (IKKα, IKKβ, IKKγ/NEMO), each of which is essential for the canonical NFκB activation pathway, limits autophagy induction by physiological or pharmacological triggers, while constitutive active IKK subunits suffice to stimulate autophagy. The activation of IKK usually relies on TGFβ-activated kinase 1 (TAK1), which is also necessary for the optimal induction of autophagy in multiple settings. TAK1 interacts with two structurally similar co-activators, TAK1-binding proteins 2 and 3 (TAB2 and TAB3). Importantly, in resting conditions both TAB2 and TAB3 bind the essential autophagic factor Beclin 1, but not TAK1. In response to pro-autophagic stimuli, TAB2 and TAB3 dissociate from Beclin 1 and engage in stimulatory interactions with TAK1. The inhibitory interaction between TABs and Beclin 1 is mediated by their coiled-coil domains (CCDs). Accordingly, the overexpression of either TAB2 or TAB3 CCD stimulates Beclin 1- and TAK1-dependent autophagy. These results point to the existence of a direct molecular crosstalk between the canonical NFκB activation pathway and the autophagic core machinery that guarantees the coordinated induction of these processes in response to stress.

Peripheral and central interactions between the renin-angiotensin system and the renal sympathetic nerves in control of renal function.

PubMed

DiBona, G F

2001-06-01

Increases in renal sympathetic nerve activity (RSNA) regulate the functions of the nephron, the vasculature, and the renin-containing juxtaglomerular granular cells. As increased activity of the renin-angiotensin system can also influence nephron and vascular function, it is important to understand the interactions between RSNA and the renin-angiotensin system in the control of renal function. These interactions can be intrarenal, that is, the direct (via specific innervation) and indirect (via angiotensin II) contributions of increased RSNA to the regulation of renal function. The effects of increased RSNA on renal function are attenuated when the activity of the renin-angiotensin system is suppressed or antagonized with angiotensin-converting enzyme inhibitors or angiotensin II-type AT1 receptor antagonists. The effects of intrarenal administration of angiotensin II are attenuated following renal denervation. These interactions can also be extrarenal, that is, in the central nervous system, wherein RSNA and its arterial baroreflex control are modulated by changes in activity of the renin-angiotensin system. In addition to the circumventricular organs, the permeable blood-brain barrier of which permits interactions with circulating angiotensin II, there are interactions at sites behind the blood-brain barrier that depend on the influence of local angiotensin II. The responses to central administration of angiotensin II type AT1 receptor antagonists, into the ventricular system or microinjected into the rostral ventrolateral medulla, are modulated by changes in activity of the renin-angiotensin system produced by physiological changes in dietary sodium intake. Similar modulation is observed in pathophysiological models wherein activity of both the renin-angiotensin and sympathetic nervous systems is increased (e.g., congestive heart failure). Thus, both renal and extrarenal sites of interaction between the renin-angiotensin system and RSNA are involved in influencing the neural control of renal function.

Activating articulation skills through theraplay.

PubMed

Kupperman, P; Bligh, S; Goodban, M

1980-11-01

Speech Theraplay, a method of remediation for children with articulation disorders, is described. The approach is based on parent-child interactions that are postulated to activate articulation acquisition. These interactions between parent and child were duplicated and intensified in the clinical setting. Target phonemes were embedded into spontaneous interactive play, both in isolation and in meaningful exchange. The results of a six-week study indicate improvement in the articulation abilities of six children with this method.

A Conserved Hydrophobic Core in Gαi1 Regulates G Protein Activation and Release from Activated Receptor.

PubMed

Kaya, Ali I; Lokits, Alyssa D; Gilbert, James A; Iverson, T M; Meiler, Jens; Hamm, Heidi E

2016-09-09

G protein-coupled receptor-mediated heterotrimeric G protein activation is a major mode of signal transduction in the cell. Previously, we and other groups reported that the α5 helix of Gαi1, especially the hydrophobic interactions in this region, plays a key role during nucleotide release and G protein activation. To further investigate the effect of this hydrophobic core, we disrupted it in Gαi1 by inserting 4 alanine amino acids into the α5 helix between residues Gln(333) and Phe(334) (Ins4A). This extends the length of the α5 helix without disturbing the β6-α5 loop interactions. This mutant has high basal nucleotide exchange activity yet no receptor-mediated activation of nucleotide exchange. By using structural approaches, we show that this mutant loses critical hydrophobic interactions, leading to significant rearrangements of side chain residues His(57), Phe(189), Phe(191), and Phe(336); it also disturbs the rotation of the α5 helix and the π-π interaction between His(57) and Phe(189) In addition, the insertion mutant abolishes G protein release from the activated receptor after nucleotide binding. Our biochemical and computational data indicate that the interactions between α5, α1, and β2-β3 are not only vital for GDP release during G protein activation, but they are also necessary for proper GTP binding (or GDP rebinding). Thus, our studies suggest that this hydrophobic interface is critical for accurate rearrangement of the α5 helix for G protein release from the receptor after GTP binding. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The role of ANK interactions with MYBBP1a and SPHK1 in catabolic events of articular chondrocytes.

PubMed

Minashima, T; Campbell, K A; Hadley, S R; Zhang, Y; Kirsch, T

2014-06-01

To determine the role of progressive ankylosis protein (ANK)/Myb-binding protein 1a (MYBBP1a) and sphingosine kinase 1 (SPHK1) interactions in catabolic events of articular chondrocytes. ANK/MYBBP1a and SPHK1 interactions were identified using yeast two-hybrid screening and co-immunoprecipitation. To determine the role of these interactions in catabolic events of articular chondrocytes, ank/ank and wild type (WT) mouse chondrocytes transfected with full-length or mutant ank expression vectors (EVs) or femoral heads were treated with interleukin-1beta (IL-1β) in the absence or presence of SPHK inhibitor. Catabolic marker mRNA levels were analyzed by real time PCR; proteoglycan loss using safranin O staining and MMP-13 immunostaining were determined in femoral head explants; NF-κB activity was determined by transfecting chondrocytes with an NF-κB-specific luciferase reporter and analyzing nuclear translocation of p65 by immunoblotting; MYBBP1a nuclear or cytoplasmic amounts were determined by immunohistochemistry and immunoblotting. The ANK N-terminal region interacted with SPHK1, whereas a cytoplasmic C-terminal loop interacted with MYBBP1a. Lack of ANK/MYBBP1a and SPHK1 interactions in ank/ank chondrocytes resulted in increased MYBBP1a nuclear amounts and decreased SPHK1 activity, and consequently decreased NF-κB activity, catabolic marker mRNA levels, proteoglycan loss, and MMP-13 immunostaining in IL-1β-treated articular chondrocytes or femoral heads. Transfection with full-length ank EV reduced nuclear MYBBP1a amounts and fully restored SPHK and NF-κB activities in IL-1β-treated ank/ank chondrocytes, whereas transfection with P5L or F376del mutant ank reduced nuclear MYBBP1a or increased SPHK activity, respectively, and consequently either transfection only partially restored NF-κB activity. ANK/MYBBP1a and SPHK1 interactions stimulate catabolic events in IL-1β-mediated cartilage degradation. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

The effects of scripted peer tutoring and programming common stimuli on social interactions of a student with autism spectrum disorder.

PubMed

Petursdottir, Anna-Lind; McComas, Jennifer; McMaster, Kristen; Horner, Kathy

2007-01-01

This study examined the effects of scripted peer-tutoring reading activities, with and without programmed common play-related stimuli, on social interactions between a kindergartner with autism spectrum disorder and his typically developing peer-tutoring partners during free play. A withdrawal design with multiple baselines across peers showed no effects of peer tutoring on social interactions. A withdrawal design with 1 peer and continuing baselines across the other 2 peers showed that adding play-related common stimuli to the peer-tutoring activity increased social interactions during free play.

The Effects of Scripted Peer Tutoring and Programming Common Stimuli on Social Interactions of a Student with Autism Spectrum Disorder

PubMed Central

Petursdottir, Anna-Lind; McComas, Jennifer; McMaster, Kristen; Horner, Kathy

2007-01-01

This study examined the effects of scripted peer-tutoring reading activities, with and without programmed common play-related stimuli, on social interactions between a kindergartner with autism spectrum disorder and his typically developing peer-tutoring partners during free play. A withdrawal design with multiple baselines across peers showed no effects of peer tutoring on social interactions. A withdrawal design with 1 peer and continuing baselines across the other 2 peers showed that adding play-related common stimuli to the peer-tutoring activity increased social interactions during free play. PMID:17624077

Social Anxiety in Online and Real-Life Interaction and Their Associated Factors

PubMed Central

Yen, Ju-Yu; Yen, Cheng-Fang; Chen, Cheng-Sheng; Wang, Peng-Wei; Chang, Yi-Hsin

2012-01-01

Abstract Social anxiety was compared between online and real-life interaction in a sample of 2,348 college students. Severity of social anxiety in both real-life and online interaction was tested for associations with depression, Internet addiction, Internet activity type (gaming versus chatting), and scores on Behavioral Inhibition System (BIS)/Behavioral Activation System (BAS) scales. The results showed that social anxiety was lower when interacting online than when interacting offline. Depression, Internet addiction, and high BIS and BAS scores were associated with high social anxiety. The social anxiety decreased more in online interaction among subjects with high social anxiety, depression, BIS, and BAS. This result suggests that the Internet has good potential as an alternative medium for delivering interventions for social anxiety. Further, the effect of BIS on social anxiety is decreased in online interaction. More attention should be paid for BIS when the treatment for social anxiety is delivered online. PMID:22175853

Social anxiety in online and real-life interaction and their associated factors.

PubMed

Yen, Ju-Yu; Yen, Cheng-Fang; Chen, Cheng-Sheng; Wang, Peng-Wei; Chang, Yi-Hsin; Ko, Chih-Hung

2012-01-01

Social anxiety was compared between online and real-life interaction in a sample of 2,348 college students. Severity of social anxiety in both real-life and online interaction was tested for associations with depression, Internet addiction, Internet activity type (gaming versus chatting), and scores on Behavioral Inhibition System (BIS)/Behavioral Activation System (BAS) scales. The results showed that social anxiety was lower when interacting online than when interacting offline. Depression, Internet addiction, and high BIS and BAS scores were associated with high social anxiety. The social anxiety decreased more in online interaction among subjects with high social anxiety, depression, BIS, and BAS. This result suggests that the Internet has good potential as an alternative medium for delivering interventions for social anxiety. Further, the effect of BIS on social anxiety is decreased in online interaction. More attention should be paid for BIS when the treatment for social anxiety is delivered online.

Second-language Acquisition, Social Interaction, and the Classroom.

ERIC Educational Resources Information Center

Pica, Teresa

1987-01-01

Data are presented to illustrate how confirmation and comprehension checks and clarification requests develops second-language skills (comprehension and production). Absence of these interactional features in the classroom reflects the unequal participant relationships which are shaped by classroom activities. Two activities (in appendix) were…

Bone sialoprotein does not interact with pro-gelatinase A (MMP-2) or mediate MMP-2 activation.

PubMed

Hwang, Queena; Cheifetz, Sela; Overall, Christopher M; McCulloch, Christopher A; Sodek, Jaro

2009-04-22

A recent model for activation of the zymogen form of matrix metalloproteinase 2 (MMP-2, also known as gelatinase A) has suggested that interactions between the SIBLING protein bone sialoprotein (BSP) and MMP-2 leads to conformational change in MMP-2 that initiates the conversion of the pro-enzyme into a catalytically active form. This model is particularly relevant to cancer cell metastasis to bone since BSP, bound to the alphavbeta3 integrin through its arginine-glycine-aspartic acid motif, could recruit MMP-2 to the cell surface. We critically assessed the relationship between BSP and proMMP-2 and its activation using various forms of recombinant and purified BSP and MMP-2. Gelatinase and collagenase assays, fluorescence binding assays, real-time PCR, cell culture and pull-down assays were employed to test the model. Studies with a fluorogenic substrate for MMP-2 showed no activation of proMMP-2 by BSP. Binding and pull-down assays demonstrated no interaction between MMP-2 and BSP. While BSP-mediated invasiveness has been shown to depend on its integrin-binding RGD sequence, analysis of proMMP-2 activation and the level of membrane type 1 (MT1)-MMP in cells grown on a BSP substratum showed that the BSP-alphavbeta3 integrin interaction does not induce the expression of MT1-MMP. These studies do not support a role for BSP in promoting metastasis through interactions with pro-MMP-2.

The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit.

PubMed

Singleton, B K; Torres-Arzayus, M I; Rottinghaus, S T; Taccioli, G E; Jeggo, P A

1999-05-01

Ku is a heterodimeric protein with double-stranded DNA end-binding activity that operates in the process of nonhomologous end joining. Ku is thought to target the DNA-dependent protein kinase (DNA-PK) complex to the DNA and, when DNA bound, can interact and activate the DNA-PK catalytic subunit (DNA-PKcs). We have carried out a 3' deletion analysis of Ku80, the larger subunit of Ku, and shown that the C-terminal 178 amino acid residues are dispensable for DNA end-binding activity but are required for efficient interaction of Ku with DNA-PKcs. Cells expressing Ku80 proteins that lack the terminal 178 residues have low DNA-PK activity, are radiation sensitive, and can recombine the signal junctions but not the coding junctions during V(D)J recombination. These cells have therefore acquired the phenotype of mouse SCID cells despite expressing DNA-PKcs protein, suggesting that an interaction between DNA-PKcs and Ku, involving the C-terminal region of Ku80, is required for DNA double-strand break rejoining and coding but not signal joint formation. To gain further insight into important domains in Ku80, we report a point mutational change in Ku80 in the defective xrs-2 cell line. This residue is conserved among species and lies outside of the previously reported Ku70-Ku80 interaction domain. The mutational change nonetheless abrogates the Ku70-Ku80 interaction and DNA end-binding activity.

Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.

PubMed

Graff, Mariaelisa; Scott, Robert A; Justice, Anne E; Young, Kristin L; Feitosa, Mary F; Barata, Llilda; Winkler, Thomas W; Chu, Audrey Y; Mahajan, Anubha; Hadley, David; Xue, Luting; Workalemahu, Tsegaselassie; Heard-Costa, Nancy L; den Hoed, Marcel; Ahluwalia, Tarunveer S; Qi, Qibin; Ngwa, Julius S; Renström, Frida; Quaye, Lydia; Eicher, John D; Hayes, James E; Cornelis, Marilyn; Kutalik, Zoltan; Lim, Elise; Luan, Jian'an; Huffman, Jennifer E; Zhang, Weihua; Zhao, Wei; Griffin, Paula J; Haller, Toomas; Ahmad, Shafqat; Marques-Vidal, Pedro M; Bien, Stephanie; Yengo, Loic; Teumer, Alexander; Smith, Albert Vernon; Kumari, Meena; Harder, Marie Neergaard; Justesen, Johanne Marie; Kleber, Marcus E; Hollensted, Mette; Lohman, Kurt; Rivera, Natalia V; Whitfield, John B; Zhao, Jing Hua; Stringham, Heather M; Lyytikäinen, Leo-Pekka; Huppertz, Charlotte; Willemsen, Gonneke; Peyrot, Wouter J; Wu, Ying; Kristiansson, Kati; Demirkan, Ayse; Fornage, Myriam; Hassinen, Maija; Bielak, Lawrence F; Cadby, Gemma; Tanaka, Toshiko; Mägi, Reedik; van der Most, Peter J; Jackson, Anne U; Bragg-Gresham, Jennifer L; Vitart, Veronique; Marten, Jonathan; Navarro, Pau; Bellis, Claire; Pasko, Dorota; Johansson, Åsa; Snitker, Søren; Cheng, Yu-Ching; Eriksson, Joel; Lim, Unhee; Aadahl, Mette; Adair, Linda S; Amin, Najaf; Balkau, Beverley; Auvinen, Juha; Beilby, John; Bergman, Richard N; Bergmann, Sven; Bertoni, Alain G; Blangero, John; Bonnefond, Amélie; Bonnycastle, Lori L; Borja, Judith B; Brage, Søren; Busonero, Fabio; Buyske, Steve; Campbell, Harry; Chines, Peter S; Collins, Francis S; Corre, Tanguy; Smith, George Davey; Delgado, Graciela E; Dueker, Nicole; Dörr, Marcus; Ebeling, Tapani; Eiriksdottir, Gudny; Esko, Tõnu; Faul, Jessica D; Fu, Mao; Færch, Kristine; Gieger, Christian; Gläser, Sven; Gong, Jian; Gordon-Larsen, Penny; Grallert, Harald; Grammer, Tanja B; Grarup, Niels; van Grootheest, Gerard; Harald, Kennet; Hastie, Nicholas D; Havulinna, Aki S; Hernandez, Dena; Hindorff, Lucia; Hocking, Lynne J; Holmens, Oddgeir L; Holzapfel, Christina; Hottenga, Jouke Jan; Huang, Jie; Huang, Tao; Hui, Jennie; Huth, Cornelia; Hutri-Kähönen, Nina; James, Alan L; Jansson, John-Olov; Jhun, Min A; Juonala, Markus; Kinnunen, Leena; Koistinen, Heikki A; Kolcic, Ivana; Komulainen, Pirjo; Kuusisto, Johanna; Kvaløy, Kirsti; Kähönen, Mika; Lakka, Timo A; Launer, Lenore J; Lehne, Benjamin; Lindgren, Cecilia M; Lorentzon, Mattias; Luben, Robert; Marre, Michel; Milaneschi, Yuri; Monda, Keri L; Montgomery, Grant W; De Moor, Marleen H M; Mulas, Antonella; Müller-Nurasyid, Martina; Musk, A W; Männikkö, Reija; Männistö, Satu; Narisu, Narisu; Nauck, Matthias; Nettleton, Jennifer A; Nolte, Ilja M; Oldehinkel, Albertine J; Olden, Matthias; Ong, Ken K; Padmanabhan, Sandosh; Paternoster, Lavinia; Perez, Jeremiah; Perola, Markus; Peters, Annette; Peters, Ulrike; Peyser, Patricia A; Prokopenko, Inga; Puolijoki, Hannu; Raitakari, Olli T; Rankinen, Tuomo; Rasmussen-Torvik, Laura J; Rawal, Rajesh; Ridker, Paul M; Rose, Lynda M; Rudan, Igor; Sarti, Cinzia; Sarzynski, Mark A; Savonen, Kai; Scott, William R; Sanna, Serena; Shuldiner, Alan R; Sidney, Steve; Silbernagel, Günther; Smith, Blair H; Smith, Jennifer A; Snieder, Harold; Stančáková, Alena; Sternfeld, Barbara; Swift, Amy J; Tammelin, Tuija; Tan, Sian-Tsung; Thorand, Barbara; Thuillier, Dorothée; Vandenput, Liesbeth; Vestergaard, Henrik; van Vliet-Ostaptchouk, Jana V; Vohl, Marie-Claude; Völker, Uwe; Waeber, Gérard; Walker, Mark; Wild, Sarah; Wong, Andrew; Wright, Alan F; Zillikens, M Carola; Zubair, Niha; Haiman, Christopher A; Lemarchand, Loic; Gyllensten, Ulf; Ohlsson, Claes; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Pérusse, Louis; Wilson, James F; Hayward, Caroline; Polasek, Ozren; Cucca, Francesco; Hveem, Kristian; Hartman, Catharina A; Tönjes, Anke; Bandinelli, Stefania; Palmer, Lyle J; Kardia, Sharon L R; Rauramaa, Rainer; Sørensen, Thorkild I A; Tuomilehto, Jaakko; Salomaa, Veikko; Penninx, Brenda W J H; de Geus, Eco J C; Boomsma, Dorret I; Lehtimäki, Terho; Mangino, Massimo; Laakso, Markku; Bouchard, Claude; Martin, Nicholas G; Kuh, Diana; Liu, Yongmei; Linneberg, Allan; März, Winfried; Strauch, Konstantin; Kivimäki, Mika; Harris, Tamara B; Gudnason, Vilmundur; Völzke, Henry; Qi, Lu; Järvelin, Marjo-Riitta; Chambers, John C; Kooner, Jaspal S; Froguel, Philippe; Kooperberg, Charles; Vollenweider, Peter; Hallmans, Göran; Hansen, Torben; Pedersen, Oluf; Metspalu, Andres; Wareham, Nicholas J; Langenberg, Claudia; Weir, David R; Porteous, David J; Boerwinkle, Eric; Chasman, Daniel I; Abecasis, Gonçalo R; Barroso, Inês; McCarthy, Mark I; Frayling, Timothy M; O'Connell, Jeffrey R; van Duijn, Cornelia M; Boehnke, Michael; Heid, Iris M; Mohlke, Karen L; Strachan, David P; Fox, Caroline S; Liu, Ching-Ti; Hirschhorn, Joel N; Klein, Robert J; Johnson, Andrew D; Borecki, Ingrid B; Franks, Paul W; North, Kari E; Cupples, L Adrienne; Loos, Ruth J F; Kilpeläinen, Tuomas O

2017-04-01

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

Interaction between Calpain 5, Peroxisome proliferator-activated receptor-gamma and Peroxisome proliferator-activated receptor-delta genes: a polygenic approach to obesity

PubMed Central

Sáez, María E; Grilo, Antonio; Morón, Francisco J; Manzano, Luis; Martínez-Larrad, María T; González-Pérez, Antonio; Serrano-Hernando, Javier; Ruiz, Agustín; Ramírez-Lorca, Reposo; Serrano-Ríos, Manuel

2008-01-01

Context Obesity is a multifactorial disorder, that is, a disease determined by the combined effect of genes and environment. In this context, polygenic approaches are needed. Objective To investigate the possibility of the existence of a crosstalk between the CALPAIN 10 homologue CALPAIN 5 and nuclear receptors of the peroxisome proliferator-activated receptors family. Design Cross-sectional, genetic association study and gene-gene interaction analysis. Subjects The study sample comprise 1953 individuals, 725 obese (defined as body mass index ≥ 30) and 1228 non obese subjects. Results In the monogenic analysis, only the peroxisome proliferator-activated receptor delta (PPARD) gene was associated with obesity (OR = 1.43 [1.04–1.97], p = 0.027). In addition, we have found a significant interaction between CAPN5 and PPARD genes (p = 0.038) that reduces the risk for obesity in a 55%. Conclusion Our results suggest that CAPN5 and PPARD gene products may also interact in vivo. PMID:18657264

Inhibition of Human Vascular NADPH Oxidase by Apocynin Derived Oligophenols

PubMed Central

Mora-Pale, Mauricio; Weïwer, Michel; Yu, Jingjing; Linhardt, Robert J.; Dordick, Jonathan S.

2009-01-01

Enzymatic oxidation of apocynin, which may mimic in vivo metabolism, affords a large number of oligomers (apocynin oxidation products, AOP) that inhibit vascular NADPH oxidase. In vitro studies of NADPH oxidase activity were performed to identify active inhibitors, resulting in a trimer hydroxylated quinone (IIIHyQ) that inhibited NADPH oxidase with an IC50 = 31 nM. Apocynin itself possessed minimal inhibitory activity. NADPH oxidase is believed to be inhibited through prevention of the interaction between two NADPH oxidase subunits, p47phox and p22phox. To that end, while apocynin was unable to block the interaction of his-tagged p47phox with a surface immobilized biotinalyted p22phox peptide, the IIIHyQ product strongly interfered with this interaction (apparent IC50 = 1.6 μM). These results provide evidence that peroxidase-catalyzed AOP, which consist of oligomeric phenols and quinones, inhibit critical interactions that are involved in the assembly and activation of human vascular NADPH oxidase. PMID:19523836

Surfactant protein B: lipid interactions of synthetic peptides representing the amino-terminal amphipathic domain.

PubMed Central

Bruni, R; Taeusch, H W; Waring, A J

1991-01-01

The mechanisms by which pulmonary surfactant protein B (SP-B) affects the surface activity of surfactant lipids are unclear. We have studied the peptide/lipid interactions of the amino-terminal amphipathic domain of SP-B by comparing the secondary conformations and surface activities of a family of synthetic peptides based on the native human SP-B sequence, modified by site-specific amino acid substitutions. Circular dichroism measurements show an alpha-helical structure correlating with the ability of the peptides to interact with lipids and with the surface activity of peptide/lipid dispersions. Amino acid substitutions altering either the charge or the hydrophobicity of the residues lowered the helical content and reduced the association of the aminoterminal segment with lipid dispersions. Surface activity of peptide/lipid mixtures was maximally altered by reversal of charge in synthetic peptides. These observations indicate that electrostatic interactions and hydrophobicity are important factors in determining optimal structure and function of surfactant peptides in lipid dispersions. Images PMID:1871144

Activation of the SN2 Reaction by Adjacent π Systems: The Critical Role of Electrostatic Interactions and of Dissociative Character.

PubMed

Robiette, Raphaël; Trieu-Van, Tran; Aggarwal, Varinder K; Harvey, Jeremy N

2016-01-27

The activation of the SN2 reaction by π systems is well documented in textbooks. It has been shown previously that this is not primarily due to classical (hyper)conjugative effects. Instead, π-conjugated substituents enhance favorable substrate-nucleophile electrostatic interactions, with electron-withdrawing groups (EWG) on the sp(2) system leading to even stronger activation. Herein we report computational and experimental results which show that this activation by sp(2) EWG-substitution only occurs in a fairly limited number of cases, when the nucleophile involves strong electrostatic interactions (usually strongly basic negatively charged nucleophiles). In other cases, where bond breaking is more advanced than bond making at the transition state, electrophile-nucleophile electrostatic interactions are less important. In such cases, (hyper)conjugative electronic effects determine the reactivity, and EWG-substitution leads to decreased reactivity. The basicity of the nucleophile as well as solvent effects can help to determine which of these two regimes occurs for a given electrophile.

The Envelope Glycoprotein of Friend Spleen Focus-Forming Virus Covalently Interacts with and Constitutively Activates a Truncated Form of the Receptor Tyrosine Kinase Stk

PubMed Central

Nishigaki, Kazuo; Thompson, Delores; Hanson, Charlotte; Yugawa, Takashi; Ruscetti, Sandra

2001-01-01

The Friend spleen focus-forming virus (SFFV) encodes a unique envelope glycoprotein, gp55, which allows erythroid cells to proliferate and differentiate in the absence of erythropoietin (Epo). SFFV gp55 has been shown to interact with the Epo receptor complex, causing constitutive activation of various signal-transducing molecules. When injected into adult mice, SFFV induces a rapid erythroleukemia, with susceptibility being determined by the host gene Fv-2, which was recently shown to be identical to the gene encoding the receptor tyrosine kinase Stk/Ron. Susceptible, but not resistant, mice encode not only full-length Stk but also a truncated form of the kinase, sf-Stk, which may mediate the biological effects of SFFV infection. To determine whether expression of SFFV gp55 leads to the activation of sf-Stk, we expressed sf-Stk, with or without SFFV gp55, in hematopoietic cells expressing the Epo receptor. Our data indicate that sf-Stk interacts with SFFV gp55 as well as gp55P, the biologically active form of the viral glycoprotein, forming disulfide-linked complexes. This covalent interaction, as well as noncovalent interactions with SFFV gp55, results in constitutive tyrosine phosphorylation of sf-Stk and its association with multiple tyrosine-phosphorylated signal-transducing molecules. In contrast, neither Epo stimulation in the absence of SFFV gp55 expression nor expression of a mutant of SFFV that cannot interact with sf-Stk was able to induce tyrosine phosphorylation of sf-Stk or its association with any signal-transducing molecules. Covalent interaction of sf-Stk with SFFV gp55 and constitutive tyrosine phosphorylation of sf-Stk can also be detected in an erythroleukemia cell line derived from an SFFV-infected mouse. Our results suggest that SFFV gp55 may mediate its biological effects in vivo by interacting with and activating a truncated form of the receptor tyrosine kinase Stk. PMID:11483734

Investigating the Use of Interactive Whiteboards during the Pre-Task Phase of Speaking Tasks in the Secondary English Classroom

ERIC Educational Resources Information Center

Handley, Zoe

2012-01-01

Working within a task-based approach to the teaching of speaking, two interactive whiteboard-based pre-task activities focusing on different phases of the speech production process (Levelt, 1989) were developed and compared with an activity based on the speaking activities currently offered in English as a foreign language course books. The first…

Cross-sectional interactions between quality of the physical and social environment and self-reported physical activity in adults living in income-deprived communities

PubMed Central

2017-01-01

Background Understanding the environmental determinants of physical activity in populations at high risk of inactivity could contribute to the development of effective interventions. Socioecological models of activity propose that environmental factors have independent and interactive effects of physical activity but there is a lack of research into interactive effects. Objectives This study aimed to explore independent and interactive effects of social and physical environmental factors on self-reported physical activity in income-deprived communities. Methods Participants were 5,923 adults in Glasgow, United Kingdom. Features of the social environment were self-reported. Quality of the physical environment was objectively-measured. Neighbourhood walking and participation in moderate physical activity [MPA] on ≥5 days/week was self-reported. Multilevel multivariate logistic regression models tested independent and interactive effects of environmental factors on activity. Results ‘Social support’ (walking: OR:1.22,95%CI = 1.06–1.41,p<0.01; MPA: OR:0.79,95%CI = 0.67–0.94,p<0.01), ‘social interaction’ (walking: OR:1.25,95%CI = 1.10–1.42,p<0.01; MPA: OR:6.16,95%CI = 5.14–7.37,p<0.001) and ‘cohesion and safety’ (walking: OR:1.78,95%CI = 1.56–2.03,p<0.001; MPA: OR:1.93,95%CI = 1.65–2.27,p<0.001), but not ‘trust and empowerment’, had independent effects on physical activity. ‘Aesthetics of built form’ (OR:1.47,95%CI = 1.22–1.77,p<0.001) and ‘aesthetics and maintenance of open space’ (OR:1.32, 95%CI = 1.13–1.54,p<0.01) were related to walking. ‘Physical disorder’ (OR:1.63,95%CI = 1.31–2.03,p<0.001) had an independent effect on MPA. Interactive effects of social and physical factors on walking and MPA were revealed. Conclusions Findings suggest that intervening to create activity-supportive environments in deprived communities may be most effective when simultaneously targeting the social and physical neighbourhood environment. PMID:29240791

Design of HIV-1 Protease Inhibitors with Amino-bis-tetrahydrofuran Derivatives as P2-Ligands to Enhance Backbone-Binding Interactions. Synthesis, Biological Evaluation, and Protein-Ligand X-ray Studies

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

Ghosh, Arun K.; Martyr, Cuthbert D.; Osswald, Heather L.

Structure-based design, synthesis, and biological evaluation of a series of very potent HIV-1 protease inhibitors are described. In an effort to improve backbone ligand–binding site interactions, we have incorporated basic-amines at the C4 position of the bis-tetrahydrofuran (bis-THF) ring. We speculated that these substituents would make hydrogen bonding interactions in the flap region of HIV-1 protease. Synthesis of these inhibitors was performed diastereoselectively. A number of inhibitors displayed very potent enzyme inhibitory and antiviral activity. Inhibitors 25f, 25i, and 25j were evaluated against a number of highly-PI-resistant HIV-1 strains, and they exhibited improved antiviral activity over darunavir. Two high resolutionmore » X-ray structures of 25f- and 25g-bound HIV-1 protease revealed unique hydrogen bonding interactions with the backbone carbonyl group of Gly48 as well as with the backbone NH of Gly48 in the flap region of the enzyme active site. These ligand–binding site interactions are possibly responsible for their potent activity.« less

Sequential CD4-Coreceptor Interactions in Human Immunodeficiency Virus Type 1 Env Function: Soluble CD4 Activates Env for Coreceptor-Dependent Fusion and Reveals Blocking Activities of Antibodies against Cryptic Conserved Epitopes on gp120

PubMed Central

Salzwedel, Karl; Smith, Erica D.; Dey, Barna; Berger, Edward A.

2000-01-01

We devised an experimental system to examine sequential events by which the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) interacts with CD4 and coreceptor to induce membrane fusion. Recombinant soluble CD4 (sCD4) activated fusion between effector cells expressing Env and target cells expressing coreceptor (CCR5 or CXCR4) but lacking CD4. sCD4-activated fusion was dose dependent, occurred comparably with two- and four-domain proteins, and demonstrated Env-coreceptor specificities parallel to those reported in conventional fusion and infectivity systems. Fusion activation occurred upon sCD4 preincubation and washing of the Env-expressing effector cells but not the coreceptor-bearing target cells, thereby demonstrating that sCD4 exerts its effects by acting on Env. These findings provide direct functional evidence for a sequential two-step model of Env-receptor interactions, whereby gp120 binds first to CD4 and becomes activated for subsequent functional interaction with coreceptor, leading to membrane fusion. We used the sCD4-activated system to explore neutralization by the anti-gp120 human monoclonal antibodies 17b and 48d. These antibodies reportedly bind conserved CD4-induced epitopes involved in coreceptor interactions but neutralize HIV-1 infection only weakly. We found that 17b and 48d had minimal effects in the standard cell fusion system using target cells expressing both CD4 and coreceptor but potently blocked sCD4-activated fusion with target cells expressing coreceptor alone. Both antibodies strongly inhibited sCD4-activated fusion by Envs from genetically diverse HIV-1 isolates. Thus, the sCD4-activated system reveals conserved Env-blocking epitopes that are masked in native Env and hence not readily detected by conventional systems. PMID:10590121

Hsp27 regulates Akt activation and polymorphonuclear leukocyte apoptosis by scaffolding MK2 to Akt signal complex.

PubMed

Wu, Rui; Kausar, Hina; Johnson, Paul; Montoya-Durango, Diego E; Merchant, Michael; Rane, Madhavi J

2007-07-27

We have shown previously that Akt exists in a signal complex with p38 MAPK, MAPK-activated protein kinase-2 (MK2), and heat shock protein 27 (Hsp27) and MK2 phosphorylates Akt on Ser-473. Additionally, dissociation of Hsp27 from Akt, prior to Akt activation, induced polymorphonuclear leukocyte (PMN) apoptosis. However, the role of Hsp27 in regulating Akt activation was not examined. This study tested the hypothesis that Hsp27 regulates Akt activation and promotes cell survival by scaffolding MK2 to the Akt signal complex. Here we show that loss of Akt/Hsp27 interaction by anti-Hsp27 antibody treatment resulted in loss of Akt/MK2 interaction, loss of Akt-Ser-473 phosphorylation, and induced PMN apoptosis. Transfection of myristoylated Akt (AktCA) in HK-11 cells induced Akt-Ser-473 phosphorylation, activation, and Hsp27-Ser-82 phosphorylation. Cotransfection of AktCA with Hsp27 short interfering RNA, but not scrambled short interfering RNA, silenced Hsp27 expression, without altering Akt expression in HK-11 cells. Silencing Hsp27 expression inhibited Akt/MK2 interaction, inhibited Akt phosphorylation and Akt activation, and induced HK-11 cell death. Deletion mutagenesis studies identified acidic linker region (amino acids 117-128) on Akt as an Hsp27 binding region. Deletion of amino acids 117-128 on Akt resulted in loss of its interaction with Hsp27 and MK2 but not with Hsp90 as demonstrated by immunoprecipitation and glutathione S-transferase pulldown studies. Co-transfection studies demonstrated that constitutively active MK2 (MK2EE) phosphorylated Aktwt (wild type) on Ser-473 but failed to phosphorylate Akt(Delta117-128) mutant in transfixed cells. These studies collectively define a novel role of Hsp27 in regulating Akt activation and cellular apoptosis by mediating interaction between Akt and its upstream activator MK2.

Anion-π interactions in active centers of superoxide dismutases.

PubMed

Ribić, Vesna R; Stojanović, Srđan Đ; Zlatović, Mario V

2018-01-01

We investigated 1060 possible anion-π interactions in a data set of 41 superoxide dismutase active centers. Our observations indicate that majority of the aromatic residues are capable to form anion-π interactions, mainly by long-range contacts, and that there is preference of Trp over other aromatic residues in these interactions. Furthermore, 68% of total predicted interactions in the dataset are multiple anion-π interactions. Anion-π interactions are distance and orientation dependent. We analyzed the energy contribution resulting from anion-π interactions using ab initio calculations. The results showed that, while most of their interaction energies lay in the range from -0 to -4kcalmol -1 , those energies can be up to -9kcalmol -1 and about 34% of interactions were found to be repulsive. Majority of the suggested anion-π interacting residues in ternary complexes are metal-assisted. Stabilization centers for these proteins showed that all the six residues found in predicted anion-π interactions are important in locating one or more of such centers. The anion-π interacting residues in these proteins were found to be highly conserved. We hope that these studies might contribute useful information regarding structural stability and its interaction in future designs of novel metalloproteins. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of idiotypic interactions in the adaptive immune system: a belief-propagation approach

NASA Astrophysics Data System (ADS)

Bartolucci, Silvia; Mozeika, Alexander; Annibale, Alessia

2016-08-01

In this work we use belief-propagation techniques to study the equilibrium behaviour of a minimal model for the immune system comprising interacting T and B clones. We investigate the effect of the so-called idiotypic interactions among complementary B clones on the system’s activation. Our results show that B-B interactions increase the system’s resilience to noise, making clonal activation more stable, while increasing the cross-talk between different clones. We derive analytically the noise level at which a B clone gets activated, in the absence of cross-talk, and find that this increases with the strength of idiotypic interactions and with the number of T cells sending signals to the B clones. We also derive, analytically and numerically, via population dynamics, the critical line where clonal cross-talk arises. Our approach allows us to derive the B clone size distribution, which can be experimentally measured and gives important information about the adaptive immune system response to antigens and vaccination.

Ubc13 and COOH Terminus of Hsp70-interacting Protein (CHIP) Are Required for Growth Hormone Receptor Endocytosis*

PubMed Central

Slotman, Johan A.; da Silva Almeida, Ana C.; Hassink, Gerco C.; van de Ven, Robert H. A.; van Kerkhof, Peter; Kuiken, Hendrik J.; Strous, Ger J.

2012-01-01

Growth hormone receptor (GHR) endocytosis is a highly regulated process that depends on the binding and activity of the multimeric ubiquitin ligase, SCFβTrCP (Skp Cullin F-box). Despite a specific interaction between β-transducin repeat-containing protein (βTrCP) and the GHR, and a strict requirement for ubiquitination activity, the receptor is not an obligatory target for SCFβTrCP-directed Lys48 polyubiquitination. We now show that also Lys63-linked ubiquitin chain formation is required for GHR endocytosis. We identified both the ubiquitin-conjugating enzyme Ubc13 and the ubiquitin ligase COOH terminus of Hsp70 interacting protein (CHIP) as being connected to this process. Ubc13 activity and its interaction with CHIP precede endocytosis of GHR. In addition to βTrCP, CHIP interacts specifically with the cytosolic tails of the dimeric GHR, identifying both Ubc13 and CHIP as novel factors in the regulation of cell surface availability of GHR. PMID:22433856

Examining elementary school children's level of enjoyment of traditional tag games vs. interactive dance games.

PubMed

Gao, Zan; Zhang, Peng; Podlog, Leslie William

2014-01-01

Enjoyment has been implicated as a determinant of physical activity among children and adolescents. However, the effect of different sport activities on children's enjoyment remains largely unexplored. This study examined whether children's enjoyment in physical education (PE) varied as a function of learning activities. Participants were 210 third- through sixth-grade children who had a 30 min PE class every week. Participants responded to a standardized self-report enjoyment survey measuring their enjoyment level in a PE class during which they participated in tag games. Students completed the same questionnaire when involved in interactive dance games in PE. The results revealed that children reported significantly higher scores in enjoyment toward interactive dance games than they did toward traditional games (p < .01). Also, girls exhibited higher enjoyment toward interactive dance games than boys did (p < .05). However, no gender difference emerged on enjoyment toward traditional games. In conclusion, it is practical and meaningful to integrate interactive dance games into PE.

Insulin-like growth factor-binding protein-5 (IGFBP-5) inhibits TNF-{alpha}-induced NF-{kappa}B activity by binding to TNFR1

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

Hwang, Jae Ryoung; Huh, Jae Ho; Lee, Yoonna

2011-02-25

Research highlights: {yields} Binding assays demonstrated that secreted- and cellular-IGFBP-5 interacted with TNFR1. {yields} The interaction between IGFBP-5 and TNFR1 was inhibited by TNF-{alpha} and was blocked TNF-{alpha}-activated NF-{kappa}B activity. {yields} IGFBP-5 interacted with TNFR1 through its N- and L-domains but the binding of L-domain to TNFR1 was blocked by TNF-{alpha}. {yields} Competition between the L-domain of IGFBP-5 and TNF-{alpha} blocked TNF-{alpha}-induced NF-{kappa}B activity. {yields} This study suggests that the L-domain of IGFBP-5 is a novel TNFR1 ligand that functions as a competitive TNF-{alpha} inhibitor. -- Abstract: IGFBP-5 is known to be involved in various cell phenomena such as proliferation,more » differentiation, and apoptosis. However, the exact mechanisms by which IGFBP-5 exerts its functions are unclear. In this study, we demonstrate for the first time that IGFBP-5 is a TNFR1-interacting protein. We found that ectopic expression of IGFBP-5 induced TNFR1 gene expression, and that IGFBP-5 interacted with TNFR1 in both an in vivo and an in vitro system. Secreted IGFBP-5 interacted with GST-TNFR1 and this interaction was blocked by TNF-{alpha}, demonstrating that IGFBP-5 might be a TNFR1 ligand. Furthermore, conditioned media containing secreted IGFBP-5 inhibited PMA-induced NF-{kappa}B activity and IL-6 expression in U-937 cells. Coimmunoprecipitation assays of TNFR1 and IGFBP-5 wild-type and truncation mutants revealed that IGFBP-5 interacts with TNFR1 through its N- and L-domains. However, only the interaction between the L-domain of IGFBP-5 and TNFR1 was blocked by TNF-{alpha} in a dose-dependent manner, suggesting that the L-domain of IGFBP-5 can function as a TNFR1 ligand. Competition between the L-domain of IGFBP-5 and TNF-{alpha} resulted in inhibition of TNF-{alpha}-induced NF-{kappa}{Beta} activity. Taken together, our results suggest that the L-domain of IGFBP-5 is a novel TNFR1 ligand that functions as a competitive TNF-{alpha} inhibitor.« less

Punctuated equilibrium dynamics in human communications

NASA Astrophysics Data System (ADS)

Peng, Dan; Han, Xiao-Pu; Wei, Zong-Wen; Wang, Bing-Hong

2015-10-01

A minimal model based on network incorporating individual interactions is proposed to study the non-Poisson statistical properties of human behavior: individuals in system interact with their neighbors, the probability of an individual acting correlates to its activity, and all the individuals involved in action will change their activities randomly. The model reproduces varieties of spatial-temporal patterns observed in empirical studies of human daily communications, providing insight into various human activities and embracing a range of realistic social interacting systems, particularly, intriguing bimodal phenomenon. This model bridges priority queueing theory and punctuated equilibrium dynamics, and our modeling and analysis is likely to shed light on non-Poisson phenomena in many complex systems.

Calorimetric studies of the interactions of metalloenzyme active site mimetics with zinc-binding inhibitors.

PubMed

Robinson, Sophia G; Burns, Philip T; Miceli, Amanda M; Grice, Kyle A; Karver, Caitlin E; Jin, Lihua

2016-07-19

The binding of drugs to metalloenzymes is an intricate process that involves several interactions, including binding of the drug to the enzyme active site metal, as well as multiple interactions between the drug and the enzyme residues. In order to determine the free energy contribution of Zn(2+) binding by known metalloenzyme inhibitors without the other interactions, valid active site zinc structural mimetics must be formed and binding studies need to be performed in biologically relevant conditions. The potential of each of five ligands to form a structural mimetic with Zn(2+) was investigated in buffer using Isothermal Titration Calorimetry (ITC). All five ligands formed strong 1 : 1 (ligand : Zn(2+)) binary complexes. The complexes were used in further ITC experiments to study their interaction with 8-hydroxyquinoline (8-HQ) and/or acetohydroxamic acid (AHA), two bidentate anionic zinc-chelating enzyme inhibitors. It was found that tetradentate ligands were not suitable for creating zinc structural mimetics for inhibitor binding in solution due to insufficient coordination sites remaining on Zn(2+). A stable binary complex, [Zn(BPA)](2+), which was formed by a tridentate ligand, bis(2-pyridylmethyl)amine (BPA), was found to bind one AHA in buffer or a methanol : buffer mixture (60 : 40 by volume) at pH 7.25 or one 8-HQ in the methanol : buffer mixture at pH 6.80, making it an effective structural mimetic for the active site of zinc metalloenzymes. These results are consistent with the observation that metalloenzyme active site zinc ions have three residues coordinated to them, leaving one or two sites open for inhibitors to bind. Our findings indicate that Zn(BPA)X2 can be used as an active site structural mimetic for zinc metalloenzymes for estimating the free energy contribution of zinc binding to the overall inhibitor active site interactions. Such use will help aid in the rational design of inhibitors to a variety of zinc metalloenzymes.

Ocellatin peptides from the skin secretion of the South American frog Leptodactylus labyrinthicus (Leptodactylidae): characterization, antimicrobial activities and membrane interactions.

PubMed

Gusmão, Karla A G; Dos Santos, Daniel M; Santos, Virgílio M; Cortés, María Esperanza; Reis, Pablo V M; Santos, Vera L; Piló-Veloso, Dorila; Verly, Rodrigo M; de Lima, Maria Elena; Resende, Jarbas M

2017-01-01

The availability of antimicrobial peptides from several different natural sources has opened an avenue for the discovery of new biologically active molecules. To the best of our knowledge, only two peptides isolated from the frog Leptodactylus labyrinthicus , namely pentadactylin and ocellatin-F1, have shown antimicrobial activities. Therefore, in order to explore the antimicrobial potential of this species, we have investigated the biological activities and membrane interactions of three peptides isolated from the anuran skin secretion. Three peptide primary structures were determined by automated Edman degradation. These sequences were prepared by solid-phase synthesis and submitted to activity assays against gram-positive and gram-negative bacteria and against two fungal strains. The hemolytic properties of the peptides were also investigated in assays with rabbit blood erythrocytes. The conformational preferences of the peptides and their membrane interactions have been investigated by circular dichroism spectroscopy and liposome dye release assays. The amino acid compositions of three ocellatins were determined and the sequences exhibit 100% homology for the first 22 residues (ocellatin-LB1 sequence). Ocellatin-LB2 carries an extra Asn residue and ocellatin-F1 extra Asn-Lys-Leu residues at C-terminus. Ocellatin-F1 presents a stronger antibiotic potential and a broader spectrum of activities compared to the other peptides. The membrane interactions and pore formation capacities of the peptides correlate directly with their antimicrobial activities, i.e., ocellatin-F1 > ocellatin-LB1 > ocellatin-LB2. All peptides acquire high helical contents in membrane environments. However, ocellatin-F1 shows in average stronger helical propensities. The obtained results indicate that the three extra amino acid residues at the ocellatin-F1 C-terminus play an important role in promoting stronger peptide-membrane interactions and antimicrobial properties. The extra Asn-23 residue present in ocellatin-LB2 sequence seems to decrease its antimicrobial potential and the strength of the peptide-membrane interactions.

Very late antigen integrins are involved in the adhesive interaction of lymphoid cells to human gingival fibroblasts.

PubMed Central

Murakami, S; Saho, T; Shimabukuro, Y; Isoda, R; Miki, Y; Okada, H

1993-01-01

To date, it is still unclear how the trafficking and retention of activated lymphocytes in periodontal lesions are regulated. In this study, we investigated the molecular basis for the adhesive interactions between lymphocytes and human gingival fibroblasts (HGF). Peripheral blood T lymphocytes (PBT) exhibited binding ability, but only when the calls were activated with phorbol 12-myristate 13-acetate (PMA). Among several human cell lines tested, PMA-stimulated Molt-4, a human T-cell leukaemia line, also displayed significant binding ability to HGF. In order to clarify the molecule(s) involved in this cell-cell interaction, a panel of monoclonal antibodies (mAb) was prepared to PMA-activated Molt-4 and one clone, 4-145, was selected on the basis of its ability to block the binding of PMA-activated Molt-4 to HGF. Moreover, 4-145 inhibited the binding of not only activated Molt-4 but also activated PBT and other cell types to HGF. Biochemical and flow cytometric analyses revealed that 4-145 probably recognizes the beta 1 chain of very late antigen (VLA) integrins. Blocking experiments using mAb specific for the alpha-chain of VLA integrins demonstrated the involvement of alpha 4 (VLA-4) and, to a lesser extent, alpha 5 (VLA-5) chains in the adhesive interactions between T cells and HGF. Despite the significant involvement of VLA integrins in the adhesive interaction between PBT and HGF, the binding of PBT to human dermal fibroblasts (HDF) was not abrogated by 4-145, suggesting that HGF and HDF differ in their requirement of VLA integrins for adhesion to activated PBT. Furthermore, the fact that vascular cell adhesion molecule-1 (VCAM-1), one of the ligands of VLA-4, was not detected on HGF by flow cytometry and anti-fibronectin (FN) Ab did not block the adhesive interaction to HGF suggests that not-yet-identified ligand(s) for VLA-4 might be present on HGF. Images Figure 4 PMID:8406571

The Impact of Teaching Presence on Online Engagement Behaviors

ERIC Educational Resources Information Center

Zhang, Huaihao; Lin, Lijia; Zhan, Yi; Ren, Youqun

2016-01-01

Guided by the Interactive-Constructive-Active-Passive framework, the purpose of the study was to investigate whether teaching presence would impact online learners' passive, active, constructive, and interactive engagement behaviors. A total of 218 middle-school English teachers participated in an online professional development course.…

Reading a Story: Different Degrees of Learning in Different Learning Environments.

PubMed

Giannini, Anna Maria; Cordellieri, Pierluigi; Piccardi, Laura

2017-01-01

The learning environment in which material is acquired may produce differences in delayed recall and in the elements that individuals focus on. These differences may appear even during development. In the present study, we compared three different learning environments in 450 normally developing 7-year-old children subdivided into three groups according to the type of learning environment. Specifically, children were asked to learn the same material shown in three different learning environments: reading illustrated books (TB); interacting with the same text displayed on a PC monitor and enriched with interactive activities (PC-IA); reading the same text on a PC monitor but not enriched with interactive narratives (PC-NoIA). Our results demonstrated that TB and PC-NoIA elicited better verbal memory recall. In contrast, PC-IA and PC-NoIA produced higher scores for visuo-spatial memory, enhancing memory for spatial relations, positions and colors with respect to TB. Interestingly, only TB seemed to produce a deeper comprehension of the story's moral. Our results indicated that PC-IA offered a different type of learning that favored visual details. In this sense, interactive activities demonstrate certain limitations, probably due to information overabundance, emotional mobilization, emphasis on images and effort exerted in interactive activities. Thus, interactive activities, although entertaining, act as disruptive elements which interfere with verbal memory and deep moral comprehension.

Non-Watson–Crick interactions between PNA and DNA inhibit the ATPase activity of bacteriophage T4 Dda helicase

PubMed Central

Tackett, Alan J.; Corey, David R.; Raney, Kevin D.

2002-01-01

Peptide nucleic acid (PNA) is a DNA mimic in which the nucleobases are linked by an N-(2-aminoethyl) glycine backbone. Here we report that PNA can interact with single-stranded DNA (ssDNA) in a non-sequence-specific fashion. We observed that a 15mer PNA inhibited the ssDNA-stimulated ATPase activity of a bacteriophage T4 helicase, Dda. Surprisingly, when a fluorescein-labeled 15mer PNA was used in binding studies no interaction was observed between PNA and Dda. However, fluorescence polarization did reveal non-sequence-specific interactions between PNA and ssDNA. Thus, the inhibition of ATPase activity of Dda appears to result from depletion of the available ssDNA due to non-Watson–Crick binding of PNA to ssDNA. Inhibition of the ssDNA-stimulated ATPase activity was observed for several PNAs of varying length and sequence. To study the basis for this phenomenon, we examined self-aggregation by PNAs. The 15mer PNA readily self-aggregates to the point of precipitation. Since PNAs are hydrophobic, they aggregate more than DNA or RNA, making the study of this phenomenon essential for understanding the properties of PNA. Non-sequence-specific interactions between PNA and ssDNA were observed at moderate concentrations of PNA, suggesting that such interactions should be considered for antisense and antigene applications. PMID:11842106

Probing the interactions between ionic liquids and water: experimental and quantum chemical approach.

PubMed

Khan, Imran; Kurnia, Kiki A; Mutelet, Fabrice; Pinho, Simão P; Coutinho, João A P

2014-02-20

For an adequate choice or design of ionic liquids, the knowledge of their interaction with other solutes and solvents is an essential feature for predicting the reactivity and selectivity of systems involving these compounds. In this work, the activity coefficient of water in several imidazolium-based ionic liquids with the common cation 1-butyl-3-methylimidazolium was measured at 298.2 K. To contribute to a deeper insight into the interaction between ionic liquids and water, COSMO-RS was used to predict the activity coefficient of water in the studied ionic liquids along with the excess enthalpies. The results showed good agreement between experimental and predicted activity coefficient of water in ionic liquids and that the interaction of water and ionic liquids was strongly influenced by the hydrogen bonding of the anion with water. Accordingly, the intensity of interaction of the anions with water can be ranked as the following: [CF3SO3](-) < [SCN](-) < [TFA](-) < Br(-) < [TOS](-) < Cl(-) < [CH3SO3](-) [DMP](-) < [Ac](-). In addition, fluorination and aromatization of anions are shown to reduce their interaction with water. The effect of temperature on the activity coefficient of water at infinite dilution was measured by inverse gas chromatography and predicted by COSMO-RS. Further analysis based on COSMO-RS provided information on the nature of hydrogen bonding between water and anion as well as the possibility of anion-water complex formation.

Reading a Story: Different Degrees of Learning in Different Learning Environments

PubMed Central

Giannini, Anna Maria; Cordellieri, Pierluigi; Piccardi, Laura

2017-01-01

The learning environment in which material is acquired may produce differences in delayed recall and in the elements that individuals focus on. These differences may appear even during development. In the present study, we compared three different learning environments in 450 normally developing 7-year-old children subdivided into three groups according to the type of learning environment. Specifically, children were asked to learn the same material shown in three different learning environments: reading illustrated books (TB); interacting with the same text displayed on a PC monitor and enriched with interactive activities (PC-IA); reading the same text on a PC monitor but not enriched with interactive narratives (PC-NoIA). Our results demonstrated that TB and PC-NoIA elicited better verbal memory recall. In contrast, PC-IA and PC-NoIA produced higher scores for visuo-spatial memory, enhancing memory for spatial relations, positions and colors with respect to TB. Interestingly, only TB seemed to produce a deeper comprehension of the story’s moral. Our results indicated that PC-IA offered a different type of learning that favored visual details. In this sense, interactive activities demonstrate certain limitations, probably due to information overabundance, emotional mobilization, emphasis on images and effort exerted in interactive activities. Thus, interactive activities, although entertaining, act as disruptive elements which interfere with verbal memory and deep moral comprehension. PMID:29085296

Neural dynamics of social tie formation in economic decision-making.

PubMed

Bault, Nadège; Pelloux, Benjamin; Fahrenfort, Johannes J; Ridderinkhof, K Richard; van Winden, Frans

2015-06-01

The disposition for prosocial conduct, which contributes to cooperation as arising during social interaction, requires cortical network dynamics responsive to the development of social ties, or care about the interests of specific interaction partners. Here, we formulate a dynamic computational model that accurately predicted how tie formation, driven by the interaction history, influences decisions to contribute in a public good game. We used model-driven functional MRI to test the hypothesis that brain regions key to social interactions keep track of dynamics in tie strength. Activation in the medial prefrontal cortex (mPFC) and posterior cingulate cortex tracked the individual's public good contributions. Activation in the bilateral posterior superior temporal sulcus (pSTS), and temporo-parietal junction was modulated parametrically by the dynamically developing social tie-as estimated by our model-supporting a role of these regions in social tie formation. Activity in these two regions further reflected inter-individual differences in tie persistence and sensitivity to behavior of the interaction partner. Functional connectivity between pSTS and mPFC activations indicated that the representation of social ties is integrated in the decision process. These data reveal the brain mechanisms underlying the integration of interaction dynamics into a social tie representation which in turn influenced the individual's prosocial decisions. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Using PyMOL to Explore the Effects of pH on Noncovalent Interactions between Immunoglobulin G and Protein A: A Guided-Inquiry Biochemistry Activity.

PubMed

Roche Allred, Zahilyn D; Tai, Heeyoung; Bretz, Stacey Lowery; Page, Richard C

2017-11-01

Students' understandings of foundational concepts such as noncovalent interactions, pH and pK a are crucial for success in undergraduate biochemistry courses. We developed a guided-inquiry activity to aid students in making connections between noncovalent interactions and pH/pK a . Students explore these concepts by examining the primary and tertiary structures of immunoglobulin G (IgG) and Protein A. Students use PyMOL, an open source molecular visualization application, to (1) identify hydrogen bonds and salt bridges between and within the proteins at physiological pH and (2) apply their knowledge of pH/pK a to association rate constant data for these proteins at pH 4 and pH 11. The laboratory activity was implemented within a one semester biochemistry laboratory for students majoring in allied health disciplines, engineering, and biological sciences. Several extensions for more advanced students are discussed. Students' overall performance highlighted their ability to successfully complete tasks such as labeling and identifying noncovalent interactions and revealed difficulties with analyzing noncovalent interactions under varying pH/pK a conditions. Students' evaluations after completing the activity indicated they felt challenged but also recognized the potential of the activity to help them gain meaningful understanding of the connections between noncovalent interactions, pH, pK a , and protein structure. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(6):528-536, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes.

PubMed

Pondman, Kirsten M; Pednekar, Lina; Paudyal, Basudev; Tsolaki, Anthony G; Kouser, Lubna; Khan, Haseeb A; Shamji, Mohamed H; Ten Haken, Bennie; Stenbeck, Gudrun; Sim, Robert B; Kishore, Uday

2015-11-01

Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

No activation of human pregnane X receptor by hyperforin-related phloroglucinols.

PubMed

Kandel, Benjamin A; Ekins, Sean; Leuner, Kristina; Thasler, Wolfgang E; Harteneck, Christian; Zanger, Ulrich M

2014-03-01

The acylated phloroglucinol, hyperforin, the main active ingredient of St. John's Wort, exerts antidepressant properties via indirect inhibition of serotonin reuptake by selectively activating the canonical transient receptor potential channel 6 (TRPC6). Hyperforin treatment can lead to drug-drug interactions due to potent activation of the nuclear receptor PXR (NR1I2), a key transcriptional regulator of genes involved in drug metabolism and transport. It was previously shown that synthetic acylated phloroglucinol derivatives activate TRPC6 with similar potency as hyperforin. However, their interaction potential with PXR remained unknown. Here we investigated five synthetic TRPC6-activating phloroglucinol derivatives and four TRPC6-nonactivating compounds compared with hyperforin and rifampicin for their potential to activate PXR in silico and in vitro. Computational PXR pharmacophore modeling did not indicate potent agonist or antagonist interactions for the TRPC6-activating derivatives, whereas one of them was suggested by docking studies to show both agonist and antagonist interactions. Hyperforin and rifampicin treatment of HepG2 cells cotransfected with human PXR expression vector and a CYP3A4 promoter-reporter construct resulted in potent PXR-dependent induction, whereas all TRPC6-activating compounds failed to show any PXR activation or to antagonize rifampicin-mediated CYP3A4 promoter induction. Hyperforin and rifampicin treatment of primary human hepatocytes resulted in highly correlated induction of PXR target genes, whereas treatment with the phloroglucinol derivatives elicited moderate gene expression changes that were only weakly correlated with those of rifampicin and hyperforin treatment. These results show that TRPC6-activating phloroglucinols do not activate PXR and should therefore be promising new candidates for further drug development.

PUB1 Interacts with the Receptor Kinase DMI2 and Negatively Regulates Rhizobial and Arbuscular Mycorrhizal Symbioses through Its Ubiquitination Activity in Medicago truncatula.

PubMed

Vernié, Tatiana; Camut, Sylvie; Camps, Céline; Rembliere, Céline; de Carvalho-Niebel, Fernanda; Mbengue, Malick; Timmers, Ton; Gasciolli, Virginie; Thompson, Richard; le Signor, Christine; Lefebvre, Benoit; Cullimore, Julie; Hervé, Christine

2016-04-01

PUB1, an E3 ubiquitin ligase, which interacts with and is phosphorylated by the LYK3 symbiotic receptor kinase, negatively regulates rhizobial infection and nodulation during the nitrogen-fixing root nodule symbiosis in Medicago truncatula In this study, we show that PUB1 also interacts with and is phosphorylated by DOES NOT MAKE INFECTIONS 2, the key symbiotic receptor kinase of the common symbiosis signaling pathway, required for both the rhizobial and the arbuscular mycorrhizal (AM) endosymbioses. We also show here that PUB1 expression is activated during successive stages of root colonization by Rhizophagus irregularis that is compatible with its interaction with DOES NOT MAKE INFECTIONS 2. Through characterization of a mutant, pub1-1, affected by the E3 ubiquitin ligase activity of PUB1, we have shown that the ubiquitination activity of PUB1 is required to negatively modulate successive stages of infection and development of rhizobial and AM symbioses. In conclusion, PUB1 represents, to our knowledge, a novel common component of symbiotic signaling integrating signal perception through interaction with and phosphorylation by two key symbiotic receptor kinases, and downstream signaling via its ubiquitination activity to fine-tune both rhizobial and AM root endosymbioses. © 2016 American Society of Plant Biologists. All Rights Reserved.

MicroRNA319-regulated TCPs interact with FBHs and PFT1 to activate CO transcription and control flowering time in Arabidopsis.

PubMed

Liu, Jie; Cheng, Xiliu; Liu, Pan; Li, Dayong; Chen, Tao; Gu, Xiaofeng; Sun, Jiaqiang

2017-05-01

The transcription factor CONSTANS (CO) is a central component that promotes Arabidopsis flowering under long-day conditions (LDs). Here, we show that the microRNA319-regulated TEOSINTE BRANCHED/CYCLOIDEA/PCF (TCP) transcription factors promote photoperiodic flowering through binding to the CO promoter and activating its transcription. Meanwhile, these TCPs directly interact with the flowering activators FLOWERING BHLH (FBHs), but not the flowering repressors CYCLING DOF FACTORs (CDFs), to additively activate CO expression. Furthermore, both the TCPs and FBHs physically interact with the flowering time regulator PHYTOCHROME AND FLOWERING TIME 1 (PFT1) to facilitate CO transcription. Our findings provide evidence that a set of transcriptional activators act directly and additively at the CO promoter to promote CO transcription, and establish a molecular mechanism underlying the regulation of photoperiodic flowering time in Arabidopsis.

MicroRNA319-regulated TCPs interact with FBHs and PFT1 to activate CO transcription and control flowering time in Arabidopsis

PubMed Central

Liu, Pan; Li, Dayong; Chen, Tao; Gu, Xiaofeng; Sun, Jiaqiang

2017-01-01

The transcription factor CONSTANS (CO) is a central component that promotes Arabidopsis flowering under long-day conditions (LDs). Here, we show that the microRNA319-regulated TEOSINTE BRANCHED/CYCLOIDEA/PCF (TCP) transcription factors promote photoperiodic flowering through binding to the CO promoter and activating its transcription. Meanwhile, these TCPs directly interact with the flowering activators FLOWERING BHLH (FBHs), but not the flowering repressors CYCLING DOF FACTORs (CDFs), to additively activate CO expression. Furthermore, both the TCPs and FBHs physically interact with the flowering time regulator PHYTOCHROME AND FLOWERING TIME 1 (PFT1) to facilitate CO transcription. Our findings provide evidence that a set of transcriptional activators act directly and additively at the CO promoter to promote CO transcription, and establish a molecular mechanism underlying the regulation of photoperiodic flowering time in Arabidopsis. PMID:28558040

Enolase from Trypanosoma cruzi is inhibited by its interaction with metallocarboxypeptidase-1 and a putative acireductone dioxygenase.

PubMed

Quintero-Troconis, E; Buelvas, N; Carrasco-López, C; Domingo-Sananes, M R; González-González, L; Ramírez-Molina, R; Osorio, L; Lobo-Rojas, A; Cáceres, A J; Michels, P A; Acosta, H; Quiñones, W; Concepción, J L

Purification of enolase (ENO) from the cytosol of Trypanosoma cruzi indicated that it may interact with at least five other proteins. Two of them were identified as metallocarboxypeptidase-1 (TcMCP-1) and a putative acireductone dioxygenase (ARDp). Subcellular localization studies confirmed the presence of ARDp in the cytosol, as is the case for ENO and TcMCP-1. Analysis of the ARDp sequence showed that this protein has two domains, an N-terminal ARD and a C-terminal TRP14 (thioredoxin-related protein) domain. The interactions between ENO, TcMCP-1 and ARDp were confirmed for the natural proteins from the trypanosome (using size-exclusion chromatography and co-immunoprecipitation from a cytosolic fraction) and recombinant forms (using ELISA ligand-binding assay and ENO activity assays). The ELISA ligand-binding assays permitted to verify the optimal physicochemical conditions for the interactions (representative for the physiological conditions) and to determine the affinity constants (Kd): ENO/ARDp: 9.54 ± 0.82 nM, ARDp/ENO 10.05 ± 1.11 nM, and ENO/TcMCP-1: 5.66 ± 0.61 nM. The data also show that the interaction between TcMCP-1 and ARDp is mediated by ENO acting as a "bridge". Furthermore, considerable inhibition of the ENO activity, up to 85%, is observed when the enzyme interacts with TcMCP-1 and ARDp simultaneously. All these data confirm that the interaction between ENO, TcMCP-1 and ARDp, occurring in T. cruzi's cytosol, modulates the ENO activity and suggest a possible physiological mechanism for regulation of the ENO activity by the protein-protein interaction. Copyright © 2018 Elsevier B.V. All rights reserved.

Learning and cognitive styles in web-based learning: theory, evidence, and application.

PubMed

Cook, David A

2005-03-01

Cognitive and learning styles (CLS) have long been investigated as a basis to adapt instruction and enhance learning. Web-based learning (WBL) can reach large, heterogenous audiences, and adaptation to CLS may increase its effectiveness. Adaptation is only useful if some learners (with a defined trait) do better with one method and other learners (with a complementary trait) do better with another method (aptitude-treatment interaction). A comprehensive search of health professions education literature found 12 articles on CLS in computer-assisted learning and WBL. Because so few reports were found, research from non-medical education was also included. Among all the reports, four CLS predominated. Each CLS construct was used to predict relationships between CLS and WBL. Evidence was then reviewed to support or refute these predictions. The wholist-analytic construct shows consistent aptitude-treatment interactions consonant with predictions (wholists need structure, a broad-before-deep approach, and social interaction, while analytics need less structure and a deep-before-broad approach). Limited evidence for the active-reflective construct suggests aptitude-treatment interaction, with active learners doing better with interactive learning and reflective learners doing better with methods to promote reflection. As predicted, no consistent interaction between the concrete-abstract construct and computer format was found, but one study suggests that there is interaction with instructional method. Contrary to predictions, no interaction was found for the verbal-imager construct. Teachers developing WBL activities should consider assessing and adapting to accommodate learners defined by the wholist-analytic and active-reflective constructs. Other adaptations should be considered experimental. Further WBL research could clarify the feasibility and effectiveness of assessing and adapting to CLS.

Ligand-independent activation of the oestrogen receptor by mutation of a conserved tyrosine.

PubMed Central

White, R; Sjöberg, M; Kalkhoven, E; Parker, M G

1997-01-01

The oestrogen receptor is a member of the nuclear receptor family of transcription factors which, on binding the steroid hormone 17beta-oestradiol, interacts with co-activator proteins and stimulates gene expression. Replacement of a single tyrosine in the hormone-binding domain generated activated forms of the receptor which stimulated transcription in the absence of hormone. This increased activation is related to a decrease in hydrophobicity and a reduction in size of the side chain of the amino acid with which the tyrosine is replaced. Ligand-independent, in common with ligand-dependent transcriptional activation, requires an amphipathic alpha-helix at the C-terminus of the ligand-binding domain which is essential for the interaction of the receptor with a number of potential co-activator proteins. In contrast to the wild-type protein, constitutively active receptors were able to bind both the receptor-interacting protein RIP-140 and the steroid receptor co-activator SRC-1 in a ligand-independent manner, although in the case of SRC-1 this was only evident when the receptors were prebound to DNA. We propose, therefore, that this tyrosine is required to maintain the receptor in a transcriptionally inactive state in the absence of hormone. Modification of this residue may generate a conformational change in the ligand-binding domain of the receptor to form an interacting surface which allows the recruitment of co-activators independent of hormone binding. This suggests that this tyrosine may be a target for a different signalling pathway which forms an alternative mechanism of activating oestrogen receptor-mediated transcription. PMID:9135157

Overweight adult cats have significantly lower voluntary physical activity than adult lean cats.

PubMed

de Godoy, Maria Rc; Shoveller, Anna K

2017-12-01

Objectives The objectives of the current pilot study were to evaluate whether body condition score (BCS) and body weight are significantly related to physical activity counts, and to evaluate potential interaction between BCS and voluntary physical activity measured over a 14 day period. Methods Ten (five lean, five overweight), neutered, adult American Shorthair cats were selected for this study (median age 4 ± 0.5 years). Cats with a BCS of ⩽3.0 were considered lean, whereas cats with a BCS >3.0 were considered overweight, using a 5-point scale. Cats were housed in a free-living environment with indoor/outdoor access and were individually fed once daily a commercially available dry extruded diet and allowed 1 h to eat. Voluntary physical activity was measured consecutively for 14 days using the Actical Activity Monitors that were worn parallel to the ribs and attached via a harness. Results Lean cats had a greater mean total daily voluntary physical activity ( P = 0.0059), and a greater voluntary physical activity during light ( P = 0.0023) and dark ( P = 0.0446) periods, with overweight cats having 60% of the physical activity of lean cats. Lean cats were more active before feeding and during animal care procedures. These data suggest that lean cats have a greater anticipatory physical activity prior to feeding and are more eager to have social interaction with humans than overweight cats. A significant interaction was observed between day of physical activity measurement and BCS for total daily voluntary physical activity ( P = 0.0133) and activity during the light period ( P = 0.0016) where lean cats were consistently more active than overweight cats. In general, cats were more active during weekdays vs weekends. Conclusions and relevance The results of this study suggest that overweight cats are less active than lean cats and that voluntary physical activity level appears to be influenced by social interaction with humans.

Patterns of Adult-Child Linguistic Interaction in Integrated Day Care Groups.

PubMed

Girolametto, Luigi; Hoaken, Lisa; Weitzman, Elaine; Lieshout, Riet van

2000-04-01

This study investigated the language input of eight childcare providers to children with developmental disabilities, including language delay, who were integrated into community day care centers. Structural and discourse features of the adults' language input was compared across two groups (integrated, typical) and two naturalistic day care contexts (book reading, play dough activity). The eight children with developmental disabilities and language delay were between 33-50 months of age; 32 normally developing peers ranged in age from 32-53 months of age. Adult-child interactions were transcribed and coded to yield estimates of structural indices (number of utterances, rate, mean length of utterances, ratio of different words to total words used (TTR) and discourse features (directive, interactive, language-modelling) of their language input. The language input addressed to the children with developmental disabilities was directive and not finely tuned to their expressive language levels. In turn, these children interacted infrequently with the adult or with the other children. Contextual comparisons indicated that the play dough activity promoted adult-child interaction that was less directive and more interaction-promoting than book reading, and that children interacted more frequently in the play-dough activity. Implications for speech-language pathologists include the need for collaborative consultation in integrated settings, modification of adult-child play contexts to promote interaction, and training childcare providers to use language input that promotes communication development.

Specificity of marine microbial surface interactions.

PubMed Central

Imam, S H; Bard, R F; Tosteson, T R

1984-01-01

The macromolecular surface components involved in intraspecific cell surface interactions of the green microalga Chlorella vulgaris and closely associated bacteria were investigated. The specific surface attachment between this alga and its associated bacteria is mediated by lectin-like macromolecules associated with the surfaces of these cells. The binding activity of these surface polymers was inhibited by specific simple sugars; this suggests the involvement of specific receptor-ligand binding sites on the interactive surfaces. Epifluorescent microscopic evaluation of bacteria-alga interactions in the presence and absence of the macromolecules that mediate these interactions showed that the glycoproteins active in these processes were specific to the microbial sources from which they were obtained. The demonstration and definition of the specificity of these interactions in mixed microbial populations may play an important role in our understanding of the dynamics of marine microbial populations in the sea. PMID:6508293

Generic Long-Range Interactions Between Passive Bodies in an Active Fluid.

PubMed

Baek, Yongjoo; Solon, Alexandre P; Xu, Xinpeng; Nikola, Nikolai; Kafri, Yariv

2018-02-02

A single nonspherical body placed in an active fluid generates currents via breaking of time-reversal symmetry. We show that, when two or more passive bodies are placed in an active fluid, these currents lead to long-range interactions. Using a multipole expansion, we characterize their leading-order behaviors in terms of single-body properties and show that they decay as a power law with the distance between the bodies, are anisotropic, and do not obey an action-reaction principle. The interactions lead to rich dynamics of the bodies, illustrated by the spontaneous synchronized rotation of pinned nonchiral bodies and the formation of traveling bound pairs. The occurrence of these phenomena depends on tunable properties of the bodies, thus opening new possibilities for self-assembly mediated by active fluids.

Ultraviolet-Visible (UV-Vis) and Fluorescence Spectroscopic Investigation of the Interactions of Ionic Liquids and Catalase.

PubMed

Dong, Xing; Fan, Yunchang; Yang, Peng; Kong, Jichuan; Li, Dandan; Miao, Juan; Hua, Shaofeng; Hu, Chaobing

2016-11-01

The inhibitory effects of nine ionic liquids (ILs) on the catalase activity were investigated using fluorescence, absorption ultraviolet-visible spectroscopy. The interactions of ILs and catalase on the molecular level were studied. The experimental results indicated that ILs could inhibit the catalase activity and their inhibitory abilities depended on their chemical structures. Fluorescence experiments showed that hydrogen bonding played an important role in the interaction process. The inhibitory abilities of ILs on catalase activity could be simply described by their hydrophobicity and hydrogen bonding abilities. Unexpected less inhibitory effects of trifluoromethanesulfonate (TfO - ) might be ascribed to its larger size, which makes it difficult to go through the substrate channel of catalase to the active site. © The Author(s) 2016.

Compassionate Love Buffers Stress-Reactive Mothers From Fight-or-Flight Parenting

PubMed Central

Miller, Jonas G.; Kahle, Sarah; Lopez, Monica; Hastings, Paul D.

2015-01-01

The links among mothers’ compassionate love for their child, autonomic nervous system activity, and parenting behavior during less and more challenging mother–child interactions were examined. Mothers expressed and reported less negative affect when they exhibited autonomic patterns of increased parasympathetic dominance (high parasympathetic and low sympathetic activation) or autonomic coactivation (high parasympathetic and high sympathetic activation) during the less challenging interaction and autonomic coactivation during the more challenging interaction. Compassionate love predicted less reported and observed negativity in mothers who showed increased sympathetic nervous system dominance (high sympathetic and low parasympathetic activation). Compassionate love appeared to help mothers, and particularly those who experienced strong physiological arousal during difficult parenting situations, establish positive socialization contexts for their children and avoid stress-induced adverse parenting. PMID:25329554

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.

The effect of peer tutoring on interaction behaviors in inclusive physical education.

PubMed

Klavina, Aija; Block, Martin E

2008-04-01

This study assessed the effect of peer tutoring on physical, instructional, and social interaction behaviors between elementary school age students with severe and multiple disabilities (SMD) and peers without disabilities. Additional measures addressed the activity time of students with SMD. The study was conducted in inclusive general physical education settings under three instructional support conditions for students with SMD: (a) teacher-directed, (b) peer-mediated, and (c) voluntary peer support. During peer-mediated and voluntary peer support conditions, the instructional and physical interaction behaviors between students with SMD and their peers increased, while social interactions remained low. The activity engagement time data increased for all target students throughout intervention sessions. Interactions between students with SMD and teachers decreased toward the end of intervention.

Conserved Arginines at the P-Protein Stalk Binding Site and the Active Site Are Critical for Ribosome Interactions of Shiga Toxins but Do Not Contribute to Differences in the Affinity of the A1 Subunits for the Ribosome.

PubMed

Basu, Debaleena; Kahn, Jennifer N; Li, Xiao-Ping; Tumer, Nilgun E

2016-12-01

The A1 subunits of Shiga toxin 1 (Stx1A1) and Shiga toxin 2 (Stx2A1) interact with the conserved C termini of ribosomal-stalk P-proteins to remove a specific adenine from the sarcin/ricin loop. We previously showed that Stx2A1 has higher affinity for the ribosome and higher catalytic activity than Stx1A1. To determine if conserved arginines at the distal face of the active site contribute to the higher affinity of Stx2A1 for the ribosome, we mutated Arg172, Arg176, and Arg179 in both toxins. We show that Arg172 and Arg176 are more important than Arg179 for the depurination activity and toxicity of Stx1A1 and Stx2A1. Mutation of a single arginine reduced the depurination activity of Stx1A1 more than that of Stx2A1. In contrast, mutation of at least two arginines was necessary to reduce depurination by Stx2A1 to a level similar to that of Stx1A1. R176A and R172A/R176A mutations eliminated interaction of Stx1A1 and Stx2A1 with ribosomes and with the stalk, while mutation of Arg170 at the active site reduced the binding affinity of Stx1A1 and Stx2A1 for the ribosome, but not for the stalk. These results demonstrate that conserved arginines at the distal face of the active site are critical for interactions of Stx1A1 and Stx2A1 with the stalk, while a conserved arginine at the active site is critical for non-stalk-specific interactions with the ribosome. Arginine mutations at either site reduced ribosome interactions of Stx1A1 and Stx2A1 similarly, indicating that conserved arginines are critical for ribosome interactions but do not contribute to the higher affinity of Stx2A1 for the ribosome. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Analysis of the STAT3 interactome using in-situ biotinylation and SILAC.

PubMed

Blumert, Conny; Kalkhof, Stefan; Brocke-Heidrich, Katja; Kohajda, Tibor; von Bergen, Martin; Horn, Friedemann

2013-12-06

Signal transducer and activator of transcription 3 (STAT3) is activated by a variety of cytokines and growth factors. To generate a comprehensive data set of proteins interacting specifically with STAT3, we applied stable isotope labeling with amino acids in cell culture (SILAC). For high-affinity pull-down using streptavidin, we fused STAT3 with a short peptide tag allowing biotinylation in situ (bio-tag), which did not affect STAT3 functions. By this approach, 3642 coprecipitated proteins were detected in human embryonic kidney-293 cells. Filtering using statistical and functional criteria finally extracted 136 proteins as putative interaction partners of STAT3. Both, a physical interaction network analysis and the enrichment of known and predicted interaction partners suggested that our filtering criteria successfully enriched true STAT3 interactors. Our approach identified numerous novel interactors, including ones previously predicted to associate with STAT3. By reciprocal coprecipitation, we were able to verify the physical association between STAT3 and selected interactors, including the novel interaction with TOX4, a member of the TOX high mobility group box family. Applying the same method, we next investigated the activation-dependency of the STAT3 interactome. Again, we identified both known and novel interactions. Thus, our approach allows to study protein-protein interaction effectively and comprehensively. The location, activity, function, degradation, and synthesis of proteins are significantly regulated by interactions of proteins with other proteins, biopolymers and small molecules. Thus, the comprehensive characterization of interactions of proteins in a given proteome is the next milestone on the path to understanding the biochemistry of the cell. In order to generate a comprehensive interactome dataset of proteins specifically interacting with a selected bait protein, we fused our bait protein STAT3 with a short peptide tag allowing biotinylation in situ (bio-tag). This bio-tag allows an affinity pull-down using streptavidin but affected neither the activation of STAT3 by tyrosine phosphorylation nor its transactivating potential. We combined SILAC for accurate relative protein quantification, subcellular fractionation to increase the coverage of interacting proteins, high-affinity pull-down and a stringent filtering method to successfully analyze the interactome of STAT3. With our approach we confirmed several already known and identified numerous novel STAT3 interactors. The approach applied provides a rapid and effective method, which is broadly applicable for studying protein-protein interactions and their dependency on post-translational modifications. © 2013. Published by Elsevier B.V. All rights reserved.

SPAK kinase is a substrate and target of PKCθ in T-cell receptor-induced AP-1 activation pathway

PubMed Central

Li, Yingqiu; Hu, Junru; Vita, Randi; Sun, Binggang; Tabata, Hiroki; Altman, Amnon

2004-01-01

Protein kinase C-θ (PKCθ) plays an important role in T-cell activation via stimulation of AP-1 and NF-κB. Here we report the isolation of SPAK, a Ste20-related upstream mitogen-activated protein kinase (MAPK), as a PKCθ-interacting kinase. SPAK interacted with PKCθ (but not with PKCα) via its 99 COOH-terminal residues. TCR/CD28 costimulation enhanced this association and stimulated the catalytic activity of SPAK. Recombinant SPAK was phosphorylated on Ser-311 in its kinase domain by PKCθ, but not by PKCα. The magnitude and duration of TCR/CD28-induced endogenous SPAK activation were markedly impaired in PKCθ-deficient T cells. Transfected SPAK synergized with constitutively active PKCθ to activate AP-1, but not NF-κB. This synergistic activity, as well as the receptor-induced SPAK activation, required the PKCθ-interacting region of SPAK, and Ser-311 mutation greatly reduced these activities of SPAK. Conversely, a SPAK-specific RNAi or a dominant-negative SPAK mutant inhibited PKCθ- and TCR/CD28-induced AP-1, but not NF-κB, activation. These results define SPAK as a substrate and target of PKCθ in a TCR/CD28-induced signaling pathway leading selectively to AP-1 (but not NF-κB) activation. PMID:14988727

Anticipation of peer evaluation in anxious adolescents: divergence in neural activation and maturation

PubMed Central

Jarcho, Johanna M.; Dahl, Ronald E.; Pine, Daniel S.; Ernst, Monique; Nelson, Eric E.

2015-01-01

Adolescence is the time of peak onset for many anxiety disorders, particularly Social Anxiety Disorder. Research using simulated social interactions consistently finds differential activation in several brain regions in anxious (vs non-anxious) youth, including amygdala, striatum and medial prefrontal cortex. However, few studies examined the anticipation of peer interactions, a key component in the etiology and maintenance of anxiety disorders. Youth completed the Chatroom Task while undergoing functional magnetic resonance imaging. Patterns of neural activation were assessed in anxious and non-anxious youth as they were cued to anticipate social feedback from peers. Anxious participants evidenced greater amygdala activation and rostral anterior cingulate (rACC)↔amygdala coupling than non-anxious participants during anticipation of feedback from peers they had previously rejected; anxious participants also evidenced less nucleus accumbens activation during anticipation of feedback from selected peers. Finally, anxiety interacted with age in rACC: in anxious participants, age was positively associated with activation to anticipated feedback from rejected peers and negatively for selected peers, whereas the opposite pattern emerged for non-anxious youth. Overall, anxious youth showed greater reactivity in anticipation of feedback from rejected peers and thus may ascribe greater salience to these potential interactions and increase the likelihood of avoidance behavior. PMID:25552568

DAT by perceived MC interaction on human prefrontal activity and connectivity during emotion processing.

PubMed

Taurisano, Paolo; Blasi, Giuseppe; Romano, Raffaella; Sambataro, Fabio; Fazio, Leonardo; Gelao, Barbara; Ursini, Gianluca; Lo Bianco, Luciana; Di Giorgio, Annabella; Ferrante, Francesca; Papazacharias, Apostolos; Porcelli, Annamaria; Sinibaldi, Lorenzo; Popolizio, Teresa; Bertolino, Alessandro

2013-12-01

Maternal care (MC) and dopamine modulate brain activity during emotion processing in inferior frontal gyrus (IFG), striatum and amygdala. Reuptake of dopamine from the synapse is performed by the dopamine transporter (DAT), whose abundance is predicted by variation in its gene (DAT 3'VNTR; 10 > 9-repeat alleles). Here, we investigated the interaction between perceived MC and DAT 3'VNTR genotype on brain activity during processing of aversive facial emotional stimuli. Sixty-one healthy subjects were genotyped for DAT 3'VNTR and categorized in low and high MC individuals. They underwent functional magnetic resonance imaging while performing a task requiring gender discrimination of facial stimuli with angry, fearful or neutral expressions. An interaction between facial expression, DAT genotype and MC was found in left IFG, such that low MC and homozygosity for the 10-repeat allele are associated with greater activity during processing of fearful faces. This greater activity was also inversely correlated with a measure of emotion control as scored with the Big Five Questionnaire. Moreover, MC and DAT genotype described a double dissociation on functional connectivity between IFG and amygdala. These findings suggest that perceived early parental bonding may interact with DAT 3'VNTR genotype in modulating brain activity during emotionally relevant inputs.

DAT by perceived MC interaction on human prefrontal activity and connectivity during emotion processing

PubMed Central

Taurisano, Paolo; Blasi, Giuseppe; Romano, Raffaella; Sambataro, Fabio; Fazio, Leonardo; Gelao, Barbara; Ursini, Gianluca; Lo Bianco, Luciana; Di Giorgio, Annabella; Ferrante, Francesca; Papazacharias, Apostolos; Porcelli, Annamaria; Sinibaldi, Lorenzo; Popolizio, Teresa

2013-01-01

Background: Maternal care (MC) and dopamine modulate brain activity during emotion processing in inferior frontal gyrus (IFG), striatum and amygdala. Reuptake of dopamine from the synapse is performed by the dopamine transporter (DAT), whose abundance is predicted by variation in its gene (DAT 3′VNTR; 10 > 9-repeat alleles). Here, we investigated the interaction between perceived MC and DAT 3′VNTR genotype on brain activity during processing of aversive facial emotional stimuli. Methods: Sixty-one healthy subjects were genotyped for DAT 3′VNTR and categorized in low and high MC individuals. They underwent functional magnetic resonance imaging while performing a task requiring gender discrimination of facial stimuli with angry, fearful or neutral expressions. Results: An interaction between facial expression, DAT genotype and MC was found in left IFG, such that low MC and homozygosity for the 10-repeat allele are associated with greater activity during processing of fearful faces. This greater activity was also inversely correlated with a measure of emotion control as scored with the Big Five Questionnaire. Moreover, MC and DAT genotype described a double dissociation on functional connectivity between IFG and amygdala. Conclusion: These findings suggest that perceived early parental bonding may interact with DAT 3′VNTR genotype in modulating brain activity during emotionally relevant inputs. PMID:22842906

Myosin II–interacting guanine nucleotide exchange factor promotes bleb retraction via stimulating cortex reassembly at the bleb membrane

PubMed Central

Jiao, Meng; Wu, Di; Wei, Qize

2018-01-01

Blebs are involved in various biological processes such as cell migration, cytokinesis, and apoptosis. While the expansion of blebs is largely an intracellular pressure-driven process, the retraction of blebs is believed to be driven by RhoA activation that leads to the reassembly of the actomyosin cortex at the bleb membrane. However, it is still poorly understood how RhoA is activated at the bleb membrane. Here, we provide evidence demonstrating that myosin II–interacting guanine nucleotide exchange factor (MYOGEF) is implicated in bleb retraction via stimulating RhoA activation and the reassembly of an actomyosin network at the bleb membrane during bleb retraction. Interaction of MYOGEF with ezrin, a well-known regulator of bleb retraction, is required for MYOGEF localization to retracting blebs. Notably, knockout of MYOGEF or ezrin not only disrupts RhoA activation at the bleb membrane, but also interferes with nonmuscle myosin II localization and activation, as well as actin polymerization in retracting blebs. Importantly, MYOGEF knockout slows down bleb retraction. We propose that ezrin interacts with MYOGEF and recruits it to retracting blebs, where MYOGEF activates RhoA and promotes the reassembly of the cortical actomyosin network at the bleb membrane, thus contributing to the regulation of bleb retraction. PMID:29321250

Clustering and phase behaviour of attractive active particles with hydrodynamics.

PubMed

Navarro, Ricard Matas; Fielding, Suzanne M

2015-10-14

We simulate clustering, phase separation and hexatic ordering in a monolayered suspension of active squirming disks subject to an attractive Lennard-Jones-like pairwise interaction potential, taking hydrodynamic interactions between the particles fully into account. By comparing the hydrodynamic case with counterpart simulations for passive and active Brownian particles, we elucidate the relative roles of self-propulsion, interparticle attraction, and hydrodynamic interactions in determining clustering and phase behaviour. Even in the presence of an attractive potential, we find that hydrodynamic interactions strongly suppress the motility induced phase separation that might a priori have been expected in a highly active suspension. Instead, we find only a weak tendency for the particles to form stringlike clusters in this regime. At lower activities we demonstrate phase behaviour that is broadly equivalent to that of the counterpart passive system at low temperatures, characterized by regimes of gas-liquid, gas-solid and liquid-solid phase coexistence. In this way, we suggest that a dimensionless quantity representing the level of activity relative to the strength of attraction plays the role of something like an effective non-equilibrium temperature, counterpart to the (dimensionless) true thermodynamic temperature in the passive system. However there are also some important differences from the equilibrium case, most notably with regards the degree of hexatic ordering, which we discuss carefully.

Nanostructure and force spectroscopy analysis of human peripheral blood CD4{sup +} T cells using atomic force microscopy

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

Hu Mingqian; Wang Jiongkun; Cai Jiye

2008-09-12

To date, nanoscale imaging of the morphological changes and adhesion force of CD4{sup +} T cells during in vitro activation remains largely unreported. In this study, we used atomic force microscopy (AFM) to study the morphological changes and specific binding forces in resting and activated human peripheral blood CD4{sup +} T cells. The AFM images revealed that the volume of activated CD4{sup +} T cells increased and the ultrastructure of these cells also became complex. Using a functionalized AFM tip, the strength of the specific binding force of the CD4 antigen-antibody interaction was found to be approximately three times thatmore » of the unspecific force. The adhesion forces were not randomly distributed over the surface of a single activated CD4{sup +} T cell, indicated that the CD4 molecules concentrated into nanodomains. The magnitude of the adhesion force of the CD4 antigen-antibody interaction did not change markedly with the activation time. Multiple bonds involved in the CD4 antigen-antibody interaction were measured at different activation times. These results suggest that the adhesion force involved in the CD4 antigen-antibody interaction is highly selective and of high affinity.« less

Helicobacter pylori induces activation of human peripheral γδ+ T lymphocytes.

PubMed

Romi, Benedetta; Soldaini, Elisabetta; Pancotto, Laura; Castellino, Flora; Del Giudice, Giuseppe; Schiavetti, Francesca

2011-04-29

Helicobacter pylori is a gram-negative bacterium that causes gastric and duodenal diseases in humans. Despite a robust antibody and cellular immune response, H. pylori infection persists chronically. To understand if and how H. pylori could modulate T cell activation, in the present study we investigated in vitro the interaction between H. pylori and human T lymphocytes freshly isolated from peripheral blood of H. pylori-negative donors. A direct interaction of live, but not killed bacteria with purified CD3+ T lymphocytes was observed by microscopy and confirmed by flow cytometry. Live H. pylori activated CD3+ T lymphocytes and predominantly γδ+ T cells bearing the TCR chain Vδ2. Upon interaction with H. pylori, these cells up-regulated the activation molecule CD69 and produced cytokines (such as TNFα, IFNγ) and chemokines (such as MIP-1β, RANTES) in a non-antigen-specific manner. This activation required viable H. pylori and was not exhibited by other gram-negative bacteria. The cytotoxin-associated antigen-A (CagA), was at least partially responsible of this activation. Our results suggest that H. pylori can directly interact with T cells and modulate the response of γδ+ T cells, thereby favouring an inflammatory environment which can contribute to the chronic persistence of the bacteria and eventually to the gastric pathology.

The human papillomavirus (HPV) E6 oncoproteins promotes nuclear localization of active caspase 8

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

Manzo-Merino, Joaquin; Massimi, Paola; Lizano, Marcela, E-mail: lizanosoberon@gmail.com

The HPV-16 E6 and E6{sup ⁎} proteins have been shown previously to be capable of regulating caspase 8 activity. We now show that the capacity of E6 to interact with caspase 8 is common to diverse HPV types, being also seen with HPV-11 E6, HPV-18 E6 and HPV-18 E6{sup ⁎}. Unlike most E6-interacting partners, caspase 8 does not appear to be a major proteasomal target of E6, but instead E6 appears able to stimulate caspase 8 activation, without affecting the overall apoptotic activity. This would appear to be mediated in part by the ability of the HPV E6 oncoproteins tomore » recruit active caspase 8 to the nucleus. - Highlights: • Multiple HPV E6 oncoproteins interact with the caspase 8 DED domain. • HPV E6 stimulates activation of caspase 8. • HPV E6 promotes nuclear accumulation of caspase 8.« less

Trans-activation of the Tetrahymena group I intron ribozyme via a non-native RNA-RNA interaction.

PubMed Central

Ikawa, Y; Shiraishi, H; Inoue, T

1999-01-01

The peripheral P2.1 domain of the Tetrahymena group I intron ribozyme has been shown to be non-essential for splicing. We found, however, that separately prepared P2.1 RNA efficiently accelerates the 3' splice-site-specific hydrolysis reaction of a mutant ribozyme lacking both P2.1 and its upstream region in trans. We report here the unusual properties of this trans-activation. Compensatory mutational analysis revealed that non-native long-range base-pairings between the loop region of P2.1 RNA and L5c region of the mutant ribozyme are needed for the activation in spite of the fact that P2.1 forms base-pairings with P9.1 in the Tetrahymena ribozyme. The trans -activation depends on the non-native RNA-RNA interaction together with the higher order structure of P2.1 RNA. This activation is unique among the known trans-activations that utilize native tertiary interactions or RNA chaperons. PMID:10075996

Further evaluation of a functional analysis of moderate-to-vigorous physical activity in young children.

PubMed

Larson, Tracy A; Normand, Matthew P; Morley, Allison J; Miller, Bryon G

2014-01-01

Inadequate physical activity increases the risks related to several health problems in children; however, increasing physical activity mitigates these risks. In this study, we examined the relations between moderate-to-vigorous physical activity (MVPA) and several environmental conditions (attention, interactive play, alone, escape) with 4 preschool children. We compared the experimental conditions to a control condition and a naturalistic baseline according to a combined multielement and reversal design. Results indicated that all participants were most active in the interactive play condition and that the percentage of MVPA varied across experimental and control conditions. In addition, the frequency and duration of bouts of MVPA were greatest in the interactive play condition. The current study presents a methodology for the identification of environmental contingencies that support increased levels of MVPA in young children, and it holds promise for improving our understanding of the variables related to physical activity. © Society for the Experimental Analysis of Behavior.

Two photon microscopy intravital study of DC-mediated anti-tumor response of NK cells

NASA Astrophysics Data System (ADS)

Caccia, Michele; Gorletta, Tatiana; Sironi, Laura; Zanoni, Ivan; Salvetti, Cristina; Collini, Maddalena; Granucci, Francesca; Chirico, Giuseppe

2010-02-01

Recent studies have demonstrated that dendritic cells (DCs) play a crucial role in the activation of Natural Killer cells (NKs) that are responsible for anti-tumor innate immune responses. The focus of this report is on the role of pathogen associated molecular pattern (PAMP) activated-DCs in inducing NK cell-mediated anti-tumor responses. Mice transplanted sub-cute (s.c.) with AK7 cells, a mesothelioma cell line sensitive to NK cell responses, are injected with fluorescent NK cells and DC activation is then induced by s.c. injection of Lipopolysaccharide (LPS). Using 4 dimensional tracking we follow the kinetic behavior of NK cells at the Draining Lymph-Node (DLN). As control, noninflammatory conditions are also evaluated. Our data suggest that NK cells are recruited to the DLN where they can interact with activated-DCs with a peculiar kinetic behavior: short lived interactions interleaved by rarer longer ones. We also found that the changes in the NK dynamic behavior in inflammatory conditions clearly affect relevant motility parameters such as the instantaneous and average velocity and the effective diffusion coefficient. This observation suggests that NK cells and activated-DCs might efficiently interact in the DLN, where cells could be activated. Therefore the interaction between activated-DCs and NK cells in DLN is not only a reality but it may be also crucial for the start of the immune response of the NKs.

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.

The Cool and Belkin Faceted Classification of Information Interactions Revisited

ERIC Educational Resources Information Center

Huvila, Isto

2010-01-01

Introduction: The complexity of human information activity is a challenge for both practice and research in information sciences and information management. Literature presents a wealth of approaches to analytically structure and make sense of human information activity including a faceted classification model of information interactions published…

Along Came a Spider: Using Live Arthropods in a Predator-Prey Activity

ERIC Educational Resources Information Center

Richardson, Matthew L.; Hari, Janice

2011-01-01

We developed a predator-prey activity with eighth-grade students in which they used wolf spiders ("Lycosa carolinensis"), house crickets ("Acheta domestica"), and abiotic factors to address how (1) adaptations in predators and prey shape their interaction and (2) abiotic factors modify the interaction between predators and…

Educating the Consumer of Television: An Interactive Approach.

ERIC Educational Resources Information Center

Splaine, John; Splaine, Pam

Incorporating skills and procedures which students can use in many areas of the curriculum, this book, and accompanying "teacher's guide," provides interactive activities that are fun and that help students in grades 4 through 12 become critical viewers of television. The book provides homework activities that turn the normally wasted…

Experiential Learning and Learning Environments: The Case of Active Listening Skills

ERIC Educational Resources Information Center

Huerta-Wong, Juan Enrique; Schoech, Richard

2010-01-01

Social work education research frequently has suggested an interaction between teaching techniques and learning environments. However, this interaction has never been tested. This study compared virtual and face-to-face learning environments and included active listening concepts to test whether the effectiveness of learning environments depends…

Learner-Interface Interaction for Technology-Enhanced Active Learning

ERIC Educational Resources Information Center

Sinha, Neelu; Khreisat, Laila; Sharma, Kiron

2009-01-01

Neelu Sinha, Laila Khreisat, and Kiron Sharma describe how learner-interface interaction promotes active learning in computer science education. In a pilot study using technology that combines DyKnow software with a hardware platform of pen-enabled HP Tablet notebook computers, Sinha, Khreisat, and Sharma created dynamic learning environments by…

Developing Interactive E-Learning Activities

ERIC Educational Resources Information Center

Watkins, Ryan

2005-01-01

Although e-learning can offer interactive and engaging learning experiences, the creative ideas that are necessary to create such environments are not always easy to come up with when designing, developing, or teaching e-learning courses. E-learning activities use online technologies such as chat rooms, discussion boards, or email to facilitate…

Interactive Video Games in Physical Education

ERIC Educational Resources Information Center

Trout, Josh; Christie, Brett

2007-01-01

As the obesity epidemic in the United States spreads among children and teenagers, due in part to sedentary lifestyles, some physical education programs are using interactive video games to keep students engaged in physical activity. These innovative games make physical activity fun and challenging for both high- and low-skilled students. Although…

Bears. Interactive Animal Kit. Grades 1-3.

ERIC Educational Resources Information Center

Bernard, Robin

This kit was created to make learning about bears a fun and meaningful experience for teachers and students. It offers students opportunities to learn about favorite animals through an assortment of fun activities filled with information. The activities interact with science, language arts, critical thinking, music, social studies, math, art, and…

Solution structure of Apaf-1 CARD and its interaction with caspase-9 CARD: a structural basis for specific adaptor/caspase interaction.

PubMed

Zhou, P; Chou, J; Olea, R S; Yuan, J; Wagner, G

1999-09-28

Direct recruitment and activation of caspase-9 by Apaf-1 through the homophilic CARD/CARD (Caspase Recruitment Domain) interaction is critical for the activation of caspases downstream of mitochondrial damage in apoptosis. Here we report the solution structure of the Apaf-1 CARD domain and its surface of interaction with caspase-9 CARD. Apaf-1 CARD consists of six tightly packed amphipathic alpha-helices and is topologically similar to the RAIDD CARD, with the exception of a kink observed in the middle of the N-terminal helix. By using chemical shift perturbation data, the homophilic interaction was mapped to the acidic surface of Apaf-1 CARD centered around helices 2 and 3. Interestingly, a significant portion of the chemically perturbed residues are hydrophobic, indicating that in addition to the electrostatic interactions predicted previously, hydrophobic interaction is also an important driving force underlying the CARD/CARD interaction. On the basis of the identified functional residues of Apaf-1 CARD and the surface charge complementarity, we propose a model of CARD/CARD interaction between Apaf-1 and caspase-9.

Marital status, labour force activity and mortality: A study of the United States and 6 European countries

PubMed Central

van Hedel, Karen; van Lenthe, Frank J; Avendano, Mauricio; Bopp, Matthias; Esnaola, Santiago; Kovács, Katalin; Martikainen, Pekka; Regidor, Enrique; Mackenbach, Johan P

2015-01-01

Aims Labour force activity and marriage share some of the pathways through which they potentially influence health. In this paper, we examine whether marriage and labour force participation interact in the way they influence mortality in the United States and six European countries. Methods We used data from the US National Health Interview Survey linked to the National Death Index, and national mortality registry data for Austria, England/Wales, Finland, Hungary, Norway and Spain (Basque country) during 1999-2007 for men and women aged 30-59 at baseline. Poisson regression was used to estimate both additive (the relative excess risk due to interaction) and multiplicative interactions between marriage and labour force activity on mortality. Results Labour force inactivity was associated with higher mortality, but this association was stronger for unmarried than married individuals. Likewise, being unmarried was associated with higher mortality, but this association was stronger for inactive than for active individuals. To illustrate, among US women out of the labour force, being unmarried was associated with a 3.98 (95%CI:3.28-4.82) times higher risk of dying than being married, whereas the relative risk was 2.49 (95%CI:2.10-2.94) for women active in the labour market. Although this interaction between marriage and labour force activity was only significant for women on a multiplicative scale, there was a significant additive interaction for both men and women. The pattern was similar across all countries. Conclusions Marriage attenuates the increased mortality risk associated with labour force inactivity, while labour force activity attenuates the mortality risk associated with being unmarried. Our study emphasizes the importance of public health and social policies that improve the health and well-being of men and women who are both unmarried and inactive. PMID:25868643

Genetic and environmental risks for high blood pressure among African American mothers and daughters.

PubMed

Taylor, Jacquelyn Y; Maddox, Rosanna; Wu, Chun Yi

2009-07-01

To determine the relationship between genetic and environmental lifestyle factors (physical activity and sodium) on blood pressure (BP) among African-American women. In this cross-sectional study involving 108 African-American mothers and daughters from a Midwestern area, investigators obtained BP measurements, information on minutes of physical activity, amount of sodium intake, and buccal swab saliva samples. Of the 4 single nucleotide polymorphisms (SNPs) on the sodium bicarbonate cotransporter gene (SLC4A5), rs8179526 had a statistically significant interaction with cytosine/thymine (C/T) genotype by sodium status on systolic BP (SBP; p=.0077). For gene x physical activity interaction, 2 significant interactions (cytosine/adenine [C/A] genotype by physical activity and adenine/adenine [A/A] genotype by physical activity, p=.0107 and p=.0171, respectively) on SBP and 1 on diastolic BP (DBP; A/A genotype by physical activity, p=.0233) were found on rs1017783. Two significant guanine/adenine [G/A] genotype by physical activity interactions were found on rs6731545 for SBP and DBP (p=.0160 and p=.0492, respectively). A gene x environmental interaction with rs8179526 has a protective effect on SBP in African-American women with high sodium intake. Participants with C/T genotype of rs8179526 who consumed greater than 2,300 mg of sodium had lower SBP than those who consumed less than recommended. Women with thymine/thymine (T/T) genotype of rs8179526 who consumed greater than 2,300 mg had lower SBP than those who consumed less. Awareness of both the protective and deleterious properties of rs8179526 in African-American women may one day assist in determining appropriate treatment plans.

New Indole Alkaloids from the Bark of Rauvolfia Reflexa and their Cholinesterase Inhibitory Activity.

PubMed

Fadaeinasab, Mehran; Basiri, Alireza; Kia, Yalda; Karimian, Hamed; Ali, Hapipah Mohd; Murugaiyah, Vikneswaran

2015-01-01

Rauvolfia reflexa is a member of the Apocynaceae family. Plants from the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders Methods and Results: Two new indole alkaloids, rauvolfine C (1) and 3-methyl-10,11-dimethoxy-6-methoxycarbonyl-β-carboline (2), along with five known, macusine B (3), vinorine (4), undulifoline (5), isoresrpiline (6) and rescinnamine (7) were isolated from the bark of Rauvolfia reflexa. Cholinesterase inhibitory assay and molecular docking were performed to get insight of the inhibitory activity and molecular interactions of the compounds. The compounds showed good to moderate cholinesterase inhibitory activity with IC50 values in the range of 8.06 to 73.23 µM. Compound 7 was found to be the most potent inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds 1, 2, 5 and 6 were found to be selective towards BChE, while compounds 3, 4 and 7 were dual inhibitors, having almost equal inhibitory activity on both AChE and BChE. Molecular docking revealed that compounds 6 and 7 interacted differently on AChE and BChE, by means of hydrophobic interactions and hydrogen bonding. In AChE, the indole moiety of both compounds interacted with the residues lining the peripheral anionic site, whereas in BChE, their methoxy groups are primarily responsible for the strong inhibitory activity via interactions with residues at the active site of the enzyme. Two new and five known indole alkaloids were isolated from R. reflexa. Among the compounds, 7 and 6 showed the most potent and promising cholinesterase inhibitory activity, worthy for further investigations. © 2015 S. Karger AG, Basel.

Active and regulatory sites of cytosolic 5'-nucleotidase.

PubMed

Pesi, Rossana; Allegrini, Simone; Careddu, Maria Giovanna; Filoni, Daniela Nicole; Camici, Marcella; Tozzi, Maria Grazia

2010-12-01

Cytosolic 5'-nucleotidase (cN-II), which acts preferentially on 6-hydroxypurine nucleotides, is essential for the survival of several cell types. cN-II catalyses both the hydrolysis of nucleotides and transfer of their phosphate moiety to a nucleoside acceptor through formation of a covalent phospho-intermediate. Both activities are regulated by a number of phosphorylated compounds, such as diadenosine tetraphosphate (Ap₄A), ADP, ATP, 2,3-bisphosphoglycerate (BPG) and phosphate. On the basis of a partial crystal structure of cN-II, we mutated two residues located in the active site, Y55 and T56. We ascertained that the ability to catalyse the transfer of phosphate depends on the presence of a bulky residue in the active site very close to the aspartate residue that forms the covalent phospho-intermediate. The molecular model indicates two possible sites at which adenylic compounds may interact. We mutated three residues that mediate interaction in the first activation site (R144, N154, I152) and three in the second (F127, M436 and H428), and found that Ap₄A and ADP interact with the same site, but the sites for ATP and BPG remain uncertain. The structural model indicates that cN-II is a homotetrameric protein that results from interaction through a specific interface B of two identical dimers that have arisen from interaction of two identical subunits through interface A. Point mutations in the two interfaces and gel-filtration experiments indicated that the dimer is the smallest active oligomerization state. Finally, gel-filtration and light-scattering experiments demonstrated that the native enzyme exists as a tetramer, and no further oligomerization is required for enzyme activation. © 2010 The Authors Journal compilation © 2010 FEBS.

Crystal Structure of a Two-domain Fragment of Hepatocyte Growth Factor Activator Inhibitor-1: FUNCTIONAL INTERACTIONS BETWEEN THE KUNITZ-TYPE INHIBITOR DOMAIN-1 AND THE NEIGHBORING POLYCYSTIC KIDNEY DISEASE-LIKE DOMAIN.

PubMed

Hong, Zebin; De Meulemeester, Laura; Jacobi, Annemarie; Pedersen, Jan Skov; Morth, J Preben; Andreasen, Peter A; Jensen, Jan K

2016-07-01

Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a type I transmembrane protein and inhibitor of several serine proteases, including hepatocyte growth factor activator and matriptase. The protein is essential for development as knock-out mice die in utero due to placental defects caused by misregulated extracellular proteolysis. HAI-1 contains two Kunitz-type inhibitor domains (Kunitz), which are generally thought of as a functionally self-contained protease inhibitor unit. This is not the case for HAI-1, where our results reveal how interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. Here we present an x-ray crystal structure of an HAI-1 fragment covering the internal domain and Kunitz-1. The structure reveals not only that the previously uncharacterized internal domain is a member of the polycystic kidney disease domain family but also how the two domains engage in interdomain interactions. Supported by solution small angle x-ray scattering and a combination of site-directed mutagenesis and functional assays, we show that interdomain interactions not only stabilize the fold of the internal domain but also stimulate the inhibitory activity of Kunitz-1. By completing our structural characterization of the previously unknown N-terminal region of HAI-1, we provide new insight into the interplay between tertiary structure and the inhibitory activity of a multidomain protease inhibitor. We propose a previously unseen mechanism by which the association of an auxiliary domain stimulates the inhibitory activity of a Kunitz-type inhibitor (i.e. the first structure of an intramolecular interaction between a Kunitz and another domain). © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Central control of cardiorespiratory interactions in fish.

PubMed

Taylor, Edwin W; Leite, Cleo A C; Levings, Jennifer J

2009-01-01

Fish control the relative flow rates of water and blood over the gills in order to optimise respiratory gas exchange. As both flows are markedly pulsatile, close beat-to-beat relationships can be predicted. Cardiorespiratory interactions in fish are controlled primarily by activity in the parasympathetic nervous system that has its origin in cardiac vagal preganglionic neurons. Recordings of efferent activity in the cardiac vagus include units firing in respiration-related bursts. Bursts of electrical stimuli delivered peripherally to the cardiac vagus or centrally to respiratory branches of cranial nerves can recruit the heart over a range of frequencies. So, phasic, efferent activity in cardiac vagi, that in the intact fish are respiration-related, can cause heart rate to be modulated by the respiratory rhythm. In elasmobranch fishes this phasic activity seems to arise primarily from central feed-forward interactions with respiratory motor neurones that have overlapping distributions with cardiac neurons in the brainstem. In teleost fish, they arise from increased levels of efferent vagal activity arising from reflex stimulation of chemoreceptors and mechanoreceptors in the orobranchial cavity. However, these differences are largely a matter of emphasis as both groups show elements of feed-forward and feed-back control of cardiorespiratory interactions.

Structural Basis of Interaction between Urokinase-Type Plasminogen Activator and Its Receptor

PubMed Central

Barinka, Cyril; Parry, Graham; Callahan, Jennifer; Shaw, David E.; Kuo, Alice; Bdeir, Khalil; Cines, Douglas B.; Mazar, Andrew; Lubkowski, Jacek

2009-01-01

Summary Recent studies indicate that binding of urokinase-type plasminogen activator (uPA) to its high affinity receptor (uPAR), orchestrates uPAR interactions with other cellular components that play a pivotal role in diverse (patho-)physiological processes including wound healing, angiogenesis, inflammation, and cancer metastasis. However, notwithstanding the wealth of biochemical data available describing the activities of uPAR, little is known as to the exact mode of uPAR-uPA interactions and the presumed conformational changes that accompanying uPA-uPAR engagement. Here we report the crystal structure of soluble urokinase plasminogen activator receptor (suPAR), which contains the three domains of the wild-type receptor but lacks the cell surface anchoring sequence, in complex with the amino terminal fragment of urokinase-type plasminogen activator (ATF), at the resolution of 2.8 Å. We also report the 1.9 Å crystal structure of the free ATF. Our results provide a structural basis, represented by conformational changes induced in uPAR, for several published biochemical observations describing the nature of uPAR-uPA interactions and provide insight into mechanisms that may be responsible for the cellular responses induced by uPA binding. PMID:16979660

Brain correlates of recognition of communicative interactions from biological motion in schizophrenia.

PubMed

Okruszek, Ł; Wordecha, M; Jarkiewicz, M; Kossowski, B; Lee, J; Marchewka, A

2017-11-27

Recognition of communicative interactions is a complex social cognitive ability which is associated with a specific neural activity in healthy individuals. However, neural correlates of communicative interaction processing from whole-body motion have not been known in patients with schizophrenia (SCZ). Therefore, the current study aims to examine the neural activity associated with recognition of communicative interactions in SCZ by using displays of the dyadic interactions downgraded to minimalistic point-light presentations. Twenty-six healthy controls (HC) and 25 SCZ were asked to judge whether two agents presented only by point-light displays were communicating or acting independently. Task-related activity and functional connectivity of brain structures were examined with General Linear Model and Generalized Psychophysiological Interaction approach, respectively. HC were significantly more efficient in recognizing each type of action than SCZ. At the neural level, the activity of the right posterior superior temporal sulcus (pSTS) was observed to be higher in HC compared with SCZ for communicative v. individual action processing. Importantly, increased connectivity of the right pSTS with structures associated with mentalizing (left pSTS) and mirroring networks (left frontal areas) was observed in HC, but not in SCZ, during the presentation of social interactions. Under-recruitment of the right pSTS, a structure known to have a pivotal role in social processing, may also be of importance for higher-order social cognitive deficits in SCZ. Furthermore, decreased task-related connectivity of the right pSTS may result in reduced use of additional sources of information (for instance motor resonance signals) during social cognitive processing in schizophrenia.

DFT study of ethyl xanthate interaction with sphalerite (1 1 0) surface in the absence and presence of copper

NASA Astrophysics Data System (ADS)

Liu, Jian; Wen, Shuming; Deng, Jiushuai; Chen, Xiumin; Feng, Qicheng

2014-08-01

The interaction among sphalerite (1 1 0) surface, copper and ethyl xanthate (EX) was simulated using the density functional theory (DFT). The results of DFT indicate that four types of stable interaction models exist among sphalerite surface, copper and EX, i.e., EX interacts with the Cu substituted for Zn, Cu adsorbed on the top site of S, Cu adsorbed on the bridge site of S and Cu(OH)2 adsorbed on the sphalerite surface. The four interaction models can result in the activation flotation of sphalerite. Density of states (DOS) analysis shows that the energy level discrepancy of the Zn 3d orbital in ZnS and the bonding S 3p orbital in EX results in the weak adsorption of EX on un-activated sphalerite surface. However, after copper activation, the Cu 3d orbital peak and bonding S 3p orbital peak are just maximally overlapped nearby the Fermi level. This study provides an insight into the nature that sphalerite responds not well to EX and also a comprehensive understanding on the possible interaction cases existing among sphalerite surface, copper and EX.

Comparisons of social interaction and activities of daily living between long-term care facility and community-dwelling stroke patients.

PubMed

Yoon, Jeong-Ae; Park, Se-Gwan; Roh, Hyo-Lyun

2015-10-01

[Purpose] This study was conducted to compare the correlation between social interaction and activities of daily living (ADL) between community-dwelling and long-term care facility stroke patients. [Subjects and Methods] The Subjects were 65 chronic stroke patients (32 facility-residing, 33 community-dwelling). The Evaluation Social Interaction (ESI) tool was used to evaluate social interaction and the Assessment of Motor and Process Skills (AMPS) measure was used to evaluate ADL. [Results] Both social interaction and ADL were higher in community-dwelling than facility-residing stroke patients. There was a correlation between ESI and ADL for both motor and process skills among facility-residing patients, while only ADL process skills and ESI correlated among community-dwelling patients. In a partial correlation analysis using ADL motor and process skills as control variables, only process skills correlated with ESI. [Conclusion] For rehabilitation of stroke patients, an extended treatment process that combines ADL and social activities is likely to be required. Furthermore, treatment programs and institutional systems that can improve social interaction and promote health maintenance for community-dwelling and facility-residing chronic stroke patients are needed throughout the rehabilitation process.

Characterization of π-stacking interactions between aromatic amino acids and quercetagetin

NASA Astrophysics Data System (ADS)

Akher, Farideh Badichi; Ebrahimi, Ali; Mostafavi, Najmeh

2017-01-01

In the present study, the π-stacking interactions between quercetagetin (QUE), which is one of the most representative flavonol compounds with biological and chemical activities, and some aromatic amino acid (AA) residues has been investigated by the quantum mechanical calculations. The trend in the absolute value of stacking interaction energy |ΔE| with respect to AAs is HIS > PHE > TYR > TPR. The results show that the sum of donor-acceptor interaction energy between AAs and QUE (∑E2) and the sum of electron densities ρ calculated at BCPs and CCPs between the rings (∑ρBCPs and ∑ρCCP) can be useful descriptors for prediction of the ΔE values of the complexes. The Osbnd H bond dissociation enthalpy (BDE) slightly decreases by the π-stacking interaction, which confirms the positive effect of that interaction on the antioxidant activity of QUE. A reverse trend is observed for BDE when is compared with the |ΔE| values. A reliable relationship is also observed between the Muliken spin density (MSD) distributions of the radical species and the most convenient Osbnd H bond dissociations. In addition, reactivity is in good correlation with the antioxidant activity of the complexes.

Multivalent Interactions of Human Primary Amine Oxidase with the V and C22 Domains of Sialic Acid-Binding Immunoglobulin-Like Lectin-9 Regulate Its Binding and Amine Oxidase Activity

PubMed Central

Fair-Mäkelä, Ruth; Salo-Ahen, Outi M. H.; Guédez, Gabriela; Bligt-Lindén, Eva; Grönholm, Janne; Jalkanen, Sirpa; Salminen, Tiina A.

2016-01-01

Sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) on leukocyte surface is a counter-receptor for endothelial cell surface adhesin, human primary amine oxidase (hAOC3), a target protein for anti-inflammatory agents. This interaction can be used to detect inflammation and cancer in vivo, since the labeled peptides derived from the second C2 domain (C22) of Siglec-9 specifically bind to the inflammation-inducible hAOC3. As limited knowledge on the interaction between Siglec-9 and hAOC3 has hampered both hAOC3-targeted drug design and in vivo imaging applications, we have now produced and purified the extracellular region of Siglec-9 (Siglec-9-EC) consisting of the V, C21 and C22 domains, modeled its 3D structure and characterized the hAOC3–Siglec-9 interactions using biophysical methods and activity/inhibition assays. Our results assign individual, previously unknown roles for the V and C22 domains. The V domain is responsible for the unusually tight Siglec-9–hAOC3 interactions whereas the intact C22 domain of Siglec-9 is required for modulating the enzymatic activity of hAOC3, crucial for the hAOC3-mediated leukocyte trafficking. By characterizing the Siglec-9-EC mutants, we could conclude that R120 in the V domain likely interacts with the terminal sialic acids of hAOC3 attached glycans whereas residues R284 and R290 in C22 are involved in the interactions with the active site channel of hAOC3. Furthermore, the C22 domain binding enhances the enzymatic activity of hAOC3 although the sialic acid-binding capacity of the V domain of Siglec-9 is abolished by the R120S mutation. To conclude, our results prove that the V and C22 domains of Siglec-9-EC interact with hAOC3 in a multifaceted and unique way, forming both glycan-mediated and direct protein-protein interactions, respectively. The reported results on the mechanism of the Siglec-9–hAOC3 interaction are valuable for the development of hAOC3-targeted therapeutics and diagnostic tools. PMID:27893774

Variable interaction specificity and symbiont performance in Panamanian Trachymyrmex and Sericomyrmex fungus-growing ants.

PubMed

De Fine Licht, Henrik H; Boomsma, Jacobus J

2014-12-04

Cooperative benefits of mutualistic interactions are affected by genetic variation among the interacting partners, which may have consequences for interaction-specificities across guilds of sympatric species with similar mutualistic life histories. The gardens of fungus-growing (attine) ants produce carbohydrate active enzymes that degrade plant material collected by the ants and offer them food in exchange. The spectrum of these enzyme activities is an important symbiont service to the host but may vary among cultivar genotypes. The sympatric occurrence of several Trachymyrmex and Sericomyrmex higher attine ants in Gamboa, Panama provided the opportunity to do a quantitative study of species-level interaction-specificity. We genotyped the ants for Cytochrome Oxidase and their Leucoagaricus fungal cultivars for ITS rDNA. Combined with activity measurements for 12 carbohydrate active enzymes, these data allowed us to test whether garden enzyme activity was affected by fungal strain, farming ants or combinations of the two. We detected two cryptic ant species, raising ant species number from four to six, and we show that the 38 sampled colonies reared a total of seven fungal haplotypes that were different enough to represent separate Leucoagaricus species. The Sericomyrmex species and one of the Trachymyrmex species reared the same fungal cultivar in all sampled colonies, but the remaining four Trachymyrmex species largely shared the other cultivars. Fungal enzyme activity spectra were significantly affected by both cultivar species and farming ant species, and more so for certain ant-cultivar combinations than others. However, relative changes in activity of single enzymes only depended on cultivar genotype and not on the ant species farming a cultivar. Ant cultivar symbiont-specificity varied from almost full symbiont sharing to one-to-one specialization, suggesting that trade-offs between enzyme activity spectra and life-history traits such as desiccation tolerance, disease susceptibility and temperature sensitivity may apply in some combinations but not in others. We hypothesize that this may be related to ecological specialization in general, but this awaits further testing. Our finding of both cryptic ant species and extensive cultivar diversity underlines the importance of identifying all species-level variation before embarking on estimates of interaction specificity.

Lectin Activation in Giardia lamblia by Host Protease: A Novel Host-Parasite Interaction

NASA Astrophysics Data System (ADS)

Lev, Boaz; Ward, Honorine; Keusch, Gerald T.; Pereira, Miercio E. A.

1986-04-01

A lectin in Giardia lamblia was activated by secretions from the human duodenum, the environment where the parasite lives. Incubation of the secretions with trypsin inhibitors prevented the appearance of lectin activity, implicating proteases as the activating agent. Accordingly, lectin activation was also produced by crystalline trypsin and Pronase; other proteases tested were ineffective. When activated, the lectin agglutinated intestinal cells to which the parasite adheres in vivo. The lectin was most specific to mannose-6-phosphate and apparently was bound to the plasma membrane. Activation of a parasite lectin by a host protease represents a novel mechanism of hostparasite interaction and may contribute to the affinity of Giardia lamblia to the infection site.

Interactive Simulations as Implicit Support for Guided-Inquiry

ERIC Educational Resources Information Center

Moore, Emily B.; Herzog, Timothy A.; Perkins, Katherine K.

2013-01-01

We present the results of a study designed to provide insight into interactive simulation use during guided-inquiry activities in chemistry classes. The PhET Interactive Simulations project at the University of Colorado develops interactive simulations that utilize implicit--rather than explicit--scaffolding to support student learning through…

Bone sialoprotein does not interact with pro-gelatinase A (MMP-2) or mediate MMP-2 activation

PubMed Central

2009-01-01

Background A recent model for activation of the zymogen form of matrix metalloproteinase 2 (MMP-2, also known as gelatinase A) has suggested that interactions between the SIBLING protein bone sialoprotein (BSP) and MMP-2 leads to conformational change in MMP-2 that initiates the conversion of the pro-enzyme into a catalytically active form. This model is particularly relevant to cancer cell metastasis to bone since BSP, bound to the αvβ3 integrin through its arginine-glycine-aspartic acid motif, could recruit MMP-2 to the cell surface. Methods We critically assessed the relationship between BSP and proMMP-2 and its activation using various forms of recombinant and purified BSP and MMP-2. Gelatinase and collagenase assays, fluorescence binding assays, real-time PCR, cell culture and pull-down assays were employed to test the model. Results Studies with a fluorogenic substrate for MMP-2 showed no activation of proMMP-2 by BSP. Binding and pull-down assays demonstrated no interaction between MMP-2 and BSP. While BSP-mediated invasiveness has been shown to depend on its integrin-binding RGD sequence, analysis of proMMP-2 activation and the level of membrane type 1 (MT1)-MMP in cells grown on a BSP substratum showed that the BSP-αvβ3 integrin interaction does not induce the expression of MT1-MMP. Conclusion These studies do not support a role for BSP in promoting metastasis through interactions with pro-MMP-2. PMID:19386107

JNK-Interacting Protein 3 Mediates the Retrograde Transport of Activated c-Jun N-Terminal Kinase and Lysosomes

PubMed Central

Drerup, Catherine M.; Nechiporuk, Alex V.

2013-01-01

Retrograde axonal transport requires an intricate interaction between the dynein motor and its cargo. What mediates this interaction is largely unknown. Using forward genetics and a novel in vivo imaging approach, we identified JNK-interacting protein 3 (Jip3) as a direct mediator of dynein-based retrograde transport of activated (phosphorylated) c-Jun N-terminal Kinase (JNK) and lysosomes. Zebrafish jip3 mutants (jip3nl7) displayed large axon terminal swellings that contained high levels of activated JNK and lysosomes, but not other retrograde cargos such as late endosomes and autophagosomes. Using in vivo analysis of axonal transport, we demonstrated that the terminal accumulations of activated JNK and lysosomes were due to a decreased frequency of retrograde movement of these cargos in jip3nl7, whereas anterograde transport was largely unaffected. Through rescue experiments with Jip3 engineered to lack the JNK binding domain and exogenous expression of constitutively active JNK, we further showed that loss of Jip3–JNK interaction underlies deficits in pJNK retrograde transport, which subsequently caused axon terminal swellings but not lysosome accumulation. Lysosome accumulation, rather, resulted from loss of lysosome association with dynein light intermediate chain (dynein accessory protein) in jip3nl7, as demonstrated by our co-transport analyses. Thus, our results demonstrate that Jip3 is necessary for the retrograde transport of two distinct cargos, active JNK and lysosomes. Furthermore, our data provide strong evidence that Jip3 in fact serves as an adapter protein linking these cargos to dynein. PMID:23468645

Childhood Trauma and COMT Genotype Interact to Increase Hippocampal Activation in Resilient Individuals.

PubMed

van Rooij, Sanne J H; Stevens, Jennifer S; Ely, Timothy D; Fani, Negar; Smith, Alicia K; Kerley, Kimberly A; Lori, Adriana; Ressler, Kerry J; Jovanovic, Tanja

2016-01-01

Both childhood trauma and a functional catechol-O-methyltransferase (COMT) genetic polymorphism have been associated with posttraumatic stress disorder (PTSD) and depression; however, it is still unclear whether the two interact and how this interaction relates to long-term risk or resilience. Imaging and genotype data were collected on 73 highly traumatized women. DNA extracted from saliva was used to determine COMT genotype (Val/Val, n = 38, Met carriers, n = 35). Functional MRI data were collected during a Go/NoGo task to investigate the neurocircuitry underlying response inhibition. Self-report measures of adult and childhood trauma exposure, PTSD and depression symptom severity, and resilience were collected. Childhood trauma was found to interact with COMT genotype to impact inhibition-related hippocampal activation. In Met carriers, more childhood trauma was associated with decreased hippocampal activation, whereas in the Val/Val group childhood trauma was related to increased hippocampal activation. Second, hippocampal activation correlated negatively with PTSD and depression symptoms and positively with trait resilience. Moreover, hippocampal activation mediated the relationship between childhood trauma and psychiatric risk or resilience in the Val/Val, but not in the Met carrier group. These data reveal a potential mechanism by which childhood trauma and COMT genotype interact to increase risk for trauma-related psychopathology or resilience. Hippocampal recruitment during inhibition may improve the ability to use contextual information to guide behavior, thereby enhancing resilience in trauma-exposed individuals. This finding may contribute to early identification of individuals at risk and suggests a mechanism that can be targeted in future studies aiming to prevent or limit negative outcomes.

Physical and functional interactions of Caenorhabditis elegans WRN-1 helicase with RPA-1.

PubMed

Hyun, Moonjung; Park, Sojin; Kim, Eunsun; Kim, Do-Hyung; Lee, Se-Jin; Koo, Hyeon-Sook; Seo, Yeon-Soo; Ahn, Byungchan

2012-02-21

The Caenorhabditis elegans Werner syndrome protein, WRN-1, a member of the RecQ helicase family, has a 3'-5' DNA helicase activity. Worms with defective wrn-1 exhibit premature aging phenotypes and an increased level of genome instability. In response to DNA damage, WRN-1 participates in the initial stages of checkpoint activation in concert with C. elegans replication protein A (RPA-1). WRN-1 helicase is stimulated by RPA-1 on long DNA duplex substrates. However, the mechanism by which RPA-1 stimulates DNA unwinding and the function of the WRN-1-RPA-1 interaction are not clearly understood. We have found that WRN-1 physically interacts with two RPA-1 subunits, CeRPA73 and CeRPA32; however, full-length WRN-1 helicase activity is stimulated by only the CeRPA73 subunit, while the WRN-1(162-1056) fragment that harbors the helicase activity requires both the CeRPA73 and CeRPA32 subunits for the stimulation. We also found that the CeRPA73(1-464) fragment can stimulate WRN-1 helicase activity and that residues 335-464 of CeRPA73 are important for physical interaction with WRN-1. Because CeRPA73 and the CeRPA73(1-464) fragment are able to bind single-stranded DNA (ssDNA), the stimulation of WRN-1 helicase by RPA-1 is most likely due to the ssDNA binding activity of CeRPA73 and the direct interaction of WRN-1 and CeRPA73.

Competition and cooperation among similar representations: toward a unified account of facilitative and inhibitory effects of lexical neighbors.

PubMed

Chen, Qi; Mirman, Daniel

2012-04-01

One of the core principles of how the mind works is the graded, parallel activation of multiple related or similar representations. Parallel activation of multiple representations has been particularly important in the development of theories and models of language processing, where coactivated representations (neighbors) have been shown to exhibit both facilitative and inhibitory effects on word recognition and production. Researchers generally ascribe these effects to interactive activation and competition, but there is no unified explanation for why the effects are facilitative in some cases and inhibitory in others. We present a series of simulations of a simple domain-general interactive activation and competition model that is broadly consistent with more specialized domain-specific models of lexical processing. The results showed that interactive activation and competition can indeed account for the complex pattern of reversals. Critically, the simulations revealed a core computational principle that determines whether neighbor effects are facilitative or inhibitory: strongly active neighbors exert a net inhibitory effect, and weakly active neighbors exert a net facilitative effect.

Interaction of alphamangostin and curcumin with dihydroartemisinin as antimalaria in vitro

NASA Astrophysics Data System (ADS)

Tjahjani, S.; Syafruddin; Tjokropranoto, R.

2018-03-01

To overcome malarial resistance tendency against the ACT (artemisinin-based combination therapy), several galenic preparations of Garciniamangostana L-rind and alphamangostin as the major xanthone in this rind have been studied, and they had antimalarial activity and showed its synergistic effect with artemisinin in vitro. Curcumin as anactive component of turmeric is also potentially to have antimalarial activity. This study aimed to evaluate the activity as antimalarial of curcumin and dihydroartemisinin, an active metabolite of all artemisinin derivates, and also to study the mechanism of action of aphamangostin, curcumin, and dihydroartemisinin as antimalaria.The interaction between them each other as the antimalarial in vitro was also investigated. The antimalarial activity was studied in in vitro 3D7 Plasmodium falciparum cultivation incubated with these compounds to look for the IC50 and ΣFIC50 of them. The mechanism of action of these compounds was observed electron microscopically. The result of this promising study showed that these compounds were active antimalaria agents which inhibited hemozoin formation and there is synergistic antimalarial activity interaction between alphamangostin and dihydroartemisinin.

Versatility of Cooperative Transcriptional Activation: A Thermodynamical Modeling Analysis for Greater-Than-Additive and Less-Than-Additive Effects

PubMed Central

Frank, Till D.; Carmody, Aimée M.; Kholodenko, Boris N.

2012-01-01

We derive a statistical model of transcriptional activation using equilibrium thermodynamics of chemical reactions. We examine to what extent this statistical model predicts synergy effects of cooperative activation of gene expression. We determine parameter domains in which greater-than-additive and less-than-additive effects are predicted for cooperative regulation by two activators. We show that the statistical approach can be used to identify different causes of synergistic greater-than-additive effects: nonlinearities of the thermostatistical transcriptional machinery and three-body interactions between RNA polymerase and two activators. In particular, our model-based analysis suggests that at low transcription factor concentrations cooperative activation cannot yield synergistic greater-than-additive effects, i.e., DNA transcription can only exhibit less-than-additive effects. Accordingly, transcriptional activity turns from synergistic greater-than-additive responses at relatively high transcription factor concentrations into less-than-additive responses at relatively low concentrations. In addition, two types of re-entrant phenomena are predicted. First, our analysis predicts that under particular circumstances transcriptional activity will feature a sequence of less-than-additive, greater-than-additive, and eventually less-than-additive effects when for fixed activator concentrations the regulatory impact of activators on the binding of RNA polymerase to the promoter increases from weak, to moderate, to strong. Second, for appropriate promoter conditions when activator concentrations are increased then the aforementioned re-entrant sequence of less-than-additive, greater-than-additive, and less-than-additive effects is predicted as well. Finally, our model-based analysis suggests that even for weak activators that individually induce only negligible increases in promoter activity, promoter activity can exhibit greater-than-additive responses when transcription factors and RNA polymerase interact by means of three-body interactions. Overall, we show that versatility of transcriptional activation is brought about by nonlinearities of transcriptional response functions and interactions between transcription factors, RNA polymerase and DNA. PMID:22506020

Platinum-catalyzed hydrolysis etching of SiC in water: A density functional theory study

NASA Astrophysics Data System (ADS)

Van Bui, Pho; Toh, Daisetsu; Isohashi, Ai; Matsuyama, Satoshi; Inagaki, Kouji; Sano, Yasuhisa; Yamauchi, Kazuto; Morikawa, Yoshitada

2018-05-01

A comprehensive study of the physicochemical interactions and the reaction mechanism of SiC etching with water by Pt catalysts can reveal key details about the surface treatment and catalytic phenomena at interfaces. Therefore, density functional theory simulations were performed to study the kinetics of Pt-assisted water dissociation and breaking of a Si–C bond compared to the HF-assisted mechanism. These calculations carefully considered the elastic and chemical interaction energies at the Pt–SiC interface, activation barriers of Si–C bond dissociation, and the catalytic role of Pt. It was found that the Pt-catalyzed etching of SiC in water is initiated via hydrolysis reactions that break the topmost Si–C bonds. The activation barrier strongly depends on the elastic and chemical interactions. However, chemical interactions are a dominant factor and mainly contribute to the lowering of the activation barrier, resulting in an increased rate of reaction.

Homeodomain-Interacting Protein Kinase-2: A Critical Regulator of the DNA Damage Response and the Epigenome

PubMed Central

Kuwano, Yuki; Nishida, Kensei; Akaike, Yoko; Kurokawa, Ken; Nishikawa, Tatsuya; Masuda, Kiyoshi; Rokutan, Kazuhito

2016-01-01

Homeodomain-interacting protein kinase 2 (HIPK2) is a serine/threonine kinase that phosphorylates and activates the apoptotic program through interaction with diverse downstream targets including tumor suppressor p53. HIPK2 is activated by genotoxic stimuli and modulates cell fate following DNA damage. The DNA damage response (DDR) is triggered by DNA lesions or chromatin alterations. The DDR regulates DNA repair, cell cycle checkpoint activation, and apoptosis to restore genome integrity and cellular homeostasis. Maintenance of the DDR is essential to prevent development of diseases caused by genomic instability, including cancer, defects of development, and neurodegenerative disorders. Recent studies reveal a novel HIPK2-mediated pathway for DDR through interaction with chromatin remodeling factor homeodomain protein 1γ. In this review, we will highlight the molecular mechanisms of HIPK2 and show its functions as a crucial DDR regulator. PMID:27689990

Stability and activity modulation of chymotrypsins in AOT reversed micelles by protein-interface interaction: interaction of alpha-chymotrypsin with a negative interface leads to a cooperative breakage of a salt bridge that keeps the catalytic active conformation (Ile16-Asp194).

PubMed

Almeida, F C; Valente, A P; Chaimovich, H

1998-08-05

The stability of alpha-chymotrypsin and delta-chymotrypsin was studied in reversed micelles of sodium bis(2-ethylhexyl)sulfosuccinate (AOT) in isooctane. alpha-Chymotrypsin is inactivated at the interface and at the water pool, while delta-chymotrypsin is inactivated only at the water pool. The mechanism of inactivation at the interface is related to the interaction of N-terminal group alanine 149 (absent in delta-chymotrypsin) with the negative interface. The dependence of enzyme activity on water content of these two enzymes in reversed micelles of AOT is also related with the interface interaction, since delta-chymotrypsin does not have a bell-shaped curve as observed for alpha-chymotrypsin. Copyright 1998 John Wiley & Sons, Inc.

Maslinic acid promotes autophagy by disrupting the interaction between Bcl2 and Beclin1 in rat pheochromocytoma PC12 cells

PubMed Central

Dong, Xiaoli; Zhang, Jiaxiao; Zhou, Zhilin; Ye, Zhennan; Chen, Jiahao; Yuan, Jifan; Cao, Fengjun; Wang, Xuanbin; Liu, Wenchao; Yu, Wenxuan; Li, Xiaohua

2017-01-01

Maslinic acid (2α, 3β-dihydroxyolean-12-en-28-oic acid, MA) was isolated from natural plants and showed anti-cancer activity in rat Pheochromocytoma PC12 cells in our previous studies. We now discover that MA disrupts the interaction between Bcl2 and autophagy scaffold protein Beclin1 in the above cell line, leading to the up-regulation of autophagy. We investigated the effect of MA on the interaction between Bcl2 and Beclin1 by biochemical and biophysical methods in combination with autophagy characterization in the above cell line. Our results suggest that MA may serve as an autophagy activator by directly blocking the Bcl2-Beclin1 interaction to release free Beclin1 required for the recruitment of autophagy positive regulators, implying MA may exert its anti-cancer activity by regulating autophagy. PMID:29088805

Temporal Interactions between Cortical Rhythms

PubMed Central

Roopun, Anita K.; Kramer, Mark A.; Carracedo, Lucy M.; Kaiser, Marcus; Davies, Ceri H.; Traub, Roger D.; Kopell, Nancy J.; Whittington, Miles A.

2008-01-01

Multiple local neuronal circuits support different, discrete frequencies of network rhythm in neocortex. Relationships between different frequencies correspond to mechanisms designed to minimise interference, couple activity via stable phase interactions, and control the amplitude of one frequency relative to the phase of another. These mechanisms are proposed to form a framework for spectral information processing. Individual local circuits can also transform their frequency through changes in intrinsic neuronal properties and interactions with other oscillating microcircuits. Here we discuss a frequency transformation in which activity in two co-active local circuits may combine sequentially to generate a third frequency whose period is the concatenation sum of the original two. With such an interaction, the intrinsic periodicity in each component local circuit is preserved – alternate, single periods of each original rhythm form one period of a new frequency – suggesting a robust mechanism for combining information processed on multiple concurrent spatiotemporal scales. PMID:19225587

CPI motif interaction is necessary for capping protein function in cells

PubMed Central

Edwards, Marc; McConnell, Patrick; Schafer, Dorothy A.; Cooper, John A.

2015-01-01

Capping protein (CP) has critical roles in actin assembly in vivo and in vitro. CP binds with high affinity to the barbed end of actin filaments, blocking the addition and loss of actin subunits. Heretofore, models for actin assembly in cells generally assumed that CP is constitutively active, diffusing freely to find and cap barbed ends. However, CP can be regulated by binding of the ‘capping protein interaction' (CPI) motif, found in a diverse and otherwise unrelated set of proteins that decreases, but does not abolish, the actin-capping activity of CP and promotes uncapping in biochemical experiments. Here, we report that CP localization and the ability of CP to function in cells requires interaction with a CPI-motif-containing protein. Our discovery shows that cells target and/or modulate the capping activity of CP via CPI motif interactions in order for CP to localize and function in cells. PMID:26412145

A developmental dose-response analysis of the effects of methylphenidate on the peer interactions of attention deficit disordered boys.

PubMed

Cunningham, C E; Siegel, L S; Offord, D R

1985-11-01

Mixed dyads of 42 normal and 42 ADD boys were videotaped in free play, co-operative task, and simulated classrooms. ADD boys received placebo, 0.15 mg/kg, and 0.50 mg/kg of methylphenidate. ADD boys were more active and off task, watched peers less, and scored lower on mathematics and visual-motor tasks. Older boys interacted less, ignored peer interactions and play more frequently, were less controlling, and more compliant. In class, methylphenidate improved visual motor scores, and reduced the controlling behaviour, activity level, and off task behaviour of ADD boys. Normal peers displayed reciprocal reductions in controlling behaviour, activity level, and off task behaviour.

Developing a Table of Forces for Human Activity as It Relates ...

EPA Pesticide Factsheets

Report The purpose of this project was to evaluate forces generated by human activity that may cause reaerosolization of Bacillus anthracis spores in the aftermath of an intentional release. Understanding human interaction is important to inform communities on activities that may cause the re-distribution of spores. This report presents the results of an extensive literature review of human-surface interaction forces with respect to Bacillus spore reaerosolization in the outdoor environment.

Green Care Farms as Innovative Nursing Homes, Promoting Activities and Social Interaction for People With Dementia.

PubMed

de Boer, Bram; Hamers, Jan P H; Zwakhalen, Sandra M G; Tan, Frans E S; Beerens, Hanneke C; Verbeek, Hilde

2017-01-01

Innovative care environments are developed for people with dementia to encourage person-centered care. This study aims to investigate whether residents of green care farms that provide 24-hour nursing care participate more in (physical) activities and social interaction compared with residents of other nursing homes. Longitudinal observation study. Nursing homes in the Netherlands (green care farms, traditional nursing homes, and regular small-scale living facilities). A total of 115 nursing home residents at baseline, 100 at follow-up. Ecological momentary assessments (n = 16,860) were conducted using the Maastricht Electronic Daily Life Observation Tool. Residents living at green care farms were compared with residents living in traditional nursing homes and regular small-scale living facilities. The following aspects were collected for this study: the activity performed by the participant or occurring in his or her vicinity, the engagement in the activity, the level of physical activity during the activity, the physical environment (location where the activity occurred), and the level of social interaction during the activity. In total, 9660 baseline observations and 7200 follow-up observations were conducted. Analyses showed that residents of green care farms significantly more often participated in domestic activities (P = .004, SE = 1.6) and outdoor/nature-related activities (P = .003, SE = 0.9), and significantly less often engaged in passive/purposeless activities (P < .001, SE = 1.7) compared with residents of traditional nursing homes. Furthermore, residents of green care farms had significantly more active engagement (P = .014, SE = 0.9), more social interaction (P = .006, SE = 1.1), and came outside significantly more (P = .010, SE = 1.1) than residents of traditional nursing homes. Residents of green care farms were significantly more physically active (P = .013, SE = 0.8) than were residents of regular small-scale living facilities. No other significant differences were found. Green care farms can be a valuable alternative to traditional nursing homes. They provide an attractive, homelike environment and activities that positively influence engagement and social interaction. Research is needed to study how successful elements of green care farms can be implemented in existing nursing homes. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Hydrodynamic interactions in dense active suspensions: From polar order to dynamical clusters

NASA Astrophysics Data System (ADS)

Yoshinaga, Natsuhiko; Liverpool, Tanniemola B.

2017-08-01

We study the role of hydrodynamic interactions in the collective behavior of collections of microscopic active particles suspended in a fluid. We introduce a calculational framework that allows us to separate the different contributions to their collective dynamics from hydrodynamic interactions on different length scales. Hence we are able to systematically show that lubrication forces when the particles are very close to each other play as important a role as long-range hydrodynamic interactions in determining their many-body behavior. We find that motility-induced phase separation is suppressed by near-field interactions, leading to open gel-like clusters rather than dense clusters. Interestingly, we find a globally polar ordered phase appears for neutral swimmers with no force dipole that is enhanced by near-field lubrication forces in which the collision process rather than long-range interaction dominates the alignment mechanism.

Mealtime Interactions and Life Satisfaction Among Older Adults in Shanghai.

PubMed

Ye, Minzhi; Chen, Lin; Kahana, Eva

2017-06-01

We examined the association between older adults' mealtime interactions at senior centers in Shanghai and their life satisfaction. Competing hypotheses, derived from socioemotional selectivity theory and activity theory, were tested. Data were obtained from the 2011 Shanghai senior center service utilization survey ( N = 320). Relationships between respondents' mealtime interactions and life satisfaction were tested using multilevel regression modeling. After adjusting for demographics, interactions with tablemates (companionship, self-disclosure, and instrumental support) were positively associated with respondents' life satisfaction. These associations varied by senior centers. However, the number of tablemates was not significantly associated with respondents' life satisfaction. Findings support the activity-theory-based hypothesis that mealtime interactions are related to older adults' life satisfaction independent of the number of tablemates. This study illuminates the value of social interactions in the context of community dining programs for the rapidly increasing older population in urban China.

Toll-like receptor 4-related immunostimulatory polysaccharides: Primary structure, activity relationships, and possible interaction models.

PubMed

Zhang, Xiaorui; Qi, Chunhui; Guo, Yan; Zhou, Wenxia; Zhang, Yongxiang

2016-09-20

Toll-like receptor (TLR) 4 is an important polysaccharide receptor; however, the relationships between the structures and biological activities of TLR4 and polysaccharides remain unknown. Many recent findings have revealed the primary structure of TLR4/MD-2-related polysaccharides, and several three-dimensional structure models of polysaccharide-binding proteins have been reported; and these models provide insights into the mechanisms through which polysaccharides interact with TLR4. In this review, we first discuss the origins of polysaccharides related to TLR4, including polysaccharides from higher plants, fungi, bacteria, algae, and animals. We then briefly describe the glucosidic bond types of TLR4-related heteroglycans and homoglycans and describe the typical molecular weights of TLR4-related polysaccharides. The primary structures and activity relationships of polysaccharides with TLR4/MD-2 are also discussed. Finally, based on the existing interaction models of LPS with TLR4/MD-2 and linear polysaccharides with proteins, we provide insights into the possible interaction models of polysaccharide ligands with TLR4/MD-2. To our knowledge, this review is the first to summarize the primary structures and activity relationships of TLR4-related polysaccharides and the possible mechanisms of interaction for TLR4 and TLR4-related polysaccharides. Copyright © 2016 Elsevier Ltd. All rights reserved.

How patients' use of social media impacts their interactions with healthcare professionals.

PubMed

Benetoli, A; Chen, T F; Aslani, P

2018-03-01

Patients are increasingly accessing online health information and have become more participatory in their engagement with the advent of social media (SM). This study explored how patients' use of SM impacted their interactions with healthcare professionals (HCPs). Focus groups (n=5) were conducted with 36 patients with chronic conditions and on medication who used SM for health-related purposes. The discussions lasted 60-90min, were audio-recorded, transcribed verbatim, and thematically analysed. Participants did not interact with HCPs on SM and were not expecting to do so as they used SM exclusively for peer interactions. Most reported improvement in the patient-HCP relationship due to increased knowledge, better communication, and empowerment. Participants supplemented HCP-provided information with peer interactions on SM, and prepared themselves for consultations. They shared online health information with HCPs, during consultations, to validate it and to actively participate in the decision-making. Although some participants reported HCP support for their online activities, most perceived overt or tacit opposition. Participants perceived that their SM use positively impacted relationships with HCPs. They felt empowered and were more assertive in participating in decision-making. HCPs should be aware of patients' activities and expectations, and support them in their online activities. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of continuous interaction sites in PLA(2)-based protein complexes by peptide arrays.

PubMed

Fortes-Dias, Consuelo Latorre; Santos, Roberta Márcia Marques dos; Magro, Angelo José; Fontes, Marcos Roberto de Mattos; Chávez-Olórtegui, Carlos; Granier, Claude

2009-01-01

Crotoxin (CA.CB) is a beta-neurotoxin from Crotalus durissus terrificus snake venom that is responsible for main envenomation effects upon biting by this snake. It is a heterodimer of an acidic protein (CA) devoid of any biological activity per se and a basic, enzymatically active, PLA(2) counterpart (CB). Both lethal and enzymatic activities of crotoxin have been shown to be inhibited by CNF, a protein from the blood of C. d. terrificus snakes. CNF replaces CA in the CA.CB complex, forming a stable, non-toxic complex CNF.CB. The molecular sites involved in the tight interfacial protein-protein interactions in these PLA(2)-based complexes have not been clearly determined. To help address this question, we used the peptide arrays approach to map possible interfacial interaction sites in CA.CB and CNF.CB. Amino acid stretches putatively involved in these interactions were firstly identified in the primary structure of CB. Further analysis of the interfacial availability of these stretches in the presumed biologically active structure of CB, suggested two interaction main sites, located at the amino-terminus and beta-wing regions. Peptide segments at the carboxyl-terminus of CB were also suggested to play a secondary role in the binding of both CA and CNF.

Interacting with wildlife tourism increases activity of white sharks.

PubMed

Huveneers, Charlie; Watanabe, Yuuki Y; Payne, Nicholas L; Semmens, Jayson M

2018-01-01

Anthropogenic activities are dramatically changing marine ecosystems. Wildlife tourism is one of the fastest growing sectors of the tourism industry and has the potential to modify the natural environment and behaviour of the species it targets. Here, we used a novel method to assess the effects of wildlife tourism on the activity of white sharks ( Carcharodon carcharias ). High frequency three-axis acceleration loggers were deployed on ten white sharks for a total of ~9 days. A combination of multivariate and univariate analysis revealed that the increased number of strong accelerations and vertical movements when sharks are interacting with cage-diving operators result in an overall dynamic body acceleration (ODBA) ~61% higher compared with other times when sharks are present in the area where cage-diving occurs. Since ODBA is considered a proxy of metabolic rate, interacting with cage-divers is probably more costly than are normal behaviours of white sharks at the Neptune Islands. However, the overall impact of cage-diving might be small if interactions with individual sharks are infrequent. This study suggests wildlife tourism changes the instantaneous activity levels of white sharks, and calls for an understanding of the frequency of shark-tourism interactions to appreciate the net impact of ecotourism on this species' fitness.

Differential manipulation of arrestin-3 binding to basal and agonist-activated G protein-coupled receptors.

PubMed

Prokop, Susanne; Perry, Nicole A; Vishnivetskiy, Sergey A; Toth, Andras D; Inoue, Asuka; Milligan, Graeme; Iverson, Tina M; Hunyady, Laszlo; Gurevich, Vsevolod V

2017-08-01

Non-visual arrestins interact with hundreds of different G protein-coupled receptors (GPCRs). Here we show that by introducing mutations into elements that directly bind receptors, the specificity of arrestin-3 can be altered. Several mutations in the two parts of the central "crest" of the arrestin molecule, middle-loop and C-loop, enhanced or reduced arrestin-3 interactions with several GPCRs in receptor subtype and functional state-specific manner. For example, the Lys139Ile substitution in the middle-loop dramatically enhanced the binding to inactive M 2 muscarinic receptor, so that agonist activation of the M 2 did not further increase arrestin-3 binding. Thus, the Lys139Ile mutation made arrestin-3 essentially an activation-independent binding partner of M 2 , whereas its interactions with other receptors, including the β 2 -adrenergic receptor and the D 1 and D 2 dopamine receptors, retained normal activation dependence. In contrast, the Ala248Val mutation enhanced agonist-induced arrestin-3 binding to the β 2 -adrenergic and D 2 dopamine receptors, while reducing its interaction with the D 1 dopamine receptor. These mutations represent the first example of altering arrestin specificity via enhancement of the arrestin-receptor interactions rather than selective reduction of the binding to certain subtypes. Copyright © 2017. Published by Elsevier Inc.

Interaction of water, alkyl hydroperoxide, and allylic alcohol with a single-site homogeneous Ti-Si epoxidation catalyst: A spectroscopic and computational study.

PubMed

Urakawa, Atsushi; Bürgi, Thomas; Skrabal, Peter; Bangerter, Felix; Baiker, Alfons

2005-02-17

Tetrakis(trimethylsiloxy)titanium (TTMST, Ti(OSiMe3)4) possesses an isolated Ti center and is a highly active homogeneous catalyst in epoxidation of various olefins. The structure of TTMST resembles that of the active sites in some heterogeneous Ti-Si epoxidation catalysts, especially silylated titania-silica mixed oxides. Water cleaves the Ti-O-Si bond and deactivates the catalyst. An alkyl hydroperoxide, TBHP (tert-butyl hydroperoxide), does not cleave the Ti-O-Si bond, but interacts via weak hydrogen-bonding as supported by NMR, DOSY, IR, and computational studies. ATR-IR spectroscopy combined with computational investigations shows that more than one, that is, up to four, TBHP can undergo hydrogen-bonding with TTMST, leading to the activation of the O-O bond of TBHP. The greater the number of TBHP molecules that form hydrogen bonds to TTMST, the more electrophilic the O-O bond becomes, and the more active the complex is for epoxidation. An allylic alcohol, 2-cyclohexen-1-ol, does not interact strongly with TTMST, but the interaction is prominent when it interacts with the TTMST-TBHP complex. On the basis of the experimental and theoretical findings, a hydrogen-bond-assisted epoxidation mechanism of TTMST is suggested.

Interacting with wildlife tourism increases activity of white sharks

PubMed Central

Watanabe, Yuuki Y; Payne, Nicholas L; Semmens, Jayson M

2018-01-01

Abstract Anthropogenic activities are dramatically changing marine ecosystems. Wildlife tourism is one of the fastest growing sectors of the tourism industry and has the potential to modify the natural environment and behaviour of the species it targets. Here, we used a novel method to assess the effects of wildlife tourism on the activity of white sharks (Carcharodon carcharias). High frequency three-axis acceleration loggers were deployed on ten white sharks for a total of ~9 days. A combination of multivariate and univariate analysis revealed that the increased number of strong accelerations and vertical movements when sharks are interacting with cage-diving operators result in an overall dynamic body acceleration (ODBA) ~61% higher compared with other times when sharks are present in the area where cage-diving occurs. Since ODBA is considered a proxy of metabolic rate, interacting with cage-divers is probably more costly than are normal behaviours of white sharks at the Neptune Islands. However, the overall impact of cage-diving might be small if interactions with individual sharks are infrequent. This study suggests wildlife tourism changes the instantaneous activity levels of white sharks, and calls for an understanding of the frequency of shark-tourism interactions to appreciate the net impact of ecotourism on this species’ fitness. PMID:29780593

Stability and activity of lactate dehydrogenase on biofunctional layers deposited by activated vapor silanization (AVS) and immersion silanization (IS)

NASA Astrophysics Data System (ADS)

Calvo, Jorge Nieto-Márquez; Elices, Manuel; Guinea, Gustavo V.; Pérez-Rigueiro, José; Arroyo-Hernández, María

2017-09-01

The interaction between surfaces and biological elements, in particular, proteins is critical for the performance of biomaterials and biosensors. This interaction can be controlled by modifying the surface in a process known as biofunctionalization. In this work, the enzyme lactate dehydrogenase (LDH) is used to study the stability of the interaction between a functional protein and amine-functionalized surfaces. Two different functionalization procedures were compared: Activated Vapor Silanization (AVS) and Immersion Silanization (IS). Adsorption kinetics is shown to follow the Langmuir model for AVS-functionalized samples, while IS-functionalized samples show a certain instability if immersed in an aqueous medium for several hours. In turn, the enzymatic activity of LDH is preserved for longer times by using glutaraldehyde as crosslinker between the AVS biofunctional surface and the enzyme.

The NASA controls-structures interaction technology program

NASA Technical Reports Server (NTRS)

Newsom, Jerry R.; Layman, W. E.; Waites, H. B.; Hayduk, R. J.

1990-01-01

The interaction between a flexible spacecraft structure and its control system is commonly referred to as controls-structures interaction (CSI). The CSI technology program is developing the capability and confidence to integrate the structure and control system, so as to avoid interactions that cause problems and to exploit interactions to increase spacecraft capability. A NASA program has been initiated to advance CSI technology to a point where it can be used in spacecraft design for future missions. The CSI technology program is a multicenter program utilizing the resources of the NASA Langley Research Center (LaRC), the NASA Marshall Space Flight Center (MSFC), and the NASA Jet Propulsion Laboratory (JPL). The purpose is to describe the current activities, results to date, and future activities of the NASA CSI technology program.

An efficient way of studying protein-protein interactions involving HIF-α, c-Myc, and Sp1.

PubMed

To, Kenneth K-W; Huang, L Eric

2013-01-01

Protein-protein interaction is an essential biochemical event that mediates various cellular processes including gene expression, intracellular signaling, and intercellular interaction. Understanding such interaction is key to the elucidation of mechanisms of cellular processes in biology and diseases. The hypoxia-inducible transcription factor HIF-1α possesses a non-transcriptional activity that competes with c-Myc for Sp1 binding, whereas its isoform HIF-2α lacks Sp1-binding activity due to phosphorylation. Here, we describe the use of in vitro translation to effectively investigate the dynamics of protein-protein interactions among HIF-1α, c-Myc, and Sp1 and to demonstrate protein phosphorylation as a molecular determinant that functionally distinguishes HIF-2α from HIF-1α.

Human Cancer and Platelet Interaction, a Potential Therapeutic Target.

PubMed

Wang, Shike; Li, Zhenyu; Xu, Ren

2018-04-20

Cancer patients experience a four-fold increase in thrombosis risk, indicating that cancer development and progression are associated with platelet activation. Xenograft experiments and transgenic mouse models further demonstrate that platelet activation and platelet-cancer cell interaction are crucial for cancer metastasis. Direct or indirect interaction of platelets induces cancer cell plasticity and enhances survival and extravasation of circulating cancer cells during dissemination. In vivo and in vitro experiments also demonstrate that cancer cells induce platelet aggregation, suggesting that platelet-cancer interaction is bidirectional. Therefore, understanding how platelets crosstalk with cancer cells may identify potential strategies to inhibit cancer metastasis and to reduce cancer-related thrombosis. Here, we discuss the potential function of platelets in regulating cancer progression and summarize the factors and signaling pathways that mediate the cancer cell-platelet interaction.

A Conceptual Framework Based on Activity Theory for Mobile CSCL

ERIC Educational Resources Information Center

Zurita, Gustavo; Nussbaum, Miguel

2007-01-01

There is a need for collaborative group activities that promote student social interaction in the classroom. Handheld computers interconnected by a wireless network allow people who work on a common task to interact face to face while maintaining the mediation afforded by a technology-based system. Wirelessly interconnected handhelds open up new…

Parent-Child Interaction and Children's Number Learning

ERIC Educational Resources Information Center

Zhou, Xin; Huang, Jin; Wang, Zhengke; Wang, Bin; Zhao, Zhenguo; Yang, Lei; Yang, Zhengzheng

2006-01-01

Two groups of Chinese four-year-olds and their parents' interaction in joint activities were analyzed and compared. The children in Group 1 were high scorers in written number skills and the children in Group 2 were low scorers. Eighty-five dyads participated in four separate 15-minute joint activities such as book reading, mathematical work…

Analysis of Peer Interaction in Learning Activities with Personal Handhelds and Shared Displays

ERIC Educational Resources Information Center

Liu, Chen-Chung; Chung, Chen-Wei; Chen, Nian-Shing; Liu, Baw-Jhiune

2009-01-01

Collaborative learning is extensively applied in classroom activities, but the screens on handheld devices are designed for individual-user mobile applications and may constrain interaction among group learners. The small screen size may lead to fragmented and tete-a-tete communication patterns and frequently obstruct the externalization of the…

Activity Theory and Technology Mediated Interaction: Cognitive Scaffolding Using Question-Based Consultation on "Facebook"

ERIC Educational Resources Information Center

Rambe, Patient

2012-01-01

Studies that employed activity theory as a theoretical lens for exploring computer-mediated interaction have not adopted social media as their object of study. However, social media provides lecturers with personalised learning environments for diagnostic and prognostic assessments of student mastery of content and deep learning. The integration…

Authentic L2 Interactions as Material for a Pragmatic Awareness-Raising Activity

ERIC Educational Resources Information Center

Cheng, Tsui-Ping

2016-01-01

This study draws on conversation analysis to explore the pedagogical possibility of using audiovisual depictions of authentic disagreement sequences from L2 interactions as sources for an awareness-raising activity in an English as a Second Language (ESL) classroom. Video excerpts of disagreement sequences collected from two ESL classes were used…

Coaching Paraprofessionals to Promote Engagement and Social Interactions during Small Group Activities

ERIC Educational Resources Information Center

Ledford, Jennifer R.; Zimmerman, Kathleen N.; Chazin, Kate T.; Patel, Natasha M.; Morales, Vivian A.; Bennett, Brittany P.

2017-01-01

Paraprofessionals need adequate training and supports to assist young children with autism spectrum disorders to engage in appropriate social interactions during small group activities with their peers. In this study, we used in-situ coaching and brief post-session feedback to improve the use of environmental arrangement, prompting, and praise by…

Coaching Paraprofessionals to Promote Engagement and Social Interactions during Small Group Activities

ERIC Educational Resources Information Center

Ledford, Jennifer R.; Zimmerman, Kathleen N.; Chazin, Kate T.; Patel, Natasha M.; Morales, Vivian A.; Bennett, Brittany P.

2017-01-01

Paraprofessionals need adequate training and supports to assist young children with autism spectrum disorders to engage in appropriate social interactions during small group activities with their peers. In this study, we used in situ coaching and brief post-session feedback to improve the use of environmental arrangement, prompting, and praise by…

Social Interaction and the Formation of Entrepreneurial Characteristics: A Case Study in Authentic Enterprise Activity

ERIC Educational Resources Information Center

Yu, Christina W. M.; Man, Thomas W. Y.

2009-01-01

Purpose: This paper is an empirical study which aims to investigate the development of social interaction and their impacts on developing learners' entrepreneurial characteristics throughout their participation in an authentic enterprise activity. Design/methodology/approach: The sample of this study was drawn from the participants of an…

Working with Pre-School Practitioners to Improve Interactions

ERIC Educational Resources Information Center

Ahsam, Suki; Shepherd, Julie; Warren-Adamson, Chris

2006-01-01

Eight pre-schools took part in offsite and onsite speech and language training to improve their interaction skills with children and learn some group language activities. An evaluation was undertaken where practitioners at one pre-school were videoed running a language activity before and after training. The video was analysed to assess change in…

Interaction Analysis for Supporting Students' Self-Regulation during Blog-Based CSCL Activities

ERIC Educational Resources Information Center

Michailidis, Nikolaos; Kapravelos, Efstathios; Tsiatsos, Thrasyvoulos

2018-01-01

Self-regulated learning is an important means of supporting students' self-awareness and self-regulation level so as to enhance their motivation and engagement. Interaction Analysis (IA) contributes to this end, and its use in studying learning dynamics involved in asynchronous Computer-Supported Collaborative Learning (CSCL) activities has…

Students' Perceptions of Reading through Peer Questioning in Cooperative

ERIC Educational Resources Information Center

Tanaka, Makiko; Sanchez, Edward

2016-01-01

This study investigated perceptions of a class of 20 first-year Japanese college students on peer questioning in cooperative reading activities. After the instructor gave an hour of interactive explanations of the reading, in which students were encouraged to interact actively with the instructor in interpreting the reading material, students were…

Peer Groups and Substance Use: Examining the Direct and Interactive Effect of Leisure Activity

ERIC Educational Resources Information Center

Thorlindsson, Thorolfur; Bernburg, Jon Gunnar

2006-01-01

This paper explores the relationships among adolescent leisure activities, peer behavior, and substance use. We suggest that peer group interaction can have a differential effect on adolescent deviant behavior depending on the type of leisure pattern adolescents engage in. We analyze data from a representative national sample of Icelandic…

Peer Interactions among Children with Profound Intellectual and Multiple Disabilities during Group Activities

ERIC Educational Resources Information Center

Nijs, Sara; Penne, Anneleen; Vlaskamp, Carla; Maes, Bea

2016-01-01

Background: Children with profound intellectual and multiple disabilities (PIMD) meet other children with PIMD in day care centres or schools. This study explores the peer-directed behaviours of children with PIMD, the peer interaction-influencing behaviour of the direct support workers and the children's positioning. Method: Group activities for…

Effects of Collaborative Activities on Group Identity in Virtual World

ERIC Educational Resources Information Center

Park, Hyungsung; Seo, Sumin

2013-01-01

The purpose of this study was to analyze the effects of collaborative activities on group identity in a virtual world such as "Second Life." To achieve this purpose, this study adopted events that promoted participants' interactions using tools inherent in "Second Life." The interactive tools given to the control group in this…

Improving Critical Thinking with Interactive Mobile Tools and Apps

ERIC Educational Resources Information Center

Lin, Lin; Widdall, Chris; Ward, Laurie

2014-01-01

In this article, the authors describe how integrating interactive mobile tools into elementary pedagogy can generate enthusiasm and critical thinking among students as they learn about the world. The activities described took place over the course of six one-hour periods spanning six days. These activities address three major social studies…

Effect of Resveratrol, a SIRT1 Activator, on the Interactions of the CLOCK/BMAL1 Complex

PubMed Central

Park, Insung; Lee, Yool; Kim, Hee-Dae

2014-01-01

Background In mammals, the CLOCK/BMAL1 heterodimer is a key transcription factor complex that drives the cyclic expression of clock-controlled genes involved in various physiological functions and behavioral consequences. Recently, a growing number of studies have reported a molecular link between the circadian clock and metabolism. In the present study, we explored the regulatory effects of SIRTUIN1 (SIRT1), an NAD+-dependent deacetylase, on CLOCK/BMAL1-mediated clock gene expression. Methods To investigate the interaction between SIRT1 and CLOCK/BMAL1, we conducted bimolecular fluorescence complementation (BiFC) analyses supplemented with immunocytochemistry assays. BiFC experiments employing deletion-specific mutants of BMAL1 were used to elucidate the specific domains that are necessary for the SIRT1-BMAL1 interaction. Additionally, luciferase reporter assays were used to delineate the effects of SIRT1 on circadian gene expression. Results BiFC analysis revealed that SIRT1 interacted with both CLOCK and BMAL1 in most cell nuclei. As revealed by BiFC assays using various BMAL1 deletion mutants, the PAS-B domain of BMAL1 was essential for interaction with SIRT1. Activation of SIRT1 with resveratrol did not exert any significant change on the interaction with the CLOCK/BMAL1 complex. However, promoter analysis using Per1-Luc and Ebox-Luc reporters showed that SIRT1 significantly downregulated both promoter activities. This inhibitory effect was intensified by treatment with resveratrol, indicating a role for SIRT1 and its activator in CLOCK/BMAL1-mediated transcription of clock genes. Conclusion These results suggest that SIRT1 may form a regulatory complex with CLOCK/BMAL1 that represses clock gene expression, probably via deacetylase activity. PMID:25309798

Fragile X mental retardation protein controls ion channel expression and activity.

PubMed

Ferron, Laurent

2016-10-15

Fragile X-associated disorders are a family of genetic conditions resulting from the partial or complete loss of fragile X mental retardation protein (FMRP). Among these disorders is fragile X syndrome, the most common cause of inherited intellectual disability and autism. FMRP is an RNA-binding protein involved in the control of local translation, which has pleiotropic effects, in particular on synaptic function. Analysis of the brain FMRP transcriptome has revealed hundreds of potential mRNA targets encoding postsynaptic and presynaptic proteins, including a number of ion channels. FMRP has been confirmed to bind voltage-gated potassium channels (K v 3.1 and K v 4.2) mRNAs and regulates their expression in somatodendritic compartments of neurons. Recent studies have uncovered a number of additional roles for FMRP besides RNA regulation. FMRP was shown to directly interact with, and modulate, a number of ion channel complexes. The sodium-activated potassium (Slack) channel was the first ion channel shown to directly interact with FMRP; this interaction alters the single-channel properties of the Slack channel. FMRP was also shown to interact with the auxiliary β4 subunit of the calcium-activated potassium (BK) channel; this interaction increases calcium-dependent activation of the BK channel. More recently, FMRP was shown to directly interact with the voltage-gated calcium channel, Ca v 2.2, and reduce its trafficking to the plasma membrane. Studies performed on animal models of fragile X syndrome have revealed links between modifications of ion channel activity and changes in neuronal excitability, suggesting that these modifications could contribute to the phenotypes observed in patients with fragile X-associated disorders. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

A conformational switch in the inhibitory gamma-subunit of PDE6 upon enzyme activation by transducin.

PubMed

Granovsky, A E; Artemyev, N O

2001-11-06

In response to light, a photoreceptor G protein, transducin, activates cGMP-phosphodiesterase (PDE6) by displacing the inhibitory gamma-subunits (Pgamma) from the enzyme's catalytic sites. Evidence suggests that the activation of PDE6 involves a conformational change of the key inhibitory C-terminal domain of Pgamma. In this study, the C-terminal region of Pgamma, Pgamma-73-85, has been targeted for Ala-scanning mutagenesis to identify the point-to-point interactions between Pgamma and the PDE6 catalytic subunits and to probe the nature of the conformational change. Pgamma mutants were tested for their ability to inhibit PDE6 and a chimeric PDE5-conePDE6 enzyme containing the Pgamma C-terminus-binding site of cone PDE. This analysis has revealed that in addition to previously characterized Ile86 and Ile87, important inhibitory contact residues of Pgamma include Asn74, His75, and Leu78. The patterns of mutant PDE5-conePDE6 enzyme inhibition suggest the interaction between the PgammaAsn74/His75 sequence and Met758 of the cone PDE6alpha' catalytic subunit. This interaction, and the interaction between the PgammaIle86/Ile87 and PDE6alpha'Phe777/Phe781 residues, is most consistent with an alpha-helical structure of the Pgamma C-terminus. The analysis of activation of PDE6 enzymes containing Pgamma mutants with Ala-substituted transducin-contact residues demonstrated the critical role of PgammaLeu76. Accordingly, we hypothesize that the initial step in PDE6 activation involves an interaction of transducin-alpha with PgammaLeu76. This interaction introduces a bend into the alpha-helical structure of the Pgamma C-terminus, allowing transducin-alpha to further twist the C-terminus thereby uncovering the catalytic pocket of PDE6.

Near-field electromagnetic holography for high-resolution analysis of network interactions in neuronal tissue

PubMed Central

Kjeldsen, Henrik D.; Kaiser, Marcus; Whittington, Miles A.

2015-01-01

Background Brain function is dependent upon the concerted, dynamical interactions between a great many neurons distributed over many cortical subregions. Current methods of quantifying such interactions are limited by consideration only of single direct or indirect measures of a subsample of all neuronal population activity. New method Here we present a new derivation of the electromagnetic analogy to near-field acoustic holography allowing high-resolution, vectored estimates of interactions between sources of electromagnetic activity that significantly improves this situation. In vitro voltage potential recordings were used to estimate pseudo-electromagnetic energy flow vector fields, current and energy source densities and energy dissipation in reconstruction planes at depth into the neural tissue parallel to the recording plane of the microelectrode array. Results The properties of the reconstructed near-field estimate allowed both the utilization of super-resolution techniques to increase the imaging resolution beyond that of the microelectrode array, and facilitated a novel approach to estimating causal relationships between activity in neocortical subregions. Comparison with existing methods The holographic nature of the reconstruction method allowed significantly better estimation of the fine spatiotemporal detail of neuronal population activity, compared with interpolation alone, beyond the spatial resolution of the electrode arrays used. Pseudo-energy flow vector mapping was possible with high temporal precision, allowing a near-realtime estimate of causal interaction dynamics. Conclusions Basic near-field electromagnetic holography provides a powerful means to increase spatial resolution from electrode array data with careful choice of spatial filters and distance to reconstruction plane. More detailed approaches may provide the ability to volumetrically reconstruct activity patterns on neuronal tissue, but the ability to extract vectored data with the method presented already permits the study of dynamic causal interactions without bias from any prior assumptions on anatomical connectivity. PMID:26026581

Near-field electromagnetic holography for high-resolution analysis of network interactions in neuronal tissue.

PubMed

Kjeldsen, Henrik D; Kaiser, Marcus; Whittington, Miles A

2015-09-30

Brain function is dependent upon the concerted, dynamical interactions between a great many neurons distributed over many cortical subregions. Current methods of quantifying such interactions are limited by consideration only of single direct or indirect measures of a subsample of all neuronal population activity. Here we present a new derivation of the electromagnetic analogy to near-field acoustic holography allowing high-resolution, vectored estimates of interactions between sources of electromagnetic activity that significantly improves this situation. In vitro voltage potential recordings were used to estimate pseudo-electromagnetic energy flow vector fields, current and energy source densities and energy dissipation in reconstruction planes at depth into the neural tissue parallel to the recording plane of the microelectrode array. The properties of the reconstructed near-field estimate allowed both the utilization of super-resolution techniques to increase the imaging resolution beyond that of the microelectrode array, and facilitated a novel approach to estimating causal relationships between activity in neocortical subregions. The holographic nature of the reconstruction method allowed significantly better estimation of the fine spatiotemporal detail of neuronal population activity, compared with interpolation alone, beyond the spatial resolution of the electrode arrays used. Pseudo-energy flow vector mapping was possible with high temporal precision, allowing a near-realtime estimate of causal interaction dynamics. Basic near-field electromagnetic holography provides a powerful means to increase spatial resolution from electrode array data with careful choice of spatial filters and distance to reconstruction plane. More detailed approaches may provide the ability to volumetrically reconstruct activity patterns on neuronal tissue, but the ability to extract vectored data with the method presented already permits the study of dynamic causal interactions without bias from any prior assumptions on anatomical connectivity. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Pokemon (FBI-1) interacts with Smad4 to repress TGF-β-induced transcriptional responses.

PubMed

Yang, Yutao; Cui, Jiajun; Xue, Feng; Zhang, Chuanfu; Mei, Zhu; Wang, Yue; Bi, Mingjun; Shan, Dapeng; Meredith, Alex; Li, Hui; Xu, Zhi-Qing David

2015-03-01

Pokemon, an important proto-oncoprotein, is a transcriptional repressor that belongs to the POK (POZ and Krüppel) family. Smad4, a key component of TGF-β pathway, plays an essential role in TGF-β-induced transcriptional responses. In this study, we show that Pokemon can interact directly with Smad4 both in vitro and in vivo. Overexpression of Pokemon decreases TGF-β-induced transcriptional activities, whereas knockdown of Pokemon increases these activities. Interestingly, Pokemon does not affect activation of Smad2/3, formation of Smads complex, or DNA binding activity of Smad4. TGF-β1 treatment increases the interaction between Pokemon and Smad4, and also enhances the recruitment of Pokemon to Smad4-DNA complex. In addition, we also find that Pokemon recruits HDAC1 to Smad4 complex but decreases the interaction between Smad4 and p300/CBP. Taken together, all these data suggest that Pokemon is a new partner of Smad4 and plays a negative role in TGF-β pathway. Copyright © 2014. Published by Elsevier B.V.

Structure-affinity relationship of the interaction between phenolic acids and their derivatives and β-lactoglobulin and effect on antioxidant activity.

PubMed

Wu, Simin; Zhang, Yunyue; Ren, Fazheng; Qin, Yinghui; Liu, Jiaxin; Liu, Jingwen; Wang, Qingyu; Zhang, Hao

2018-04-15

In this study, 71 phenolic acids and their derivatives were used to investigate the structure-affinity relationship of β-lactoglobulin binding, and the effect of this interaction on antioxidant activity. Based on a fluorescence quenching method, an improved mathematical model was adopted to calculate the binding constants, with a correction for the inner-filter effect. Hydroxylation at the 3-position increased the affinity of the phenolic acids for β-lactoglobulin, while hydroxylation at the 2- or 4-positions had a negative effect. Complete methylation of all hydroxy groups, except at the 3-position, enhanced the binding affinity. Replacing the hydroxy groups with methyl groups at the 2-position also had a positive effect. Hydrogen bonding was one of the binding forces for the interaction. The antioxidant activity of phenolic acid-β-lactoglobulin complexes was higher than that of phenolic acids alone. These findings provide an understanding of the structure-activity relationship of the interaction between β-lactoglobulin and phenolic acids. Copyright © 2017 Elsevier Ltd. All rights reserved.

A conserved role for the ESCRT membrane budding complex in LINE retrotransposition

PubMed Central

Dong, Chun; Han, Jeffrey S.

2017-01-01

Long interspersed nuclear element-1s (LINE-1s, or L1s) are an active family of retrotransposable elements that continue to mutate mammalian genomes. Despite the large contribution of L1 to mammalian genome evolution, we do not know where active L1 particles (particles in the process of retrotransposition) are located in the cell, or how they move towards the nucleus, the site of L1 reverse transcription. Using a yeast model of LINE retrotransposition, we identified ESCRT (endosomal sorting complex required for transport) as a critical complex for LINE retrotransposition, and verified that this interaction is conserved for human L1. ESCRT interacts with L1 via a late domain motif, and this interaction facilitates L1 replication. Loss of the L1/ESCRT interaction does not impair RNP formation or enzymatic activity, but leads to loss of retrotransposition and reduced L1 endonuclease activity in the nucleus. This study highlights the importance of the ESCRT complex in the L1 life cycle and suggests an unusual mode for L1 RNP trafficking. PMID:28586350

Angiopoietin-like proteins stimulate HSPC development through interaction with notch receptor signaling

PubMed Central

Lin, Michelle I; Price, Emily N; Boatman, Sonja; Hagedorn, Elliott J; Trompouki, Eirini; Satishchandran, Sruthi; Carspecken, Charles W; Uong, Audrey; DiBiase, Anthony; Yang, Song; Canver, Matthew C; Dahlberg, Ann; Lu, Zhigang; Zhang, Cheng Cheng; Orkin, Stuart H; Bernstein, Irwin D; Aster, Jon C; White, Richard M; Zon, Leonard I

2015-01-01

Angiopoietin-like proteins (angptls) are capable of ex vivo expansion of mouse and human hematopoietic stem and progenitor cells (HSPCs). Despite this intriguing ability, their mechanism is unknown. In this study, we show that angptl2 overexpression is sufficient to expand definitive HSPCs in zebrafish embryos. Angptl1/2 are required for definitive hematopoiesis and vascular specification of the hemogenic endothelium. The loss-of-function phenotype is reminiscent of the notch mutant mindbomb (mib), and a strong genetic interaction occurs between angptls and notch. Overexpressing angptl2 rescues mib while overexpressing notch rescues angptl1/2 morphants. Gene expression studies in ANGPTL2-stimulated CD34+ cells showed a strong MYC activation signature and myc overexpression in angptl1/2 morphants or mib restored HSPCs formation. ANGPTL2 can increase NOTCH activation in cultured cells and ANGPTL receptor interacted with NOTCH to regulate NOTCH cleavage. Together our data provide insight to the angptl-mediated notch activation through receptor interaction and subsequent activation of myc targets. DOI: http://dx.doi.org/10.7554/eLife.05544.001 PMID:25714926

Spontaneous triadic engagement in bonobos (Pan paniscus) and chimpanzees (Pan troglodytes).

PubMed

MacLean, Evan; Hare, Brian

2013-08-01

Humans are believed to have evolved a unique motivation to participate in joint activities that first develops during infancy and supports the development of shared intentionality. We conducted five experiments with bonobos (Pan paniscus) and chimpanzees (Pan troglodytes) (Total n = 119) to assess their motivation to spontaneously participate in joint activities with a conspecific or a human. We found that even the youngest subjects preferred to interact together with a human and a toy rather than engaging in an identical game alone. In addition, we found that subjects could spontaneously interact with a human in a turn-taking game involving passing a ball back and forth and used behaviors to elicit additional interaction when the game was disrupted. However, when paired with a conspecific, subjects preferred to interact with an object individually rather than together. Our results indicate that nonhuman apes are motivated to engage in triadic activities if they occur spontaneously with humans and require a minimum amount of coordination. These findings leave open the question of whether these activities are coordinated through shared intentions.

[The structure of micromycete communities and their synecologic interactions with basidiomycetes during decomposition of plant debris].

PubMed

Terekhova, V A; Semenova, T A

2005-01-01

We investigated the interactions between micromycetes and basidiomycete mycelium on plant substrates in the course of their 3-year incubation in the litter of ecologically intact spruce forests of the Central State Biosphere Forest Sanctuary (Nelidovo District, Tver oblast). Only 40-60% of the micromycetes were involved in direct antagonistic interactions with basidiomycetous fungi. In terms of the ratio between physiologically active strains and those which did not interact with basidiomycete mycelium, we revealed differences in the structure of micromycete communities developing on various types of substrates (xylem, bark, sphagnum, leaves, needles, litter, and cotton grass). The micromycetes tested belonged to 49 species. At the end of the observation period, the fraction of microscopic fungi that actively influenced basidiomycete mycelium was four times lower in the inactive litter fraction (lignin-containing xylem debris) than in the active fraction (grass substrates). The mechanisms of indirect regulation of the structure and functions of micromycete communities are discussed, which may be based on the accumulation of phenolic compounds in the medium and changes in the enzyme activities of basidiomycete mycelium.

Enzyme Active Site Interactions by Raman/FTIR, NMR, and Ab Initio Calculations

PubMed Central

Deng, Hua

2017-01-01

Characterization of enzyme active site structure and interactions at high resolution is important for the understanding of the enzyme catalysis. Vibrational frequency and NMR chemical shift measurements of enzyme-bound ligands are often used for such purpose when X-ray structures are not available or when higher resolution active site structures are desired. This review is focused on how ab initio calculations may be integrated with vibrational and NMR chemical shift measurements to quantitatively determine high-resolution ligand structures (up to 0.001 Å for bond length and 0.01 Å for hydrogen bonding distance) and how interaction energies between bound ligand and its surroundings at the active site may be determined. Quantitative characterization of substrate ionic states, bond polarizations, tautomeric forms, conformational changes and its interactions with surroundings in enzyme complexes that mimic ground state or transition state can provide snapshots for visualizing the substrate structural evolution along enzyme-catalyzed reaction pathway. Our results have shown that the integration of spectroscopic studies with theoretical computation greatly enhances our ability to interpret experimental data and significantly increases the reliability of the theoretical analysis. PMID:24018325

The innate immune sensor NLRC3 attenuates Toll-like receptor signaling via modification of the signaling adaptor TRAF6 and transcription factor NF-κB.

PubMed

Schneider, Monika; Zimmermann, Albert G; Roberts, Reid A; Zhang, Lu; Swanson, Karen V; Wen, Haitao; Davis, Beckley K; Allen, Irving C; Holl, Eda K; Ye, Zhengmao; Rahman, Adeeb H; Conti, Brian J; Eitas, Timothy K; Koller, Beverly H; Ting, Jenny P-Y

2012-09-01

Several members of the NLR family of sensors activate innate immunity. In contrast, we found here that NLRC3 inhibited Toll-like receptor (TLR)-dependent activation of the transcription factor NF-κB by interacting with the TLR signaling adaptor TRAF6 to attenuate Lys63 (K63)-linked ubiquitination of TRAF6 and activation of NF-κB. We used bioinformatics to predict interactions between NLR and TRAF proteins, including interactions of TRAF with NLRC3. In vivo, macrophage expression of Nlrc3 mRNA was diminished by the administration of lipopolysaccharide (LPS) but was restored when cellular activation subsided. To assess biologic relevance, we generated Nlrc3(-/-) mice. LPS-treated Nlrc3(-/-) macrophages had more K63-ubiquitinated TRAF6, nuclear NF-κB and proinflammatory cytokines. Finally, LPS-treated Nlrc3(-/-) mice had more signs of inflammation. Thus, signaling via NLRC3 and TLR constitutes a negative feedback loop. Furthermore, prevalent NLR-TRAF interactions suggest the formation of a 'TRAFasome' complex.

Development of a skin for intuitive interaction with an assistive robot.

PubMed

Markham, Heather C; Brewer, Bambi R

2009-01-01

Assistive robots for persons with physical limitations need to interact with humans in a manner that is safe to the user and the environment. Early work in this field centered on task specific robots. Recent work has focused on the use of the MANUS ARM and the development of different interfaces. The most intuitive interaction with an object is through touch. By creating a skin for the robot arm which will directly control its movement compliance, we have developed a novel and intuitive method of interaction. This paper describes the development of a skin which acts as a switch. When activated through touch, the skin will put the arm into compliant mode allowing it to be moved to the desired location safely, and when released will put the robot into non-compliant mode thereby keeping it in place. We investigated four conductive materials and four insulators, selecting the best combination based on our design goals of the need for a continuous activation surface, the least amount of force required for skin activation, and the most consistent voltage change between the conductive surfaces measured during activation.

The interaction of methanol dehydrogenase and cytochrome cL in the acidophilic methylotroph Acetobacter methanolicus.

PubMed Central

Chan, H T; Anthony, C

1991-01-01

The quinoprotein methanol dehydrogenase (MDH) of Acetobacter methanolicus has an alpha 2 beta 2 structure. By contrast with other MDHs, the beta-subunit (approx. 8.5 kDa) does not contain the five lysine residues previously proposed to be involved in ionic interactions with the electron acceptor cytochrome cL. That electrostatic interactions are involved was confirmed by the demonstration that methanol:cytochrome cL oxidoreductase activity was inhibited by high ionic strength (I), the strength of interaction being inversely related to the square root of I. Specific modifiers of arginine residues on MDH inhibited this reaction but not the dye-linked MDH activity. Modification of lysine residues on MDH that altered its charge had no effect on the dye-linked activity but inhibited reaction with cytochrome cL. When the charge was retained on modification of lysine residues, little effect on either activity was observed. Cross-linking experiments confirmed that lysine residues on the alpha-subunit, but not the beta-subunit, are involved in the 'docking' process between the proteins. Images Fig. 4. PMID:1660263

Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults

PubMed Central

Feitosa, Mary F.; Barata, Llilda; Chu, Audrey Y.; Mahajan, Anubha; Hadley, David; Xue, Luting; Workalemahu, Tsegaselassie; den Hoed, Marcel; Ahluwalia, Tarunveer S.; Qi, Qibin; Ngwa, Julius S.; Quaye, Lydia; Eicher, John D.; Hayes, James E.; Cornelis, Marilyn; Kutalik, Zoltan; Lim, Elise; Luan, Jian’an; Huffman, Jennifer E.; Zhang, Weihua; Zhao, Wei; Griffin, Paula J.; Haller, Toomas; Ahmad, Shafqat; Marques-Vidal, Pedro M.; Bien, Stephanie; Yengo, Loic; Teumer, Alexander; Smith, Albert Vernon; Kumari, Meena; Harder, Marie Neergaard; Justesen, Johanne Marie; Kleber, Marcus E.; Hollensted, Mette; Lohman, Kurt; Rivera, Natalia V.; Whitfield, John B.; Zhao, Jing Hua; Stringham, Heather M.; Lyytikäinen, Leo-Pekka; Huppertz, Charlotte; Willemsen, Gonneke; Peyrot, Wouter J.; Wu, Ying; Kristiansson, Kati; Demirkan, Ayse; Fornage, Myriam; Hassinen, Maija; Bielak, Lawrence F.; Cadby, Gemma; Tanaka, Toshiko; Mägi, Reedik; van der Most, Peter J.; Jackson, Anne U.; Bragg-Gresham, Jennifer L.; Vitart, Veronique; Marten, Jonathan; Navarro, Pau; Bellis, Claire; Pasko, Dorota; Johansson, Åsa; Snitker, Søren; Cheng, Yu-Ching; Eriksson, Joel; Lim, Unhee; Aadahl, Mette; Adair, Linda S.; Amin, Najaf; Balkau, Beverley; Auvinen, Juha; Beilby, John; Bergman, Richard N.; Bergmann, Sven; Bertoni, Alain G.; Blangero, John; Bonnefond, Amélie; Bonnycastle, Lori L.; Borja, Judith B.; Brage, Søren; Busonero, Fabio; Buyske, Steve; Campbell, Harry; Chines, Peter S.; Collins, Francis S.; Corre, Tanguy; Smith, George Davey; Delgado, Graciela E.; Dueker, Nicole; Dörr, Marcus; Ebeling, Tapani; Eiriksdottir, Gudny; Esko, Tõnu; Faul, Jessica D.; Fu, Mao; Færch, Kristine; Gieger, Christian; Gläser, Sven; Gong, Jian; Gordon-Larsen, Penny; Grallert, Harald; Grammer, Tanja B.; Grarup, Niels; van Grootheest, Gerard; Harald, Kennet; Hastie, Nicholas D.; Havulinna, Aki S.; Hernandez, Dena; Hindorff, Lucia; Hocking, Lynne J.; Holmens, Oddgeir L.; Holzapfel, Christina; Hottenga, Jouke Jan; Huang, Jie; Huang, Tao; Hui, Jennie; Huth, Cornelia; Hutri-Kähönen, Nina; James, Alan L.; Jansson, John-Olov; Jhun, Min A.; Juonala, Markus; Kinnunen, Leena; Koistinen, Heikki A.; Kolcic, Ivana; Komulainen, Pirjo; Kuusisto, Johanna; Kvaløy, Kirsti; Kähönen, Mika; Lakka, Timo A.; Launer, Lenore J.; Lehne, Benjamin; Lindgren, Cecilia M.; Lorentzon, Mattias; Luben, Robert; Marre, Michel; Milaneschi, Yuri; Monda, Keri L.; Montgomery, Grant W.; De Moor, Marleen H. M.; Mulas, Antonella; Müller-Nurasyid, Martina; Musk, A. W.; Männikkö, Reija; Männistö, Satu; Narisu, Narisu; Nauck, Matthias; Nettleton, Jennifer A.; Nolte, Ilja M.; Oldehinkel, Albertine J.; Olden, Matthias; Ong, Ken K.; Padmanabhan, Sandosh; Paternoster, Lavinia; Perez, Jeremiah; Perola, Markus; Peters, Annette; Peters, Ulrike; Peyser, Patricia A.; Prokopenko, Inga; Puolijoki, Hannu; Raitakari, Olli T.; Rankinen, Tuomo; Rasmussen-Torvik, Laura J.; Rawal, Rajesh; Ridker, Paul M.; Rose, Lynda M.; Rudan, Igor; Sarti, Cinzia; Sarzynski, Mark A.; Savonen, Kai; Scott, William R.; Sanna, Serena; Shuldiner, Alan R.; Sidney, Steve; Silbernagel, Günther; Smith, Blair H.; Smith, Jennifer A.; Snieder, Harold; Stančáková, Alena; Sternfeld, Barbara; Swift, Amy J.; Tammelin, Tuija; Tan, Sian-Tsung; Thorand, Barbara; Thuillier, Dorothée; Vandenput, Liesbeth; Vestergaard, Henrik; van Vliet-Ostaptchouk, Jana V.; Vohl, Marie-Claude; Völker, Uwe; Waeber, Gérard; Walker, Mark; Wild, Sarah; Wong, Andrew; Wright, Alan F.; Zillikens, M. Carola; Zubair, Niha; Haiman, Christopher A.; Lemarchand, Loic; Gyllensten, Ulf; Ohlsson, Claes; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G.; Pérusse, Louis; Wilson, James F.; Hayward, Caroline; Polasek, Ozren; Cucca, Francesco; Hveem, Kristian; Hartman, Catharina A.; Tönjes, Anke; Bandinelli, Stefania; Palmer, Lyle J.; Kardia, Sharon L. R.; Rauramaa, Rainer; Sørensen, Thorkild I. A.; Tuomilehto, Jaakko; Salomaa, Veikko; Penninx, Brenda W. J. H.; de Geus, Eco J. C.; Boomsma, Dorret I.; Lehtimäki, Terho; Mangino, Massimo; Laakso, Markku; Bouchard, Claude; Martin, Nicholas G.; Kuh, Diana; Liu, Yongmei; Linneberg, Allan; März, Winfried; Strauch, Konstantin; Kivimäki, Mika; Harris, Tamara B.; Gudnason, Vilmundur; Völzke, Henry; Qi, Lu; Järvelin, Marjo-Riitta; Chambers, John C.; Kooner, Jaspal S.; Froguel, Philippe; Kooperberg, Charles; Vollenweider, Peter; Hallmans, Göran; Hansen, Torben; Pedersen, Oluf; Metspalu, Andres; Wareham, Nicholas J.; Langenberg, Claudia; Weir, David R.; Porteous, David J.; Boerwinkle, Eric; Chasman, Daniel I.; Abecasis, Gonçalo R.; McCarthy, Mark I.; Frayling, Timothy M.; O’Connell, Jeffrey R.; van Duijn, Cornelia M.; Boehnke, Michael; Heid, Iris M.; Mohlke, Karen L.; Fox, Caroline S.; Hirschhorn, Joel N.; Johnson, Andrew D.; Borecki, Ingrid B.; Franks, Paul W.; North, Kari E.; Cupples, L. Adrienne; Loos, Ruth J. F.; Kilpeläinen, Tuomas O.

2017-01-01

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery. PMID:28448500

Molecular docking of bacosides with tryptophan hydroxylase: a model to understand the bacosides mechanism.

PubMed

Rajathei, David Mary; Preethi, Jayakumar; Singh, Hemant K; Rajan, Koilmani Emmanuvel

2014-08-01

Tryptophan hydroxylase (TPH) catalyses l-tryptophan into 5-hydroxy-l-tryptophan, which is the first and rate-limiting step of serotonin (5-HT) biosynthesis. Earlier, we found that TPH2 up-regulated in the hippocampus of postnatal rats after the oral treatment of Bacopa monniera leaf extract containing the active compound bacosides. However, the knowledge about the interactions between bacosides with TPH is limited. In this study, we take advantage of in silico approach to understand the interaction of bacoside-TPH complex using three different docking algorithms such as HexDock, PatchDock and AutoDock. All these three algorithms showed that bacoside A and A3 well fit into the cavity consists of active sites. Further, our analysis revealed that major active compounds bacoside A3 and A interact with different residues of TPH through hydrogen bond. Interestingly, Tyr235, Thr265 and Glu317 are the key residues among them, but none of them are either at tryptophan or BH4 binding region. However, its note worthy to mention that Tyr 235 is a catalytic sensitive residue, Thr265 is present in the flexible loop region and Glu317 is known to interacts with Fe. Interactions with these residues may critically regulate TPH function and thus serotonin synthesis. Our study suggested that the interaction of bacosides (A3/A) with TPH might up-regulate its activity to elevate the biosynthesis of 5-HT, thereby enhances learning and memory formation.

Chronobiology of interspecific interactions in a changing world.

PubMed

Kronfeld-Schor, Noga; Visser, Marcel E; Salis, Lucia; van Gils, Jan A

2017-11-19

Animals should time activities, such as foraging, migration and reproduction, as well as seasonal physiological adaptation, in a way that maximizes fitness. The fitness outcome of such activities depends largely on their interspecific interactions; the temporal overlap with other species determines when they should be active in order to maximize their encounters with food and to minimize their encounters with predators, competitors and parasites. To cope with the constantly changing, but predictable structure of the environment, organisms have evolved internal biological clocks, which are synchronized mainly by light, the most predictable and reliable environmental cue (but which can be masked by other variables), which enable them to anticipate and prepare for predicted changes in the timing of the species they interact with, on top of responding to them directly. Here, we review examples where the internal timing system is used to predict interspecific interactions, and how these interactions affect the internal timing system and activity patterns. We then ask how plastic these mechanisms are, how this plasticity differs between and within species and how this variability in plasticity affects interspecific interactions in a changing world, in which light, the major synchronizer of the biological clock, is no longer a reliable cue owing to the rapidly changing climate, the use of artificial light and urbanization.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'. © 2017 The Author(s).

Compensating for intersegmental dynamics across the shoulder, elbow, and wrist joints during feedforward and feedback control.

PubMed

Maeda, Rodrigo S; Cluff, Tyler; Gribble, Paul L; Pruszynski, J Andrew

2017-10-01

Moving the arm is complicated by mechanical interactions that arise between limb segments. Such intersegmental dynamics cause torques applied at one joint to produce movement at multiple joints, and in turn, the only way to create single joint movement is by applying torques at multiple joints. We investigated whether the nervous system accounts for intersegmental limb dynamics across the shoulder, elbow, and wrist joints during self-initiated planar reaching and when countering external mechanical perturbations. Our first experiment tested whether the timing and amplitude of shoulder muscle activity account for interaction torques produced during single-joint elbow movements from different elbow initial orientations and over a range of movement speeds. We found that shoulder muscle activity reliably preceded movement onset and elbow agonist activity, and was scaled to compensate for the magnitude of interaction torques arising because of forearm rotation. Our second experiment tested whether elbow muscles compensate for interaction torques introduced by single-joint wrist movements. We found that elbow muscle activity preceded movement onset and wrist agonist muscle activity, and thus the nervous system predicted interaction torques arising because of hand rotation. Our third and fourth experiments tested whether shoulder muscles compensate for interaction torques introduced by different hand orientations during self-initiated elbow movements and to counter mechanical perturbations that caused pure elbow motion. We found that the nervous system predicted the amplitude and direction of interaction torques, appropriately scaling the amplitude of shoulder muscle activity during self-initiated elbow movements and rapid feedback control. Taken together, our results demonstrate that the nervous system robustly accounts for intersegmental dynamics and that the process is similar across the proximal to distal musculature of the arm as well as between feedforward (i.e., self-initiated) and feedback (i.e., reflexive) control. NEW & NOTEWORTHY Intersegmental dynamics complicate the mapping between applied joint torques and the resulting joint motions. We provide evidence that the nervous system robustly predicts these intersegmental limb dynamics across the shoulder, elbow, and wrist joints during reaching and when countering external perturbations. Copyright © 2017 the American Physiological Society.

Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways.

PubMed

Sancho, Rosa M; Law, Bernard M H; Harvey, Kirsten

2009-10-15

Mutations in PARK8, encoding LRRK2, are the most common known cause of Parkinson's disease. The LRRK2 Roc-COR tandem domain exhibits GTPase activity controlling LRRK2 kinase activity via an intramolecular process. We report the interaction of LRRK2 with the dishevelled family of phosphoproteins (DVL1-3), key regulators of Wnt (Wingless/Int) signalling pathways important for axon guidance, synapse formation and neuronal maintenance. Interestingly, DVLs can interact with and mediate the activation of small GTPases with structural similarity to the LRRK2 Roc domain. The LRRK2 Roc-COR domain and the DVL1 DEP domain were necessary and sufficient for LRRK2-DVL1 interaction. Co-expression of DVL1 increased LRRK2 steady-state protein levels, an effect that was dependent on the DEP domain. Strikingly, LRRK2-DVL1-3 interactions were disrupted by the familial PARK8 mutation Y1699C, whereas pathogenic mutations at residues R1441 and R1728 strengthened LRRK2-DVL1 interactions. Co-expression of DVL1 with LRRK2 in mammalian cells resulted in the redistribution of LRRK2 to typical cytoplasmic DVL1 aggregates in HEK293 and SH-SY5Y cells and co-localization in neurites and growth cones of differentiated dopaminergic SH-SY5Y cells. This is the first report of the modulation of a key LRRK2-accessory protein interaction by PARK8 Roc-COR domain mutations segregating with Parkinson's disease. Since the DVL1 DEP domain is known to be involved in the regulation of small GTPases, we propose that: (i) DVLs may influence LRRK2 GTPase activity, and (ii) Roc-COR domain mutations modulating LRRK2-DVL interactions indirectly influence kinase activity. Our findings also link LRRK2 to Wnt signalling pathways, suggesting novel pathogenic mechanisms and new targets for genetic analysis in Parkinson's disease.

Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways

PubMed Central

Sancho, Rosa M.; Law, Bernard M.H.; Harvey, Kirsten

2009-01-01

Mutations in PARK8, encoding LRRK2, are the most common known cause of Parkinson's disease. The LRRK2 Roc-COR tandem domain exhibits GTPase activity controlling LRRK2 kinase activity via an intramolecular process. We report the interaction of LRRK2 with the dishevelled family of phosphoproteins (DVL1-3), key regulators of Wnt (Wingless/Int) signalling pathways important for axon guidance, synapse formation and neuronal maintenance. Interestingly, DVLs can interact with and mediate the activation of small GTPases with structural similarity to the LRRK2 Roc domain. The LRRK2 Roc-COR domain and the DVL1 DEP domain were necessary and sufficient for LRRK2–DVL1 interaction. Co-expression of DVL1 increased LRRK2 steady-state protein levels, an effect that was dependent on the DEP domain. Strikingly, LRRK2–DVL1-3 interactions were disrupted by the familial PARK8 mutation Y1699C, whereas pathogenic mutations at residues R1441 and R1728 strengthened LRRK2–DVL1 interactions. Co-expression of DVL1 with LRRK2 in mammalian cells resulted in the redistribution of LRRK2 to typical cytoplasmic DVL1 aggregates in HEK293 and SH-SY5Y cells and co-localization in neurites and growth cones of differentiated dopaminergic SH-SY5Y cells. This is the first report of the modulation of a key LRRK2-accessory protein interaction by PARK8 Roc-COR domain mutations segregating with Parkinson's disease. Since the DVL1 DEP domain is known to be involved in the regulation of small GTPases, we propose that: (i) DVLs may influence LRRK2 GTPase activity, and (ii) Roc-COR domain mutations modulating LRRK2–DVL interactions indirectly influence kinase activity. Our findings also link LRRK2 to Wnt signalling pathways, suggesting novel pathogenic mechanisms and new targets for genetic analysis in Parkinson's disease. PMID:19625296

Non-canonical dynamic mechanisms of interaction between the p66Shc protein and Met receptor

PubMed Central

Landry, Mélissa; Pomerleau, Véronique; Saucier, Caroline

2016-01-01

Met receptor tyrosine kinase (RTK) is known to bind to the three distinct protein isoforms encoded by the ShcA (Shc) gene. Structure–function studies have unveiled critical roles for p52Shc-dependent signalling pathways in Met-regulated biological functions. The molecular basis of the interaction between the Met and p52Shc proteins is well-defined, but not for the longest protein isoform, p66Shc. In the present study, co-immunoprecipitation assays were performed in human embryonic kidney 293 (HEK293) cells, transiently co-transfected with Met and p66Shc mutants, in order to define the molecular determinants involved in mediating Met–p66Shc interaction. Our results show that p66Shc interacts constitutively with the receptor Met, and the Grb2 (growth factor receptor-bound protein-2) and Gab1 (Grb2-associated binder-1) adaptor proteins. Although its phosphotyrosine-binding domain (PTB) and Src homology 2 (SH2) domains co-ordinate p66Shc binding to non-activated Met receptor, these phosphotyrosine-binding modules, and its collagen homology domain 2 (CH2) region, exert negative constraints. In contrast, p66Shc interaction with the activated Met depends mainly on the integrity of its PTB domain, and to a lesser extent of its SH2 domain. Even though not required for the recruitment of p66Shc, tyrosine phosphorylation of p66Shc by activated Met enhances these interactions by mechanisms not reliant on the integrity of the Met multisubstrate-binding site. In turn, this increases phosphotyrosine-dependent p66Shc–Grb2–Gab1 complex formation away from the receptor, while blocking Grb2 and Gab1 recruitment to activated Met. In conclusion, we identify, for the first time, a novel non-canonical dynamic mode of interaction between Met and the p66 protein isoform of Shc and its effects on rewiring binding effector complexes according to the activation state of the receptor. PMID:27048591

Environmental influences on physical activity in rural adults: the relative contributions of home, church and work settings.

PubMed

Kegler, Michelle C; Swan, Deanne W; Alcantara, Iris; Wrensford, Louise; Glanz, Karen

2012-09-01

This study examines the relative contribution of social (eg, social support) and physical (eg, programs and facilities) aspects of worksite, church, and home settings to physical activity levels among adults in rural communities. Data are from a cross-sectional survey of 268 African American and Caucasian adults, ages 40-70, living in southwest Georgia. Separate regression models were developed for walking, moderate, vigorous, and total physical activity as measured in METs-minutes-per-week. Social support for physical activity was modest in all 3 settings (mean scores 1.5-1.9 on a 4-point scale). Participants reported limited (<1) programs and facilities for physical activity at their worksites and churches. An interaction of physical and social aspects of the home setting was observed for vigorous and moderate physical activity and total METs. There were also interactions between gender and social support at church for vigorous activity among women, and between race and the physical environment at church for moderate physical activity. A cross-over interaction was found between home and church settings for vigorous physical activity. Social support at church was associated with walking and total METs. Homes and churches may be important behavioral settings for physical activity among adults in rural communities.

Pathogen-regulated genes in wheat isogenic lines differing in resistance to brown rust Puccinia triticina.

PubMed

Dmochowska-Boguta, Marta; Alaba, Sylwia; Yanushevska, Yuliya; Piechota, Urszula; Lasota, Elzbieta; Nadolska-Orczyk, Anna; Karlowski, Wojciech M; Orczyk, Waclaw

2015-10-05

Inoculation of wheat plants with Puccinia triticina (Pt) spores activates a wide range of host responses. Compatible Pt interaction with susceptible Thatcher plants supports all stages of the pathogen life cycle. Incompatible interaction with TcLr9 activates defense responses including oxidative burst and micronecrotic reactions associated with the pathogen's infection structures and leads to complete termination of pathogen development. These two contrasting host-pathogen interactions were a foundation for transcriptome analysis of incompatible wheat-Pt interaction. A suppression subtractive hybridization (SSH) library was constructed using cDNA from pathogen-inoculated susceptible Thatcher and resistant TcLr9 isogenic lines. cDNA represented steps of wheat-brown rust interactions: spore germination, haustorium mother cell (HMC) formation and micronecrotic reactions. All ESTs were clustered and validated by similarity search to wheat genome using BLASTn and sim4db tools. qRT-PCR was used to determine transcript levels of selected ESTs after inoculation in both lines. Out of 793 isolated cDNA clones, 183 were classified into 152 contigs. 89 cDNA clones and encoded proteins were functionally annotated and assigned to 5 Gene Ontology categories: catalytic activity 48 clones (54 %), binding 32 clones (36 %), transporter activity 6 clones (7 %), structural molecule activity 2 clones (2 %) and molecular transducer activity 1 clone (1 %). Detailed expression profiles of 8 selected clones were analyzed using the same plant-pathogen system. The strongest induction after pathogen infection and the biggest differences between resistant and susceptible interactions were detected for clones encoding wall-associated kinase (GenBank accession number JG969003), receptor with leucine-rich repeat domain (JG968955), putative serine/threonine protein kinase (JG968944), calcium-mediated signaling protein (JG968925) and 14-3-3 protein (JG968969). The SSH library represents transcripts regulated by pathogen infection during compatible and incompatible interactions of wheat with P. triticina. Annotation of selected clones confirms their putative roles in successive steps of plant-pathogen interactions. The transcripts can be categorized as defense-related due to their involvement in either basal defense or resistance through an R-gene mediated reaction. The possible involvement of selected clones in pathogen recognition and pathogen-induced signaling as well as resistance mechanisms such as cell wall enforcement, oxidative burst and micronecrotic reactions is discussed.

Exact solutions to a spatially extended model of kinase-receptor interaction.

PubMed

Szopa, Piotr; Lipniacki, Tomasz; Kazmierczak, Bogdan

2011-10-01

B and Mast cells are activated by the aggregation of the immune receptors. Motivated by this phenomena we consider a simple spatially extended model of mutual interaction of kinases and membrane receptors. It is assumed that kinase activates membrane receptors and in turn the kinase molecules bound to the active receptors are activated by transphosphorylation. Such a type of interaction implies positive feedback and may lead to bistability. In this study we apply the Steklov eigenproblem theory to analyze the linearized model and find exact solutions in the case of non-uniformly distributed membrane receptors. This approach allows us to determine the critical value of receptor dephosphorylation rate at which cell activation (by arbitrary small perturbation of the inactive state) is possible. We found that cell sensitivity grows with decreasing kinase diffusion and increasing anisotropy of the receptor distribution. Moreover, these two effects are cooperating. We showed that the cell activity can be abruptly triggered by the formation of the receptor aggregate. Since the considered activation mechanism is not based on receptor crosslinking by polyvalent antigens, the proposed model can also explain B cell activation due to receptor aggregation following binding of monovalent antigens presented on the antigen presenting cell.

Human-robot interaction: kinematics and muscle activity inside a powered compliant knee exoskeleton.

PubMed

Knaepen, Kristel; Beyl, Pieter; Duerinck, Saartje; Hagman, Friso; Lefeber, Dirk; Meeusen, Romain

2014-11-01

Until today it is not entirely clear how humans interact with automated gait rehabilitation devices and how we can, based on that interaction, maximize the effectiveness of these exoskeletons. The goal of this study was to gain knowledge on the human-robot interaction, in terms of kinematics and muscle activity, between a healthy human motor system and a powered knee exoskeleton (i.e., KNEXO). Therefore, temporal and spatial gait parameters, human joint kinematics, exoskeleton kinetics and muscle activity during four different walking trials in 10 healthy male subjects were studied. Healthy subjects can walk with KNEXO in patient-in-charge mode with some slight constraints in kinematics and muscle activity primarily due to inertia of the device. Yet, during robot-in-charge walking the muscular constraints are reversed by adding positive power to the leg swing, compensating in part this inertia. Next to that, KNEXO accurately records and replays the right knee kinematics meaning that subject-specific trajectories can be implemented as a target trajectory during assisted walking. No significant differences in the human response to the interaction with KNEXO in low and high compliant assistance could be pointed out. This is in contradiction with our hypothesis that muscle activity would decrease with increasing assistance. It seems that the differences between the parameter settings of low and high compliant control might not be sufficient to observe clear effects in healthy subjects. Moreover, we should take into account that KNEXO is a unilateral, 1 degree-of-freedom device.

Volatiles in Inter-Specific Bacterial Interactions

PubMed Central

Tyc, Olaf; Zweers, Hans; de Boer, Wietse; Garbeva, Paolina

2015-01-01

The importance of volatile organic compounds for functioning of microbes is receiving increased research attention. However, to date very little is known on how inter-specific bacterial interactions effect volatiles production as most studies have been focused on volatiles produced by monocultures of well-described bacterial genera. In this study we aimed to understand how inter-specific bacterial interactions affect the composition, production and activity of volatiles. Four phylogenetically different bacterial species namely: Chryseobacterium, Dyella, Janthinobacterium, and Tsukamurella were selected. Earlier results had shown that pairwise combinations of these bacteria induced antimicrobial activity in agar media whereas this was not the case for monocultures. In the current study, we examined if these observations were also reflected by the production of antimicrobial volatiles. Thus, the identity and antimicrobial activity of volatiles produced by the bacteria were determined in monoculture as well in pairwise combinations. Antimicrobial activity of the volatiles was assessed against fungal, oomycetal, and bacterial model organisms. Our results revealed that inter-specific bacterial interactions affected volatiles blend composition. Fungi and oomycetes showed high sensitivity to bacterial volatiles whereas the effect of volatiles on bacteria varied between no effects, growth inhibition to growth promotion depending on the volatile blend composition. In total 35 volatile compounds were detected most of which were sulfur-containing compounds. Two commonly produced sulfur-containing volatile compounds (dimethyl disulfide and dimethyl trisulfide) were tested for their effect on three target bacteria. Here, we display the importance of inter-specific interactions on bacterial volatiles production and their antimicrobial activities. PMID:26733959

The Secretory Response of Rat Peritoneal Mast Cells on Exposure to Mineral Fibers.

PubMed

Borelli, Violetta; Trevisan, Elisa; Francesca, Vita; Zabucchi, Giuliano

2018-01-10

Exposure to mineral fibers is of substantial relevance to human health. A key event in exposure is the interaction with inflammatory cells and the subsequent generation of pro-inflammatory factors. Mast cells (MCs) have been shown to interact with titanium oxide (TiO₂) and asbestos fibers. In this study, we compared the response of rat peritoneal MCs challenged with the asbestos crocidolite and nanowires of TiO₂ to that induced by wollastonite employed as a control fiber. Rat peritoneal MCs (RPMCs), isolated from peritoneal lavage, were incubated in the presence of mineral fibers. The quantities of secreted enzymes were evaluated together with the activity of fiber-associated enzymes. The ultrastructural morphology of fiber-interacting RPMCs was analyzed with electron microscopy. Asbestos and TiO₂ stimulate MC secretion. Secreted enzymes bind to fibers and exhibit higher activity. TiO₂ and wollastonite bind and improve enzyme activity, but to a lesser degree than crocidolite. (1) Mineral fibers are able to stimulate the mast cell secretory process by both active (during membrane interaction) and/or passive (during membrane penetration) interaction; (2) fibers can be found to be associated with secreted enzymes-this process appears to create long-lasting pro-inflammatory environments and may represent the active contribution of MCs in maintaining the inflammatory process; (3) MCs and their enzymes should be considered as a therapeutic target in the pathogenesis of asbestos-induced lung inflammation; and (4) MCs can contribute to the inflammatory effect associated with selected engineered nanomaterials, such as TiO₂ nanoparticles.

SIRT1 interacts with and protects glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from nuclear translocation: Implications for cell survival after irradiation

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

Joo, Hyun-Yoo; Laboratory of Biochemistry, School of Life Sciences and Biotechnology, Korea University, Seoul 136-713; Woo, Seon Rang

2012-08-10

Highlights: Black-Right-Pointing-Pointer SIRT1 serves to retain GAPDH in the cytosol, preventing GAPDH nuclear translocation. Black-Right-Pointing-Pointer When SIRT1 is depleted, GAPDH translocation occurs even in the absence of stress. Black-Right-Pointing-Pointer Upon irradiation, SIRT1 interacts with GAPDH. Black-Right-Pointing-Pointer SIRT1 prevents irradiation-induced nuclear translocation of GAPDH. Black-Right-Pointing-Pointer SIRT1 presence rather than activity is essential for inhibiting GAPDH translocation. -- Abstract: Upon apoptotic stimulation, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a cytosolic enzyme normally active in glycolysis, translocates into the nucleus and activates an apoptotic cascade therein. In the present work, we show that SIRT1 prevents nuclear translocation of GAPDH via interaction with GAPDH. SIRT1 depletion triggeredmore » nuclear translocation of cytosolic GAPDH even in the absence of apoptotic stress. Such translocation was not, however, observed when SIRT1 enzymatic activity was inhibited, indicating that SIRT1 protein per se, rather than the deacetylase activity of the protein, is required to inhibit GAPDH translocation. Upon irradiation, SIRT1 prevented irradiation-induced nuclear translocation of GAPDH, accompanied by interaction of SIRT1 and GAPDH. Thus, SIRT1 functions to retain GAPDH in the cytosol, protecting the enzyme from nuclear translocation via interaction with these two proteins. This serves as a mechanism whereby SIRT1 regulates cell survival upon induction of apoptotic stress by means that include irradiation.« less

Protein corona changes mediated by surface modification of amorphous silica nanoparticles suppress acute toxicity and activation of intrinsic coagulation cascade in mice

NASA Astrophysics Data System (ADS)

Yoshida, Tokuyuki; Yoshioka, Yasuo; Morishita, Yuki; Aoyama, Michihiko; Tochigi, Saeko; Hirai, Toshiro; Tanaka, Kota; Nagano, Kazuya; Kamada, Haruhiko; Tsunoda, Shin-ichi; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Higashisaka, Kazuma; Tsutsumi, Yasuo

2015-06-01

Recently, nanomaterial-mediated biological effects have been shown to be governed by the interaction of nanomaterials with some kinds of proteins in biological fluids, and the physical characteristics of the nanomaterials determine the extent and type of their interactions with proteins. Here, we examined the relationships between the surface properties of amorphous silica nanoparticles with diameters of 70 nm (nSP70), their interactions with some proteins in biological fluids, and their toxicity in mice after intravenous administration. The surface modification of nSP70 with amino groups (nSP70-N) prevented acute lethality and abnormal activation of the coagulation cascade found in the nSP70-treated group of mice. Since our previous study showed that coagulation factor XII played a role in the nSP70-mediated abnormal activation of the coagulation cascade, we examined the interaction of nSP70 and nSP70-N with coagulation factor XII. Coagulation factor XII bonded to the surface of nSP70 to a greater extent than that observed for nSP70-N, and consequently more activation of coagulation factor XII was observed for nSP70 than for nSP70-N. Collectively, our results suggest that controlling the interaction of nSP70 with blood coagulation factor XII by modifying the surface properties would help to inhibit the nSP70-mediated abnormal activation of the blood coagulation cascade.

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.

Dynamics of two interacting active Janus particles.

PubMed

Bayati, Parvin; Najafi, Ali

2016-04-07

Starting from a microscopic model for a spherically symmetric active Janus particle, we study the interactions between two such active motors. The ambient fluid mediates a long range hydrodynamic interaction between two motors. This interaction has both direct and indirect hydrodynamic contributions. The direct contribution is due to the propagation of fluid flow that originated from a moving motor and affects the motion of the other motor. The indirect contribution emerges from the re-distribution of the ionic concentrations in the presence of both motors. Electric force exerted on the fluid from this ionic solution enhances the flow pattern and subsequently changes the motion of both motors. By formulating a perturbation method for very far separated motors, we derive analytic results for the translation and rotational dynamics of the motors. We show that the overall interaction at the leading order modifies the translational and rotational speeds of motors which scale as O[1/D](3) and O[1/D](4) with their separation, respectively. Our findings open up the way for studying the collective dynamics of synthetic micro-motors.

An experimental test of the fluctuation relation in an active camphor boat system

NASA Astrophysics Data System (ADS)

Paroor, H. M.; Nambiar, N.; Bandi, M. M.

The Gallavotti-Cohen fluctuation relation (FR) posits a specific symmetry between positive and negative fluctuations in entropy production, or a related quantity (e.g power) for systems in non-equilibrium stationary state. Successful tests in a variety of systems suggest the FR may be more generally applicable than the conditions under which it was originally derived. Systems where the FR fails are therefore valuable for the insight they provide into the FR's general success. It has recently been suggested that ``active matter'' should not satisfy the fluctuation-dissipation theorem or FR. We experimentally test this possibility in a system of active camphor boats, self-propelled by surface tension gradients at air-water interfaces. The boats interact via short-range capillary attraction which competes with long-range surface tension mediated repulsion. Tuning interaction strength with number density, we test the FR through the statistics of power as one goes from a free non-interacting camphor boat, through a few weakly interacting boats to several, strongly interacting boats. We present preliminary results of our experiments and data analysis.

Interaction of AIP with protein kinase A (cAMP-dependent protein kinase).

PubMed

Schernthaner-Reiter, Marie Helene; Trivellin, Giampaolo; Stratakis, Constantine A

2018-05-02

Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene cause mostly somatotropinomas and/or prolactinomas in a subset of familial isolated pituitary adenomas (FIPA). AIP has been shown to interact with phosphodiesterases (PDEs) and G proteins, suggesting a link to the cyclic AMP (cAMP)-dependent protein kinase (PKA) pathway. Upregulation of PKA is seen in sporadic somatotropinomas that carry GNAS1 mutations, and those in Carney complex that are due to PRKAR1A mutations. To elucidate the mechanism of AIP-dependent pituitary tumorigenesis, we studied potential functional and physical interactions of AIP with PKA's main subunits PRKAR1A (R1α) and PRKACA (Cα). We found that AIP physically interacts with both R1α and Cα; this interaction is enhanced when all three components are present, but maintained during Cα-R1α dissociation by PKA pathway activation, indicating that AIP binds Cα/R1α both in complex and separately. The interaction between AIP and R1α/Cα is reduced when the frequent AIP pathogenic mutation p.R304* is present. AIP protein levels are regulated both by translation and the ubiquitin/proteasome pathway and Cα stabilizes both AIP and R1α protein levels. AIP reduction by siRNA leads to an increase of PKA pathway activity, which is disproportionately enhanced during PDE4-inhibition. We show that AIP interacts with the PKA pathway on multiple levels, including a physical interaction with both the main regulatory (R1α) and catalytic (Cα) PKA subunits and a functional interaction with PDE4-dependent PKA activation. These findings provide novel insights on the mechanisms of AIP-dependent pituitary tumorigenesis.

Marburg Virus VP24 Protein Relieves Suppression of the NF-κB Pathway Through Interaction With Kelch-like ECH-Associated Protein 1.

PubMed

Edwards, Megan R; Basler, Christopher F

2015-10-01

Marburg virus (MARV) is an emerging zoonotic pathogen that causes hemorrhagic fever. MARV VP24 (mVP24) protein interacts with the host cell protein Kelch-like-ECH-associated protein 1 (Keap1). Keap1 interacts with and promotes the degradation of IκB kinase β (IKKβ), a component of the IκB kinase (IKK) complex that regulates nuclear factor-κB (NF-κB) activity. We studied whether mVP24 could relieve Keap1 repression of the NF-κB pathway. Coimmunoprecipitation assays were used to examine the interaction between Keap1 and IKKβ in the presence of wild-type mVP24 and mutants of mVP24 defective for binding to Keap1. Western blotting was used to determine levels of IKKβ expression in the presence of Keap1 and mVP24. NF-κB promoter-luciferase assays were used to determine the effect of mVP24 on Keap1-induced repression of activity. Expression of wild-type mVP24 disrupted the interaction of IKKβ and Keap1, whereas weakly interacting and noninteracting mVP24 mutants did not disrupt the interaction between Keap1 and IKKβ. The interaction of mVP24 with Keap1 enhanced IKKβ levels in the presence of Keap1. The interaction of mVP24 with Keap1 also relieved Keap1 repression of NF-κB reporter activity. mVP24 can relieve Keap1 repression of the NF-κB pathway through its interaction with Keap1. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Arginine 26 and aspartic acid 69 of the regulatory subunit are key residues of subunits interaction of acetohydroxyacid synthase isozyme III from E. coli.

PubMed

Zhao, Yuefang; Wen, Xin; Niu, Congwei; Xi, Zhen

2012-11-05

Acetohydroxyacid synthase (AHAS), which catalyzes the first step in the biosynthesis of branched-chain amino acids, is composed of catalytic and regulatory subunits. The enzyme exhibits full activity only when the regulatory subunit (RSU) binds to the catalytic subunit (CSU). However, the crystal structure of the holoenzyme has not been reported yet, and the molecular interaction between the CSU and RSU is also unknown. Herein, we introduced a global-surface, site-directed labeling scanning method to determine the potential interaction region of the RSU. This approach relies on the insertion of a bulky fluorescent probe at the designated site on the surface of the RSU to cause a dramatic change in holoenzyme activity by perturbing subunit interaction. Then, the key amino acid residues in the potential interaction regions were identified by site-directed mutagenesis. Compared to the wild-type, the single-point mutants R26A and D69A showed 54 and 64 % activity, respectively, whereas the double mutant (R26A+D69A) gave 14 %, thus suggesting that residues Arg26 and Asp69 are the key residues of subunit interaction with cooperative action. Additionally, the results of GST pull-down assays and pH-dependence experiments suggested that polar interaction is the main force for subunits interaction. A plausible protein-protein interaction model of the holoenzyme of Escherichia coli AHAS III is proposed, based on the mutagenesis and protein docking studies. The protocol established here should be useful for the identification of the molecular interactions between proteins. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Protein Kinase A Modulates Transforming Growth Factor-β Signaling through a Direct Interaction with Smad4 Protein*

PubMed Central

Yang, Huibin; Li, Gangyong; Wu, Jing-Jiang; Wang, Lidong; Uhler, Michael; Simeone, Diane M.

2013-01-01

Transforming growth factor β (TGFβ) signaling normally functions to regulate embryonic development and cellular homeostasis. It is increasingly recognized that TGFβ signaling is regulated by cross-talk with other signaling pathways. We previously reported that TGFβ activates protein kinase A (PKA) independent of cAMP through an interaction of an activated Smad3-Smad4 complex and the regulatory subunit of the PKA holoenzyme (PKA-R). Here we define the interaction domains of Smad4 and PKA-R and the functional consequences of this interaction. Using a series of Smad4 and PKA-R truncation mutants, we identified amino acids 290–300 of the Smad4 linker region as critical for the specific interaction of Smad4 and PKA-R. Co-immunoprecipitation assays showed that the B cAMP binding domain of PKA-R was sufficient for interaction with Smad4. Targeting of B domain regions conserved among all PKA-R isoforms and exposed on the molecular surface demonstrated that amino acids 281–285 and 320–329 were required for complex formation with Smad4. Interactions of these specific regions of Smad4 and PKA-R were necessary for TGFβ-mediated increases in PKA activity, CREB (cAMP-response element-binding protein) phosphorylation, induction of p21, and growth inhibition. Moreover, this Smad4-PKA interaction was required for TGFβ-induced epithelial mesenchymal transition, invasion of pancreatic tumor cells, and regulation of tumor growth in vivo. PMID:23362281

WW domain-mediated interaction with Wbp2 is important for the oncogenic property of TAZ

PubMed Central

Chan, S W; Lim, C J; Huang, C; Chong, Y F; Gunaratne, H J; Hogue, K A; Blackstock, W P; Harvey, K F; Hong, W

2011-01-01

The transcriptional co-activators YAP and TAZ are downstream targets inhibited by the Hippo tumor suppressor pathway. YAP and TAZ both possess WW domains, which are important protein–protein interaction modules that mediate interaction with proline-rich motifs, most commonly PPXY. The WW domains of YAP have complex regulatory roles as exemplified by recent reports showing that they can positively or negatively influence YAP activity in a cell and context-specific manner. In this study, we show that the WW domain of TAZ is important for it to transform both MCF10A and NIH3T3 cells and to activate transcription of ITGB2 but not CTGF, as introducing point mutations into the WW domain of TAZ (WWm) abolished its transforming and transcription-promoting ability. Using a proteomic approach, we discovered potential regulatory proteins that interact with TAZ WW domain and identified Wbp2. The interaction of Wbp2 with TAZ is dependent on the WW domain of TAZ and the PPXY-containing C-terminal region of Wbp2. Knockdown of endogenous Wbp2 suppresses, whereas overexpression of Wbp2 enhances, TAZ-driven transformation. Forced interaction of WWm with Wbp2 by direct C-terminal fusion of full-length Wbp2 or its TAZ-interacting C-terminal domain restored the transforming and transcription-promoting ability of TAZ. These results suggest that the WW domain-mediated interaction with Wbp2 promotes the transforming ability of TAZ. PMID:20972459

Melatonin biosynthesis enzymes recruit WRKY transcription factors to regulate melatonin accumulation and transcriptional activity on W-box in cassava.

PubMed

Wei, Yunxie; Liu, Guoyin; Chang, Yanli; Lin, Daozhe; Reiter, Russel J; He, Chaozu; Shi, Haitao

2018-03-12

Melatonin is widely involved in growth, development, and stress responses in plants. Although the melatonin synthesis enzymes have been identified in various plants, their interacting proteins remain unknown. Herein, overexpression of tryptophan decarboxylase 2 (MeTDC2)-interacting proteins, N-acetylserotonin O-methyltransferase 2 (MeASMT2) interacting proteins, and N-acetylserotonin O-methyltransferase 3 (MeASMT3) in cassava leaf protoplasts resulted in more melatonin than when other enzymes were overexpressed. Through yeast two-hybrid, 14 MeTDC2-interacting proteins, 24 MeASMT2 interacting proteins, and 9 MeASMT3-interacting proteins were identified. Notably, we highlighted MeWRKY20 and MeWRKY75 as common interacting proteins of the 3 enzymes, as evidenced by yeast two-hybrid, and in vivo bimolecular fluorescence complementation (BiFC). Moreover, co-overexpression of MeTDC2/MeASMT2/3 with MeWRKY20/75 in cassava leaf protoplasts did not only activated the transcriptional activities of MeWRKY20 and MeWRKY75 on W-box, but also induced the effects of MeTDC2, MeASMT2/3 on endogenous melatonin levels. Taken together, 3 melatonin synthesis enzymes (MeTDC2, MeASMT2/3) interact with MeWRKY20/75 to form a protein complex in cassava. This information significantly extends the knowledge of the complex modulation of plant melatonin signaling. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Interactive Whole Class Teaching in the National Literacy and Numeracy Strategies

ERIC Educational Resources Information Center

Smith, Fay; Hardman, Frank; Wall, Kate; Mroz, Maria

2004-01-01

The study set out to investigate the impact of the official endorsement of 'interactive whole class teaching' on the interaction and discourse styles of primary teachers while teaching the National Literacy and Numeracy Strategies. In both strategies, interactive whole class teaching is seen as an 'active teaching' model promoting high quality…

Social Interactions of Preschool Children as Correlates of Play Activities.

ERIC Educational Resources Information Center

Beehler, Kay A.; And Others

The purpose of this study was to summarize an examination of the social interactions of a sample of 370 preschool children and to demonstrate from the summary that social settings within the preschool environment differentially affect both the quality and quantity of social interaction. The Social Interaction Observation Procedure was used to…

In silico study of protein to protein interaction analysis of AMP-activated protein kinase and mitochondrial activity in three different farm animal species

NASA Astrophysics Data System (ADS)

Prastowo, S.; Widyas, N.

2018-03-01

AMP-activated protein kinase (AMPK) is cellular energy censor which works based on ATP and AMP concentration. This protein interacts with mitochondria in determine its activity to generate energy for cell metabolism purposes. For that, this paper aims to compare the protein to protein interaction of AMPK and mitochondrial activity genes in the metabolism of known animal farm (domesticated) that are cattle (Bos taurus), pig (Sus scrofa) and chicken (Gallus gallus). In silico study was done using STRING V.10 as prominent protein interaction database, followed with biological function comparison in KEGG PATHWAY database. Set of genes (12 in total) were used as input analysis that are PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2, PRKAG3, PPARGC1, ACC, CPT1B, NRF2 and SOD. The first 7 genes belong to gene in AMPK family, while the last 5 belong to mitochondrial activity genes. The protein interaction result shows 11, 8 and 5 metabolism pathways in Bos taurus, Sus scrofa and Gallus gallus, respectively. The top pathway in Bos taurus is AMPK signaling pathway (10 genes), Sus scrofa is Adipocytokine signaling pathway (8 genes) and Gallus gallus is FoxO signaling pathway (5 genes). Moreover, the common pathways found in those 3 species are Adipocytokine signaling pathway, Insulin signaling pathway and FoxO signaling pathway. Genes clustered in Adipocytokine and Insulin signaling pathway are PRKAA2, PPARGC1A, PRKAB1 and PRKAG2. While, in FoxO signaling pathway are PRKAA2, PRKAB1, PRKAG2. According to that, we found PRKAA2, PRKAB1 and PRKAG2 are the common genes. Based on the bioinformatics analysis, we can demonstrate that protein to protein interaction shows distinct different of metabolism in different species. However, further validation is needed to give a clear explanation.

Imaging oxytocin × dopamine interactions: an epistasis effect of CD38 and COMT gene variants influences the impact of oxytocin on amygdala activation to social stimuli

PubMed Central

Sauer, Carina; Montag, Christian; Reuter, Martin; Kirsch, Peter

2013-01-01

Although oxytocin (OT) has become a major target for the investigation of positive social processes, it can be assumed that it exerts its effects in concert with other neurotransmitters. One candidate for such an interaction is dopamine (DA). For both systems, genetic variants have been identified that influence the availability of the particular substance. A variant of the gene coding for the transmembrane protein CD38 (rs3796863), which is engaged in OT secretion, has been associated with OT plasma level. The common catechol-O-methyltransferase (COMT) val158met polymorphism is known to influence COMT activity and therefore the degradation of DA. The present study aimed to investigate OT × DA interactions in the context of an OT challenge study. Hence, we tested the influence of the above mentioned genetic variants and their interaction on the activation of different brain regions (amygdala, VTA, ventral striatum and fusiform gyrus) during the presentation of social stimuli. In a pharmacological cross-over design 55 participants were investigated under OT and placebo (PLA) by means of fMRI. Brain imaging results revealed no significant effects for VTA or ventral striatum. Regarding the fusiform gyrus, we could not find any effects apart from those already described in Sauer et al. (2012). Analyses of amygdala activation resulted in no gene main effect, no gene × substance interaction but a significant gene × gene × substance interaction. While under PLA the effect of CD38 on bilateral amygdala activation to social stimuli was modulated by the COMT genotype, no such epistasis effect was found under OT. Our results provide evidence for an OT × DA interaction during responses to social stimuli. We postulate that the effect of central OT secretion on amygdala response is modulated by the availability of DA. Therefore, for an understanding of the effect of social hormones on social behavior, interactions of OT with other transmitter systems have to be taken into account. PMID:23554586

Mirroring and beyond: coupled dynamics as a generalized framework for modelling social interactions

PubMed Central

Hasson, Uri; Frith, Chris D.

2016-01-01

When people observe one another, behavioural alignment can be detected at many levels, from the physical to the mental. Likewise, when people process the same highly complex stimulus sequences, such as films and stories, alignment is detected in the elicited brain activity. In early sensory areas, shared neural patterns are coupled to the low-level properties of the stimulus (shape, motion, volume, etc.), while in high-order brain areas, shared neural patterns are coupled to high-levels aspects of the stimulus, such as meaning. Successful social interactions require such alignments (both behavioural and neural), as communication cannot occur without shared understanding. However, we need to go beyond simple, symmetric (mirror) alignment once we start interacting. Interactions are dynamic processes, which involve continuous mutual adaptation, development of complementary behaviour and division of labour such as leader–follower roles. Here, we argue that interacting individuals are dynamically coupled rather than simply aligned. This broader framework for understanding interactions can encompass both processes by which behaviour and brain activity mirror each other (neural alignment), and situations in which behaviour and brain activity in one participant are coupled (but not mirrored) to the dynamics in the other participant. To apply these more sophisticated accounts of social interactions to the study of the underlying neural processes we need to develop new experimental paradigms and novel methods of data analysis PMID:27069044

Studies of Dynamic Protein-Protein Interactions in Bacteria Using Renilla Luciferase Complementation Are Undermined by Nonspecific Enzyme Inhibition

PubMed Central

Hatzios, Stavroula K.; Ringgaard, Simon; Davis, Brigid M.; Waldor, Matthew K.

2012-01-01

The luciferase protein fragment complementation assay is a powerful tool for studying protein-protein interactions. Two inactive fragments of luciferase are genetically fused to interacting proteins, and when these two proteins interact, the luciferase fragments can reversibly associate and reconstitute enzyme activity. Though this technology has been used extensively in live eukaryotic cells, split luciferase complementation has not yet been applied to studies of dynamic protein-protein interactions in live bacteria. As proof of concept and to develop a new tool for studies of bacterial chemotaxis, fragments of Renilla luciferase (Rluc) were fused to the chemotaxis-associated response regulator CheY3 and its phosphatase CheZ in the enteric pathogen Vibrio cholerae. Luciferase activity was dependent on the presence of both CheY3 and CheZ fusion proteins, demonstrating the specificity of the assay. Furthermore, enzyme activity was markedly reduced in V. cholerae chemotaxis mutants, suggesting that this approach can measure defects in chemotactic signaling. However, attempts to measure changes in dynamic CheY3-CheZ interactions in response to various chemoeffectors were undermined by nonspecific inhibition of the full-length luciferase. These observations reveal an unexpected limitation of split Rluc complementation that may have implications for existing data and highlight the need for great caution when evaluating small molecule effects on dynamic protein-protein interactions using the split luciferase technology. PMID:22905225

Studies of dynamic protein-protein interactions in bacteria using Renilla luciferase complementation are undermined by nonspecific enzyme inhibition.

PubMed

Hatzios, Stavroula K; Ringgaard, Simon; Davis, Brigid M; Waldor, Matthew K

2012-01-01

The luciferase protein fragment complementation assay is a powerful tool for studying protein-protein interactions. Two inactive fragments of luciferase are genetically fused to interacting proteins, and when these two proteins interact, the luciferase fragments can reversibly associate and reconstitute enzyme activity. Though this technology has been used extensively in live eukaryotic cells, split luciferase complementation has not yet been applied to studies of dynamic protein-protein interactions in live bacteria. As proof of concept and to develop a new tool for studies of bacterial chemotaxis, fragments of Renilla luciferase (Rluc) were fused to the chemotaxis-associated response regulator CheY3 and its phosphatase CheZ in the enteric pathogen Vibrio cholerae. Luciferase activity was dependent on the presence of both CheY3 and CheZ fusion proteins, demonstrating the specificity of the assay. Furthermore, enzyme activity was markedly reduced in V. cholerae chemotaxis mutants, suggesting that this approach can measure defects in chemotactic signaling. However, attempts to measure changes in dynamic CheY3-CheZ interactions in response to various chemoeffectors were undermined by nonspecific inhibition of the full-length luciferase. These observations reveal an unexpected limitation of split Rluc complementation that may have implications for existing data and highlight the need for great caution when evaluating small molecule effects on dynamic protein-protein interactions using the split luciferase technology.

Characterization of a novel transcriptionally active domain in the transforming growth factor beta-regulated Smad3 protein.

PubMed

Prokova, Vassiliki; Mavridou, Sofia; Papakosta, Paraskevi; Kardassis, Dimitris

2005-01-01

Transforming growth factor beta (TGFbeta) regulates transcriptional responses via activation of cytoplasmic effector proteins termed Smads. Following their phosphorylation by the type I TGFbeta receptor, Smads form oligomers and translocate to the nucleus where they activate the transcription of TGFbeta target genes in cooperation with nuclear cofactors and coactivators. In the present study, we have undertaken a deletion analysis of human Smad3 protein in order to characterize domains that are essential for transcriptional activation in mammalian cells. With this analysis, we showed that Smad3 contains two domains with transcriptional activation function: the MH2 domain and a second middle domain that includes the linker region and the first two beta strands of the MH2 domain. Using a protein-protein interaction assay based on biotinylation in vivo, we were able to show that a Smad3 protein bearing an internal deletion in the middle transactivation domain is characterized by normal oligomerization and receptor activation properties. However, this mutant has reduced transactivation capacity on synthetic or natural promoters and is unable to interact physically and functionally with the histone acetyltransferase p/CAF. The loss of interaction with p/CAF or other coactivators could account, at least in part, for the reduced transactivation capacity of this Smad3 mutant. Our data support an essential role of the previously uncharacterized middle region of Smad3 for nuclear functions, such as transcriptional activation and interaction with coactivators.

The arachidonic acid-binding protein S100A8/A9 promotes NADPH oxidase activation by interaction with p67phox and Rac-2.

PubMed

Kerkhoff, Claus; Nacken, Wolfgang; Benedyk, Malgorzata; Dagher, Marie Claire; Sopalla, Claudia; Doussiere, Jacques

2005-03-01

The Ca2+- and arachidonic acid-binding S100A8/A9 protein complex was recently identified by in vitro studies as a novel partner of the phagocyte NADPH oxidase. The present study demonstrated its functional relevance by the impaired oxidase activity in neutrophil-like NB4 cells, after specific blockage of S100A9 expression, and bone marrow polymorphonuclear neutrophils from S100A9-/- mice. The impaired oxidase activation could also be mimicked in a cell-free system by pretreatment of neutrophil cytosol with an S100A9-specific antibody. Further analyses gave insights into the molecular mechanisms by which S100A8/A9 promoted NADPH oxidase activation. In vitro analysis of oxidase activation as well as protein-protein interaction studies revealed that S100A8 is the privileged interaction partner for the NADPH oxidase complex since it bound to p67phox and Rac, whereas S100A9 did interact with neither p67phox nor p47phox. Moreover, S100A8/A9 transferred the cofactor arachidonic acid to NADPH oxidase as shown by the impotence of a mutant S100A8/A9 complex unable to bind arachidonic acid to enhance NADPH oxidase activity. It is concluded that S100A8/A9 plays an important role in phagocyte NADPH oxidase activation.

Interaction of Triton X-100 with acyl pocket of butyrylcholinesterase: effect on esterase activity and inhibitor sensitivity of the enzyme.

PubMed

Jaganathan, L; Boopathy, R

1998-06-01

The effect of non-ionic detergents like Triton X-100, Lubrol PX, Brij 35 and Tween 80 on the esterase activity and inhibitor sensitivity of human serum butyrylcholinesterase (BuChE) were studied. The results showed that though BuChE is not a detergent dependent enzyme, the esterase activity and inhibitor sensitivity of it can be modulated by the presence of detergents. All the detergents caused a marginal activation of the esterase activity. The presence of Lubrol PX, Brij 35 or Tween 80 did not affect the 50% molar inhibition concentration (IC50) of the inhibitors tested. But in the presence of Triton X-100 the IC50 values were increased for neostigmine, eserine and tetraisopropylpyrophosphoramide (acylation site interacting inhibitors), whereas for inhibitors like ethopropazine, imipramine and procainamide (choline binding pocket specific inhibitors) the IC50 values were unaltered. In addition, in the presence of Triton X-100 the bimolecular reaction constant for phosphorylation reaction (ki) of BuChE for the acyl pocket specific tetraisopropylpyrophosphoramide was reduced. Triton X-100 partially protected BuChE against this tetraisopropylpyrophosphoramide inactivation. These results indicate that Triton X-100 by interacting with the acyl pocket hydrophobic region is able to activate the esterase activity of BuChE. Further it reduces the capacity of the enzyme to react with inhibitors that inactivate it by interacting with the serine residue of the acylation site.

Interactions of Neuromodulators with Cells of the Immune System

DTIC Science & Technology

1991-06-20

that cyclic AMP (cAMP), minoxidil and norepinephrine inhibit ConA- mediated lymphocyte activation. These experiments test the effects of these... minoxidil or 8x0W1M norepinephrine markedly inhibited IL2 activation (95%, 50% and 60% respec- tively) and showed similar effects in a ConA-activated...and 2) suggest that the inhibi- tory effects of cAMP, minoxidil and norepinephrine occur at points distal to 1L2 interaction in the lymphocyte

Passport to Knowledge: Electronic Field Trips to Scientific Frontiers Via Interactive TV and the Internet

NASA Technical Reports Server (NTRS)

Haines-Stiles, Geoff

1995-01-01

The Passport to Knowledge project delivered its initial 3-year NASA supported activity in December 1994 and January 1995. Live from Antarctica was an integrated, multimedia activity, including four one hour-long video programs, all with live components as well as taped segments, together with an extensive online element containing interactive as well as background information, and the printed Live from Antarctica Teacher's Guide, suggesting hands-on, in-class activities.

Identification of Aspergillus fumigatus Surface Components That Mediate Interaction of Conidia and Hyphae With Human Platelets.

PubMed

Rambach, Günter; Blum, Gerhard; Latgé, Jean-Paul; Fontaine, Thierry; Heinekamp, Thorsten; Hagleitner, Magdalena; Jeckström, Hanna; Weigel, Günter; Würtinger, Philipp; Pfaller, Kristian; Krappmann, Sven; Löffler, Jürgen; Lass-Flörl, Cornelia; Speth, Cornelia

2015-10-01

Platelets were recently identified as a part of innate immunity. They are activated by contact with Aspergillus fumigatus; putative consequences include antifungal defense but also thrombosis, excessive inflammation, and thrombocytopenia. We aimed to identify those fungal surface structures that mediate interaction with platelets. Human platelets were incubated with Aspergillus conidia and hyphae, isolated wall components, or fungal surface mutants. Interaction was visualized microscopically; activation was quantified by flow cytometry of specific markers. The capacity of A. fumigatus conidia to activate platelets is at least partly due to melanin, because this effect can be mimicked with "melanin ghosts"; a mutant lacking melanin showed reduced platelet stimulating potency. In contrast, conidial hydrophobin masks relevant structures, because an A. fumigatus mutant lacking the hydrophobin protein induced stronger platelet activation than wild-type conidia. A. fumigatus hyphae also contain surface structures that interact with platelets. Wall proteins, galactomannan, chitin, and β-glucan are not the relevant hyphal components; instead, the recently identified fungal polysaccharide galactosaminogalactan potently triggered platelet activation. Conidial melanin and hydrophobin as well as hyphal galactosaminogalactan represent important pathogenicity factors that modulate platelet activity and thus might influence immune responses, inflammation, and thrombosis in infected patients. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Anticipation of peer evaluation in anxious adolescents: divergence in neural activation and maturation.

PubMed

Spielberg, Jeffrey M; Jarcho, Johanna M; Dahl, Ronald E; Pine, Daniel S; Ernst, Monique; Nelson, Eric E

2015-08-01

Adolescence is the time of peak onset for many anxiety disorders, particularly Social Anxiety Disorder. Research using simulated social interactions consistently finds differential activation in several brain regions in anxious (vs non-anxious) youth, including amygdala, striatum and medial prefrontal cortex. However, few studies examined the anticipation of peer interactions, a key component in the etiology and maintenance of anxiety disorders. Youth completed the Chatroom Task while undergoing functional magnetic resonance imaging. Patterns of neural activation were assessed in anxious and non-anxious youth as they were cued to anticipate social feedback from peers. Anxious participants evidenced greater amygdala activation and rostral anterior cingulate (rACC)↔amygdala coupling than non-anxious participants during anticipation of feedback from peers they had previously rejected; anxious participants also evidenced less nucleus accumbens activation during anticipation of feedback from selected peers. Finally, anxiety interacted with age in rACC: in anxious participants, age was positively associated with activation to anticipated feedback from rejected peers and negatively for selected peers, whereas the opposite pattern emerged for non-anxious youth. Overall, anxious youth showed greater reactivity in anticipation of feedback from rejected peers and thus may ascribe greater salience to these potential interactions and increase the likelihood of avoidance behavior. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Evidence for triclosan-induced activation of human and rodent xenobiotic nuclear receptors.

PubMed

Paul, Katie B; Thompson, Jerry T; Simmons, Steven O; Vanden Heuvel, John P; Crofton, Kevin M

2013-10-01

The bacteriostat triclosan (2,4,4'-trichloro-2'-hydroxydiphenylether) (TCS) decreases rat serum thyroxine via putative nuclear receptor (NR) interaction(s) and subsequent transcriptional up-regulation of hepatic catabolism and clearance. However, due to the evolutionary divergence of the constitutive androstane and pregnane-X receptors (CAR, PXR), TCS-mediated downstream effects may be species-dependent. To test the hypothesis that TCS activates xenobiotic NRs across species, cell-based NR reporter assays were employed to assess potential activation of rat, mouse, and human PXR, and rat, mouse, and three splice variants of human CAR. TCS activated hPXR, acted as an inverse agonist of hCAR1, and as a weak agonist of hCAR3. TCS failed to activate rPXR in full-length receptor reporter assays, and instead acted as a modest inverse agonist of rCAR. Consistent with the rat data, TCS also failed to activate mPXR and was a modest inverse agonist of mCAR. These data suggest that TCS may interact with multiple NRs, including hPXR, hCAR1, hCAR3, and rCAR in order to potentially affect hepatic catabolism. Overall these data support the conclusion that TCS may interact with NRs to regulate hepatic catabolism and downstream thyroid hormone homeostasis in both rat and human models, though perhaps by divergent mechanisms. Published by Elsevier Ltd.

Dynamic conformational switching in the chemokine ligand is essential for G-protein-coupled receptor activation

PubMed Central

Joseph, Prem Raj B.; Sawant, Kirti V.; Isley, Angela; Pedroza, Mesias; Garofalo, Roberto P.; Richardson, Ricardo M.; Rajarathnam, Krishna

2014-01-01

Chemokines mediate diverse functions from organogenesis to mobilizing leucocytes, and are unusual agonists for class-A GPCRs (G-protein-coupled receptors) because of their large size and multi-domain structure. The current model for receptor activation, which involves interactions between chemokine N-loop and receptor N-terminal residues (Site-I) and between chemokine N-terminal and receptor extracellular loop/transmembrane residues (Site-II), fails to describe differences in ligand/receptor selectivity and the activation of multiple signalling pathways. In the present study, we show in neutrophil-activating chemokine CXCL8 that the highly conserved GP (glycine-proline) motif located distal to both N-terminal and N-loop residues couples Site-I and Site-II interactions. Mutations in the GP motif caused various differences from native-like function to complete loss of activity that could not be correlated with the specific mutation, receptor affinity or subtype, or a specific signalling pathway. NMR studies indicated that the GP motif does not influence Site-I interactions, but molecular dynamics simulations suggested that this motif dictates substates of the CXCL8 conformational ensemble. We conclude that the GP motif enables diverse receptor functions by controlling cross-talk between Site-I and Site-II, and further propose that the repertoire of chemokine functions is best described by a conformational ensemble model in which a network of long-range coupled indirect interactions mediate receptor activity. PMID:24032673

Roles of germline JAK2 activation mutation JAK2 V625F in the pathology of myeloproliferative neoplasms.

PubMed

Wu, Qing-Yun; Ma, Meng-Meng; Fu, Lin; Zhu, Yuan-Yuan; Liu, Yang; Cao, Jiang; Zhou, Ping; Li, Zhen-Yu; Zeng, Ling-Yu; Li, Feng; Wang, Xiao-Yun; Xu, Kai-Lin

2018-05-18

Janus tyrosine kinase 2 (JAK2) mediates downstream signaling of cytokine receptors in all hematological lineages, constitutively active somatic JAK2 mutations play key roles in the pathology of myeloproliferative neoplasms (MPNs). Recently, germline JAK2 mutations are also associated with triple-negative MPNs. A novel germline mutation JAK2 V625F is reported to be involved in a subset of MPNs patients. However, the pathogenesis of this mutation caused MPN is still unclear. In this study, the homology models of JAK2 V625F showed that the newly formed interaction between F625 and Y613 disrupted the JAK2 JH1-JH2 domain interactions was responsible for its activation, when F625 and Y613 interaction was disrupted, its activity significantly decreased. While, when this interaction was repaired whether by forming hydrogen bond or salt bond, it would cause JAK2 activation. Biochemical studies also demonstrated that JAK2 V625F mutation led to JAK2-STAT5 pathway activation and promoted the proliferation of BaF3 cells. Thus, our results herein provide clues to understand the mechanism JAK2 V625F mutation caused MPNs and give information for the development of JAK2 mutation specific inhibitors. Copyright © 2018 Elsevier B.V. All rights reserved.

Repression by Homeoprotein Pitx1 of Virus-Induced Interferon A Promoters Is Mediated by Physical Interaction and trans Repression of IRF3 and IRF7

PubMed Central

Island, Marie-Laure; Mesplede, Thibault; Darracq, Nicole; Bandu, Marie-Thérèse; Christeff, Nicolas; Djian, Philippe; Drouin, Jacques; Navarro, Sébastien

2002-01-01

Interferon A (IFN-A) genes are differentially expressed after virus induction. The differential expression of individual IFN-A genes is modulated by the specific transcription activators IFN regulatory factor 3 (IRF3) and IRF-7 and the homeoprotein transcription repressor Pitx1. We now show that repression by Pitx1 does not appear to be due to the recruitment of histone deacetylases. On the other hand, Pitx1 inhibits the IRF3 and IRF7 transcriptional activity of the IFN-A11 and IFN-A5 promoters and interacts physically with IRF3 and IRF7. Pitx1 trans-repression activity maps to specific C-terminal domains, and the Pitx1 homeodomain is involved in physical interaction with IRF3 or IRF7. IRF3 is able to bind to the antisilencer region of the IFN-A4 promoter, which overrides the repressive activity of Pitx1. These results indicate that interaction between the Pitx1 homeodomain and IRF3 or IRF7 and the ability of the Pitx1 C-terminal repressor domains to block IFN-A11 and IFN-A5 but not IFN-A4 promoter activities may contribute to our understanding of the complex differential transcriptional activation, repression, and antirepression of the IFN-A genes. PMID:12242290

Effects of human chromosome 12 on interactions between Tat and TAR of human immunodeficiency virus type 1.

PubMed Central

Alonso, A; Cujec, T P; Peterlin, B M

1994-01-01

Rates of transcriptions of the human immunodeficiency virus are greatly increased by the viral trans activator Tat. In vitro, Tat binds to the 5' bulge of the trans-activation response (TAR) RNA stem-loop, which is present in all viral transcripts. In human cells, the central loop in TAR and its cellular RNA-binding proteins are also critical for the function of Tat. Previously, we demonstrated that in rodent cells (CHO cells), but not in those which contain the human chromosome 12 (CHO12 cells), Tat-TAR interactions are compromised. In this study, we examined the roles of the bulge and loop in TAR in Tat trans activation in these cells. Whereas low levels of trans activation depended solely on interactions between Tat and the bulge in CHO cells, high levels of trans activation depended also on interactions between Tat and the loop in CHO12 cells. Since the TAR loop binding proteins in these two cell lines were identical and different from their human counterpart, the human chromosome 12 does not encode TAR loop binding proteins. In vivo binding competition studies with TAR decoys confirmed that the binding of Tat to TAR is more efficient in CHO12 cells. Thus, the protein(s) encoded on human chromosome 12 helps to tether Tat to TAR via its loop, which results in high levels of trans activation. Images PMID:8083988

Visualizing Active Enzyme Complexes Using a Photoreactive Inhibitor for Proximity Ligation – Application on γ-Secretase

PubMed Central

Schedin-Weiss, Sophia; Inoue, Mitsuhiro; Teranishi, Yasuhiro; Yamamoto, Natsuko Goto; Karlström, Helena; Winblad, Bengt; Tjernberg, Lars O.

2013-01-01

Here, we present a highly sensitive method to study protein-protein interactions and subcellular location selectively for active multicomponent enzymes. We apply the method on γ-secretase, the enzyme complex that catalyzes the cleavage of the amyloid precursor protein (APP) to generate amyloid β-peptide (Aβ), the major causative agent in Alzheimer disease (AD). The novel assay is based on proximity ligation, which can be used to study protein interactions in situ with very high sensitivity. In traditional proximity ligation assay (PLA), primary antibody recognition is typically accompanied by oligonucleotide-conjugated secondary antibodies as detection probes. Here, we first performed PLA experiments using antibodies against the γ-secretase components presenilin 1 (PS1), containing the catalytic site residues, and nicastrin, suggested to be involved in substrate recognition. To selectively study the interactions of active γ-secretase, we replaced one of the primary antibodies with a photoreactive γ-secretase inhibitor containing a PEG linker and a biotin group (GTB), and used oligonucleotide-conjugated streptavidin as a probe. Interestingly, significantly fewer interactions were detected with the latter, novel, assay, which is a reasonable finding considering that a substantial portion of PS1 is inactive. In addition, the PLA signals were located more peripherally when GTB was used instead of a PS1 antibody, suggesting that γ-secretase matures distal from the perinuclear ER region. This novel technique thus enables highly sensitive protein interaction studies, determines the subcellular location of the interactions, and differentiates between active and inactive γ-secretase in intact cells. We suggest that similar PLA assays using enzyme inhibitors could be useful also for other enzyme interaction studies. PMID:23717518

Synaptic activity induces input-specific rearrangements in a targeted synaptic protein interaction network.

PubMed

Lautz, Jonathan D; Brown, Emily A; VanSchoiack, Alison A Williams; Smith, Stephen E P

2018-05-27

Cells utilize dynamic, network level rearrangements in highly interconnected protein interaction networks to transmit and integrate information from distinct signaling inputs. Despite the importance of protein interaction network dynamics, the organizational logic underlying information flow through these networks is not well understood. Previously, we developed the quantitative multiplex co-immunoprecipitation platform, which allows for the simultaneous and quantitative measurement of the amount of co-association between large numbers of proteins in shared complexes. Here, we adapt quantitative multiplex co-immunoprecipitation to define the activity dependent dynamics of an 18-member protein interaction network in order to better understand the underlying principles governing glutamatergic signal transduction. We first establish that immunoprecipitation detected by flow cytometry can detect activity dependent changes in two known protein-protein interactions (Homer1-mGluR5 and PSD-95-SynGAP). We next demonstrate that neuronal stimulation elicits a coordinated change in our targeted protein interaction network, characterized by the initial dissociation of Homer1 and SynGAP-containing complexes followed by increased associations among glutamate receptors and PSD-95. Finally, we show that stimulation of distinct glutamate receptor types results in different modular sets of protein interaction network rearrangements, and that cells activate both modules in order to integrate complex inputs. This analysis demonstrates that cells respond to distinct types of glutamatergic input by modulating different combinations of protein co-associations among a targeted network of proteins. Our data support a model of synaptic plasticity in which synaptic stimulation elicits dissociation of preexisting multiprotein complexes, opening binding slots in scaffold proteins and allowing for the recruitment of additional glutamatergic receptors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Inhibitor-κB kinase attenuates Hsp90-dependent endothelial nitric oxide synthase function in vascular endothelial cells

PubMed Central

Konopinski, Ryszard; Krishnan, Manickam; Roman, Linda; Bera, Alakesh; Hongying, Zheng; Habib, Samy L.; Mohan, Sumathy

2015-01-01

Endothelial nitric oxide (NO) synthase (eNOS) is the predominant isoform that generates NO in the blood vessels. Many different regulators, including heat shock protein 90 (Hsp90), govern eNOS function. Hsp90-dependent phosphorylation of eNOS is a critical event that determines eNOS activity. In our earlier study we demonstrated an inhibitor-κB kinase-β (IKKβ)-Hsp90 interaction in a high-glucose environment. In the present study we further define the putative binding domain of IKKβ on Hsp90. Interestingly, IKKβ binds to the middle domain of Hsp90, which has been shown to interact with eNOS to stimulate its activity. This new finding suggests a tighter regulation of eNOS activity than was previously assumed. Furthermore, addition of purified recombinant IKKβ to the eNOS-Hsp90 complex reduces the eNOS-Hsp90 interaction and eNOS activity, indicating a competition for Hsp90 between eNOS and IKKβ. The pathophysiological relevance of the IKKβ-Hsp90 interaction has also been demonstrated using in vitro vascular endothelial growth factor-mediated signaling and an Ins2Akita in vivo model. Our study further defines the preferential involvement of α- vs. β-isoforms of Hsp90 in the IKKβ-eNOS-Hsp90 interaction, even though both Hsp90α and Hsp90β stimulate NO production. These studies not only reinforce the significance of maintaining a homeostatic balance of eNOS and IKKβ within the cell system that regulates NO production, but they also confirm that the IKKβ-Hsp90 interaction is favored in a high-glucose environment, leading to impairment of the eNOS-Hsp90 interaction, which contributes to endothelial dysfunction and vascular complications in diabetes. PMID:25652452

Interaction of a genetic risk score with physical activity, physical inactivity, and body mass index in relation to venous thromboembolism risk.

PubMed

Kim, Jihye; Kraft, Peter; Hagan, Kaitlin A; Harrington, Laura B; Lindstroem, Sara; Kabrhel, Christopher

2018-06-01

Venous thromboembolism (VTE) is highly heritable. Physical activity, physical inactivity and body mass index (BMI) are also risk factors, but evidence of interaction between genetic and environmental risk factors is limited. Data on 2,134 VTE cases and 3,890 matched controls were obtained from the Nurses' Health Study (NHS), Nurses' Health Study II (NHS II), and Health Professionals Follow-up Study (HPFS). We calculated a weighted genetic risk score (wGRS) using 16 single nucleotide polymorphisms associated with VTE risk in published genome-wide association studies (GWAS). Data on three risk factors, physical activity (metabolic equivalent [MET] hours per week), physical inactivity (sitting hours per week) and BMI, were obtained from biennial questionnaires. VTE cases were incident since cohort inception; controls were matched to cases on age, cohort, and genotype array. Using conditional logistic regression, we assessed joint effects and interaction effects on both additive and multiplicative scales. We also ran models using continuous wGRS stratified by risk-factor categories. We observed a supra-additive interaction between wGRS and BMI. Having both high wGRS and high BMI was associated with a 3.4-fold greater risk of VTE (relative excess risk due to interaction = 0.69, p = 0.046). However, we did not find evidence for a multiplicative interaction with BMI. No interactions were observed for physical activity or inactivity. We found a synergetic effect between a genetic risk score and high BMI on the risk of VTE. Intervention efforts lowering BMI to decrease VTE risk may have particularly large beneficial effects among individuals with high genetic risk. © 2018 WILEY PERIODICALS, INC.

Does family interaction prevent adolescent pregnancy?

PubMed

Casper, L M

1990-01-01

This study uses data from the 1982 National Survey of Family Growth to ascertain whether family interaction can avert adolescent sexual activity, pregnancy, childbearing and parenthood. The results obtained from using logistic regression procedures indicate that the family may be effective in increasing adolescents' use of contraceptives and selection of abortion or adoption as alternatives to parenthood. Family interaction, however, was not associated with forestalling adolescent sexual activity or with providing for the well-being of the adolescent and her child and it is unlikely that a policy based solely on family interaction will be effective. Characteristics associated with effectiveness in preventing adolescent pregnancy included race, religion, residence, mother's education, the adolescent's age and family income.

Interaction of vitamin E and exercise training on oxidative stress and antioxidant enzyme activities in rat skeletal muscles.

PubMed

Chang, Chen-Kang; Huang, Hui-Yu; Tseng, Hung-Fu; Hsuuw, Yan-Der; Tso, Tim K

2007-01-01

It has been shown that free radicals are increased during intensive exercise. We hypothesized that vitamin E (vit E) deficiency, which will increase oxidative stress, would augment the training-induced adaptation of antioxidant enzymes. This study investigated the interaction effect of vit E and exercise training on oxidative stress markers and activities of antioxidant enzymes in red quadriceps and white gastrocnemius of rats in a 2x2 design. Thirty-two male rats were divided into trained vit E-adequate, trained vit E-deficient, untrained vit E-adequate, and untrained vit E-deficient groups. The two trained groups swam 6 h/day, 6 days/week for 8 weeks. The two vit E-deficient groups consumed vit E-free diet for 8 weeks. Vitamin E-training interaction effect was significant on thiobarbituric acid reactive substances (TBARSs), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in both muscles. The trained vit E-deficient group showed the highest TBARS and GPX activity and the lowest SOD activity in both muscles. A significant vit E effect on glutathione reductase and catalase was present in both muscles. Glutathione reductase and catalase activities were significantly lower in the two vit E-adequate groups combined than in the two vit E-deficient groups combined in both muscles. This study shows that vit E status and exercise training have interactive effect on oxidative stress and GPX and SOD activities in rat skeletal muscles. Vitamin E deprivation augmented the exercise-induced elevation in GPX activity while inhibiting exercise-induced SOD activity, possibly through elevated oxidative stress.

Effects of dopaminergic genes, prenatal adversities, and their interaction on attention-deficit/hyperactivity disorder and neural correlates of response inhibition.

PubMed

van der Meer, Dennis; Hartman, Catharina A; van Rooij, Daan; Franke, Barbara; Heslenfeld, Dirk J; Oosterlaan, Jaap; Faraone, Stephen V; Buitelaar, Jan K; Hoekstra, Pieter J

2017-03-01

Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by impaired response inhibition; both have been associated with aberrant dopamine signalling. Given that prenatal exposure to alcohol or smoking is known to affect dopamine-rich brain regions, we hypothesized that individuals carrying the ADHD risk alleles of the dopamine receptor D4 ( DRD4 ) and dopamine transporter ( DAT1 ) genes may be especially sensitive to their effects. Functional MRI data, information on prenatal adversities and genetic data were available for 239 adolescents and young adults participating in the multicentre ADHD cohort study NeuroIMAGE (average age 17.3 yr). We analyzed the effects of DRD4 and DAT1 , prenatal exposure to alcohol and smoking and their interactions on ADHD severity, response inhibition and neural activity. We found no significant gene × environment interaction effects. We did find that the DRD4 7-repeat allele was associated with less superior frontal and parietal brain activity and with greater activity in the frontal pole and occipital cortex. Prenatal exposure to smoking was also associated with lower superior frontal activity, but with greater activity in the parietal lobe. Further, those exposed to alcohol had more activity in the lateral orbitofrontal cortex, and the DAT1 risk variant was associated with lower cerebellar activity. Retrospective reports of maternal substance use and the cross-sectional study design restrict causal inference. While we found no evidence of gene × environment interactions, the risk factors under investigation influenced activity of brain regions associated with response inhibition, suggesting they may add to problems with inhibiting behaviour.

SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex.

PubMed

Chen, Xiaojuan; Yang, Xingxing; Zheng, Yang; Yang, Yudong; Xing, Yaling; Chen, Zhongbin

2014-05-01

SARS coronavirus (SARS-CoV) develops an antagonistic mechanism by which to evade the antiviral activities of interferon (IFN). Previous studies suggested that SARS-CoV papain-like protease (PLpro) inhibits activation of the IRF3 pathway, which would normally elicit a robust IFN response, but the mechanism(s) used by SARS PLpro to inhibit activation of the IRF3 pathway is not fully known. In this study, we uncovered a novel mechanism that may explain how SARS PLpro efficiently inhibits activation of the IRF3 pathway. We found that expression of the membrane-anchored PLpro domain (PLpro-TM) from SARS-CoV inhibits STING/TBK1/IKKε-mediated activation of type I IFNs and disrupts the phosphorylation and dimerization of IRF3, which are activated by STING and TBK1. Meanwhile, we showed that PLpro-TM physically interacts with TRAF3, TBK1, IKKε, STING, and IRF3, the key components that assemble the STING-TRAF3-TBK1 complex for activation of IFN expression. However, the interaction between the components in STING-TRAF3-TBK1 complex is disrupted by PLpro-TM. Furthermore, SARS PLpro-TM reduces the levels of ubiquitinated forms of RIG-I, STING, TRAF3, TBK1, and IRF3 in the STING-TRAF3-TBK1 complex. These results collectively point to a new mechanism used by SARS-CoV through which PLpro negatively regulates IRF3 activation by interaction with STING-TRAF3-TBK1 complex, yielding a SARS-CoV countermeasure against host innate immunity.

Luciferase Complementation Imaging Assay in Nicotiana benthamiana Leaves for Transiently Determining Protein-protein Interaction Dynamics.

PubMed

Sun, Kaiwen; Zheng, Yuyu; Zhu, Ziqiang

2017-11-20

Protein-protein interactions are fundamental mechanisms for relaying signal transduction in most cellular processes; therefore, identification of novel protein-protein interaction pairs and monitoring protein interaction dynamics are of particular interest for revealing how plants respond to environmental factors and/or developmental signals. A plethora of approaches have been developed to examine protein-protein interactions, either in vitro or in vivo. Among them, the recently established luciferase complementation imaging (LCI) assay is the simplest and fastest method for demonstrating in vivo protein-protein interactions. In this assay, protein A or protein B is fused with the amino-terminal or carboxyl-terminal half of luciferase, respectively. When protein A interacts with protein B, the two halves of luciferase will be reconstituted to form a functional and active luciferase enzyme. Luciferase activity can be recorded with a luminometer or CCD-camera. Compared with other approaches, the LCI assay shows protein-protein interactions both qualitatively and quantitatively. Agrobacterium infiltration in Nicotiana benthamiana leaves is a widely used system for transient protein expression. With the combination of LCI and transient expression, these approaches show that the physical interaction between COP1 and SPA1 was gradually reduced after jasmonate treatment.

Haemocytes control stem cell activity in the Drosophila intestine.

PubMed

Ayyaz, Arshad; Li, Hongjie; Jasper, Heinrich

2015-06-01

Coordination of stem cell activity with inflammatory responses is critical for regeneration and homeostasis of barrier epithelia. The temporal sequence of cell interactions during injury-induced regeneration is only beginning to be understood. Here we show that intestinal stem cells (ISCs) are regulated by macrophage-like haemocytes during the early phase of regenerative responses of the Drosophila intestinal epithelium. On tissue damage, haemocytes are recruited to the intestine and secrete the BMP homologue DPP, inducing ISC proliferation by activating the type I receptor Saxophone and the Smad homologue SMOX. Activated ISCs then switch their response to DPP by inducing expression of Thickveins, a second type I receptor that has previously been shown to re-establish ISC quiescence by activating MAD. The interaction between haemocytes and ISCs promotes infection resistance, but also contributes to the development of intestinal dysplasia in ageing flies. We propose that similar interactions influence pathologies such as inflammatory bowel disease and colorectal cancer in humans.

Hemocytes control stem cell activity in the Drosophila intestine

PubMed Central

Ayyaz, Arshad; Li, Hongjie; Jasper, Heinrich

2015-01-01

SUMMARY Coordination of stem cell activity with inflammatory responses is critical for regeneration and homeostasis of barrier epithelia. The temporal sequence of cell interactions during injury-induced regeneration is only beginning to be understood. Here we show that intestinal stem cells (ISCs) are regulated by macrophage-like hemocytes during the early phase of regenerative responses of the Drosophila intestinal epithelium. Upon tissue damage, hemocytes are recruited to the intestine and secrete the TGFβ/BMP homologue Dpp, inducing ISC proliferation by activating the Type I receptor Saxophone and the Smad homologue Smox. Activated ISCs then switch their response to Dpp by inducing expression of Thickveins, a second Type I receptor that has previously been shown to re-establish ISC quiescence by activating Mad. The interaction between hemocytes and ISCs promotes infection resistance, but also contributes to the development of intestinal dysplasia in aging flies. We propose that similar interactions influence pathologies like inflammatory bowel disease and colorectal cancer in humans. PMID:26005834

Structure-activity relationships of an antimicrobial peptide plantaricin s from two-peptide class IIb bacteriocins.

PubMed

Soliman, Wael; Wang, Liru; Bhattacharjee, Subir; Kaur, Kamaljit

2011-04-14

Class IIb bacteriocins are ribosomally synthesized antimicrobial peptides comprising two different peptides synergistically acting in equal amounts for optimal potency. In this study, we demonstrate for the first time potent (nanomolar) antimicrobial activity of a representative class IIb bacteriocin, plantaricin S (Pls), against four pathogenic gram-positive bacteria, including Listeria monocytogenes. The structure-activity relationships for Pls were studied using activity assays, circular dichroism (CD), and molecular dynamics (MD) simulations. The two Pls peptides and five Pls derived fragments were synthesized. The CD spectra of the Pls and selected fragments revealed helical conformations in aqueous 2,2,2-trifluoroethanol. The MD simulations showed that when the two Pls peptides are in antiparallel orientation, the helical regions interact and align, mediated by strong attraction between conserved GxxxG/AxxxA motifs. The results strongly correlate with the antimicrobial activity suggesting that helix-helix alignment of the two Pls peptides and interaction between the conserved motifs are crucial for interaction with the target cell membrane.

Top 10 research questions related to growth and maturation of relevance to physical activity, performance, and fitness.

PubMed

Malina, Robert M

2014-06-01

Growth, maturation, and development dominate the daily lives of children and adolescents for approximately the first 2 decades of life. Growth and maturation are biological processes, while development is largely a behavioral process. The 3 processes occur simultaneously and interact. They can be influenced by physical activity and also can influence activity, performance, and fitness. Allowing for these potential interactions, 10 questions on growth and maturation that have relevance to physical activity, performance, and fitness are presented. The questions are not mutually exclusive and address several broadly defined topical areas: exercise and growth, body weight status (body mass index, adiposity rebound, "unhealthy weight gain"), movement proficiency (hypothesized barrier, role in obesity), individual differences, tracking, maturity-associated variation in performance, and corresponding variation in physical activity. Central to the discussion of each is the need for a biocultural approach recognizing the interactions of biology and behavior as potential influences on the variables of interest.

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. Social interaction with anthropomorphic or intelligent-looking agents may distinctly shape the internal representation of our social brain, which may in turn determine how we behave for various agents that we encounter in our society. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

The in vitro antimicrobial evaluation of commercially essential oils and their combinations against acne.

PubMed

Orchard, A; van Vuuren, S F; Viljoen, A; Kamatou, Guy

2018-03-24

The study investigated the efficacy of commercial essential oil combinations against the two pathogens responsible for acne with the aim to identify synergy and favourable oils to possibly use in a blend. Antimicrobial activity was assessed using the minimum inhibitory concentration (MIC) assay against Staphylococcus epidermidis (ATCC 2223) and Propionibacterium acnes (ATCC 11827), and the fractional inhibitory concentration index (ΣFIC) was calculated. Combinations displaying synergistic interactions were further investigated at varied ratios and the results plotted on isobolograms. From the 408 combinations investigated, 167 combinations were identified as displaying noteworthy antimicrobial activity (MIC value ≤ 1.00 mg ml -1 ). Thirteen synergistic interactions were observed against S. epidermidis and three synergistic combinations were observed against P. acnes. It was found that not one of the synergistic interactions identified were based on the combinations recommended in the layman's aroma-therapeutic literature. Synergy was evident rather from leads based on antimicrobial activity from previous studies, thus emphasising the importance of scientific validation. Leptospermum scoparium J.R.Forst. and G.Forst (manuka) was the essential oil mostly involved in synergistic interactions (four) against S. epidermidis. Cananga odorata (Lam.) Hook.f. and Thomson (ylang ylang) essential oil was also frequently involved in synergy where synergistic interactions could be observed against both pathogens. The combination with the lowest MIC value against both acne pathogens was and Vetiveria zizanioides Stapf (vetiver) with Cinnamomum verum J.Presl (cinnamon bark) (MIC values 0.19-0.25 mg ml -1 ). Pogostemon patchouli Benth. (patchouli), V. zizanioides, C. verum and Santalum spp. (sandalwood) could be identified as the oils that contributed the most noteworthy antimicrobial activity towards the combinations. The different chemotypes of the essential oils used in the combinations predominantly resulted in similar antimicrobial activity. The investigated essential oil combinations resulted in at least 50% of the combinations displaying noteworthy antimicrobial activity. Most of the synergistic interactions do not necessarily correspond to the recommended aroma-therapeutic literature, which highlights a need for scientific validation of essential oil antimicrobial activity. No antagonism was observed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Components of the CCR4-NOT complex function as nuclear hormone receptor coactivators via association with the NRC-interacting Factor NIF-1.

PubMed

Garapaty, Shivani; Mahajan, Muktar A; Samuels, Herbert H

2008-03-14

CCR4-NOT is an evolutionarily conserved, multicomponent complex known to be involved in transcription as well as mRNA degradation. Various subunits (e.g. CNOT1 and CNOT7/CAF1) have been reported to be involved in influencing nuclear hormone receptor activities. Here, we show that CCR4/CNOT6 and RCD1/CNOT9, members of the CCR4-NOT complex, potentiate nuclear receptor activity. RCD1 interacts in vivo and in vitro with NIF-1 (NRC-interacting factor), a previously characterized nuclear receptor cotransducer that activates nuclear receptors via its interaction with NRC. As with NIF-1, RCD1 and CCR4 do not directly associate with nuclear receptors; however, they enhance ligand-dependent transcriptional activation by nuclear hormone receptors. CCR4 mediates its effect through the ligand binding domain of nuclear receptors and small interference RNA-mediated silencing of endogenous CCR4 results in a marked decrease in nuclear receptor activation. Furthermore, knockdown of CCR4 results in an attenuated stimulation of RARalpha target genes (e.g. Sox9 and HoxA1) as shown by quantitative PCR assays. The silencing of endogenous NIF-1 also resulted in a comparable decrease in the RAR-mediated induction of both Sox9 and HoxA1. Furthermore, CCR4 associates in vivo with NIF-1. In addition, the CCR4-enhanced transcriptional activation by nuclear receptors is dependent on NIF-1. The small interference RNA-mediated knockdown of NIF-1 blocks the ligand-dependent potentiating effect of CCR4. Our results suggest that CCR4 plays a role in the regulation of certain endogenous RARalpha target genes and that RCD1 and CCR4 might mediate their function through their interaction with NIF-1.