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…

Recognition of human activity characteristics based on state transitions modeling technique

NASA Astrophysics Data System (ADS)

Elangovan, Vinayak; Shirkhodaie, Amir

2012-06-01

Human Activity Discovery & Recognition (HADR) is a complex, diverse and challenging task but yet an active area of ongoing research in the Department of Defense. By detecting, tracking, and characterizing cohesive Human interactional activity patterns, potential threats can be identified which can significantly improve situation awareness, particularly, in Persistent Surveillance Systems (PSS). Understanding the nature of such dynamic activities, inevitably involves interpretation of a collection of spatiotemporally correlated activities with respect to a known context. In this paper, we present a State Transition model for recognizing the characteristics of human activities with a link to a prior contextbased ontology. Modeling the state transitions between successive evidential events determines the activities' temperament. The proposed state transition model poses six categories of state transitions including: Human state transitions of Object handling, Visibility, Entity-entity relation, Human Postures, Human Kinematics and Distance to Target. The proposed state transition model generates semantic annotations describing the human interactional activities via a technique called Casual Event State Inference (CESI). The proposed approach uses a low cost kinect depth camera for indoor and normal optical camera for outdoor monitoring activities. Experimental results are presented here to demonstrate the effectiveness and efficiency of the proposed technique.

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

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…

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

Structural Stereochemistry of Androstene Hormones Determines Interactions with Human Androgen, Estrogen, and Glucocorticoid Receptors

PubMed Central

Shaak, Thomas L.; Wijesinghe, Dayanjan S.; Chalfant, Charles E.; Diegelmann, Robert F.; Ward, Kevin R.; Loria, Roger M.

2013-01-01

DHEA, 17α-AED, 17β-AED, and 17β-AET exhibit strong biological activity that has been attributed to androgenic, estrogenic, or antiglucocorticoid activity in vivo and in vitro. This study compared DHEA, 17α-AED, 17β-AED, and 17β-AET for their ability to activate the human AR, ER, and GR and determine the relative androgenicity, estrogenicity, and glucocorticoid activity. The results show that, at the receptor level, these androstene hormones are weak AR and even weaker ER activators. Direct androstene hormone activation of the human AR, ERα, and ERβ may not be essential for their biological function. Similarly, these hormones indirectly activated the human GR, only in the presence of high dexamethasone concentrations. These results underscore the major difference between androstene hormone interactions with these nuclear receptors and their biological effects. PMID:24729874

Evidence for a bimodal distribution in human communication.

PubMed

Wu, Ye; Zhou, Changsong; Xiao, Jinghua; Kurths, Jürgen; Schellnhuber, Hans Joachim

2010-11-02

Interacting human activities underlie the patterns of many social, technological, and economic phenomena. Here we present clear empirical evidence from Short Message correspondence that observed human actions are the result of the interplay of three basic ingredients: Poisson initiation of tasks and decision making for task execution in individual humans as well as interaction among individuals. This interplay leads to new types of interevent time distribution, neither completely Poisson nor power-law, but a bimodal combination of them. We show that the events can be separated into independent bursts which are generated by frequent mutual interactions in short times following random initiations of communications in longer times by the individuals. We introduce a minimal model of two interacting priority queues incorporating the three basic ingredients which fits well the distributions using the parameters extracted from the empirical data. The model can also embrace a range of realistic social interacting systems such as e-mail and letter communications when taking the time scale of processing into account. Our findings provide insight into various human activities both at the individual and network level. Our analysis and modeling of bimodal activity in human communication from the viewpoint of the interplay between processes of different time scales is likely to shed light on bimodal phenomena in other complex systems, such as interevent times in earthquakes, rainfall, forest fire, and economic systems, etc.

Evidence for a bimodal distribution in human communication

PubMed Central

Wu, Ye; Zhou, Changsong; Xiao, Jinghua; Kurths, Jürgen; Schellnhuber, Hans Joachim

2010-01-01

Interacting human activities underlie the patterns of many social, technological, and economic phenomena. Here we present clear empirical evidence from Short Message correspondence that observed human actions are the result of the interplay of three basic ingredients: Poisson initiation of tasks and decision making for task execution in individual humans as well as interaction among individuals. This interplay leads to new types of interevent time distribution, neither completely Poisson nor power-law, but a bimodal combination of them. We show that the events can be separated into independent bursts which are generated by frequent mutual interactions in short times following random initiations of communications in longer times by the individuals. We introduce a minimal model of two interacting priority queues incorporating the three basic ingredients which fits well the distributions using the parameters extracted from the empirical data. The model can also embrace a range of realistic social interacting systems such as e-mail and letter communications when taking the time scale of processing into account. Our findings provide insight into various human activities both at the individual and network level. Our analysis and modeling of bimodal activity in human communication from the viewpoint of the interplay between processes of different time scales is likely to shed light on bimodal phenomena in other complex systems, such as interevent times in earthquakes, rainfall, forest fire, and economic systems, etc. PMID:20959414

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

Cooperative Activities in Young Children and Chimpanzees

ERIC Educational Resources Information Center

Warneken, Felix; Chen, Frances; Tomasello, Michael

2006-01-01

Human children 18-24 months of age and 3 young chimpanzees interacted in 4 cooperative activities with a human adult partner. The human children successfully participated in cooperative problem-solving activities and social games, whereas the chimpanzees were uninterested in the social games. As an experimental manipulation, in each task the adult…

Tools to Support Human Factors and Systems Engineering Interactions During Early Analysis

NASA Technical Reports Server (NTRS)

Thronesbery, Carroll; Malin, Jane T.; Holden, Kritina; Smith, Danielle Paige

2005-01-01

We describe an approach and existing software tool support for effective interactions between human factors engineers and systems engineers in early analysis activities during system acquisition. We examine the tasks performed during this stage, emphasizing those tasks where system engineers and human engineers interact. The Concept of Operations (ConOps) document is an important product during this phase, and particular attention is paid to its influences on subsequent acquisition activities. Understanding this influence helps ConOps authors describe a complete system concept that guides subsequent acquisition activities. We identify commonly used system engineering and human engineering tools and examine how they can support the specific tasks associated with system definition. We identify possible gaps in the support of these tasks, the largest of which appears to be creating the ConOps document itself. Finally, we outline the goals of our future empirical investigations of tools to support system concept definition.

Tools to Support Human Factors and Systems Engineering Interactions During Early Analysis

NASA Technical Reports Server (NTRS)

Thronesbery, Carroll; Malin, Jane T.; Holden, Kritina; Smith, Danielle Paige

2006-01-01

We describe an approach and existing software tool support for effective interactions between human factors engineers and systems engineers in early analysis activities during system acquisition. We examine the tasks performed during this stage, emphasizing those tasks where system engineers and human engineers interact. The Concept of Operations (ConOps) document is an important product during this phase, and particular attention is paid to its influences on subsequent acquisition activities. Understanding this influence helps ConOps authors describe a complete system concept that guides subsequent acquisition activities. We identify commonly used system engineering and human engineering tools and examine how they can support the specific tasks associated with system definition. We identify possible gaps in the support of these tasks, the largest of which appears to be creating the ConOps document itself. Finally, we outline the goals of our future empirical investigations of tools to support system concept definition.

Design, Development, Testing, and Evaluation: Human Factors Engineering

NASA Technical Reports Server (NTRS)

Adelstein, Bernard; Hobbs, Alan; OHara, John; Null, Cynthia

2006-01-01

While human-system interaction occurs in all phases of system development and operation, this chapter on Human Factors in the DDT&E for Reliable Spacecraft Systems is restricted to the elements that involve "direct contact" with spacecraft systems. Such interactions will encompass all phases of human activity during the design, fabrication, testing, operation, and maintenance phases of the spacecraft lifespan. This section will therefore consider practices that would accommodate and promote effective, safe, reliable, and robust human interaction with spacecraft systems. By restricting this chapter to what the team terms "direct contact" with the spacecraft, "remote" factors not directly involved in the development and operation of the vehicle, such as management and organizational issues, have been purposely excluded. However, the design of vehicle elements that enable and promote ground control activities such as monitoring, feedback, correction and reversal (override) of on-board human and automation process are considered as per NPR8705.2A, Section 3.3.

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.

Estimation of the binding modes with important human cytochrome P450 enzymes, drug interaction potential, pharmacokinetics, and hepatotoxicity of ginger components using molecular docking, computational, and pharmacokinetic modeling studies.

PubMed

Qiu, Jia-Xuan; Zhou, Zhi-Wei; He, Zhi-Xu; Zhang, Xueji; Zhou, Shu-Feng; Zhu, Shengrong

2015-01-01

Ginger is one of the most commonly used herbal medicines for the treatment of numerous ailments and improvement of body functions. It may be used in combination with prescribed drugs. The coadministration of ginger with therapeutic drugs raises a concern of potential deleterious drug interactions via the modulation of the expression and/or activity of drug-metabolizing enzymes and drug transporters, resulting in unfavorable therapeutic outcomes. This study aimed to determine the molecular interactions between 12 main active ginger components (6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 8-shogaol, 10-shogaol, ar-curcumene, β-bisabolene, β-sesquiphelandrene, 6-gingerdione, (-)-zingiberene, and methyl-6-isogingerol) and human cytochrome P450 (CYP) 1A2, 2C9, 2C19, 2D6, and 3A4 and to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the 12 ginger components using computational approaches and comprehensive literature search. Docking studies showed that ginger components interacted with a panel of amino acids in the active sites of CYP1A2, 2C9, 2C19, 2D6, and 3A4 mainly through hydrogen bond formation, to a lesser extent, via π-π stacking. The pharmacokinetic simulation studies showed that the [I]/[Ki ] value for CYP2C9, 2C19, and 3A4 ranged from 0.0002 to 19.6 and the R value ranged from 1.0002 to 20.6 and that ginger might exhibit a high risk of drug interaction via inhibition of the activity of human CYP2C9 and CYP3A4, but a low risk of drug interaction toward CYP2C19-mediated drug metabolism. Furthermore, it has been evaluated that the 12 ginger components possessed a favorable ADMET profiles with regard to the solubility, absorption, permeability across the blood-brain barrier, interactions with CYP2D6, hepatotoxicity, and plasma protein binding. The validation results showed that there was no remarkable effect of ginger on the metabolism of warfarin in humans, whereas concurrent use of ginger and nifedipine exhibited a synergistic effect on platelet aggregation in humans. Moreover, ginger components showed a rapid half-life and no to low toxicity in humans. Taken together, this study shows that ginger components may regulate the activity and expression of various human CYPs, probably resulting in alterations in drug clearance and response. More studies are warranted to identify and confirm potential ginger-drug interactions and explore possible interactions of ginger with human CYPs and other functionally important proteins, to reduce and avoid side effects induced by unfavorable ginger-drug interactions.

Estimation of the binding modes with important human cytochrome P450 enzymes, drug interaction potential, pharmacokinetics, and hepatotoxicity of ginger components using molecular docking, computational, and pharmacokinetic modeling studies

PubMed Central

Qiu, Jia-Xuan; Zhou, Zhi-Wei; He, Zhi-Xu; Zhang, Xueji; Zhou, Shu-Feng; Zhu, Shengrong

2015-01-01

Ginger is one of the most commonly used herbal medicines for the treatment of numerous ailments and improvement of body functions. It may be used in combination with prescribed drugs. The coadministration of ginger with therapeutic drugs raises a concern of potential deleterious drug interactions via the modulation of the expression and/or activity of drug-metabolizing enzymes and drug transporters, resulting in unfavorable therapeutic outcomes. This study aimed to determine the molecular interactions between 12 main active ginger components (6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 8-shogaol, 10-shogaol, ar-curcumene, β-bisabolene, β-sesquiphelandrene, 6-gingerdione, (−)-zingiberene, and methyl-6-isogingerol) and human cytochrome P450 (CYP) 1A2, 2C9, 2C19, 2D6, and 3A4 and to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the 12 ginger components using computational approaches and comprehensive literature search. Docking studies showed that ginger components interacted with a panel of amino acids in the active sites of CYP1A2, 2C9, 2C19, 2D6, and 3A4 mainly through hydrogen bond formation, to a lesser extent, via π–π stacking. The pharmacokinetic simulation studies showed that the [I]/[Ki] value for CYP2C9, 2C19, and 3A4 ranged from 0.0002 to 19.6 and the R value ranged from 1.0002 to 20.6 and that ginger might exhibit a high risk of drug interaction via inhibition of the activity of human CYP2C9 and CYP3A4, but a low risk of drug interaction toward CYP2C19-mediated drug metabolism. Furthermore, it has been evaluated that the 12 ginger components possessed a favorable ADMET profiles with regard to the solubility, absorption, permeability across the blood–brain barrier, interactions with CYP2D6, hepatotoxicity, and plasma protein binding. The validation results showed that there was no remarkable effect of ginger on the metabolism of warfarin in humans, whereas concurrent use of ginger and nifedipine exhibited a synergistic effect on platelet aggregation in humans. Moreover, ginger components showed a rapid half-life and no to low toxicity in humans. Taken together, this study shows that ginger components may regulate the activity and expression of various human CYPs, probably resulting in alterations in drug clearance and response. More studies are warranted to identify and confirm potential ginger–drug interactions and explore possible interactions of ginger with human CYPs and other functionally important proteins, to reduce and avoid side effects induced by unfavorable ginger–drug interactions. PMID:25733806

The Science of Human Interaction and Teaching

ERIC Educational Resources Information Center

Yano, Kazuo

2013-01-01

There is a missing link between our understanding of teaching as high-level social phenomenon and teaching as a physiological phenomenon of brain activity. We suggest that the science of human interaction is the missing link. Using over one-million days of human-behavior data, we have discovered that "collective activenes" (CA), which indicates…

Online mentalising investigated with functional MRI.

PubMed

Kircher, Tilo; Blümel, Isabelle; Marjoram, Dominic; Lataster, Tineke; Krabbendam, Lydia; Weber, Jochen; van Os, Jim; Krach, Sören

2009-05-01

For successful interpersonal communication, inferring intentions, goals or desires of others is highly advantageous. Increasingly, humans also interact with computers or robots. In this study, we sought to determine to what degree an interactive task, which involves receiving feedback from social partners that can be used to infer intent, engaged the medial prefrontal cortex, a region previously associated with Theory of Mind processes among others. Participants were scanned using fMRI as they played an adapted version of the Prisoner's Dilemma Game with alleged human and computer partners who were outside the scanner. The medial frontal cortex was activated when both human and computer partner were played, while the direct contrast revealed significantly stronger signal change during the human-human interaction. The results suggest a link between activity in the medial prefrontal cortex and the partner played in a mentalising task. This signal change was also present for to the computers partner. Implying agency or a will to non-human actors might be an innate human resource that could lead to an evolutionary advantage.

Modulation of Human Leukocyte Antigen-C by Human Cytomegalovirus Stimulates KIR2DS1 Recognition by Natural Killer Cells

PubMed Central

van der Ploeg, Kattria; Chang, Chiwen; Ivarsson, Martin A.; Moffett, Ashley; Wills, Mark R.; Trowsdale, John

2017-01-01

The interaction of inhibitory killer cell Ig-like receptors (KIRs) with human leukocyte antigen (HLA) class I molecules has been characterized in detail. By contrast, activating members of the KIR family, although closely related to inhibitory KIRs, appear to interact weakly, if at all, with HLA class I. KIR2DS1 is the best studied activating KIR and it interacts with C2 group HLA-C (C2-HLA-C) in some assays, but not as strongly as KIR2DL1. We used a mouse 2B4 cell reporter system, which carries NFAT-green fluorescent protein with KIR2DS1 and a modified DAP12 adaptor protein. KIR2DS1 reporter cells were not activated upon coculture with 721.221 cells transfected with different HLA-C molecules, or with interferon-γ stimulated primary dermal fibroblasts. However, KIR2DS1 reporter cells and KIR2DS1+ primary natural killer (NK) cells were activated by C2-HLA-C homozygous human fetal foreskin fibroblasts (HFFFs) but only after infection with specific clones of a clinical strain of human cytomegalovirus (HCMV). Active viral gene expression was required for activation of both cell types. Primary NKG2A−KIR2DS1+ NK cell subsets degranulated after coculture with HCMV-infected HFFFs. The W6/32 antibody to HLA class I blocked the KIR2DS1 reporter cell interaction with its ligand on HCMV-infected HFFFs but did not block interaction with KIR2DL1. This implies a differential recognition of HLA-C by KIR2DL1 and KIR2DS1. The data suggest that modulation of HLA-C by HCMV is required for a potent KIR2DS1-mediated NK cell activation. PMID:28424684

Integrating ecology and social science using two examples of wandering wildlife and human activity

EPA Science Inventory

Many researchers have studied impacts of human activity on wildlife or human attitudes toward wildlife, but not both simultaneously. Understanding these interactions is critical to better understand the intricacies of real world conservation issues. The goal of my presentation ...

Living with Bats: The Case of Ve Golokuati Township in the Volta Region of Ghana

PubMed Central

Ohemeng, Fidelia; Tweneboah Lawson, Elaine; Waldman, Linda

2017-01-01

Transmission of zoonotic pathogens from bats to humans through direct and indirect contact with bats raises public apprehension about living close to bats. In the township of Ve Golokuati in Ghana, several “camps” of Epomophorus gambianus roost in fruit trees that provide ecosystems services for residents. This study explored human-bat interaction in the township and the potential risks of disease transmission from bats to humans. Data were derived through questionnaire administration and participatory appraisal approach involving focus group discussions, participatory landscape mapping, and transect walk. The study found that most human activities within the township, such as petty-trading, domestic chores, and children's outdoor recreation, exposed people to bats. Though there have been no reported cases of disease spillover from bats to humans from the perspective of residents and from medical records, respondents whose activities brought them closer to bats within the township were found to be more likely to experience fevers than those who do not interact with bats frequently. The study recommends education of community members about the potential risks involved in human-bat interactions and makes suggestions for reducing the frequent interactions with and exposure to bats by humans. PMID:29081813

Of Men Not Mice: Bactericidal/Permeability-Increasing Protein Expressed in Human Macrophages Acts as a Phagocytic Receptor and Modulates Entry and Replication of Gram-Negative Bacteria

PubMed Central

Balakrishnan, Arjun; Schnare, Markus; Chakravortty, Dipshikha

2016-01-01

Macrophages as immune cells prevent the spreading of pathogens by means of active phagocytosis and killing. We report here the presence of an antimicrobial protein, bactericidal/permeability-increasing protein (BPI) in human macrophages, which actively participates in engulfment and killing of Gram-negative pathogens. Our studies revealed increased expression of BPI in human macrophages during bacterial infection and upon stimulation with various pathogen-associated molecular patterns, viz., LPS and flagellin. Furthermore, during the course of an infection, BPI interacted with Gram-negative bacteria, resulting in enhanced phagocytosis and subsequent control of the bacterial replication. However, it was observed that bacteria which can maintain an active replicating niche (Salmonella Typhimurium) avoid the interaction with BPI during later stages of infection. On the other hand, Salmonella mutants, which cannot maintain a replicating niche, as well as Shigella flexneri, which quit the endosomal vesicle, showed interaction with BPI. These results propose an active role of BPI in Gram-negative bacterial clearance by human macrophages. PMID:27822215

Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Nef Proteins Show Distinct Patterns and Mechanisms of Src Kinase Activation

PubMed Central

Greenway, Alison L.; Dutartre, Hélène; Allen, Kelly; McPhee, Dale A.; Olive, Daniel; Collette, Yves

1999-01-01

The nef gene from human and simian immunodeficiency viruses (HIV and SIV) regulates cell function and viral replication, possibly through binding of the nef product to cellular proteins, including Src family tyrosine kinases. We show here that the Nef protein encoded by SIVmac239 interacts with and also activates the human Src kinases Lck and Hck. This is in direct contrast to the inhibitory effect of HIV type 1 (HIV-1) Nef on Lck catalytic activity. Unexpectedly, however, the interaction of SIV Nef with human Lck or Hck is not mediated via its consensus proline motif, which is known to mediate HIV-1 Nef binding to Src homology 3 (SH3) domains, and various experimental analyses failed to show significant interaction of SIV Nef with the SH3 domain of either kinase. Instead, SIV Nef can bind Lck and Hck SH2 domains, and its N-terminal 50 amino acid residues are sufficient for Src kinase binding and activation. Our results provide evidence for multiple mechanisms by which Nef binds to and regulates Src kinases. PMID:10364375

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.

Crabby Interactions: Fifth Graders Explore Human Impact on the Blue Crab Population

ERIC Educational Resources Information Center

Jeffery, Tonya D.; McCollough, Cherie A.; Moore, Kim

2016-01-01

This article describes a two-day lesson in which fifth-grade students took on the role of marine biology scientists, using their critical-thinking and problem-solving skills to explore human impact on the blue crab ecosystem. The purpose of "Crabby Interactions" was to help students understand the impact of human activities on the local…

Disruption of PH–kinase domain interactions leads to oncogenic activation of AKT in human cancers

PubMed Central

Parikh, Chaitali; Janakiraman, Vasantharajan; Wu, Wen-I; Foo, Catherine K.; Kljavin, Noelyn M.; Chaudhuri, Subhra; Stawiski, Eric; Lee, Brian; Lin, Jie; Li, Hong; Lorenzo, Maria N.; Yuan, Wenlin; Guillory, Joseph; Jackson, Marlena; Rondon, Jesus; Franke, Yvonne; Bowman, Krista K.; Sagolla, Meredith; Stinson, Jeremy; Wu, Thomas D.; Wu, Jiansheng; Stokoe, David; Stern, Howard M.; Brandhuber, Barbara J.; Lin, Kui; Skelton, Nicholas J.; Seshagiri, Somasekar

2012-01-01

The protein kinase v-akt murine thymoma viral oncogene homolog (AKT), a key regulator of cell survival and proliferation, is frequently hyperactivated in human cancers. Intramolecular pleckstrin homology (PH) domain–kinase domain (KD) interactions are important in maintaining AKT in an inactive state. AKT activation proceeds after a conformational change that dislodges the PH from the KD. To understand these autoinhibitory interactions, we generated mutations at the PH–KD interface and found that most of them lead to constitutive activation of AKT. Such mutations are likely another mechanism by which activation may occur in human cancers and other diseases. In support of this likelihood, we found somatic mutations in AKT1 at the PH–KD interface that have not been previously described in human cancers. Furthermore, we show that the AKT1 somatic mutants are constitutively active, leading to oncogenic signaling. Additionally, our studies show that the AKT1 mutants are not effectively inhibited by allosteric AKT inhibitors, consistent with the requirement for an intact PH–KD interface for allosteric inhibition. These results have important implications for therapeutic intervention in patients with AKT mutations at the PH–KD interface. PMID:23134728

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 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.

Inquiry-Based Investigation on the Internet: Sound and the Human Ear

ERIC Educational Resources Information Center

Quinlan, Kevin; Sterling, Donna R.

2006-01-01

In this online exploration of sound energy and the human ear, students carry out an inquiry-based activity, which leads them to websites featuring a diagram of a human ear, an interactive demonstration of the Doppler effect, a model of longitudinal waves, and an animation of human hearing. In the activity, students formulate, justify, and evaluate…

The vestibulosympathetic reflex in humans: neural interactions between cardiovascular reflexes

NASA Technical Reports Server (NTRS)

Ray, Chester A.; Monahan, Kevin D.

2002-01-01

1. Over the past 5 years, there has been emerging evidence that the vestibular system regulates sympathetic nerve activity in humans. We have studied this issue in humans by using head-down rotation (HDR) in the prone position. 2. These studies have clearly demonstrated increases in muscle sympathetic nerve activity (MSNA) and calf vascular resistance during HDR. These responses are mediated by engagement of the otolith organs and not the semicircular canals. 3. However, differential activation of sympathetic nerve activity has been observed during HDR. Unlike MSNA, skin sympathetic nerve activity does not increase with HDR. 4. Examination of the vestibulosympathetic reflex with other cardiovascular reflexes (i.e. barorereflexes and skeletal muscle reflexes) has shown an additive interaction for MSNA. 5. The additive interaction between the baroreflexes and vestibulosympathetic reflex suggests that the vestibular system may assist in defending against orthostatic challenges in humans by elevating MSNA beyond that of the baroreflexes. 6. In addition, the further increase in MSNA via otolith stimulation during isometric handgrip, when arterial pressure is elevated markedly, indicates that the vestibulosympathetic reflex is a powerful activator of MSNA and may contribute to blood pressure and flow regulation during dynamic exercise. 7. Future studies will help evaluate the importance of the vestibulosympathetic reflex in clinical conditions associated with orthostatic hypotension.

Comparison of Interactive Computer-Based and Classroom Training on Human Rights Awareness in Persons with Intellectual Disabilities

ERIC Educational Resources Information Center

Tardif-Williams, Christine Y.; Owen, Frances; Feldman, Maurice; Tarulli, Donato; Griffiths, Dorothy; Sales, Carol; McQueen-Fuentes, Glenys; Stoner, Karen

2007-01-01

We tested the effectiveness of an interactive, video CD-ROM in teaching persons with intellectual disabilities (ID) about their human rights. Thirty-nine participants with ID were trained using both a classroom activity-based version of the training program and the interactive CD-ROM in a counterbalanced presentation. All individuals were pre- and…

Quantifying the influences of various ecological factors on land surface temperature of urban forests.

PubMed

Ren, Yin; Deng, Lu-Ying; Zuo, Shu-Di; Song, Xiao-Dong; Liao, Yi-Lan; Xu, Cheng-Dong; Chen, Qi; Hua, Li-Zhong; Li, Zheng-Wei

2016-09-01

Identifying factors that influence the land surface temperature (LST) of urban forests can help improve simulations and predictions of spatial patterns of urban cool islands. This requires a quantitative analytical method that combines spatial statistical analysis with multi-source observational data. The purpose of this study was to reveal how human activities and ecological factors jointly influence LST in clustering regions (hot or cool spots) of urban forests. Using Xiamen City, China from 1996 to 2006 as a case study, we explored the interactions between human activities and ecological factors, as well as their influences on urban forest LST. Population density was selected as a proxy for human activity. We integrated multi-source data (forest inventory, digital elevation models (DEM), population, and remote sensing imagery) to develop a database on a unified urban scale. The driving mechanism of urban forest LST was revealed through a combination of multi-source spatial data and spatial statistical analysis of clustering regions. The results showed that the main factors contributing to urban forest LST were dominant tree species and elevation. The interactions between human activity and specific ecological factors linearly or nonlinearly increased LST in urban forests. Strong interactions between elevation and dominant species were generally observed and were prevalent in either hot or cold spots areas in different years. In conclusion, quantitative studies based on spatial statistics and GeogDetector models should be conducted in urban areas to reveal interactions between human activities, ecological factors, and LST. Copyright © 2016 Elsevier Ltd. All rights reserved.

Human-Computer Interaction in Smart Environments

PubMed Central

Paravati, Gianluca; Gatteschi, Valentina

2015-01-01

Here, we provide an overview of the content of the Special Issue on “Human-computer interaction in smart environments”. The aim of this Special Issue is to highlight technologies and solutions encompassing the use of mass-market sensors in current and emerging applications for interacting with Smart Environments. Selected papers address this topic by analyzing different interaction modalities, including hand/body gestures, face recognition, gaze/eye tracking, biosignal analysis, speech and activity recognition, and related issues.

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

Human protein Staufen-2 promotes HIV-1 proliferation by positively regulating RNA export activity of viral protein Rev.

PubMed

Banerjee, Atoshi; Benjamin, Ronald; Balakrishnan, Kannan; Ghosh, Payel; Banerjee, Sharmistha

2014-02-13

The export of intron containing viral RNAs from the nucleus to the cytoplasm is an essential step in the life cycle of Human Immunodeficiency Virus-1 (HIV-1). As the eukaryotic system does not permit the transport of intron containing RNA out of the nucleus, HIV-1 makes a regulatory protein, Rev, that mediates the transportation of unspliced and partially spliced viral mRNA from the nucleus to the cytoplasm, thereby playing a decisive role in the generation of new infectious virus particles. Therefore, the host factors modulating the RNA export activity of Rev can be major determinants of virus production in an infected cell. In this study, human Staufen-2 (hStau-2) was identified as a host factor interacting with HIV-1 Rev through affinity chromatography followed by MALDI analyses. Our experiments involving transient expressions, siRNA mediated knockdowns and infection assays conclusively established that hStau-2 is a positive regulator of HIV-1 pathogenesis. We demonstrated that Rev-hStau-2 interactions positively regulated the RNA export activity of Rev and promoted progeny virus synthesis. The Rev-hStau-2 interaction was independent of RNA despite both being RNA binding proteins. hStau-2 mutant, with mutations at Q314R-A318F-K319E, deficient of binding Rev, failed to promote hStau-2 dependent Rev activity and viral production, validating the essentiality of this protein-protein interaction. The expression of this positive regulator was elevated upon HIV-1 infection in both human T-lymphocyte and astrocyte cell lines. With this study, we establish that human Staufen-2, a host factor which is up-regulated upon HIV-1 infection, interacts with HIV-1 Rev, thereby promoting its RNA export activity and progeny virus formation. Altogether, our study provides new insights into the emerging role of the Staufen family of mRNA transporters in host-pathogen interaction and supports the notion that obliterating interactions between viral and host proteins that positively regulate HIV-1 proliferation can significantly contribute to anti-retroviral treatments.

Restoration of the Mississippi Delta: Lessons from Hurricanes Katrina and Rita

NASA Astrophysics Data System (ADS)

Day, John W.; Boesch, Donald F.; Clairain, Ellis J.; Kemp, G. Paul; Laska, Shirley B.; Mitsch, William J.; Orth, Kenneth; Mashriqui, Hassan; Reed, Denise J.; Shabman, Leonard; Simenstad, Charles A.; Streever, Bill J.; Twilley, Robert R.; Watson, Chester C.; Wells, John T.; Whigham, Dennis F.

2007-03-01

Hurricanes Katrina and Rita showed the vulnerability of coastal communities and how human activities that caused deterioration of the Mississippi Deltaic Plain (MDP) exacerbated this vulnerability. The MDP formed by dynamic interactions between river and coast at various temporal and spatial scales, and human activity has reduced these interactions at all scales. Restoration efforts aim to re-establish this dynamic interaction, with emphasis on reconnecting the river to the deltaic plain. Science must guide MDP restoration, which will provide insights into delta restoration elsewhere and generally into coasts facing climate change in times of resource scarcity.

Beyond information access: Support for complex cognitive activities in public health informatics tools.

PubMed

Sedig, Kamran; Parsons, Paul; Dittmer, Mark; Ola, Oluwakemi

2012-01-01

Public health professionals work with a variety of information sources to carry out their everyday activities. In recent years, interactive computational tools have become deeply embedded in such activities. Unlike the early days of computational tool use, the potential of tools nowadays is not limited to simply providing access to information; rather, they can act as powerful mediators of human-information discourse, enabling rich interaction with public health information. If public health informatics tools are designed and used properly, they can facilitate, enhance, and support the performance of complex cognitive activities that are essential to public health informatics, such as problem solving, forecasting, sense-making, and planning. However, the effective design and evaluation of public health informatics tools requires an understanding of the cognitive and perceptual issues pertaining to how humans work and think with information to perform such activities. This paper draws on research that has examined some of the relevant issues, including interaction design, complex cognition, and visual representations, to offer some human-centered design and evaluation considerations for public health informatics tools.

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.…

Astaxanthin and withaferin A block paracrine cytokine interactions between UVB-exposed human keratinocytes and human melanocytes via the attenuation of endothelin-1 secretion and its downstream intracellular signaling.

PubMed

Niwano, Takao; Terazawa, Shuko; Nakajima, Hiroaki; Wakabayashi, Yuki; Imokawa, Genji

2015-06-01

Paracrine interactions between keratinocytes and melanocytes via cytokines play an essential role in regulating pigmentation in epidermal hyperpigmentary disorders. There is an urgent need for a human epidermal model in which melanogenic paracrine interactions between UVB-exposed keratinocytes and melanocytes can be precisely evaluated because human epidermal equivalents consisting of multilayered keratinocytes and melanocytes have significant limitations in this respect. To resolve this challenge, we established a co-culture system with cell inserts using human keratinocytes and human melanocytes that serves as an appropriate new model for UVB-induced hyperpigmentation. Using that new model, we examined the blocking effects of two natural chemicals, astaxanthin and withaferin A, on paracrine cytokine interactions between UVB-exposed keratinocytes and melanocytes and characterized their mechanisms of action. RT-PCR analysis showed that co-culture of human keratinocytes that had been exposed to UVB significantly stimulated human melanocytes to increase their expression of genes encoding microphthalmia-associated transcription factor, tyrosinase and tyrosinase-related protein 1. The catalytic activity of tyrosinase was also increased. ELISA assays revealed that UVB significantly increased the secretion of interleukin-1α, interleukin-6/8, granulocyte macrophage stimulatory factor and endothelin-1 but not α-melanocyte stimulating hormone. The addition of an endothelin-1 neutralizing antibody significantly abrogated the increase of tyrosinase activity. Post-irradiation treatment with astaxanthin or withaferin A significantly abolished the up-regulation of tyrosinase activity induced by UVB. Treatment with astaxanthin or withaferin A significantly reduced the increased levels of interleukin-1α, interleukin-6/8, granulocyte macrophage stimulatory factor and endothelin-1. Withaferin A but not astaxanthin also significantly abrogated the endothelin-1-stimulated activity of tyrosinase in melanocytes. Western blot analysis of intracellular signaling factors revealed that withaferin A but not astaxanthin significantly abolished the endothelin-1-stimulated phosphorylation of Raf-1, MEK, ERK, MITF and CREB in human melanocytes. These results demonstrate that this co-culture system is an appropriate model to characterize melanogenic paracrine interactions and that astaxanthin and withaferin A serve as potent inhibitors of those interactions. Their effects are caused not only by down-regulating the increased secretion of an intrinsic melanogenic cytokine, endothelin-1, by UVB-exposed human keratinocytes, but also by interrupting the endothelin-1-triggered downstream intracellular signaling between protein kinase C and Raf-1 in human melanocytes (only for withaferin A). Copyright © 2015 Elsevier Ltd. All rights reserved.

Confronting Analytical Dilemmas for Understanding Complex Human Interactions in Design-Based Research from a Cultural-Historical Activity Theory (CHAT) Framework

ERIC Educational Resources Information Center

Yamagata-Lynch, Lisa C.

2007-01-01

Understanding human activity in real-world situations often involves complicated data collection, analysis, and presentation methods. This article discusses how Cultural-Historical Activity Theory (CHAT) can inform design-based research practices that focus on understanding activity in real-world situations. I provide a sample data set with…

Simulating Activities: Relating Motives, Deliberation and Attentive Coordination

NASA Technical Reports Server (NTRS)

Clancey, William J.; Clancy, Daniel (Technical Monitor)

2002-01-01

Activities are located behaviors, taking time, conceived as socially meaningful, and usually involving interaction with tools and the environment. In modeling human cognition as a form of problem solving (goal-directed search and operator sequencing), cognitive science researchers have not adequately studied "off-task" activities (e.g., waiting), non-intellectual motives (e.g., hunger), sustaining a goal state (e.g., playful interaction), and coupled perceptual-motor dynamics (e.g., following someone). These aspects of human behavior have been considered in bits and pieces in past research, identified as scripts, human factors, behavior settings, ensemble, flow experience, and situated action. More broadly, activity theory provides a comprehensive framework relating motives, goals, and operations. This paper ties these ideas together, using examples from work life in a Canadian High Arctic research station. The emphasis is on simulating human behavior as it naturally occurs, such that "working" is understood as an aspect of living. The result is a synthesis of previously unrelated analytic perspectives and a broader appreciation of the nature of human cognition. Simulating activities in this comprehensive way is useful for understanding work practice, promoting learning, and designing better tools, including human-robot systems.

Human-Human Interaction Forces and Interlimb Coordination During Side-by-Side Walking With Hand Contact.

PubMed

Sylos-Labini, Francesca; d'Avella, Andrea; Lacquaniti, Francesco; Ivanenko, Yury

2018-01-01

Handholding can naturally occur between two walkers. When people walk side-by-side, either with or without hand contact, they often synchronize their steps. However, despite the importance of haptic interaction in general and the natural use of hand contact between humans during walking, few studies have investigated forces arising from physical interactions. Eight pairs of adult subjects participated in this study. They walked on side-by-side treadmills at 4 km/h independently and with hand contact. Only hand contact-related sensory information was available for unintentional synchronization, while visual and auditory communication was obstructed. Subjects walked at their natural cadences or following a metronome. Limb kinematics, hand contact 3D interaction forces and EMG activity of 12 upper limb muscles were recorded. Overall, unintentional step frequency locking was observed during about 40% of time in 88% of pairs walking with hand contact. On average, the amplitude of contact arm oscillations decreased while the contralateral (free) arm oscillated in the same way as during normal walking. Interestingly, EMG activity of the shoulder muscles of the contact arm did not decrease, and their synergistic pattern remained similar. The amplitude of interaction forces and of trunk oscillations was similar for synchronized and non-synchronized steps, though the synchronized steps were characterized by significantly more regular orientations of interaction forces. Our results further support the notion that gait synchronization during natural walking is common, and that it may occur through interaction forces. Conservation of the proximal muscle activity of the contact (not oscillating) arm is consistent with neural coupling between cervical and lumbosacral pattern generation circuitries ("quadrupedal" arm-leg coordination) during human gait. Overall, the findings suggest that individuals might integrate force interaction cues to communicate and coordinate steps during walking.

Human-Human Interaction Forces and Interlimb Coordination During Side-by-Side Walking With Hand Contact

PubMed Central

Sylos-Labini, Francesca; d'Avella, Andrea; Lacquaniti, Francesco; Ivanenko, Yury

2018-01-01

Handholding can naturally occur between two walkers. When people walk side-by-side, either with or without hand contact, they often synchronize their steps. However, despite the importance of haptic interaction in general and the natural use of hand contact between humans during walking, few studies have investigated forces arising from physical interactions. Eight pairs of adult subjects participated in this study. They walked on side-by-side treadmills at 4 km/h independently and with hand contact. Only hand contact-related sensory information was available for unintentional synchronization, while visual and auditory communication was obstructed. Subjects walked at their natural cadences or following a metronome. Limb kinematics, hand contact 3D interaction forces and EMG activity of 12 upper limb muscles were recorded. Overall, unintentional step frequency locking was observed during about 40% of time in 88% of pairs walking with hand contact. On average, the amplitude of contact arm oscillations decreased while the contralateral (free) arm oscillated in the same way as during normal walking. Interestingly, EMG activity of the shoulder muscles of the contact arm did not decrease, and their synergistic pattern remained similar. The amplitude of interaction forces and of trunk oscillations was similar for synchronized and non-synchronized steps, though the synchronized steps were characterized by significantly more regular orientations of interaction forces. Our results further support the notion that gait synchronization during natural walking is common, and that it may occur through interaction forces. Conservation of the proximal muscle activity of the contact (not oscillating) arm is consistent with neural coupling between cervical and lumbosacral pattern generation circuitries (“quadrupedal” arm-leg coordination) during human gait. Overall, the findings suggest that individuals might integrate force interaction cues to communicate and coordinate steps during walking. PMID:29563883

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...

What Has Caused Desertification in China?

PubMed

Feng, Qi; Ma, Hua; Jiang, Xuemei; Wang, Xin; Cao, Shixiong

2015-11-03

Desertification is the result of complex interactions among various factors, including climate change and human activities. However, previous research generally focused on either meteorological factors associated with climate change or human factors associated with human activities, and lacked quantitative assessments of their interaction combined with long-term monitoring. Thus, the roles of climate change and human factors in desertification remain uncertain. To understand the factors that determine whether mitigation programs can contribute to desertification control and vegetation cover improvements in desertified areas of China, and the complex interactions that affect their success, we used a pooled regression model based on panel data to calculate the relative roles of climate change and human activities on the desertified area and on vegetation cover (using the normalized-difference vegetation index, NDVI, which decreases with increasing desertification) from 1983 to 2012. We found similar effect magnitudes for socioeconomic and environmental factors for NDVI but different results for desertification: socioeconomic factors were the dominant factor that affected desertification, accounting for 79.3% of the effects. Climate change accounted for 46.6 and 20.6% of the effects on NDVI and desertification, respectively. Therefore, desertification control programs must account for the integrated effects of both socioeconomic and natural factors.

What Has Caused Desertification in China?

PubMed Central

Feng, Qi; Ma, Hua; Jiang, Xuemei; Wang, Xin; Cao, Shixiong

2015-01-01

Desertification is the result of complex interactions among various factors, including climate change and human activities. However, previous research generally focused on either meteorological factors associated with climate change or human factors associated with human activities, and lacked quantitative assessments of their interaction combined with long-term monitoring. Thus, the roles of climate change and human factors in desertification remain uncertain. To understand the factors that determine whether mitigation programs can contribute to desertification control and vegetation cover improvements in desertified areas of China, and the complex interactions that affect their success, we used a pooled regression model based on panel data to calculate the relative roles of climate change and human activities on the desertified area and on vegetation cover (using the normalized-difference vegetation index, NDVI, which decreases with increasing desertification) from 1983 to 2012. We found similar effect magnitudes for socioeconomic and environmental factors for NDVI but different results for desertification: socioeconomic factors were the dominant factor that affected desertification, accounting for 79.3% of the effects. Climate change accounted for 46.6 and 20.6% of the effects on NDVI and desertification, respectively. Therefore, desertification control programs must account for the integrated effects of both socioeconomic and natural factors. PMID:26525278

Integrin activation controls metastasis in human breast cancer

NASA Astrophysics Data System (ADS)

Felding-Habermann, Brunhilde; O'Toole, Timothy E.; Smith, Jeffrey W.; Fransvea, Emilia; Ruggeri, Zaverio M.; Ginsberg, Mark H.; Hughes, Paul E.; Pampori, Nisar; Shattil, Sanford J.; Saven, Alan; Mueller, Barbara M.

2001-02-01

Metastasis is the primary cause of death in human breast cancer. Metastasis to bone, lungs, liver, and brain involves dissemination of breast cancer cells via the bloodstream and requires adhesion within the vasculature. Blood cell adhesion within the vasculature depends on integrins, a family of transmembrane adhesion receptors, and is regulated by integrin activation. Here we show that integrin v3 supports breast cancer cell attachment under blood flow conditions in an activation-dependent manner. Integrin v3 was found in two distinct functional states in human breast cancer cells. The activated, but not the nonactivated, state supported tumor cell arrest during blood flow through interaction with platelets. Importantly, activated αvβ3 was expressed by freshly isolated metastatic human breast cancer cells and variants of the MDA-MB 435 human breast cancer cell line, derived from mammary fat pad tumors or distant metastases in severe combined immunodeficient mice. Expression of constitutively activated mutant αvβ3D723R, but not αvβ3WT, in MDA-MB 435 cells strongly promoted metastasis in the mouse model. Thus breast cancer cells can exhibit a platelet-interactive and metastatic phenotype that is controlled by the activation of integrin αvβ3. Consequently, alterations within tumors that lead to the aberrant control of integrin activation are expected to adversely affect the course of human breast cancer.

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

Interactions Between Adrenal and Calcium-Regulatory Hormones in Human Health

PubMed Central

Brown, Jenifer M.; Vaidya, Anand

2014-01-01

Purpose of Review To summarize evidence characterizing the interactions between adrenal- and calcium-regulating hormones, and the relevance of these interactions to human cardiovascular and skeletal health. Recent Findings Human studies support the regulation of parathyroid hormone (PTH) by the renin-angiotensin-aldosterone system (RAAS): angiotensin II may stimulate PTH secretion via an acute and direct mechanism, whereas aldosterone may exert a chronic stimulation of PTH secretion. Studies in primary aldosteronism, congestive heart failure, and chronic kidney disease have identified associations between hyperaldosteronism, hyperparathyroidism, and bone loss, which appear to improve when inhibiting the RAAS. Conversely, elevated PTH and insufficient vitamin D status have been associated with adverse cardiovascular outcomes, which may be mediated by the RAAS. Studies of primary hyperparathyroidism implicate PTH-mediated stimulation of the RAAS, and recent evidence shows that the vitamin D-vitamin D receptor (VDR) complex may negatively regulate renin expression and RAAS activity. Ongoing human interventional studies are evaluating the influence of RAAS inhibition on PTH and the influence of VDR agonists on RAAS activity. Summary While previously considered independent endocrine systems, emerging evidence supports a complex web of interactions between adrenal and calcium-regulating hormones, with implications for human cardiovascular and skeletal health. PMID:24694551

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".

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.

Interactions of endosulfan and methoxychlor involving CYP3A4 and CYP2B6 in human HepaRG cells.

PubMed

Savary, Camille C; Jossé, Rozenn; Bruyère, Arnaud; Guillet, Fabrice; Robin, Marie-Anne; Guillouzo, André

2014-08-01

Humans are usually exposed to several pesticides simultaneously; consequently, combined actions between pesticides themselves or between pesticides and other chemicals need to be addressed in the risk assessment. Many pesticides are efficient activators of pregnane X receptor (PXR) and/or constitutive androstane receptor (CAR), two major nuclear receptors that are also activated by other substrates. In the present work, we searched for interactions between endosulfan and methoxychlor, two organochlorine pesticides whose major routes of metabolism involve CAR- and PXR-regulated CYP3A4 and CYP2B6, and whose mechanisms of action in humans remain poorly understood. For this purpose, HepaRG cells were treated with both pesticides separately or in mixture for 24 hours or 2 weeks at concentrations relevant to human exposure levels. In combination they exerted synergistic cytotoxic effects. Whatever the duration of treatment, both compounds increased CYP3A4 and CYP2B6 mRNA levels while differently affecting their corresponding activities. Endosulfan exerted a direct reversible inhibition of CYP3A4 activity that was confirmed in human liver microsomes. By contrast, methoxychlor induced this activity. The effects of the mixture on CYP3A4 activity were equal to the sum of those of each individual compound, suggesting an additive effect of each pesticide. Despite CYP2B6 activity being unchanged and increased with endosulfan and methoxychlor, respectively, no change was observed with their mixture, supporting an antagonistic effect. Altogether, our data suggest that CAR and PXR activators endosulfan and methoxychlor can interact together and with other exogenous substrates in human hepatocytes. Their effects on CYP3A4 and CYP2B6 activities could have important consequences if extrapolated to the in vivo situation. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Activating Humans with Humor——A Dialogue System That Users Want to Interact with

NASA Astrophysics Data System (ADS)

Dybala, Pawel; Ptaszynski, Michal; Rzepka, Rafal; Araki, Kenji

The topic of Human Computer Interaction (HCI) has been gathering more and more scientific attention of late. A very important, but often undervalued area in this field is human engagement. That is, a person's commitment to take part in and continue the interaction. In this paper we describe work on a humor-equipped casual conversational system (chatterbot) and investigate the effect of humor on a user's engagement in the conversation. A group of users was made to converse with two systems: one with and one without humor. The chat logs were then analyzed using an emotive analysis system to check user reactions and attitudes towards each system. Results were projected on Russell's two-dimensional emotiveness space to evaluate the positivity/negativity and activation/deactivation of these emotions. This analysis indicated emotions elicited by the humor-equipped system were more positively active and less negatively active than by the system without humor. The implications of results and relation between them and user engagement in the conversation are discussed. We also propose a distinction between positive and negative engagement.

NASA human factors programmatic overview

NASA Technical Reports Server (NTRS)

Connors, Mary M.

1992-01-01

Human factors addresses humans in their active and interactive capacities, i.e., in the mental and physical activities that they perform and in the contributions they make to achieving the goals of the mission. The overall goal of space human factors in NASA is to support the safety, productivity, and reliability of both the on-board crew and the ground support staff. Safety and reliability are fundamental requirements that human factors shares with other disciplines, while productivity represents the defining contribution of the human factors discipline.

A pairwise maximum entropy model accurately describes resting-state human brain networks

PubMed Central

Watanabe, Takamitsu; Hirose, Satoshi; Wada, Hiroyuki; Imai, Yoshio; Machida, Toru; Shirouzu, Ichiro; Konishi, Seiki; Miyashita, Yasushi; Masuda, Naoki

2013-01-01

The resting-state human brain networks underlie fundamental cognitive functions and consist of complex interactions among brain regions. However, the level of complexity of the resting-state networks has not been quantified, which has prevented comprehensive descriptions of the brain activity as an integrative system. Here, we address this issue by demonstrating that a pairwise maximum entropy model, which takes into account region-specific activity rates and pairwise interactions, can be robustly and accurately fitted to resting-state human brain activities obtained by functional magnetic resonance imaging. Furthermore, to validate the approximation of the resting-state networks by the pairwise maximum entropy model, we show that the functional interactions estimated by the pairwise maximum entropy model reflect anatomical connexions more accurately than the conventional functional connectivity method. These findings indicate that a relatively simple statistical model not only captures the structure of the resting-state networks but also provides a possible method to derive physiological information about various large-scale brain networks. PMID:23340410

Proteomic analysis of the gamma human papillomavirus type 197 E6 and E7 associated cellular proteins

PubMed Central

Grace, Miranda; Munger, Karl

2016-01-01

Gamma HPV197 was the most frequently identified HPV when human skin cancer specimens were analyzed by deep sequencing. To gain insight into the biological activities of HPV197, we investigated the cellular interactomes of HPV197 E6 and E7. HPV197 E6 protein interacts with a broad spectrum of cellular LXXLL domain proteins, including UBE3A and MAML1. HPV197 E6 also binds and inhibits the TP53 tumor suppressor and interacts with the CCR4-NOT ubiquitin ligase and deadenylation complex. Despite lacking a canonical retinoblastoma (RB1) tumor suppressor binding site, HPV197 E7 binds RB1 and activates E2F transcription. Hence, HPV197 E6 and E7 proteins interact with a similar set of cellular proteins as E6 and E7 proteins encoded by HPVs that have been linked to human carcinogenesis and/or have transforming activities in vitro. PMID:27771561

How do we think machines think? An fMRI study of alleged competition with an artificial intelligence

PubMed Central

Chaminade, Thierry; Rosset, Delphine; Da Fonseca, David; Nazarian, Bruno; Lutcher, Ewald; Cheng, Gordon; Deruelle, Christine

2012-01-01

Mentalizing is defined as the inference of mental states of fellow humans, and is a particularly important skill for social interactions. Here we assessed whether activity in brain areas involved in mentalizing is specific to the processing of mental states or can be generalized to the inference of non-mental states by comparing brain responses during the interaction with an intentional and an artificial agent. Participants were scanned using fMRI during interactive rock-paper-scissors games while believing their opponent was a fellow human (Intentional agent, Int), a humanoid robot endowed with an artificial intelligence (Artificial agent, Art), or a computer playing randomly (Random agent, Rnd). Participants' subjective reports indicated that they adopted different stances against the three agents. The contrast of brain activity during interaction with the artificial and the random agents didn't yield any cluster at the threshold used, suggesting the absence of a reproducible stance when interacting with an artificial intelligence. We probed response to the artificial agent in regions of interest corresponding to clusters found in the contrast between the intentional and the random agents. In the precuneus involved in working memory, the posterior intraparietal suclus, in the control of attention and the dorsolateral prefrontal cortex, in executive functions, brain activity for Art was larger than for Rnd but lower than for Int, supporting the intrinsically engaging nature of social interactions. A similar pattern in the left premotor cortex and anterior intraparietal sulcus involved in motor resonance suggested that participants simulated human, and to a lesser extend humanoid robot actions, when playing the game. Finally, mentalizing regions, the medial prefrontal cortex and right temporoparietal junction, responded to the human only, supporting the specificity of mentalizing areas for interactions with intentional agents. PMID:22586381

How do we think machines think? An fMRI study of alleged competition with an artificial intelligence.

PubMed

Chaminade, Thierry; Rosset, Delphine; Da Fonseca, David; Nazarian, Bruno; Lutcher, Ewald; Cheng, Gordon; Deruelle, Christine

2012-01-01

Mentalizing is defined as the inference of mental states of fellow humans, and is a particularly important skill for social interactions. Here we assessed whether activity in brain areas involved in mentalizing is specific to the processing of mental states or can be generalized to the inference of non-mental states by comparing brain responses during the interaction with an intentional and an artificial agent. Participants were scanned using fMRI during interactive rock-paper-scissors games while believing their opponent was a fellow human (Intentional agent, Int), a humanoid robot endowed with an artificial intelligence (Artificial agent, Art), or a computer playing randomly (Random agent, Rnd). Participants' subjective reports indicated that they adopted different stances against the three agents. The contrast of brain activity during interaction with the artificial and the random agents didn't yield any cluster at the threshold used, suggesting the absence of a reproducible stance when interacting with an artificial intelligence. We probed response to the artificial agent in regions of interest corresponding to clusters found in the contrast between the intentional and the random agents. In the precuneus involved in working memory, the posterior intraparietal suclus, in the control of attention and the dorsolateral prefrontal cortex, in executive functions, brain activity for Art was larger than for Rnd but lower than for Int, supporting the intrinsically engaging nature of social interactions. A similar pattern in the left premotor cortex and anterior intraparietal sulcus involved in motor resonance suggested that participants simulated human, and to a lesser extend humanoid robot actions, when playing the game. Finally, mentalizing regions, the medial prefrontal cortex and right temporoparietal junction, responded to the human only, supporting the specificity of mentalizing areas for interactions with intentional agents.

Pathways of Understanding: the Interactions of Humanity and Global Environmental Change

NASA Technical Reports Server (NTRS)

Jacobson, Harold K.; Katzenberger, John; Lousma, Jack; Mooney, Harold A.; Moss, Richard H.; Kuhn, William; Luterbacher, Urs; Wiegandt, Ellen

1992-01-01

How humans, interacting within social systems, affect and are affected by global change is explored. Recognizing the impact human activities have on the environment and responding to the need to document the interactions among human activities, the Consortium for International Earth Science Information Network (CIESIN) commissioned a group of 12 scientists to develop a framework illustrating the key human systems that contribute to global change. This framework, called the Social Process Diagram, will help natural and social scientists, educators, resource managers and policy makers envision and analyze how human systems interact among themselves and with the natural system. The Social Process Diagram consists of the following blocks that constitute the Diagram's structural framework: (1) fund of knowledge and experience; (2) preferences and expectations; (3) factors of production and technology; (4) population and social structure; (5) economic systems; (6) political systems and institutions; and (7) global scale environmental processes. To demonstrate potential ways the Diagram can be used, this document includes 3 hypothetical scenarios of global change issues: global warming and sea level rise; the environmental impact of human population migration; and energy and the environment. These scenarios demonstrate the Diagram's usefulness for visualizing specific processes that might be studied to evaluate a particular global change issues. The scenario also shows that interesting and unanticipated questions may emerge as links are explored between categories on the Diagram.

Feedbacks in human-landscape systems

NASA Astrophysics Data System (ADS)

Chin, Anne

2015-04-01

As human interactions with Earth systems intensify in the "Anthropocene", understanding the complex relationships among human activity, landscape change, and societal responses to those changes is increasingly important. Interdisciplinary research centered on the theme of "feedbacks" in human-landscape systems serves as a promising focus for unraveling these interactions. Deciphering interacting human-landscape feedbacks extends our traditional approach of considering humans as unidirectional drivers of change. Enormous challenges exist, however, in quantifying impact-feedback loops in landscapes with significant human alterations. This paper illustrates an example of human-landscape interactions following a wildfire in Colorado (USA) that elicited feedback responses. After the 2012 Waldo Canyon Fire, concerns for heightened flood potential and debris flows associated with post-fire hydrologic changes prompted local landowners to construct tall fences at the base of a burned watershed. These actions changed the sediment transport regime and promoted further landscape change and human responses in a positive feedback cycle. The interactions ultimately increase flood and sediment hazards, rather than dampening the effects of fire. A simple agent-based model, capable of integrating social and hydro-geomorphological data, demonstrates how such interacting impacts and feedbacks could be simulated. Challenges for fully capturing human-landscape feedback interactions include the identification of diffuse and subtle feedbacks at a range of scales, the availability of data linking impact with response, the identification of multiple thresholds that trigger feedback mechanisms, and the varied metrics and data needed to represent both the physical and human systems. By collaborating with social scientists with expertise in the human causes of landscape change, as well as the human responses to those changes, geoscientists could more fully recognize and anticipate the coupled human-landscape interactions that will drive the evolution of Earth systems into the future.

Role of adapter function in oncoprotein-mediated activation of NF-kappaB. Human T-cell leukemia virus type I Tax interacts directly with IkappaB kinase gamma.

PubMed

Jin, D Y; Giordano, V; Kibler, K V; Nakano, H; Jeang, K T

1999-06-18

Mechanisms by which the human T-cell leukemia virus type I Tax oncoprotein activates NF-kappaB remain incompletely understood. Although others have described an interaction between Tax and a holo-IkappaB kinase (IKK) complex, the exact details of protein-protein contact are not fully defined. Here we show that Tax binds to neither IKK-alpha nor IKK-beta but instead complexes directly with IKK-gamma, a newly characterized component of the IKK complex. This direct interaction with IKK-gamma correlates with Tax-induced IkappaB-alpha phosphorylation and NF-kappaB activation. Thus, our findings establish IKK-gamma as a key molecule for adapting an oncoprotein-specific signaling to IKK-alpha and IKK-beta.

Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin αVβ8.

PubMed

Stockis, Julie; Liénart, Stéphanie; Colau, Didier; Collignon, Amandine; Nishimura, Stephen L; Sheppard, Dean; Coulie, Pierre G; Lucas, Sophie

2017-11-21

Human regulatory T cells (Tregs) suppress other T cells by converting the latent, inactive form of TGF-β1 into active TGF-β1. In Tregs, TGF-β1 activation requires GARP, a transmembrane protein that binds and presents latent TGF-β1 on the surface of Tregs stimulated through their T cell receptor. However, GARP is not sufficient because transduction of GARP in non-Treg T cells does not induce active TGF-β1 production. RGD-binding integrins were shown to activate TGF-β1 in several non-T cell types. Here we show that αVβ8 dimers are present on stimulated human Tregs but not in other T cells, and that antibodies against αV or β8 subunits block TGF-β1 activation in vitro. We also show that αV and β8 interact with GARP/latent TGF-β1 complexes in human Tregs. Finally, a blocking antibody against β8 inhibited immunosuppression by human Tregs in a model of xenogeneic graft-vs.-host disease induced by the transfer of human T cells in immunodeficient mice. These results show that TGF-β1 activation on the surface of human Tregs implies an interaction between the integrin αVβ8 and GARP/latent TGF-β1 complexes. Immunosuppression by human Tregs can be inhibited by antibodies against GARP or against the integrin β8 subunit. Such antibodies may prove beneficial against cancer or chronic infections.

Groundwater and surface-water interactions and impacts of human activities in the Hailiutu catchment, northwest China

NASA Astrophysics Data System (ADS)

Yang, Zhi; Zhou, Yangxiao; Wenninger, Jochen; Uhlenbrook, Stefan; Wang, Xusheng; Wan, Li

2017-08-01

The interactions between groundwater and surface water have been significantly affected by human activities in the semi-arid Hailiutu catchment, northwest China. Several methods were used to investigate the spatial and temporal interactions between groundwater and surface water. Isotopic and chemical analyses of water samples determined that groundwater discharges to the Hailiutu River, and mass balance equations were employed to estimate groundwater seepage rates along the river using chemical profiles. The hydrograph separation method was used to estimate temporal variations of groundwater discharges to the river. A numerical groundwater model was constructed to simulate groundwater discharges along the river and to analyze effects of water use in the catchment. The simulated seepage rates along the river compare reasonably well with the seepage estimates derived from a chemical profile in 2012. The impacts of human activities (river-water diversion and groundwater abstraction) on the river discharge were analyzed by calculating the differences between the simulated natural groundwater discharge and the measured river discharge. Water use associated with the Hailiutu River increased from 1986 to 1991, reached its highest level from 1992 to 2000, and decreased from 2001 onwards. The reduction of river discharge might have negative impacts on the riparian ecosystem and the water availability for downstream users. The interactions between groundwater and surface water as well as the consequences of human activities should be taken into account when implementing sustainable water resources management in the Hailiutu catchment.

The effects of Andrographis paniculata (Burm.f.) Nees extract and diterpenoids on the CYP450 isoforms' activities, a review of possible herb-drug interaction risks.

PubMed

Tan, Mei Lan; Lim, Lin Ee

2015-01-01

Andrographis paniculata (Burm.f.) Nees is a popular medicinal plant and its components are used in various traditional product preparations. However, its herb-drug interactions risks remain unclear. This review specifically discusses the various published studies carried out to evaluate the effects of Andrographis paniculata (Burm.f.) Nees plant extracts and diterpenoids on the CYP450 metabolic enzyme and if the plant components pose a possible herb-drug interaction risk. Unfortunately, the current data are insufficient to indicate if the extracts or diterpenoids can be labeled as in vitro CYP1A2, CYP2C9 or CYP3A4 inhibitors. A complete CYP inhibition assay utilizing human liver microsomes and the derivation of relevant parameters to predict herb-drug interaction risks may be necessary for these isoforms. However, based on the current studies, none of the extracts and diterpenoids exhibited CYP450 induction activity in human hepatocytes or human-derived cell lines. It is crucial that a well-defined experimental design is needed to make a meaningful herb-drug interaction prediction.

A Physical Interaction Network of Dengue Virus and Human Proteins*

PubMed Central

Khadka, Sudip; Vangeloff, Abbey D.; Zhang, Chaoying; Siddavatam, Prasad; Heaton, Nicholas S.; Wang, Ling; Sengupta, Ranjan; Sahasrabudhe, Sudhir; Randall, Glenn; Gribskov, Michael; Kuhn, Richard J.; Perera, Rushika; LaCount, Douglas J.

2011-01-01

Dengue virus (DENV), an emerging mosquito-transmitted pathogen capable of causing severe disease in humans, interacts with host cell factors to create a more favorable environment for replication. However, few interactions between DENV and human proteins have been reported to date. To identify DENV-human protein interactions, we used high-throughput yeast two-hybrid assays to screen the 10 DENV proteins against a human liver activation domain library. From 45 DNA-binding domain clones containing either full-length viral genes or partially overlapping gene fragments, we identified 139 interactions between DENV and human proteins, the vast majority of which are novel. These interactions involved 105 human proteins, including six previously implicated in DENV infection and 45 linked to the replication of other viruses. Human proteins with functions related to the complement and coagulation cascade, the centrosome, and the cytoskeleton were enriched among the DENV interaction partners. To determine if the cellular proteins were required for DENV infection, we used small interfering RNAs to inhibit their expression. Six of 12 proteins targeted (CALR, DDX3X, ERC1, GOLGA2, TRIP11, and UBE2I) caused a significant decrease in the replication of a DENV replicon. We further showed that calreticulin colocalized with viral dsRNA and with the viral NS3 and NS5 proteins in DENV-infected cells, consistent with a direct role for calreticulin in DENV replication. Human proteins that interacted with DENV had significantly higher average degree and betweenness than expected by chance, which provides additional support for the hypothesis that viruses preferentially target cellular proteins that occupy central position in the human protein interaction network. This study provides a valuable starting point for additional investigations into the roles of human proteins in DENV infection. PMID:21911577

The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A

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

Sato, Shoko, E-mail: satosho@rs.tus.ac.jp; Shirakawa, Hitoshi, E-mail: shirakah@m.tohoku.ac.jp; Tomita, Shuhei, E-mail: tomita@med.tottori-u.ac.jp

2013-11-15

Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHRmore » or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein–protein interactions with GR. - Highlights: • Aryl hydrocarbon receptor forms a complex with glucocorticoid receptor in cells. • Human metallothionein gene is regulated by the AHR and GR interaction. • AHR–GR complex binds to glucocorticoid response element in metallothionein gene. • We demonstrated a novel transcriptional mechanism via AHR and GR interaction.« less

Computational identification of gene–social environment interaction at the human IL6 locus

PubMed Central

Cole, Steven W.; Arevalo, Jesusa M. G.; Takahashi, Rie; Sloan, Erica K.; Lutgendorf, Susan K.; Sood, Anil K.; Sheridan, John F.; Seeman, Teresa E.

2010-01-01

To identify genetic factors that interact with social environments to impact human health, we used a bioinformatic strategy that couples expression array–based detection of environmentally responsive transcription factors with in silico discovery of regulatory polymorphisms to predict genetic loci that modulate transcriptional responses to stressful environments. Tests of one predicted interaction locus in the human IL6 promoter (SNP rs1800795) verified that it modulates transcriptional response to β-adrenergic activation of the GATA1 transcription factor in vitro. In vivo validation studies confirmed links between adverse social conditions and increased transcription of GATA1 target genes in primary neural, immune, and cancer cells. Epidemiologic analyses verified the health significance of those molecular interactions by documenting increased 10-year mortality risk associated with late-life depressive symptoms that occurred solely for homozygous carriers of the GATA1-sensitive G allele of rs1800795. Gating of depression-related mortality risk by IL6 genotype pertained only to inflammation-related causes of death and was associated with increased chronic inflammation as indexed by plasma C-reactive protein. Computational modeling of molecular interactions, in vitro biochemical analyses, in vivo animal modeling, and human molecular epidemiologic analyses thus converge in identifying β-adrenergic activation of GATA1 as a molecular pathway by which social adversity can alter human health risk selectively depending on individual genetic status at the IL6 locus. PMID:20176930

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

Distinct brain activity in processing negative pictures of animals and objects --- the role of human contexts

PubMed Central

Cao, Zhijun; Zhao, Yanbing; Tan, Tengteng; Chen, Gang; Ning, Xueling; Zhan, Lexia; Yang, Jiongjiong

2013-01-01

Previous studies have shown that the amygdala is important in processing not only animate entities but also social information. It remains to be determined to what extent the factors of category and social context interact to modulate the activities of the amygdala and cortical regions. In this study, pictures depicting animals and inanimate objects in negative and neutral levels were presented. The contexts of the pictures differed in whether they included human/human parts. The factors of valence, arousal, familiarity and complexity of pictures were controlled across categories. The results showed that the amygdala activity was modulated by category and contextual information. Under the nonhuman context condition, the amygdala responded more to animals than objects for both negative and neutral pictures. In contrast, under the human context condition, the amygdala showed stronger activity for negative objects than animals. In addition to cortical regions related to object action, functional and effective connectivity analyses showed that the anterior prefrontal cortex interacted with the amygdala more for negative objects (vs. animals) in the human context condition, by a top-down modulation of the anterior prefrontal cortex to the amygdala. These results highlighted the effects of category and human contexts on modulating brain activity in emotional processing. PMID:24099847

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.

An fMRI Study of the Social Competition in Healthy Subjects

ERIC Educational Resources Information Center

Polosan, M.; Baciu, M.; Cousin, E.; Perrone, M.; Pichat, C.; Bougerol, T.

2011-01-01

Social interaction requires the ability to infer another person's mental state (Theory of Mind, ToM) and also executive functions. This fMRI study aimed to identify the cerebral correlates activated by ToM during a specific social interaction, the human-human competition. In this framework, we tested a conflict resolution task (Stroop) adapted to…

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…

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.

Simian Immunodeficiency Virus Vif and Human APOBEC3B Interactions Resemble Those between HIV-1 Vif and Human APOBEC3G.

PubMed

Wang, Jiayi; Shaban, Nadine M; Land, Allison M; Brown, William L; Harris, Reuben S

2018-06-15

Several members of the APOBEC3 DNA cytosine deaminase family can potently inhibit Vif-deficient human immunodeficiency virus type 1 (HIV-1) by catalyzing cytosine deamination in viral cDNA and impeding reverse transcription. HIV-1 counteracts restriction with the virally encoded Vif protein, which targets relevant APOBEC3 proteins for proteasomal degradation. HIV-1 Vif is optimized for degrading the restrictive human APOBEC3 repertoire, and, in general, lentiviral Vif proteins specifically target the restricting APOBEC3 enzymes of each host species. However, simian immunodeficiency virus SIV mac239 Vif elicits a curiously wide range of APOBEC3 degradation capabilities that include degradation of several human APOBEC3s and even human APOBEC3B, a non-HIV-1-restricting APOBEC3 enzyme. To better understand the molecular determinants of the interaction between SIV mac239 Vif and human APOBEC3B, we analyzed an extensive series of mutants. We found that SIV mac239 Vif interacts with the N-terminal domain of human APOBEC3B and, interestingly, that this occurs within a structural region homologous to the HIV-1 Vif interaction surface of human APOBEC3G. An alanine scan of SIV mac239 Vif revealed several residues required for human APOBEC3B degradation activity. These residues overlap HIV-1 Vif surface residues that interact with human APOBEC3G and are distinct from those that engage APOBEC3F or APOBEC3H. Overall, these studies indicate that the molecular determinants of the functional interaction between human APOBEC3B and SIV mac239 Vif resemble those between human APOBEC3G and HIV-1 Vif. These studies contribute to the growing knowledge of the APOBEC-Vif interaction and may help guide future efforts to disrupt this interaction as an antiviral therapy or exploit the interaction as a novel strategy to inhibit APOBEC3B-dependent tumor evolution. IMPORTANCE Primate APOBEC3 proteins provide innate immunity against retroviruses such as HIV and SIV. HIV-1, the primary cause of AIDS, utilizes its Vif protein to specifically counteract restrictive human APOBEC3 enzymes. SIV mac239 Vif exhibits a much wider range of anti-APOBEC3 activities that includes several rhesus macaque enzymes and extends to multiple proteins in the human APOBEC3 repertoire, including APOBEC3B. Understanding the molecular determinants of the interaction between SIV mac239 Vif and human APOBEC3B adds to existing knowledge on the APOBEC3-Vif interaction and has potential to shed light on what processes may have shaped Vif functionality over evolutionary time. An intimate understanding of this interaction may also lead to a novel cancer therapy because, for instance, creating a derivative of SIV mac239 Vif that specifically targets human APOBEC3B could be used to suppress tumor genomic DNA mutagenesis by this enzyme, slow ongoing tumor evolution, and help prevent poor clinical outcomes. Copyright © 2018 American Society for Microbiology.

Proteasomal interaction as a critical activity modulator of the human constitutive androstane receptor

PubMed Central

Chen, Tao; Laurenzana, Elizabeth M.; Coslo, Denise M.; Chen, Fengming; Omiecinski, Curtis J.

2014-01-01

The CAR (constitutive androstane receptor; NR1I3) is a critical xenobiotic sensor that regulates xenobiotic metabolism, drug clearance, energy and lipid homoeostasis, cell proliferation and development. Although constitutively active, in hepatocytes CAR is normally held quiescent through a tethering mechanism in the cytosol, anchored to a protein complex that includes several components, including heat-shock protein 90. Release and subsequent nuclear translocation of CAR is triggered through either direct binding to ligand activators such as CITCO {6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime} or through indirect chemical activation, such as with PB (phenobarbital). In the present study, we demonstrate that proteasomal inhibition markedly disrupts CAR function, repressing CAR nuclear trafficking, disrupting CAR’s interaction with nuclear co-activators and inhibiting induction of CAR target gene responses in human primary hepatocytes following treatment with either PB or CITCO. Paradoxically, these effects occur following accumulation of ubiquitinated hCAR (human CAR). Furthermore, a non-proteolytic function was indicated by its interaction with a SUG1 (suppressor for Gal1), a subunit of the 26S proteasome. Taken together, these data demonstrate that the proteasome complex functions at multiple levels to regulate the functional biology of hCAR activity. PMID:24224465

Alaskan brown bears, humans, and habituation

USGS Publications Warehouse

Smith, Thomas; Herrero, Stephen; DeBruyn, Terry D.

2005-01-01

We present a new paradigm for understanding habituation and the role it plays in brown bear (Ursus arctos) populations and interactions with humans in Alaska. We assert that 3 forms of habituation occur in Alaska: bear-to-bear, bear-to-human, and human-to-bear. We present data that supports our theory that bear density is an important factor influencing a bear’s overt reaction distance (ORD); that as bear density increases, overt reaction distance decreases, as does the likelihood of bear– human interactions. We maintain that the effects of bear-to-bear habituation are largely responsible for not only shaping bear aggregations but also for creating the relatively safe environment for bear viewing experienced at areas where there are high densities of brown bears. By promoting a better understanding of the forces that shape bear social interactions within populations and with humans that mingle with them, we can better manage human activities and minimize bear–human conflict.

Fabrication of enzyme-degradable and size-controlled protein nanowires using single particle nano-fabrication technique

PubMed Central

Omichi, Masaaki; Asano, Atsushi; Tsukuda, Satoshi; Takano, Katsuyoshi; Sugimoto, Masaki; Saeki, Akinori; Sakamaki, Daisuke; Onoda, Akira; Hayashi, Takashi; Seki, Shu

2014-01-01

Protein nanowires exhibiting specific biological activities hold promise for interacting with living cells and controlling and predicting biological responses such as apoptosis, endocytosis and cell adhesion. Here we report the result of the interaction of a single high-energy charged particle with protein molecules, giving size-controlled protein nanowires with an ultra-high aspect ratio of over 1,000. Degradation of the human serum albumin nanowires was examined using trypsin. The biotinylated human serum albumin nanowires bound avidin, demonstrating the high affinity of the nanowires. Human serum albumin–avidin hybrid nanowires were also fabricated from a solid state mixture and exhibited good mechanical strength in phosphate-buffered saline. The biotinylated human serum albumin nanowires can be transformed into nanowires exhibiting a biological function such as avidin–biotinyl interactions and peroxidase activity. The present technique is a versatile platform for functionalizing the surface of any protein molecule with an extremely large surface area. PMID:24770668

When a robot is social: spatial arrangements and multimodal semiotic engagement in the practice of social robotics.

PubMed

Alac, Morana; Movellan, Javier; Tanaka, Fumihide

2011-12-01

Social roboticists design their robots to function as social agents in interaction with humans and other robots. Although we do not deny that the robot's design features are crucial for attaining this aim, we point to the relevance of spatial organization and coordination between the robot and the humans who interact with it. We recover these interactions through an observational study of a social robotics laboratory and examine them by applying a multimodal interactional analysis to two moments of robotics practice. We describe the vital role of roboticists and of the group of preverbal infants, who are involved in a robot's design activity, and we argue that the robot's social character is intrinsically related to the subtleties of human interactional moves in laboratories of social robotics. This human involvement in the robot's social agency is not simply controlled by individual will. Instead, the human-machine couplings are demanded by the situational dynamics in which the robot is lodged.

Development of Methodologies, Metrics, and Tools for Investigating Human-Robot Interaction in Space Robotics

NASA Technical Reports Server (NTRS)

Ezer, Neta; Zumbado, Jennifer Rochlis; Sandor, Aniko; Boyer, Jennifer

2011-01-01

Human-robot systems are expected to have a central role in future space exploration missions that extend beyond low-earth orbit [1]. As part of a directed research project funded by NASA s Human Research Program (HRP), researchers at the Johnson Space Center have started to use a variety of techniques, including literature reviews, case studies, knowledge capture, field studies, and experiments to understand critical human-robot interaction (HRI) variables for current and future systems. Activities accomplished to date include observations of the International Space Station s Special Purpose Dexterous Manipulator (SPDM), Robonaut, and Space Exploration Vehicle (SEV), as well as interviews with robotics trainers, robot operators, and developers of gesture interfaces. A survey of methods and metrics used in HRI was completed to identify those most applicable to space robotics. These methods and metrics included techniques and tools associated with task performance, the quantification of human-robot interactions and communication, usability, human workload, and situation awareness. The need for more research in areas such as natural interfaces, compensations for loss of signal and poor video quality, psycho-physiological feedback, and common HRI testbeds were identified. The initial findings from these activities and planned future research are discussed. Human-robot systems are expected to have a central role in future space exploration missions that extend beyond low-earth orbit [1]. As part of a directed research project funded by NASA s Human Research Program (HRP), researchers at the Johnson Space Center have started to use a variety of techniques, including literature reviews, case studies, knowledge capture, field studies, and experiments to understand critical human-robot interaction (HRI) variables for current and future systems. Activities accomplished to date include observations of the International Space Station s Special Purpose Dexterous Manipulator (SPDM), Robonaut, and Space Exploration Vehicle (SEV), as well as interviews with robotics trainers, robot operators, and developers of gesture interfaces. A survey of methods and metrics used in HRI was completed to identify those most applicable to space robotics. These methods and metrics included techniques and tools associated with task performance, the quantification of human-robot interactions and communication, usability, human workload, and situation awareness. The need for more research in areas such as natural interfaces, compensations for loss of signal and poor video quality, psycho-physiological feedback, and common HRI testbeds were identified. The initial findings from these activities and planned future research are discussed.

Non-covalent interaction between dietary stilbenoids and human serum albumin: Structure-affinity relationship, and its influence on the stability, free radical scavenging activity and cell uptake of stilbenoids.

PubMed

Cao, Hui; Jia, Xueping; Shi, Jian; Xiao, Jianbo; Chen, Xiaoqing

2016-07-01

Dietary stilbenoids are associated with many benefits for human health, which depend on their bioavailability and bioaccessibility. The stilbenoid-human serum albumin (HSA) interactions are investigated to explore the structure-affinity relationship and influence on the stability, free radical scavenging activity and cell uptake of stilbenoids. The structure-affinity relationship of the stilbenoids-HSA interaction was found as: (1) the methoxylation enhanced the affinity, (2) an additional hydroxyl group increases the affinity and (3) the glycosylation significantly weakened the affinity. HSA obviously masked the free radical scavenging potential of stilbenoids. The stabilities of stilbenoids in different medium were determined as: HSA solution>human plasma>Dulbecco's modified Eagle's medium. It appears that the milk enhanced the cell uptake of stilbenoids with multi-hydroxyl groups and weakened the cell uptake of stilbenoids with methoxyl group on EA.hy 926 endothelial cells. The stilbenoids are hardly absorbed by human umbilical vein endothelial cells in the presence of milk. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biophysical studies of interaction between hydrolysable tannins isolated from Oenothera gigas and Geranium sanguineum with human serum albumin.

PubMed

Sekowski, Szymon; Ionov, Maksim; Kaszuba, Mateusz; Mavlyanov, Saidmukhtar; Bryszewska, Maria; Zamaraeva, Maria

2014-11-01

Tannins, secondary plant metabolites, possess diverse biological activities and can interact with biopolymers such as lipids or proteins. Interactions between tannins and proteins depend on the structures of both and can result in changes in protein structure and activity. Because human serum albumin is the most abundant protein in plasma and responsible for interactions with important biological compounds (e.g. bilirubin) and proper blood pressure, therefore, it is very important to investigate reactions between HSA and tannins. This paper describes the interaction between human serum albumin (HSA) and two tannins: bihexahydroxydiphenoyl-trigalloylglucose (BDTG) and 1-O-galloyl-4,6-hexahydroxydiphenoyl-β-d-glucose (OGβDG), isolated from Geranium sanguineum and Oenothera gigas leafs, respectively. Optical (spectrofluorimetric) and chiral optical (circular dichroism) methods were used in this study. Fluorescence analysis demonstrated that OGβDG quenched HSA fluorescence more strongly than BDTG. Both OGβDG and BDTG formed complexes with albumin and caused a red shift of the fluorescence spectra but did not significantly change the protein secondary structure. Our studies clearly demonstrate that the tested tannins interact very strongly with human serum albumin (quenching constant K=88,277.26±407.04 M(-1) and K=55,552.67±583.07 M(-1) respectively for OGβDG and BDTG) in a manner depending on their chemical structure. Copyright © 2014 Elsevier B.V. All rights reserved.

A novel cervical cancer suppressor 3 (CCS-3) interacts with the BTB domain of PLZF and inhibits the cell growth by inducing apoptosis.

PubMed

Rho, Seung Bae; Park, Young Gyo; Park, Kyoungsook; Lee, Seung-Hoon; Lee, Je-Ho

2006-07-24

Promyelocytic leukemia zinc finger protein (PLZF) is a sequence-specific, DNA binding, transcriptional repressor differentially expressed during embryogenesis and in adult tissues. PLZF is known to be a negative regulator of cell cycle progression. We used PLZF as bait in a yeast two-hybrid screen with a cDNA library from the human ovary tissue. A novel cervical cancer suppressor 3 (CCS-3) was identified as a PLZF interacting partner. Further characterization revealed the BTB domain as an interacting domain of PLZF. Interaction of CCS-3 with PLZF in mammalian cells was also confirmed by co-immunoprecipitation and in vitro binding assays. It was found that, although CCS-3 shares similar homology with eEF1A, the study determined CCS-3 to be an isoform. CCS-3 was observed to be downregulated in human cervical cell lines as well as in cervical tumors when compared to those from normal tissues. Overexpression of CCS-3 in human cervical cell lines inhibits cell growth by inducing apoptosis and suppressing human cyclin A2 promoter activity. These combined results suggest that the potential tumor suppressor activity of CCS-3 may be mediated by its interaction with PLZF.

SARS coronavirus protein 7a interacts with human Ap4A-hydrolase.

PubMed

Vasilenko, Natalia; Moshynskyy, Igor; Zakhartchouk, Alexander

2010-02-09

The SARS coronavirus (SARS-CoV) open reading frame 7a (ORF 7a) encodes a 122 amino acid accessory protein. It has no significant sequence homology with any other known proteins. The 7a protein is present in the virus particle and has been shown to interact with several host proteins; thereby implicating it as being involved in several pathogenic processes including apoptosis, inhibition of cellular protein synthesis, and activation of p38 mitogen activated protein kinase. In this study we present data demonstrating that the SARS-CoV 7a protein interacts with human Ap4A-hydrolase (asymmetrical diadenosine tetraphosphate hydrolase, EC 3.6.1.17). Ap4A-hydrolase is responsible for metabolizing the "allarmone" nucleotide Ap4A and therefore likely involved in regulation of cell proliferation, DNA replication, RNA processing, apoptosis and DNA repair. The interaction between 7a and Ap4A-hydrolase was identified using yeast two-hybrid screening. The interaction was confirmed by co-immunoprecipitation from cultured human cells transiently expressing V5-His tagged 7a and HA tagged Ap4A-hydrolase. Human tissue culture cells transiently expressing 7a and Ap4A-hydrolase tagged with EGFP and Ds-Red2 respectively show these proteins co-localize in the cytoplasm.

Differential transcriptional activation by human T-cell leukemia virus type 1 Tax mutants is mediated by distinct interactions with CREB binding protein and p300.

PubMed

Bex, F; Yin, M J; Burny, A; Gaynor, R B

1998-04-01

The human T-cell leukemia virus type 1 Tax protein transforms human T lymphocytes, which can lead to the development of adult T-cell leukemia. Tax transformation is related to its ability to activate gene expression via the ATF/CREB and the NF-kappaB pathways. Transcriptional activation of these pathways is mediated by the actions of the related coactivators CREB binding protein (CBP) and p300. In this study, immunocytochemistry and confocal microscopy were used to localize CBP and p300 in cells expressing wild-type Tax or Tax mutants that are able to selectively activate gene expression from either the NF-kappaB or ATF/CREB pathway. Wild-type Tax colocalized with both CBP and p300 in nuclear bodies which also contained ATF-1 and the RelA subunit of NF-kappaB. However, a Tax mutant that selectively activates gene expression from only the ATF/CREB pathway colocalized with CBP but not p300, while a Tax mutant that selectively activates gene expression from only the NF-kappaB pathway colocalized with p300 but not CBP. In vitro and in vivo protein interaction studies indicated that the integrity of two independent domains of Tax delineated by these mutants was involved in the direct interaction of Tax with either CBP or p300. These studies are consistent with a model in which activation of either the NF-kappaB or the ATF/CREB pathway by specific Tax mutants is mediated by distinct interactions with related coactivator proteins.

Occupational stress in human computer interaction.

PubMed

Smith, M J; Conway, F T; Karsh, B T

1999-04-01

There have been a variety of research approaches that have examined the stress issues related to human computer interaction including laboratory studies, cross-sectional surveys, longitudinal case studies and intervention studies. A critical review of these studies indicates that there are important physiological, biochemical, somatic and psychological indicators of stress that are related to work activities where human computer interaction occurs. Many of the stressors of human computer interaction at work are similar to those stressors that have historically been observed in other automated jobs. These include high workload, high work pressure, diminished job control, inadequate employee training to use new technology, monotonous tasks, por supervisory relations, and fear for job security. New stressors have emerged that can be tied primarily to human computer interaction. These include technology breakdowns, technology slowdowns, and electronic performance monitoring. The effects of the stress of human computer interaction in the workplace are increased physiological arousal; somatic complaints, especially of the musculoskeletal system; mood disturbances, particularly anxiety, fear and anger; and diminished quality of working life, such as reduced job satisfaction. Interventions to reduce the stress of computer technology have included improved technology implementation approaches and increased employee participation in implementation. Recommendations for ways to reduce the stress of human computer interaction at work are presented. These include proper ergonomic conditions, increased organizational support, improved job content, proper workload to decrease work pressure, and enhanced opportunities for social support. A model approach to the design of human computer interaction at work that focuses on the system "balance" is proposed.

Tristetraprolin regulates the expression of the human inducible nitric-oxide synthase gene.

PubMed

Fechir, Marcel; Linker, Katrin; Pautz, Andrea; Hubrich, Thomas; Förstermann, Ulrich; Rodriguez-Pascual, Fernando; Kleinert, Hartmut

2005-06-01

The expression of human inducible NO synthase (iNOS) is regulated both by transcriptional and post-transcriptional mechanisms. Stabilization of mRNAs often depends on activation of p38 mitogen-activated protein kinase (p38 MAPK). In human DLD-1 cells, inhibition of p38 MAPK by the compound 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580) or by overexpression of a dominant-negative p38 MAPKalpha protein resulted in a reduction of human iNOS mRNA and protein expression, whereas human iNOS promoter activity was not affected. An important RNA binding protein regulated by the p38 MAPK pathway and involved in the regulation of the stability of several mRNAs is tristetraprolin. RNase protection, quantitative real-time polymerase chain reaction, and Western blot experiments showed that cytokines used to induce iNOS expression in DLD-1 cells also enhanced tristetraprolin expression. SB203580 incubation reduced cytokine-mediated enhancement of tristetraprolin expression. Overexpression or down-regulation of tristetraprolin in stably transfected DLD-1- or A549/8 cells consistently resulted in enhanced or reduced iNOS expression by modulating iNOS-mRNA stability. In UV cross-linking experiments, recombinant tristetraprolin did not interact with the human iNOS mRNA. However, coimmunoprecipitation experiments showed interaction of tristetraprolin with the KH-type splicing regulatory protein (KSRP), which is known to recruit mRNAs containing AU-rich elements to the exosome for degradation. This tristetraprolin-KSRP interaction was enhanced by cytokines and reduced by SB203580 treatment. We conclude that tristetraprolin positively regulates human iNOS expression by enhancing the stability of human iNOS mRNA. Because tristetraprolin does not directly bind to the human iNOS mRNA but interacts with KSRP, tristetraprolin is likely to stabilize iNOS mRNA by capturing the KSRP-exosome complex.

Human Activity Helps Prey Win the Predator-Prey Space Race

PubMed Central

Muhly, Tyler B.; Semeniuk, Christina; Massolo, Alessandro; Hickman, Laura; Musiani, Marco

2011-01-01

Predator-prey interactions, including between large mammalian wildlife species, can be represented as a “space race”, where prey try to minimize and predators maximize spatial overlap. Human activity can also influence the distribution of wildlife species. In particular, high-human disturbance can displace large carnivore predators, a trait-mediated direct effect. Predator displacement by humans could then indirectly benefit prey species by reducing predation risk, a trait-mediated indirect effect of humans that spatially decouples predators from prey. The purpose of this research was to test the hypothesis that high-human activity was displacing predators and thus indirectly creating spatial refuge for prey species, helping prey win the “space race”. We measured the occurrence of eleven large mammal species (including humans and cattle) at 43 camera traps deployed on roads and trails in southwest Alberta, Canada. We tested species co-occurrence at camera sites using hierarchical cluster and nonmetric multidimensional scaling (NMS) analyses; and tested whether human activity, food and/or habitat influenced predator and prey species counts at camera sites using regression tree analysis. Cluster and NMS analysis indicated that at camera sites humans co-occurred with prey species more than predator species and predator species had relatively low co-occurrence with prey species. Regression tree analysis indicated that prey species were three times more abundant on roads and trails with >32 humans/day. However, predators were less abundant on roads and trails that exceeded 18 humans/day. Our results support the hypothesis that high-human activity displaced predators but not prey species, creating spatial refuge from predation. High-human activity on roads and trails (i.e., >18 humans/day) has the potential to interfere with predator-prey interactions via trait-mediated direct and indirect effects. We urge scientist and managers to carefully consider and quantify the trait-mediated indirect effects of humans, in addition to direct effects, when assessing human impacts on wildlife and ecosystems. PMID:21399682

Structure and signalling functions of C3 receptors on human B cells.

PubMed

Frade, R

1990-03-01

CR1 (C3b receptor) and CR2 (C3d/EBV receptor) are two C3 receptors expressed on B lymphocytes. CR1 and CR2 have structural similarities and their cross-linking at the B cell surface by antibodies or specific ligands in multimeric forms induce B cell activation. However, activation of human B cells through cell surface interactions or by intracellular protein kinase C activators leads to phosphorylation of CR2 but not CR1. CR2 is phosphorylated on serine and tyrosine residues. Analysis of post-membrane events associated with CR2 revealed intracellular interactions of CR2 with p53, a plasma membrane anti-oncogene-encoded phosphoprotein, and with p120, a nuclear phosphoribonucleoprotein. These intracellular interactions probably represent important steps in the signalling functions of CR2.

Distributed Neural Activity Patterns during Human-to-Human Competition

PubMed Central

Piva, Matthew; Zhang, Xian; Noah, J. Adam; Chang, Steve W. C.; Hirsch, Joy

2017-01-01

Interpersonal interaction is the essence of human social behavior. However, conventional neuroimaging techniques have tended to focus on social cognition in single individuals rather than on dyads or groups. As a result, relatively little is understood about the neural events that underlie face-to-face interaction. We resolved some of the technical obstacles inherent in studying interaction using a novel imaging modality and aimed to identify neural mechanisms engaged both within and across brains in an ecologically valid instance of interpersonal competition. Functional near-infrared spectroscopy was utilized to simultaneously measure hemodynamic signals representing neural activity in pairs of subjects playing poker against each other (human–human condition) or against computer opponents (human–computer condition). Previous fMRI findings concerning single subjects confirm that neural areas recruited during social cognition paradigms are individually sensitive to human–human and human–computer conditions. However, it is not known whether face-to-face interactions between opponents can extend these findings. We hypothesize distributed effects due to live processing and specific variations in across-brain coherence not observable in single-subject paradigms. Angular gyrus (AG), a component of the temporal-parietal junction (TPJ) previously found to be sensitive to socially relevant cues, was selected as a seed to measure within-brain functional connectivity. Increased connectivity was confirmed between AG and bilateral dorsolateral prefrontal cortex (dlPFC) as well as a complex including the left subcentral area (SCA) and somatosensory cortex (SS) during interaction with a human opponent. These distributed findings were supported by contrast measures that indicated increased activity at the left dlPFC and frontopolar area that partially overlapped with the region showing increased functional connectivity with AG. Across-brain analyses of neural coherence between the players revealed synchrony between dlPFC and supramarginal gyrus (SMG) and SS in addition to synchrony between AG and the fusiform gyrus (FG) and SMG. These findings present the first evidence of a frontal-parietal neural complex including the TPJ, dlPFC, SCA, SS, and FG that is more active during human-to-human social cognition both within brains (functional connectivity) and across brains (across-brain coherence), supporting a model of functional integration of socially and strategically relevant information during live face-to-face competitive behaviors. PMID:29218005

Sphingosine kinase inhibition alleviates endothelial permeability induced by thrombin and activated neutrophils.

PubMed

Itagaki, Kiyoshi; Zhang, Qin; Hauser, Carl J

2010-04-01

Inflammation and microvascular thrombosis are interrelated causes of acute lung injury in the systemic inflammatory response syndrome. Neutrophils (polymorphonuclear neutrophil [PMN]) and endothelial cells (EC) activated by systemic inflammatory response syndrome interact to increase pulmonary vascular permeability, but the interactions between PMN and EC are difficult to study. Recently, we reported that sphingosine 1-phosphate is a second messenger eliciting store-operated calcium entry (SOCE) in response to inflammatory agonists in both PMN and EC. Store-operated calcium entry is therefore a target mechanism for the therapeutic modulation of inflammatory PMN-EC interactions. Here, we isolated, modeled, and studied the effects of pharmacologic SOCE inhibition using real-time systems to monitor EC permeability after exposure to activated PMN. We created systems to continuously assess permeability of human pulmonary artery endothelial cells and human microvascular endothelial cells from lung. Endothelial cells show increased permeability after challenge by activated PMN. Such permeability increases can be attenuated by exposure of the cocultures to sphingosine kinase (SK) inhibitors (SKI-2, N,N-dimethylsphingosine [DMS]) or Ca2+ entry inhibitors (Gd3+, MRS-1845). Human microvascular endothelial cells from lung pretreated with SKI-2 or DMS showed decreased permeability when later exposed to activated PMN. Likewise, when PMNs were activated with thapsigargin (TG) in the presence of SKI-2, DMS, Gd, or MRS-1845, their ability to cause EC permeability subsequently was reduced. SKI-2 also inhibited the activation of human pulmonary artery ECs by thrombin. These studies will provide a firm mechanistic foundation for understanding how systemic SOCE inhibition may be used to prevent acute lung injury in vivo.

Hands-On! Living in the Biosphere: Production, Pattern, Population, and Diversity. Developing Active Learning Module on the Human Dimensions of Global Change.

ERIC Educational Resources Information Center

Brown, Dwight

Biogeography examines questions of organism inventory and pattern, organisms' interactions with the environment, and the processes that create and change inventory, pattern, and interactions. This learning module uses time series maps and simple simulation models to illustrate how human actions alter biological productivity patterns at local and…

Simulating forest landscape disturbances as coupled human and natural systems

USGS Publications Warehouse

Wimberly, Michael; Sohl, Terry L.; Liu, Zhihua; Lamsal, Aashis

2015-01-01

Anthropogenic disturbances resulting from human land use affect forest landscapes over a range of spatial and temporal scales, with diverse influences on vegetation patterns and dynamics. These processes fall within the scope of the coupled human and natural systems (CHANS) concept, which has emerged as an important framework for understanding the reciprocal interactions and feedbacks that connect human activities and ecosystem responses. Spatial simulation modeling of forest landscape change is an important technique for exploring the dynamics of CHANS over large areas and long time periods. Landscape models for simulating interactions between human activities and forest landscape dynamics can be grouped into two main categories. Forest landscape models (FLMs) focus on landscapes where forests are the dominant land cover and simulate succession and natural disturbances along with forest management activities. In contrast, land change models (LCMs) simulate mosaics of different land cover and land use classes that include forests in addition to other land uses such as developed areas and agricultural lands. There are also several examples of coupled models that combine elements of FLMs and LCMs. These integrated models are particularly useful for simulating human–natural interactions in landscapes where human settlement and agriculture are expanding into forested areas. Despite important differences in spatial scale and disciplinary scope, FLMs and LCMs have many commonalities in conceptual design and technical implementation that can facilitate continued integration. The ultimate goal will be to implement forest landscape disturbance modeling in a CHANS framework that recognizes the contextual effects of regional land use and other human activities on the forest ecosystem while capturing the reciprocal influences of forests and their disturbances on the broader land use mosaic.

Quantifying human-environment interactions using videography in the context of infectious disease transmission.

PubMed

Julian, Timothy R; Bustos, Carla; Kwong, Laura H; Badilla, Alejandro D; Lee, Julia; Bischel, Heather N; Canales, Robert A

2018-05-08

Quantitative data on human-environment interactions are needed to fully understand infectious disease transmission processes and conduct accurate risk assessments. Interaction events occur during an individual's movement through, and contact with, the environment, and can be quantified using diverse methodologies. Methods that utilize videography, coupled with specialized software, can provide a permanent record of events, collect detailed interactions in high resolution, be reviewed for accuracy, capture events difficult to observe in real-time, and gather multiple concurrent phenomena. In the accompanying video, the use of specialized software to capture humanenvironment interactions for human exposure and disease transmission is highlighted. Use of videography, combined with specialized software, allows for the collection of accurate quantitative representations of human-environment interactions in high resolution. Two specialized programs include the Virtual Timing Device for the Personal Computer, which collects sequential microlevel activity time series of contact events and interactions, and LiveTrak, which is optimized to facilitate annotation of events in real-time. Opportunities to annotate behaviors at high resolution using these tools are promising, permitting detailed records that can be summarized to gain information on infectious disease transmission and incorporated into more complex models of human exposure and risk.

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

PubMed Central

Su, Qiao; Guan, Tianbing; Lv, Haitao

2016-01-01

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

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

PubMed

Su, Qiao; Guan, Tianbing; Lv, Haitao

2016-04-14

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

Human Engineering Operations and Habitability Assessment: A Process for Advanced Life Support Ground Facility Testbeds

NASA Technical Reports Server (NTRS)

Connolly, Janis H.; Arch, M.; Elfezouaty, Eileen Schultz; Novak, Jennifer Blume; Bond, Robert L. (Technical Monitor)

1999-01-01

Design and Human Engineering (HE) processes strive to ensure that the human-machine interface is designed for optimal performance throughout the system life cycle. Each component can be tested and assessed independently to assure optimal performance, but it is not until full integration that the system and the inherent interactions between the system components can be assessed as a whole. HE processes (which are defining/app lying requirements for human interaction with missions/systems) are included in space flight activities, but also need to be included in ground activities and specifically, ground facility testbeds such as Bio-Plex. A unique aspect of the Bio-Plex Facility is the integral issue of Habitability which includes qualities of the environment that allow humans to work and live. HE is a process by which Habitability and system performance can be assessed.

Robots As Intentional Agents: Using Neuroscientific Methods to Make Robots Appear More Social.

PubMed

Wiese, Eva; Metta, Giorgio; Wykowska, Agnieszka

2017-01-01

Robots are increasingly envisaged as our future cohabitants. However, while considerable progress has been made in recent years in terms of their technological realization, the ability of robots to interact with humans in an intuitive and social way is still quite limited. An important challenge for social robotics is to determine how to design robots that can perceive the user's needs, feelings, and intentions, and adapt to users over a broad range of cognitive abilities. It is conceivable that if robots were able to adequately demonstrate these skills, humans would eventually accept them as social companions. We argue that the best way to achieve this is using a systematic experimental approach based on behavioral and physiological neuroscience methods such as motion/eye-tracking, electroencephalography, or functional near-infrared spectroscopy embedded in interactive human-robot paradigms. This approach requires understanding how humans interact with each other, how they perform tasks together and how they develop feelings of social connection over time, and using these insights to formulate design principles that make social robots attuned to the workings of the human brain. In this review, we put forward the argument that the likelihood of artificial agents being perceived as social companions can be increased by designing them in a way that they are perceived as intentional agents that activate areas in the human brain involved in social-cognitive processing. We first review literature related to social-cognitive processes and mechanisms involved in human-human interactions, and highlight the importance of perceiving others as intentional agents to activate these social brain areas. We then discuss how attribution of intentionality can positively affect human-robot interaction by (a) fostering feelings of social connection, empathy and prosociality, and by (b) enhancing performance on joint human-robot tasks. Lastly, we describe circumstances under which attribution of intentionality to robot agents might be disadvantageous, and discuss challenges associated with designing social robots that are inspired by neuroscientific principles.

Human Neutrophil Peptides Mediate Endothelial-Monocyte Interaction, Foam Cell Formation, and Platelet Activation

PubMed Central

Quinn, Kieran L.; Henriques, Melanie; Tabuchi, Arata; Han, Bing; Yang, Hong; Cheng, Wei-Erh; Tole, Soumitra; Yu, Hanpo; Luo, Alice; Charbonney, Emmanuel; Tullis, Elizabeth; Lazarus, Alan; Robinson, Lisa A.; Ni, Heyu; Peterson, Blake R.; Kuebler, Wolfgang M.; Slutsky, Arthur S.; Zhang, Haibo

2016-01-01

Objective Neutrophils are involved in the inflammatory responses during atherosclerosis. Human neutrophil peptides (HNPs) released from activated neutrophils exert immune modulating properties. We hypothesized that HNPs play an important role in neutrophil-mediated inflammatory cardiovascular responses in atherosclerosis. Methods and Results We examined the role of HNPs in endothelial-leukocyte interaction, platelet activation, and foam cell formation in vitro and in vivo. We demonstrated that stimulation of human coronary artery endothelial cells with clinically relevant concentrations of HNPs resulted in monocyte adhesion and transmigration; induction of oxidative stress in human macrophages, which accelerates foam cell formation; and activation and aggregation of human platelets. The administration of superoxide dismutase or anti-CD36 antibody reduced foam cell formation and cholesterol efflux. Mice deficient in double genes of low-density lipoprotein receptor and low-density lipoprotein receptor–related protein (LRP), and mice deficient in a single gene of LRP8, the only LRP phenotype expressed in platelets, showed reduced leukocyte rolling and decreased platelet aggregation and thrombus formation in response to HNP stimulation. Conclusion HNPs exert proatherosclerotic properties that appear to be mediated through LRP8 signaling pathways, suggesting an important role for HNPs in the development of inflammatory cardiovascular diseases. PMID:21817096

Interaction of the Human Contact System with Pathogens-An Update.

PubMed

Oehmcke-Hecht, Sonja; Köhler, Juliane

2018-01-01

The name human contact system is related to its mode of action, as "contact" with artificial negatively charged surfaces triggers its activation. Today, it is generally believed that the contact system is an inflammatory response mechanism not only against artificial material but also against misfolded proteins and foreign organisms. Upon activation, the contact system is involved in at least two distinct (patho)physiologic processes: i . the trigger of the intrinsic coagulation via factor XI and ii . the cleavage of high molecular weight kininogen with release of bradykinin and antimicrobial peptides (AMPs). Bradykinin is involved in the regulation of inflammatory processes, vascular permeability, and blood pressure. Due to the release of AMPs, the contact system is regarded as a branch of the innate immune defense against microorganisms. There is an increasing list of pathogens that interact with contact factors, in addition to bacteria also fungi and viruses bind and activate the system. In spite of that, pathogens have developed their own mechanisms to activate the contact system, resulting in manipulation of this host immune response. In this up-to-date review, we summarize present research on the interaction of pathogens with the human contact system, focusing particularly on bacterial and viral mechanisms that trigger inflammation via contact system activation.

Interaction between vestibulosympathetic and skeletal muscle reflexes on sympathetic activity in humans

NASA Technical Reports Server (NTRS)

Ray, C. A.

2001-01-01

Evidence from animals indicates that skeletal muscle afferents activate the vestibular nuclei and that both vestibular and skeletal muscle afferents have inputs to the ventrolateral medulla. The purpose of the present study was to investigate the interaction between the vestibulosympathetic and skeletal muscle reflexes on muscle sympathetic nerve activity (MSNA) and arterial pressure in humans. MSNA, arterial pressure, and heart rate were measured in 17 healthy subjects in the prone position during three experimental trials. The three trials were 2 min of 1) head-down rotation (HDR) to engage the vestibulosympathetic reflex, 2) isometric handgrip (IHG) at 30% maximal voluntary contraction to activate skeletal muscle afferents, and 3) HDR and IHG performed simultaneously. The order of the three trials was randomized. HDR and IHG performed alone increased total MSNA by 46 +/- 16 and 77 +/- 24 units, respectively (P < 0.01). During the HDR plus IHG trial, MSNA increased 142 +/- 38 units (P < 0.01). This increase was not significantly different from the sum of the individual trials (130 +/- 41 units). This finding was also observed with mean arterial pressure (sum = 21 +/- 2 mmHg and HDR + IHG = 22 +/- 2 mmHg). These findings suggest that there is an additive interaction for MSNA and arterial pressure when the vestibulosympathetic and skeletal muscle reflexes are engaged simultaneously in humans. Therefore, no central modulation exists between these two reflexes with regard to MSNA output in humans.

Ternary Complex Factors and Cofactors Are Essential for Human T-Cell Leukemia Virus Type 1 Tax Transactivation of the Serum Response Element

PubMed Central

Shuh, Maureen; Derse, David

2000-01-01

The human T-cell leukemia virus type 1 Tax protein activates the expression of cellular immediate early genes controlled by the serum response element (SRE), which contains both the serum response factor (SRF) binding element (CArG box) and the ternary complex factor (TCF) binding element (Ets box). We show that TCF binding is necessary for Tax activation of the SRE and that Tax directly interacts with TCFs in vitro. In addition, Tax interactions with CREB binding protein (CBP) and p300- and CBP-associated factor were found to be essential for Tax activation of SRF-mediated transcription. PMID:11070040

Lack of discrimination between DNA ligases I and III by two classes of inhibitors, anthracyclines and distamycins.

PubMed

Montecucco, A; Lestingi, M; Rossignol, J M; Elder, R H; Ciarrocchi, G

1993-04-06

We have measured the effects of eight distamycin and two anthracycline derivatives on polynucleotide joining and self-adenylating activities of human DNA ligase I and rat DNA ligases I and III. All test drugs show good inhibitory activity against the three enzymes in the poly[d(A-T)] joining assay. Several distamycins also inhibit the DNA-independent self-adenylation reaction catalysed by the human enzyme and, to a lesser extent, by rat DNA ligases. These results confirm that anthracyclines and distamycins express their inhibitory action against DNA joining activities mainly via specific interactions with the substrate, and suggest that the three test DNA ligases utilize similar, if not identical, mechanisms of recognition and interaction with DNA-drug complexes. Our findings also indicate that distamycins have a greater affinity for human DNA ligase I than for rat enzymes, suggesting that, in this respect, rat DNA ligase I is more similar to rat DNA ligase III than to human DNA ligase I.

Activity Catalog Tool (ACT) user manual, version 2.0

NASA Technical Reports Server (NTRS)

Segal, Leon D.; Andre, Anthony D.

1994-01-01

This report comprises the user manual for version 2.0 of the Activity Catalog Tool (ACT) software program, developed by Leon D. Segal and Anthony D. Andre in cooperation with NASA Ames Aerospace Human Factors Research Division, FLR branch. ACT is a software tool for recording and analyzing sequences of activity over time that runs on the Macintosh platform. It was designed as an aid for professionals who are interested in observing and understanding human behavior in field settings, or from video or audio recordings of the same. Specifically, the program is aimed at two primary areas of interest: human-machine interactions and interactions between humans. The program provides a means by which an observer can record an observed sequence of events, logging such parameters as frequency and duration of particular events. The program goes further by providing the user with a quantified description of the observed sequence, through application of a basic set of statistical routines, and enables merging and appending of several files and more extensive analysis of the resultant data.

Predicting human activities in sequences of actions in RGB-D videos

NASA Astrophysics Data System (ADS)

Jardim, David; Nunes, Luís.; Dias, Miguel

2017-03-01

In our daily activities we perform prediction or anticipation when interacting with other humans or with objects. Prediction of human activity made by computers has several potential applications: surveillance systems, human computer interfaces, sports video analysis, human-robot-collaboration, games and health-care. We propose a system capable of recognizing and predicting human actions using supervised classifiers trained with automatically labeled data evaluated in our human activity RGB-D dataset (recorded with a Kinect sensor) and using only the position of the main skeleton joints to extract features. Using conditional random fields (CRFs) to model the sequential nature of actions in a sequence has been used before, but where other approaches try to predict an outcome or anticipate ahead in time (seconds), we try to predict what will be the next action of a subject. Our results show an activity prediction accuracy of 89.9% using an automatically labeled dataset.

The Murine Factor H-Related Protein FHR-B Promotes Complement Activation.

PubMed

Cserhalmi, Marcell; Csincsi, Ádám I; Mezei, Zoltán; Kopp, Anne; Hebecker, Mario; Uzonyi, Barbara; Józsi, Mihály

2017-01-01

Factor H-related (FHR) proteins consist of varying number of complement control protein domains that display various degrees of sequence identity to respective domains of the alternative pathway complement inhibitor factor H (FH). While such FHR proteins are described in several species, only human FHRs were functionally investigated. Their biological role is still poorly understood and in part controversial. Recent studies on some of the human FHRs strongly suggest a role for FHRs in enhancing complement activation via competing with FH for binding to certain ligands and surfaces. The aim of the current study was the functional characterization of a murine FHR, FHR-B. To this end, FHR-B was expressed in recombinant form. Recombinant FHR-B bound to human C3b and was able to compete with human FH for C3b binding. FHR-B supported the assembly of functionally active C3bBb alternative pathway C3 convertase via its interaction with C3b. This activity was confirmed by demonstrating C3 activation in murine serum. In addition, FHR-B bound to murine pentraxin 3 (PTX3), and this interaction resulted in murine C3 fragment deposition due to enhanced complement activation in mouse serum. FHR-B also induced C3 deposition on C-reactive protein, the extracellular matrix (ECM) extract Matrigel, and endothelial cell-derived ECM when exposed to mouse serum. Moreover, mouse C3 deposition was strongly enhanced on necrotic Jurkat T cells and the mouse B cell line A20 by FHR-B. FHR-B also induced lysis of sheep erythrocytes when incubated in mouse serum with FHR-B added in excess. Altogether, these data demonstrate that, similar to human FHR-1 and FHR-5, mouse FHR-B modulates complement activity by promoting complement activation via interaction with C3b and via competition with murine FH.

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

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

Effects of Human-Nature Interactions on Wildlife Habitat Dynamics: The Case of Wolong Nature Reserve for Giant Pandas

NASA Astrophysics Data System (ADS)

Vina, A.; Tuanmu, M.; Yang, W.; Liu, J.

2012-12-01

Human activities continue to induce the degradation of natural ecosystems, thus threatening not only the long-term survival of many wildlife species around the world, but also the resilience of natural ecosystems to global environmental changes. In response, many conservation efforts are emerging as adaptive strategies for coping with the degradation of natural ecosystems. Among them, the establishment of nature reserves is considered to be the most effective. However the effectiveness of nature reserves depends on the type and intensity of human activities occurring within their boundaries. But many of these activities constitute important livelihood systems for local human populations. Therefore, to enhance the effectiveness of conservation actions without significantly affecting local livelihood systems, it is essential to understand the complexity of human-nature interactions and their effects on the spatio-temporal dynamics of natural ecosystems. In this study, we evaluated the relation between giant panda habitat dynamics, conservation efforts and human activities in Wolong Nature Reserve for Giant Pandas, Sichuan Province, China. This reserve supports ca. 10% of the entire wild giant panda population but is also home to ca. 4,900 local residents. The spatio-temporal dynamics of giant panda habitat over the last four decades were analyzed using a time series of remotely sensed imagery acquired by different satellite sensor systems, including the Landsat Multi-Spectral Scanner, the Landsat Thematic Mapper and the Moderate Resolution Imaging Spectroradiometer (MODIS). Our assessment suggests that when local residents were actively involved in conservation efforts (through a payment for ecosystem services scheme established since around 2000) panda habitat started to recover, thus enhancing the resilience capacity of natural ecosystems in the Reserve. This reversed a long-term (> 30 years) trend of panda habitat degradation. The study not only has direct implications for wildlife habitat conservation but also increases our understanding of the complexity of human-nature interactions and their effects on the resilience of natural ecosystems.

Social Capital, Human Capital and Parent-Child Relation Quality: Interacting for Children's Educational Achievement?

ERIC Educational Resources Information Center

von Otter, Cecilia; Stenberg, Sten-Åke

2015-01-01

We analyse the utility of social capital for children's achievement, and if this utility interacts with family human capital and the quality of the parent-child relationship. Our focus is on parental activities directly related to children's school work. Our data stem from a Swedish cohort born in 1953 and consist of both survey and register data.…

Human DHEA sulfation requires direct interaction between PAPS synthase 2 and DHEA sulfotransferase SULT2A1.

PubMed

Mueller, Jonathan W; Idkowiak, Jan; Gesteira, Tarsis F; Vallet, Cecilia; Hardman, Rebecca; van den Boom, Johannes; Dhir, Vivek; Knauer, Shirley K; Rosta, Edina; Arlt, Wiebke

2018-06-22

The high-energy sulfate donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS), generated by human PAPS synthase isoforms PAPSS1 and PAPSS2, is required for all human sulfation pathways. Sulfotransferase SULT2A1 uses PAPS for sulfation of the androgen precursor dehydroepiandrosterone (DHEA), thereby reducing downstream activation of DHEA to active androgens. Human PAPSS2 mutations manifest with undetectable DHEA sulfate, androgen excess, and metabolic disease, suggesting that ubiquitous PAPSS1 cannot compensate for deficient PAPSS2 in supporting DHEA sulfation. In knockdown studies in human adrenocortical NCI-H295R1 cells, we found that PAPSS2, but not PAPSS1, is required for efficient DHEA sulfation. Specific APS kinase activity, the rate-limiting step in PAPS biosynthesis, did not differ between PAPSS1 and PAPSS2. Co-expression of cytoplasmic SULT2A1 with a cytoplasmic PAPSS2 variant supported DHEA sulfation more efficiently than co-expression with nuclear PAPSS2 or nuclear/cytosolic PAPSS1. Proximity ligation assays revealed protein-protein interactions between SULT2A1 and PAPSS2 and, to a lesser extent, PAPSS1. Molecular docking studies showed a putative binding site for SULT2A1 within the PAPSS2 APS kinase domain. Energy-dependent scoring of docking solutions identified the interaction as specific for the PAPSS2 and SULT2A1 isoforms. These findings elucidate the mechanistic basis for the selective requirement for PAPSS2 in human DHEA sulfation. © 2018 Mueller et al.

Digital item for digital human memory--television commerce application: family tree albuming system

NASA Astrophysics Data System (ADS)

Song, Jaeil; Lee, Hyejoo; Hong, JinWoo

2004-01-01

Technical advance in creating, storing digital media in daily life enables computers to capture human life and remember it as people do. A critical point with digitizing human life is how to recall bits of experience that are associated by semantic information. This paper proposes a technique for structuring dynamic digital object based on MPEG-21 Digital Item (DI) in order to recall human"s memory and providing interactive TV service on family tree albuming system as one of its applications. DIs are a dynamically reconfigurable, uniquely identified, described by a descriptor language, logical unit for structuring relationship among multiple media resources. Digital Item Processing (DIP) provides the means to interact with DIs to remind context to user, with active properties where objects have executable properties. Each user can adapt DIs" active properties to tailor the behavior of DIs to match his/her own specific needs. DIs" technologies in Intellectual Property Management and Protection (IPMP) can be used for privacy protection. In the interaction between the social space and technological space, the internal dynamics of family life fits well sharing family albuming service via family television. Family albuming service can act as virtual communities builders for family members. As memory is shared between family members, multiple annotations (including active properties on contextual information) will be made with snowballing value.

Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers

PubMed Central

Raj, Ganesh V; Sareddy, Gangadhara Reddy; Ma, Shihong; Lee, Tae-Kyung; Viswanadhapalli, Suryavathi; Li, Rui; Liu, Xihui; Murakami, Shino; Chen, Chien-Cheng; Lee, Wan-Ru; Mann, Monica; Krishnan, Samaya Rajeshwari; Manandhar, Bikash; Gonugunta, Vijay K; Strand, Douglas; Tekmal, Rajeshwar Rao; Ahn, Jung-Mo; Vadlamudi, Ratna K

2017-01-01

The majority of human breast cancer is estrogen receptor alpha (ER) positive. While anti-estrogens/aromatase inhibitors are initially effective, resistance to these drugs commonly develops. Therapy-resistant tumors often retain ER signaling, via interaction with critical oncogenic coregulator proteins. To address these mechanisms of resistance, we have developed a novel ER coregulator binding modulator, ERX-11. ERX-11 interacts directly with ER and blocks the interaction between a subset of coregulators with both native and mutant forms of ER. ERX-11 effectively blocks ER-mediated oncogenic signaling and has potent anti-proliferative activity against therapy-sensitive and therapy-resistant human breast cancer cells. ERX-11 is orally bioavailable, with no overt signs of toxicity and potent activity in both murine xenograft and patient-derived breast tumor explant models. This first-in-class agent, with its novel mechanism of action of disrupting critical protein-protein interactions, overcomes the limitations of current therapies and may be clinically translatable for patients with therapy-sensitive and therapy-resistant breast cancers. DOI: http://dx.doi.org/10.7554/eLife.26857.001 PMID:28786813

A Novel Biclustering Approach to Association Rule Mining for Predicting HIV-1–Human Protein Interactions

PubMed Central

Mukhopadhyay, Anirban; Maulik, Ujjwal; Bandyopadhyay, Sanghamitra

2012-01-01

Identification of potential viral-host protein interactions is a vital and useful approach towards development of new drugs targeting those interactions. In recent days, computational tools are being utilized for predicting viral-host interactions. Recently a database containing records of experimentally validated interactions between a set of HIV-1 proteins and a set of human proteins has been published. The problem of predicting new interactions based on this database is usually posed as a classification problem. However, posing the problem as a classification one suffers from the lack of biologically validated negative interactions. Therefore it will be beneficial to use the existing database for predicting new viral-host interactions without the need of negative samples. Motivated by this, in this article, the HIV-1–human protein interaction database has been analyzed using association rule mining. The main objective is to identify a set of association rules both among the HIV-1 proteins and among the human proteins, and use these rules for predicting new interactions. In this regard, a novel association rule mining technique based on biclustering has been proposed for discovering frequent closed itemsets followed by the association rules from the adjacency matrix of the HIV-1–human interaction network. Novel HIV-1–human interactions have been predicted based on the discovered association rules and tested for biological significance. For validation of the predicted new interactions, gene ontology-based and pathway-based studies have been performed. These studies show that the human proteins which are predicted to interact with a particular viral protein share many common biological activities. Moreover, literature survey has been used for validation purpose to identify some predicted interactions that are already validated experimentally but not present in the database. Comparison with other prediction methods is also discussed. PMID:22539940

Human mast cell neutral proteases generate modified LDL particles with increased proteoglycan binding.

PubMed

Maaninka, Katariina; Nguyen, Su Duy; Mäyränpää, Mikko I; Plihtari, Riia; Rajamäki, Kristiina; Lindsberg, Perttu J; Kovanen, Petri T; Öörni, Katariina

2018-04-13

Subendothelial interaction of LDL with extracellular matrix drives atherogenesis. This interaction can be strengthened by proteolytic modification of LDL. Mast cells (MCs) are present in atherosclerotic lesions, and upon activation, they degranulate and release a variety of neutral proteases. Here we studied the ability of MC proteases to cleave apoB-100 of LDL and affect the binding of LDL to proteoglycans. Mature human MCs were differentiated from human peripheral blood-derived CD34 + progenitors in vitro and activated with calcium ionophore to generate MC-conditioned medium. LDL was incubated in the MC-conditioned medium or with individual MC proteases, and the binding of native and modified LDL to isolated human aortic proteoglycans or to human atherosclerotic plaques ex vivo was determined. MC proteases in atherosclerotic human coronary artery lesions were detected by immunofluorescence and qPCR. Activated human MCs released the neutral proteases tryptase, chymase, carboxypeptidase A3, cathepsin G, and granzyme B. Of these, cathepsin G degraded most efficiently apoB-100, induced LDL fusion, and enhanced binding of LDL to isolated human aortic proteoglycans and human atherosclerotic lesions ex vivo. Double immunofluoresence staining of human atherosclerotic coronary arteries for tryptase and cathepsin G indicated that lesional MCs contain cathepsin G. In the lesions, expression of cathepsin G correlated with the expression of tryptase and chymase, but not with that of neutrophil proteinase 3. The present study suggests that cathepsin G in human atherosclerotic lesions is largely derived from MCs and that activated MCs may contribute to atherogenesis by enhancing LDL retention. Copyright © 2018 Elsevier B.V. All rights reserved.

Insight into bacterial virulence mechanisms against host immune response via the Yersinia pestis-human protein-protein interaction network.

PubMed

Yang, Huiying; Ke, Yuehua; Wang, Jian; Tan, Yafang; Myeni, Sebenzile K; Li, Dong; Shi, Qinghai; Yan, Yanfeng; Chen, Hui; Guo, Zhaobiao; Yuan, Yanzhi; Yang, Xiaoming; Yang, Ruifu; Du, Zongmin

2011-11-01

A Yersinia pestis-human protein interaction network is reported here to improve our understanding of its pathogenesis. Up to 204 interactions between 66 Y. pestis bait proteins and 109 human proteins were identified by yeast two-hybrid assay and then combined with 23 previously published interactions to construct a protein-protein interaction network. Topological analysis of the interaction network revealed that human proteins targeted by Y. pestis were significantly enriched in the proteins that are central in the human protein-protein interaction network. Analysis of this network showed that signaling pathways important for host immune responses were preferentially targeted by Y. pestis, including the pathways involved in focal adhesion, regulation of cytoskeleton, leukocyte transendoepithelial migration, and Toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) signaling. Cellular pathways targeted by Y. pestis are highly relevant to its pathogenesis. Interactions with host proteins involved in focal adhesion and cytoskeketon regulation pathways could account for resistance of Y. pestis to phagocytosis. Interference with TLR and MAPK signaling pathways by Y. pestis reflects common characteristics of pathogen-host interaction that bacterial pathogens have evolved to evade host innate immune response by interacting with proteins in those signaling pathways. Interestingly, a large portion of human proteins interacting with Y. pestis (16/109) also interacted with viral proteins (Epstein-Barr virus [EBV] and hepatitis C virus [HCV]), suggesting that viral and bacterial pathogens attack common cellular functions to facilitate infections. In addition, we identified vasodilator-stimulated phosphoprotein (VASP) as a novel interaction partner of YpkA and showed that YpkA could inhibit in vitro actin assembly mediated by VASP.

Prosthetic Leg Control in the Nullspace of Human Interaction.

PubMed

Gregg, Robert D; Martin, Anne E

2016-07-01

Recent work has extended the control method of virtual constraints, originally developed for autonomous walking robots, to powered prosthetic legs for lower-limb amputees. Virtual constraints define desired joint patterns as functions of a mechanical phasing variable, which are typically enforced by torque control laws that linearize the output dynamics associated with the virtual constraints. However, the output dynamics of a powered prosthetic leg generally depend on the human interaction forces, which must be measured and canceled by the feedback linearizing control law. This feedback requires expensive multi-axis load cells, and actively canceling the interaction forces may minimize the human's influence over the prosthesis. To address these limitations, this paper proposes a method for projecting virtual constraints into the nullspace of the human interaction terms in the output dynamics. The projected virtual constraints naturally render the output dynamics invariant with respect to the human interaction forces, which instead enter into the internal dynamics of the partially linearized prosthetic system. This method is illustrated with simulations of a transfemoral amputee model walking with a powered knee-ankle prosthesis that is controlled via virtual constraints with and without the proposed projection.

Hunter-Gatherer Inter-Band Interaction Rates: Implications for Cumulative Culture

PubMed Central

Hill, Kim R.; Wood, Brian M.; Baggio, Jacopo; Hurtado, A. Magdalena; Boyd, Robert T.

2014-01-01

Our species exhibits spectacular success due to cumulative culture. While cognitive evolution of social learning mechanisms may be partially responsible for adaptive human culture, features of early human social structure may also play a role by increasing the number potential models from which to learn innovations. We present interview data on interactions between same-sex adult dyads of Ache and Hadza hunter-gatherers living in multiple distinct residential bands (20 Ache bands; 42 Hadza bands; 1201 dyads) throughout a tribal home range. Results show high probabilities (5%–29% per year) of cultural and cooperative interactions between randomly chosen adults. Multiple regression suggests that ritual relationships increase interaction rates more than kinship, and that affinal kin interact more often than dyads with no relationship. These may be important features of human sociality. Finally, yearly interaction rates along with survival data allow us to estimate expected lifetime partners for a variety of social activities, and compare those to chimpanzees. Hadza and Ache men are estimated to observe over 300 men making tools in a lifetime, whereas male chimpanzees interact with only about 20 other males in a lifetime. High intergroup interaction rates in ancestral humans may have promoted the evolution of cumulative culture. PMID:25047714

Hunter-gatherer inter-band interaction rates: implications for cumulative culture.

PubMed

Hill, Kim R; Wood, Brian M; Baggio, Jacopo; Hurtado, A Magdalena; Boyd, Robert T

2014-01-01

Our species exhibits spectacular success due to cumulative culture. While cognitive evolution of social learning mechanisms may be partially responsible for adaptive human culture, features of early human social structure may also play a role by increasing the number potential models from which to learn innovations. We present interview data on interactions between same-sex adult dyads of Ache and Hadza hunter-gatherers living in multiple distinct residential bands (20 Ache bands; 42 Hadza bands; 1201 dyads) throughout a tribal home range. Results show high probabilities (5%-29% per year) of cultural and cooperative interactions between randomly chosen adults. Multiple regression suggests that ritual relationships increase interaction rates more than kinship, and that affinal kin interact more often than dyads with no relationship. These may be important features of human sociality. Finally, yearly interaction rates along with survival data allow us to estimate expected lifetime partners for a variety of social activities, and compare those to chimpanzees. Hadza and Ache men are estimated to observe over 300 men making tools in a lifetime, whereas male chimpanzees interact with only about 20 other males in a lifetime. High intergroup interaction rates in ancestral humans may have promoted the evolution of cumulative culture.

Exploring relationship between face-to-face interaction and team performance using wearable sensor badges.

PubMed

Watanabe, Jun-ichiro; Ishibashi, Nozomu; Yano, Kazuo

2014-01-01

Quantitative analyses of human-generated data collected in various fields have uncovered many patterns of complex human behaviors. However, thus far the quantitative evaluation of the relationship between the physical behaviors of employees and their performance has been inadequate. Here, we present findings demonstrating the significant relationship between the physical behaviors of employees and their performance via experiments we conducted in inbound call centers while the employees wore sensor badges. There were two main findings. First, we found that face-to-face interaction among telecommunicators and the frequency of their bodily movements caused by the face-to-face interaction had a significant correlation with the entire call center performance, which we measured as "Calls per Hour." Second, our trial to activate face-to-face interaction on the basis of data collected by the wearable sensor badges the employees wore significantly increased their performance. These results demonstrate quantitatively that human-human interaction in the physical world plays an important role in team performance.

Exploring Relationship between Face-to-Face Interaction and Team Performance Using Wearable Sensor Badges

PubMed Central

Watanabe, Jun-ichiro; Ishibashi, Nozomu; Yano, Kazuo

2014-01-01

Quantitative analyses of human-generated data collected in various fields have uncovered many patterns of complex human behaviors. However, thus far the quantitative evaluation of the relationship between the physical behaviors of employees and their performance has been inadequate. Here, we present findings demonstrating the significant relationship between the physical behaviors of employees and their performance via experiments we conducted in inbound call centers while the employees wore sensor badges. There were two main findings. First, we found that face-to-face interaction among telecommunicators and the frequency of their bodily movements caused by the face-to-face interaction had a significant correlation with the entire call center performance, which we measured as “Calls per Hour.” Second, our trial to activate face-to-face interaction on the basis of data collected by the wearable sensor badges the employees wore significantly increased their performance. These results demonstrate quantitatively that human-human interaction in the physical world plays an important role in team performance. PMID:25501748

Interactions between human behaviour and ecological systems.

PubMed

Milner-Gulland, E J

2012-01-19

Research on the interactions between human behaviour and ecological systems tends to focus on the direct effects of human activities on ecosystems, such as biodiversity loss. There is also increasing research effort directed towards ecosystem services. However, interventions to control people's use of the environment alter the incentives that natural resource users face, and therefore their decisions about resource use. The indirect effects of conservation interventions on biodiversity, modulated through human decision-making, are poorly studied but are likely to be significant and potentially counterintuitive. This is particularly so where people are dependent on multiple natural resources for their livelihoods, when both poverty and biodiversity loss are acute. An inter-disciplinary approach is required to quantify these interactions, with an understanding of human decision-making at its core; otherwise, predictions about the impacts of conservation policies may be highly misleading.

Interactions between human behaviour and ecological systems

PubMed Central

Milner-Gulland, E. J.

2012-01-01

Research on the interactions between human behaviour and ecological systems tends to focus on the direct effects of human activities on ecosystems, such as biodiversity loss. There is also increasing research effort directed towards ecosystem services. However, interventions to control people's use of the environment alter the incentives that natural resource users face, and therefore their decisions about resource use. The indirect effects of conservation interventions on biodiversity, modulated through human decision-making, are poorly studied but are likely to be significant and potentially counterintuitive. This is particularly so where people are dependent on multiple natural resources for their livelihoods, when both poverty and biodiversity loss are acute. An inter-disciplinary approach is required to quantify these interactions, with an understanding of human decision-making at its core; otherwise, predictions about the impacts of conservation policies may be highly misleading. PMID:22144389

Identifying and modeling the structural discontinuities of human interactions

NASA Astrophysics Data System (ADS)

Grauwin, Sebastian; Szell, Michael; Sobolevsky, Stanislav; Hövel, Philipp; Simini, Filippo; Vanhoof, Maarten; Smoreda, Zbigniew; Barabási, Albert-László; Ratti, Carlo

2017-04-01

The idea of a hierarchical spatial organization of society lies at the core of seminal theories in human geography that have strongly influenced our understanding of social organization. Along the same line, the recent availability of large-scale human mobility and communication data has offered novel quantitative insights hinting at a strong geographical confinement of human interactions within neighboring regions, extending to local levels within countries. However, models of human interaction largely ignore this effect. Here, we analyze several country-wide networks of telephone calls - both, mobile and landline - and in either case uncover a systematic decrease of communication induced by borders which we identify as the missing variable in state-of-the-art models. Using this empirical evidence, we propose an alternative modeling framework that naturally stylizes the damping effect of borders. We show that this new notion substantially improves the predictive power of widely used interaction models. This increases our ability to understand, model and predict social activities and to plan the development of infrastructures across multiple scales.

Identifying and modeling the structural discontinuities of human interactions

PubMed Central

Grauwin, Sebastian; Szell, Michael; Sobolevsky, Stanislav; Hövel, Philipp; Simini, Filippo; Vanhoof, Maarten; Smoreda, Zbigniew; Barabási, Albert-László; Ratti, Carlo

2017-01-01

The idea of a hierarchical spatial organization of society lies at the core of seminal theories in human geography that have strongly influenced our understanding of social organization. Along the same line, the recent availability of large-scale human mobility and communication data has offered novel quantitative insights hinting at a strong geographical confinement of human interactions within neighboring regions, extending to local levels within countries. However, models of human interaction largely ignore this effect. Here, we analyze several country-wide networks of telephone calls - both, mobile and landline - and in either case uncover a systematic decrease of communication induced by borders which we identify as the missing variable in state-of-the-art models. Using this empirical evidence, we propose an alternative modeling framework that naturally stylizes the damping effect of borders. We show that this new notion substantially improves the predictive power of widely used interaction models. This increases our ability to understand, model and predict social activities and to plan the development of infrastructures across multiple scales. PMID:28443647

Identifying and modeling the structural discontinuities of human interactions.

PubMed

Grauwin, Sebastian; Szell, Michael; Sobolevsky, Stanislav; Hövel, Philipp; Simini, Filippo; Vanhoof, Maarten; Smoreda, Zbigniew; Barabási, Albert-László; Ratti, Carlo

2017-04-26

The idea of a hierarchical spatial organization of society lies at the core of seminal theories in human geography that have strongly influenced our understanding of social organization. Along the same line, the recent availability of large-scale human mobility and communication data has offered novel quantitative insights hinting at a strong geographical confinement of human interactions within neighboring regions, extending to local levels within countries. However, models of human interaction largely ignore this effect. Here, we analyze several country-wide networks of telephone calls - both, mobile and landline - and in either case uncover a systematic decrease of communication induced by borders which we identify as the missing variable in state-of-the-art models. Using this empirical evidence, we propose an alternative modeling framework that naturally stylizes the damping effect of borders. We show that this new notion substantially improves the predictive power of widely used interaction models. This increases our ability to understand, model and predict social activities and to plan the development of infrastructures across multiple scales.

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.

ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5.

PubMed

Hsu, H; Solovyev, I; Colombero, A; Elliott, R; Kelley, M; Boyle, W J

1997-05-23

Members of tumor necrosis factor receptor (TNFR) family signal largely through interactions with death domain proteins and TRAF proteins. Here we report the identification of a novel TNFR family member ATAR. Human and mouse ATAR contain 283 and 276 amino acids, respectively, making them the shortest known members of the TNFR superfamily. The receptor is expressed mainly in spleen, thymus, bone marrow, lung, and small intestine. The intracellular domains of human and mouse ATAR share only 25% identity, yet both interact with TRAF5 and TRAF2. This TRAF interaction domain resides at the C-terminal 20 amino acids. Like most other TRAF-interacting receptors, overexpression of ATAR activates the transcription factor NF-kappaB. Co-expression of ATAR with TRAF5, but not TRAF2, results in synergistic activation of NF-kappaB, suggesting potentially different roles for TRAF2 and TRAF5 in post-receptor signaling.

Human I-mfa domain proteins specifically interact with KSHV LANA and affect its regulation of Wnt signaling-dependent transcription

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

Kusano, Shuichi, E-mail: skusano@m2.kufm.kagoshima-u.ac.jp; Eizuru, Yoshito

2010-06-04

Kaposi's sarcoma-associated herpes virus (KSHV)-encoded latency-associated nuclear antigen (LANA) protein has been reported to interact with glycogen synthase kinase 3{beta} (GSK-3{beta}) and to negatively regulate its activity, leading to stimulation of GSK-3{beta}-dependent {beta}-catenin degradation. We show here that the I-mfa domain proteins, HIC (human I-mfa domain-containing protein) and I-mfa (inhibitor of MyoD family a), interacted in vivo with LANA through their C-terminal I-mfa domains. This interaction affected the intracellular localization of HIC, inhibited the LANA-dependent transactivation of a {beta}-catenin-regulated reporter construct, and decreased the level of the LANA.GSK-3{beta} complex. These data reveal for the first time that I-mfa domain proteinsmore » interact with LANA and negatively regulate LANA-mediated activation of Wnt signaling-dependent transcription by inhibiting the formation of the LANA.GSK-3{beta} complex.« less

N-Glycosylation of the alpha subunit does not influence trafficking or functional activity of the human organic solute transporter alpha/beta

PubMed Central

Soroka, Carol J; Xu, Shuhua; Mennone, Albert; Lam, Ping; Boyer, James L

2008-01-01

Background The organic solute transporter (OSTα-OSTβ) is a heteromeric transporter that is expressed on the basolateral membrane of epithelium in intestine, kidney, liver, testis and adrenal gland and facilitates efflux of bile acids and other steroid solutes. Both subunits are required for plasma membrane localization of the functional transporter but it is unclear how and where the subunits interact and whether glycosylation is required for functional activity. We sought to examine these questions for the human OSTα-OSTβ transporter using the human hepatoma cell line, HepG2, and COS7 cells transfected with constructs of human OSTα-FLAG and OSTβ-Myc. Results Tunicamycin treatment demonstrated that human OSTα is glycosylated. In COS7 cells Western blotting identified the unglycosylated form (~31 kD), the core precursor form (~35 kD), and the mature, complex glycoprotein (~40 kD). Immunofluorescence of both cells indicated that, in the presence of OSTβ, the alpha subunit could still be expressed on the plasma membrane after tunicamycin treatment. Furthermore, the functional uptake of 3H-estrone sulfate was unchanged in the absence of N-glycosylation. Co-immunoprecipitation indicates that the immature form of OSTα interact with OSTβ. However, immunoprecipitation of OSTβ using an anti-Myc antibody did not co-precipitate the mature, complex glycosylated form of OSTα, suggesting that the primary interaction occurs early in the biosynthetic pathway and may be transient. Conclusion In conclusion, human OSTα is a glycoprotein that requires interaction with OSTβ to reach the plasma membrane. However, glycosylation of OSTα is not necessary for interaction with the beta subunit or for membrane localization or function of the heteromeric transporter. PMID:18847488

Network of Surface-Displayed Glycolytic Enzymes in Mycoplasma pneumoniae and Their Interactions with Human Plasminogen

PubMed Central

Gründel, Anne; Pfeiffer, Melanie; Jacobs, Enno

2015-01-01

In different bacteria, primarily cytosolic and metabolic proteins are characterized as surface localized and interacting with different host factors. These moonlighting proteins include glycolytic enzymes, and it has been hypothesized that they influence the virulence of pathogenic species. The presence of surface-displayed glycolytic enzymes and their interaction with human plasminogen as an important host factor were investigated in the genome-reduced and cell wall-less microorganism Mycoplasma pneumoniae, a common agent of respiratory tract infections of humans. After successful expression of 19 glycolytic enzymes and production of polyclonal antisera, the localization of proteins in the mycoplasma cell was characterized using fractionation of total proteins, colony blot, mild proteolysis and immunofluorescence of M. pneumoniae cells. Eight glycolytic enzymes, pyruvate dehydrogenases A to C (PdhA-C), glyceraldehyde-3-phosphate dehydrogenase (GapA), lactate dehydrogenase (Ldh), phosphoglycerate mutase (Pgm), pyruvate kinase (Pyk), and transketolase (Tkt), were confirmed as surface expressed and all are able to interact with plasminogen. Plasminogen bound to recombinant proteins PdhB, GapA, and Pyk was converted to plasmin in the presence of urokinase plasminogen activator and plasmin-specific substrate d-valyl-leucyl-lysine-p-nitroanilide dihydrochloride. Furthermore, human fibrinogen was degraded by the complex of plasminogen and recombinant protein PdhB or Pgm. In addition, surface-displayed proteins (except PdhC) bind to human lung epithelial cells, and the interaction was reduced significantly by preincubation of cells with antiplasminogen. Our results suggest that plasminogen binding and activation by different surface-localized glycolytic enzymes of M. pneumoniae may play a role in successful and long-term colonization of the human respiratory tract. PMID:26667841

The Synthetic Antimicrobial Peptide 19-2.5 Interacts with Heparanase and Heparan Sulfate in Murine and Human Sepsis.

PubMed

Martin, Lukas; De Santis, Rebecca; Koczera, Patrick; Simons, Nadine; Haase, Hajo; Heinbockel, Lena; Brandenburg, Klaus; Marx, Gernot; Schuerholz, Tobias

2015-01-01

Heparanase is an endo-β-glucuronidase that cleaves heparan sulfate side chains from their proteoglycans. Thereby, heparanase liberates highly potent circulating heparan sulfate-fragments (HS-fragments) and triggers the fatal and excessive inflammatory response in sepsis. As a potential anti-inflammatory agent for sepsis therapy, peptide 19-2.5 belongs to the class of synthetic anti-lipopolysaccharide peptides; however, its activity is not restricted to Gram-negative bacterial infection. We hypothesized that peptide 19-2.5 interacts with heparanase and/or HS, thereby reducing the levels of circulating HS-fragments in murine and human sepsis. Our data indicate that the treatment of septic mice with peptide 19-2.5 compared to untreated control animals lowers levels of plasma heparanase and circulating HS-fragments and reduces heparanase activity. Additionally, mRNA levels of heparanase in heart, liver, lung, kidney and spleen are downregulated in septic mice treated with peptide 19-2.5 compared to untreated control animals. In humans, plasma heparanase level and activity are elevated in septic shock. The ex vivo addition of peptide 19-2.5 to plasma of septic shock patients decreases heparanase activity but not heparanase level. Isothermal titration calorimetry revealed a strong exothermic reaction between peptide 19-2.5 and heparanase and HS-fragments. However, a saturation character has been identified only in the peptide 19-2.5 and HS interaction. In conclusion, the findings of our current study indicate that peptide 19-2.5 interacts with heparanase, which is elevated in murine and human sepsis and consecutively attenuates the generation of circulating HS-fragments in systemic inflammation. Thus, peptide 19-2.5 seems to be a potential anti-inflammatory agent in sepsis.

Sailing the Cyber Sea

DTIC Science & Technology

2012-04-01

chatting, tweeting, blogging, social networking, retail activity, or business interactions, military organizations, govern- ment entities, nongovernmental...connected. The use of social media is a great idea that is growing in popularity and can be a great tool for all kinds of activities. Audience size can...realities of human expansion , commerce, and interaction typically outpace policies and regulations, much as during the days of the Wild West and

Interaction of proliferating cell nuclear antigen with PMS2 is required for MutLα activation and function in mismatch repair

PubMed Central

Genschel, Jochen; Kadyrova, Lyudmila Y.; Iyer, Ravi R.; Dahal, Basanta K.; Kadyrov, Farid A.; Modrich, Paul

2017-01-01

Eukaryotic MutLα (mammalian MLH1–PMS2 heterodimer; MLH1–PMS1 in yeast) functions in early steps of mismatch repair as a latent endonuclease that requires a mismatch, MutSα/β, and DNA-loaded proliferating cell nuclear antigen (PCNA) for activation. We show here that human PCNA and MutLα interact specifically but weakly in solution to form a complex of approximately 1:1 stoichiometry that depends on PCNA interaction with the C-terminal endonuclease domain of the MutLα PMS2 subunit. Amino acid substitution mutations within a PMS2 C-terminal 721QRLIAP motif attenuate or abolish human MutLα interaction with PCNA, as well as PCNA-dependent activation of MutLα endonuclease, PCNA- and DNA-dependent activation of MutLα ATPase, and MutLα function in in vitro mismatch repair. Amino acid substitution mutations within the corresponding yeast PMS1 motif (723QKLIIP) reduce or abolish mismatch repair in vivo. Coupling of a weak allele within this motif (723AKLIIP) with an exo1Δ null mutation, which individually confer only weak mutator phenotypes, inactivates mismatch repair in the yeast cell. PMID:28439008

Interaction of proliferating cell nuclear antigen with PMS2 is required for MutLα activation and function in mismatch repair.

PubMed

Genschel, Jochen; Kadyrova, Lyudmila Y; Iyer, Ravi R; Dahal, Basanta K; Kadyrov, Farid A; Modrich, Paul

2017-05-09

Eukaryotic MutLα (mammalian MLH1-PMS2 heterodimer; MLH1-PMS1 in yeast) functions in early steps of mismatch repair as a latent endonuclease that requires a mismatch, MutSα/β, and DNA-loaded proliferating cell nuclear antigen (PCNA) for activation. We show here that human PCNA and MutLα interact specifically but weakly in solution to form a complex of approximately 1:1 stoichiometry that depends on PCNA interaction with the C-terminal endonuclease domain of the MutLα PMS2 subunit. Amino acid substitution mutations within a PMS2 C-terminal 721 QRLIAP motif attenuate or abolish human MutLα interaction with PCNA, as well as PCNA-dependent activation of MutLα endonuclease, PCNA- and DNA-dependent activation of MutLα ATPase, and MutLα function in in vitro mismatch repair. Amino acid substitution mutations within the corresponding yeast PMS1 motif ( 723 QKLIIP) reduce or abolish mismatch repair in vivo. Coupling of a weak allele within this motif ( 723 AKLIIP) with an exo1 Δ null mutation, which individually confer only weak mutator phenotypes, inactivates mismatch repair in the yeast cell.

Deciphering human motion to discriminate social interactions: a developmental neuroimaging study

PubMed Central

Sapey-Triomphe, Laurie-Anne; Centelles, Laurie; Roth, Muriel; Fonlupt, Pierre; Hénaff, Marie-Anne; Assaiante, Christine

2017-01-01

Abstract Non-verbal communication plays a major role in social interaction understanding. Using functional magnetic resonance imaging, we explored the development of the neural networks involved in social interaction recognition based on human motion in children (8–11), adolescents (13–17), and adults (20–41). Participants watched point-light videos depicting two actors interacting or moving independently and were asked whether these agents were interacting or not. All groups successfully performed the discrimination task, but children had a lower performance and longer response times than the older groups. In all three groups, the posterior parts of the superior temporal sulci and middle temporal gyri, the inferior frontal gyri and the anterior temporal lobes showed greater activation when observing social interactions. In addition, adolescents and adults recruited the caudate nucleus and some frontal regions that are part of the mirror system. Adults showed greater activations in parietal and frontal regions (part of them belonging to the social brain) than adolescents. An increased number of regions that are part of the mirror system network or the social brain, as well as the caudate nucleus, were recruited with age. In conclusion, a shared set of brain regions enabling the discrimination of social interactions from neutral movements through human motion is already present in 8-year-old children. Developmental processes such as refinements in the social brain and mirror system would help grasping subtle cues in non-verbal aspects of social interactions. PMID:28008075

Low-affinity FcγR interactions can decide the fate of novel human IgG-sensitised red blood cells and platelets

PubMed Central

Armour, Kathryn L; Smith, Cheryl S; Turner, Craig P; Kirton, Christopher M; Wilkes, Anthony M; Hadley, Andrew G; Ghevaert, Cedric; Williamson, Lorna M; Clark, Michael R

2014-01-01

G1Δnab is a mutant human IgG1 constant region with a lower ability to interact with FcγR than the natural IgG constant regions. Radiolabelled RBCs and platelets sensitised with specific G1Δnab Abs were cleared more slowly from human circulation than IgG1-sensitised counterparts. However, non-destructive splenic retention of G1Δnab-coated RBCs required investigation and plasma radioactivities now suggest this also occurred for platelets sensitised with an IgG1/G1Δnab mixture. In vitro assays with human cells showed that G1Δnab-sensitised RBCs did not cause FcγRI-mediated monocyte activation, FcγRIIIa-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) or macrophage phagocytosis although they did adhere to macrophages. Thus, FcγRII was implicated in the adhesion despite the Δnab mutation reducing the already low-affinity binding to this receptor class. Additional contacts via P-selectin enhance the interaction of sensitised platelets with monocytes and this system provided evidence of FcγRII-dependent activation by G1Δnab. These results emphasise the physiological relevance of low-affinity interactions: It appears that FcγRII interactions of G1Δnab allowed splenic retention of G1Δnab-coated RBCs with inhibitory FcγRIIb binding preventing RBC destruction and that FcγRIIb engagement by G1Δnab on IgG1/G1Δnab-sensitised platelets overcame activation by IgG1. Considering therapeutic blocking Abs, G1Δnab offers lower FcγR binding and a greater bias towards inhibition than IgG2 and IgG4 constant regions. PMID:24285214

DRD2/CHRNA5 Interaction on Prefrontal Biology and Physiology during Working Memory

PubMed Central

Fazio, Leonardo; D'Ambrosio, Enrico; Gelao, Barbara; Tomasicchio, Aldo; Selvaggi, Pierluigi; Taurisano, Paolo; Quarto, Tiziana; Masellis, Rita; Rampino, Antonio; Caforio, Grazia; Popolizio, Teresa; Blasi, Giuseppe; Sadee, Wolfgang; Bertolino, Alessandro

2014-01-01

Background Prefrontal behavior and activity in humans are heritable. Studies in animals demonstrate an interaction between dopamine D2 receptors and nicotinic acetylcholine receptors on prefrontal behavior but evidence in humans is weak. Therefore, we hypothesize that genetic variation regulating dopamine D2 and nicotinic acetylcholine receptor signaling impact prefrontal cortex activity and related cognition. To test this hypothesis in humans, we explored the interaction between functional genetic variants in the D2 receptor gene (DRD2, rs1076560) and in the nicotinic receptor α5 gene (CHRNA5, rs16969968) on both dorsolateral prefrontal cortex mediated behavior and physiology during working memory and on prefrontal gray matter volume. Methods A large sample of healthy subjects was compared for genotypic differences for DRD2 rs1076560 (G>T) and CHNRA5 rs16969968 (G>A) on prefrontal phenotypes, including cognitive performance at the N-Back task, prefrontal physiology with BOLD fMRI during performance of the 2-Back working memory task, and prefrontal morphometry with structural MRI. Results We found that DRD2 rs1076560 and CHNRA5 rs16969968 interact to modulate cognitive function, prefrontal physiology during working memory, and prefrontal gray matter volume. More specifically, CHRNA5-AA/DRD2-GT subjects had greater behavioral performance, more efficient prefrontal cortex activity at 2Back working memory task, and greater prefrontal gray matter volume than the other genotype groups. Conclusions The present data extend previous studies in animals and enhance our understanding of dopamine and acetylcholine signaling in the human prefrontal cortex, demonstrating interactions elicited by working memory that are modulated by genetic variants in DRD2 and CHRNA5. PMID:24819610

DRD2/CHRNA5 interaction on prefrontal biology and physiology during working memory.

PubMed

Di Giorgio, Annabella; Smith, Ryan M; Fazio, Leonardo; D'Ambrosio, Enrico; Gelao, Barbara; Tomasicchio, Aldo; Selvaggi, Pierluigi; Taurisano, Paolo; Quarto, Tiziana; Masellis, Rita; Rampino, Antonio; Caforio, Grazia; Popolizio, Teresa; Blasi, Giuseppe; Sadee, Wolfgang; Bertolino, Alessandro

2014-01-01

Prefrontal behavior and activity in humans are heritable. Studies in animals demonstrate an interaction between dopamine D2 receptors and nicotinic acetylcholine receptors on prefrontal behavior but evidence in humans is weak. Therefore, we hypothesize that genetic variation regulating dopamine D2 and nicotinic acetylcholine receptor signaling impact prefrontal cortex activity and related cognition. To test this hypothesis in humans, we explored the interaction between functional genetic variants in the D2 receptor gene (DRD2, rs1076560) and in the nicotinic receptor α5 gene (CHRNA5, rs16969968) on both dorsolateral prefrontal cortex mediated behavior and physiology during working memory and on prefrontal gray matter volume. A large sample of healthy subjects was compared for genotypic differences for DRD2 rs1076560 (G>T) and CHNRA5 rs16969968 (G>A) on prefrontal phenotypes, including cognitive performance at the N-Back task, prefrontal physiology with BOLD fMRI during performance of the 2-Back working memory task, and prefrontal morphometry with structural MRI. We found that DRD2 rs1076560 and CHNRA5 rs16969968 interact to modulate cognitive function, prefrontal physiology during working memory, and prefrontal gray matter volume. More specifically, CHRNA5-AA/DRD2-GT subjects had greater behavioral performance, more efficient prefrontal cortex activity at 2Back working memory task, and greater prefrontal gray matter volume than the other genotype groups. The present data extend previous studies in animals and enhance our understanding of dopamine and acetylcholine signaling in the human prefrontal cortex, demonstrating interactions elicited by working memory that are modulated by genetic variants in DRD2 and CHRNA5.

Suramin blocks interaction between human FGF1 and FGFR2 D2 domain and reduces downstream signaling activity

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

Wu, Zong-Sian, E-mail: gary810426@hotmail.com; Liu, Che Fu, E-mail: s9823002@m98.nthu.edu.tw; Fu, Brian, E-mail: brianfu9@gmail.com

2016-09-02

The extracellular portion of the human fibroblast growth factor receptor2 D2 domain (FGFR2 D2) interacts with human fibroblast growth factor 1 (hFGF1) to activate a downstream signaling cascade that ultimately affects mitosis and differentiation. Suramin is an antiparasiticdrug and a potent inhibitor of FGF-induced angiogenesis. Suramin has been shown to bind to hFGF1, and might block the interaction between hFGF1 and FGFR2 D2. Here, we titrated hFGF1 with FGFR2 D2 and suramin to elucidate their interactions using the detection of NMR. The docking results of both hFGF1-FGFR2 D2 domain and hFGF1-suramin complex were superimposed. The results indicate that suramin blocksmore » the interaction between hFGF1 and FGFR2 D2. We used the PyMOL software to show the hydrophobic interaction of hFGF1-suramin. In addition, we used a Water-soluble Tetrazolium salts assay (WST1) to assess hFGF1 bioactivity. The results will be useful for the development of new antimitogenic activity drugs. - Highlights: • The interfacial residues on hFGF1-FGFR2 D2 and hFGF1-Suramin contact surface were mapped by {sup 1}H-{sup 15}N HSQC experiments. • hFGF1-FGFR2 D2 and hFGF1-Suramin complex models were generated from NMR restraints by using HADDOCK program. • We analyzed hFGF1-Suramin complex models and found the interaction between hFGF1-Suramin is hydrophobic. • The bioactivity of the hFGF1-FGFR2 D2 and hFGF1-Suramin complex was studied by using WST1 assay.« less

In our own image? Emotional and neural processing differences when observing human–human vs human–robot interactions

PubMed Central

Wang, Yin

2015-01-01

Notwithstanding the significant role that human–robot interactions (HRI) will play in the near future, limited research has explored the neural correlates of feeling eerie in response to social robots. To address this empirical lacuna, the current investigation examined brain activity using functional magnetic resonance imaging while a group of participants (n = 26) viewed a series of human–human interactions (HHI) and HRI. Although brain sites constituting the mentalizing network were found to respond to both types of interactions, systematic neural variation across sites signaled diverging social-cognitive strategies during HHI and HRI processing. Specifically, HHI elicited increased activity in the left temporal–parietal junction indicative of situation-specific mental state attributions, whereas HRI recruited the precuneus and the ventromedial prefrontal cortex (VMPFC) suggestive of script-based social reasoning. Activity in the VMPFC also tracked feelings of eeriness towards HRI in a parametric manner, revealing a potential neural correlate for a phenomenon known as the uncanny valley. By demonstrating how understanding social interactions depends on the kind of agents involved, this study highlights pivotal sub-routes of impression formation and identifies prominent challenges in the use of humanoid robots. PMID:25911418

Quantitative Modeling of Human-Environment Interactions in Preindustrial Time

NASA Astrophysics Data System (ADS)

Sommer, Philipp S.; Kaplan, Jed O.

2017-04-01

Quantifying human-environment interactions and anthropogenic influences on the environment prior to the Industrial revolution is essential for understanding the current state of the earth system. This is particularly true for the terrestrial biosphere, but marine ecosystems and even climate were likely modified by human activities centuries to millennia ago. Direct observations are however very sparse in space and time, especially as one considers prehistory. Numerical models are therefore essential to produce a continuous picture of human-environment interactions in the past. Agent-based approaches, while widely applied to quantifying human influence on the environment in localized studies, are unsuitable for global spatial domains and Holocene timescales because of computational demands and large parameter uncertainty. Here we outline a new paradigm for the quantitative modeling of human-environment interactions in preindustrial time that is adapted to the global Holocene. Rather than attempting to simulate agency directly, the model is informed by a suite of characteristics describing those things about society that cannot be predicted on the basis of environment, e.g., diet, presence of agriculture, or range of animals exploited. These categorical data are combined with the properties of the physical environment in coupled human-environment model. The model is, at its core, a dynamic global vegetation model with a module for simulating crop growth that is adapted for preindustrial agriculture. This allows us to simulate yield and calories for feeding both humans and their domesticated animals. We couple this basic caloric availability with a simple demographic model to calculate potential population, and, constrained by labor requirements and land limitations, we create scenarios of land use and land cover on a moderate-resolution grid. We further implement a feedback loop where anthropogenic activities lead to changes in the properties of the physical environment, e.g., through soil erosion.

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.

Molecular modeling and analysis of human and plant endo-β-N-acetyl- glucosaminidases for mutations effects on function

PubMed Central

Choragudi, Shechinah Felice; Veeramachaneni, Ganesh Kumar; Raman, BV; JS, Bondili

2014-01-01

Endo- β-N-acetylgucosaminidases (ENGases) are the enzymes that catalyze both hydrolysis and transglycosylation reactions. It is of interest to study ENGases because of their ability to synthesize glycopeptides. Homology models of Human, Arabidopsis thaliana and Sorghum ENGases were developed and their active sites marked based on information available from Arthrobacter protophormiae (PDB ID: 3FHQ) ENGase. Further, these models were docked with the natural substrate GlcNAc-Asn and the inhibitor Man3GlcNAc-thiazoline. The catalytic triad of Asn, Glu and Tyr (N171, E173 and Y205 of bacteria) were found to be conserved across the phyla. The crucial Y299F mutation showing 3 times higher transglycosylation activity than in wild type Endo-A is known. The hydrolytic activity remained unchanged in bacteria, while the transglycosylation activity increased. This Y to F change is found to be naturally evolved and should be attributing higher transglycosylation rates in human and Arabidopsis thaliana ENGases. Ligand interactions Ligplots revealed the interaction of amino acids with hydrophobic side chains and polar uncharged side chain amino acids. Thus, structure based molecular model-ligand interactions provide insights into the catalytic mechanism of ENGases and assist in the rational engineering of ENGases. PMID:25258486

Molecular modeling and analysis of human and plant endo-β-N-acetyl- glucosaminidases for mutations effects on function.

PubMed

Choragudi, Shechinah Felice; Veeramachaneni, Ganesh Kumar; Raman, Bv; Js, Bondili

2014-01-01

Endo- β-N-acetylgucosaminidases (ENGases) are the enzymes that catalyze both hydrolysis and transglycosylation reactions. It is of interest to study ENGases because of their ability to synthesize glycopeptides. Homology models of Human, Arabidopsis thaliana and Sorghum ENGases were developed and their active sites marked based on information available from Arthrobacter protophormiae (PDB ID: 3FHQ) ENGase. Further, these models were docked with the natural substrate GlcNAc-Asn and the inhibitor Man3GlcNAc-thiazoline. The catalytic triad of Asn, Glu and Tyr (N171, E173 and Y205 of bacteria) were found to be conserved across the phyla. The crucial Y299F mutation showing 3 times higher transglycosylation activity than in wild type Endo-A is known. The hydrolytic activity remained unchanged in bacteria, while the transglycosylation activity increased. This Y to F change is found to be naturally evolved and should be attributing higher transglycosylation rates in human and Arabidopsis thaliana ENGases. Ligand interactions Ligplots revealed the interaction of amino acids with hydrophobic side chains and polar uncharged side chain amino acids. Thus, structure based molecular model-ligand interactions provide insights into the catalytic mechanism of ENGases and assist in the rational engineering of ENGases.

Human Health in the Balance. Hands-On! Developing Active Learning Modules on the Human Dimensions of Global Change.

ERIC Educational Resources Information Center

Meade, Melinda S.; Washburn, Sarah; Holman, Jeremy T.

This learning module aims to engage students in problem solving, critical thinking, scientific inquiry, and cooperative learning. The module is appropriate for use in any introductory or intermediate undergraduate course that focuses on human-environment relationships. The module states that human health is a product of complex interactions among…

Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells

PubMed Central

Freire-Pritchett, Paula; Schoenfelder, Stefan; Várnai, Csilla; Wingett, Steven W; Cairns, Jonathan; Collier, Amanda J; García-Vílchez, Raquel; Furlan-Magaril, Mayra; Osborne, Cameron S; Fraser, Peter; Rugg-Gunn, Peter J; Spivakov, Mikhail

2017-01-01

Long-range cis-regulatory elements such as enhancers coordinate cell-specific transcriptional programmes by engaging in DNA looping interactions with target promoters. Deciphering the interplay between the promoter connectivity and activity of cis-regulatory elements during lineage commitment is crucial for understanding developmental transcriptional control. Here, we use Promoter Capture Hi-C to generate a high-resolution atlas of chromosomal interactions involving ~22,000 gene promoters in human pluripotent and lineage-committed cells, identifying putative target genes for known and predicted enhancer elements. We reveal extensive dynamics of cis-regulatory contacts upon lineage commitment, including the acquisition and loss of promoter interactions. This spatial rewiring occurs preferentially with predicted changes in the activity of cis-regulatory elements and is associated with changes in target gene expression. Our results provide a global and integrated view of promoter interactome dynamics during lineage commitment of human pluripotent cells. DOI: http://dx.doi.org/10.7554/eLife.21926.001 PMID:28332981

Adrenodoxin supports reactions catalyzed by microsomal steroidogenic cytochrome P450s

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

Pechurskaya, Tatiana A.; Harnastai, Ivan N.; Grabovec, Irina P.

2007-02-16

The interaction of adrenodoxin (Adx) and NADPH cytochrome P450 reductase (CPR) with human microsomal steroidogenic cytochrome P450s was studied. It is found that Adx, mitochondrial electron transfer protein, is able to support reactions catalyzed by human microsomal P450s: full length CYP17, truncated CYP17, and truncated CYP21. CPR, but not Adx, supports activity of truncated CYP19. Truncated and the full length CYP17s show distinct preference for electron donor proteins. Truncated CYP17 has higher activity with Adx compared to CPR. The alteration in preference to electron donor does not change product profile for truncated enzymes. The electrostatic contacts play a major rolemore » in the interaction of truncated CYP17 with either CPR or Adx. Similarly electrostatic contacts are predominant in the interaction of full length CYP17 with Adx. We speculate that Adx might serve as an alternative electron donor for CYP17 at the conditions of CPR deficiency in human.« less

Two spatiotemporally distinct value systems shape reward-based learning in the human brain.

PubMed

Fouragnan, Elsa; Retzler, Chris; Mullinger, Karen; Philiastides, Marios G

2015-09-08

Avoiding repeated mistakes and learning to reinforce rewarding decisions is critical for human survival and adaptive actions. Yet, the neural underpinnings of the value systems that encode different decision-outcomes remain elusive. Here coupling single-trial electroencephalography with simultaneously acquired functional magnetic resonance imaging, we uncover the spatiotemporal dynamics of two separate but interacting value systems encoding decision-outcomes. Consistent with a role in regulating alertness and switching behaviours, an early system is activated only by negative outcomes and engages arousal-related and motor-preparatory brain structures. Consistent with a role in reward-based learning, a later system differentially suppresses or activates regions of the human reward network in response to negative and positive outcomes, respectively. Following negative outcomes, the early system interacts and downregulates the late system, through a thalamic interaction with the ventral striatum. Critically, the strength of this coupling predicts participants' switching behaviour and avoidance learning, directly implicating the thalamostriatal pathway in reward-based learning.

Sin3b interacts with Myc and decreases Myc levels.

PubMed

Garcia-Sanz, Pablo; Quintanilla, Andrea; Lafita, M Carmen; Moreno-Bueno, Gema; García-Gutierrez, Lucia; Tabor, Vedrana; Varela, Ignacio; Shiio, Yuzuru; Larsson, Lars-Gunnar; Portillo, Francisco; Leon, Javier

2014-08-08

Myc expression is deregulated in many human cancers. A yeast two-hybrid screen has revealed that the transcriptional repressor Sin3b interacts with Myc protein. Endogenous Myc and Sin3b co-localize and interact in the nuclei of human and rat cells, as assessed by co-immunoprecipitation, immunofluorescence, and proximity ligation assay. The interaction is Max-independent. A conserved Myc region (amino acids 186-203) is required for the interaction with Sin3 proteins. Histone deacetylase 1 is recruited to Myc-Sin3b complexes, and its deacetylase activity is required for the effects of Sin3b on Myc. Myc and Sin3a/b co-occupied many sites on the chromatin of human leukemia cells, although the presence of Sin3 was not associated with gene down-regulation. In leukemia cells and fibroblasts, Sin3b silencing led to Myc up-regulation, whereas Sin3b overexpression induced Myc deacetylation and degradation. An analysis of Sin3b expression in breast tumors revealed an association between low Sin3b expression and disease progression. The data suggest that Sin3b decreases Myc protein levels upon Myc deacetylation. As Sin3b is also required for transcriptional repression by Mxd-Max complexes, our results suggest that, at least in some cell types, Sin3b limits Myc activity through two complementary activities: Mxd-dependent gene repression and reduction of Myc levels. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Enhancement of human DNA polymerase η activity and fidelity is dependent upon a bipartite interaction with the Werner syndrome protein.

PubMed

Maddukuri, Leena; Ketkar, Amit; Eddy, Sarah; Zafar, Maroof K; Griffin, Wezley C; Eoff, Robert L

2012-12-07

We have investigated the interaction between human DNA polymerase η (hpol η) and the Werner syndrome protein (WRN). Functional assays revealed that the WRN exonuclease and RecQ C-terminal (RQC) domains are necessary for full stimulation of hpol η-catalyzed formation of correct base pairs. We find that WRN does not stimulate hpol η-catalyzed formation of mispairs. Moreover, the exonuclease activity of WRN prevents stable mispair formation by hpol η. These results are consistent with a proofreading activity for WRN during single-nucleotide additions. ATP hydrolysis by WRN appears to attenuate stimulation of hpol η. Pre-steady-state kinetic results show that k(pol) is increased 4-fold by WRN. Finally, pulldown assays reveal a bipartite physical interaction between hpol η and WRN that is mediated by the exonuclease and RQC domains. Taken together, these results are consistent with alteration of the rate-limiting step in polymerase catalysis by direct protein-protein interactions between WRN and hpol η. In summary, WRN improves the efficiency and fidelity of hpol η to promote more effective replication of DNA.

High Efficiency Latency and Activation of Herpes Simplex Virus in Human Cells

NASA Astrophysics Data System (ADS)

Wigdahl, Brian L.; Scheck, Adrienne C.; de Clercq, Erik; Rapp, Fred

1982-09-01

Herpes simplex virus (HSV) exists in humans in a latent form that can be activated. To characterize the molecular basis of the cell-virus interactions and to analyze the state of the latent HSV genome, an in vitro model system was established. In this system a large fraction of the latently infected cells contain an HSV genome that can be activated. Cell survival was reduced minimally after repression of high multiplicity HSV type 1 (HSV-1) infection of human fibroblast cells with (E)-5-(2-bromovinyl)-2'-deoxyuridine in combination with human leukocyte interferon (IFN-α ). A minimum of 1 to 3 percent of the surviving cells contained an HSV genome that could be activated either by human cytomegalovirus superinfection or reduction in incubation temperature.

Discovery Proteomics Identifies a Molecular Link between the Coatomer Protein Complex I and Androgen Receptor-dependent Transcription*

PubMed Central

Hsiao, Jordy J.; Smits, Melinda M.; Ng, Brandon H.; Lee, Jinhee; Wright, Michael E.

2016-01-01

Aberrant androgen receptor (AR)-dependent transcription is a hallmark of human prostate cancers. At the molecular level, ligand-mediated AR activation is coordinated through spatial and temporal protein-protein interactions involving AR-interacting proteins, which we designate the “AR-interactome.” Despite many years of research, the ligand-sensitive protein complexes involved in ligand-mediated AR activation in prostate tumor cells have not been clearly defined. Here, we describe the development, characterization, and utilization of a novel human LNCaP prostate tumor cell line, N-AR, which stably expresses wild-type AR tagged at its N terminus with the streptavidin-binding peptide epitope (streptavidin-binding peptide-tagged wild-type androgen receptor; SBP-AR). A bioanalytical workflow involving streptavidin chromatography and label-free quantitative mass spectrometry was used to identify SBP-AR and associated ligand-sensitive cytosolic proteins/protein complexes linked to AR activation in prostate tumor cells. Functional studies verified that ligand-sensitive proteins identified in the proteomic screen encoded modulators of AR-mediated transcription, suggesting that these novel proteins were putative SBP-AR-interacting proteins in N-AR cells. This was supported by biochemical associations between recombinant SBP-AR and the ligand-sensitive coatomer protein complex I (COPI) retrograde trafficking complex in vitro. Extensive biochemical and molecular experiments showed that the COPI retrograde complex regulates ligand-mediated AR transcriptional activation, which correlated with the mobilization of the Golgi-localized ARA160 coactivator to the nuclear compartment of prostate tumor cells. Collectively, this study provides a bioanalytical strategy to validate the AR-interactome and define novel AR-interacting proteins involved in ligand-mediated AR activation in prostate tumor cells. Moreover, we describe a cellular system to study how compartment-specific AR-interacting proteins influence AR activation and contribute to aberrant AR-dependent transcription that underlies the majority of human prostate cancers. PMID:27365400

Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo

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

Poulton, Emma Jane; Department of Environmental and Occupational Health Sciences, University of Washington; Levy, Lisa

2013-01-01

Sulforaphane (SFN), is an effective in vitro antagonist of ligand activation of the human pregnane and xenobiotic receptor (PXR). PXR mediated CYP3A4 up-regulation is implicated in adverse drug-drug interactions making identification of small molecule antagonists a desirable therapeutic goal. SFN is not an antagonist to mouse or rat PXR in vitro; thus, normal rodent species are not suitable as in vivo models for human response. To evaluate whether SFN can effectively antagonize ligand activation of human PXR in vivo, a three-armed, randomized, crossover trial was conducted with 24 healthy adults. The potent PXR ligand — rifampicin (300 mg/d) was givenmore » alone for 7 days in arm 1, or in daily combination with 450 μmol SFN (Broccoli Sprout extract) in arm 2; SFN was given alone in arm 3. Midazolam as an in vivo phenotype marker of CYP3A was administered before and after each treatment arm. Rifampicin alone decreased midazolam AUC by 70%, indicative of the expected increase in CYP3A4 activity. Co-treatment with SFN did not reduce CYP3A4 induction. Treatment with SFN alone also did not affect CYP3A4 activity in the cohort as a whole, although in the subset with the highest basal CYP3A4 activity there was a statistically significant increase in midazolam AUC (i.e., decrease in CYP3A4 activity). A parallel study in humanized PXR mice yielded similar results. The parallel effects of SFN between humanized PXR mice and human subjects demonstrate the predictive value of humanized mouse models in situations where species differences in ligand-receptor interactions preclude the use of a native mouse model for studying human ligand-receptor pharmacology. -- Highlights: ► The effects of SFN on PXR mediated CYP3A4 induction in humanized PXR mice and humans were examined. ► SFN had no effect on rifampicin mediated CYP3A4 induction in humans or humanized mice. ► SFN had a modest effect on basal CYP3A4 activity among subjects with higher baseline activity. ► Humanized PXR mice were generally predictive of the in vivo human response.« less

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

Awake canine fMRI predicts dogs’ preference for praise vs food

PubMed Central

Cook, Peter F.; Prichard, Ashley; Spivak, Mark

2016-01-01

Dogs are hypersocial with humans, and their integration into human social ecology makes dogs a unique model for studying cross-species social bonding. However, the proximal neural mechanisms driving dog–human social interaction are unknown. We used functional magnetic resonance imaging in 15 awake dogs to probe the neural basis for their preferences for social interaction and food reward. In a first experiment, we used the ventral caudate as a measure of intrinsic reward value and compared activation to conditioned stimuli that predicted food, praise or nothing. Relative to the control stimulus, the caudate was significantly more active to the reward-predicting stimuli and showed roughly equal or greater activation to praise vs food in 13 of 15 dogs. To confirm that these differences were driven by the intrinsic value of social praise, we performed a second imaging experiment in which the praise was withheld on a subset of trials. The difference in caudate activation to the receipt of praise, relative to its withholding, was strongly correlated with the differential activation to the conditioned stimuli in the first experiment. In a third experiment, we performed an out-of-scanner choice task in which the dog repeatedly selected food or owner in a Y-maze. The relative caudate activation to food- and praise-predicting stimuli in Experiment 1 was a strong predictor of each dog’s sequence of choices in the Y-maze. Analogous to similar neuroimaging studies of individual differences in human social reward, our findings demonstrate a neural mechanism for preference in domestic dogs that is stable within, but variable between, individuals. Moreover, the individual differences in the caudate responses indicate the potentially higher value of social than food reward for some dogs and may help to explain the apparent efficacy of social interaction in dog training. PMID:27521302

Activation of EGF receptor kinase by L1-mediated homophilic cell interactions.

PubMed

Islam, Rafique; Kristiansen, Lars V; Romani, Susana; Garcia-Alonso, Luis; Hortsch, Michael

2004-04-01

Neural cell adhesion molecules (CAMs) are important players during neurogenesis and neurite outgrowth as well as axonal fasciculation and pathfinding. Some of these developmental processes entail the activation of cellular signaling cascades. Pharmacological and genetic evidence indicates that the neurite outgrowth-promoting activity of L1-type CAMs is at least in part mediated by the stimulation of neuronal receptor tyrosine kinases (RTKs), especially FGF and EGF receptors. It has long been suspected that neural CAMs might physically interact with RTKs, but their activation by specific cell adhesion events has not been directly demonstrated. Here we report that gain-of-function conditions of the Drosophila L1-type CAM Neuroglian result in profound sensory axon pathfinding defects in the developing Drosophila wing. This phenotype can be suppressed by decreasing the normal gene dosage of the Drosophila EGF receptor gene. Furthermore, in Drosophila S2 cells, cell adhesion mediated by human L1-CAM results in the specific activation of human EGF tyrosine kinase at cell contact sites and EGF receptors engage in a physical interaction with L1-CAM molecules. Thus L1-type CAMs are able to promote the adhesion-dependent activation of EGF receptor signaling in vitro and in vivo.

K.E.E.P. - Kentucky's Energy Education Program Activities for the Classroom, K-6.

ERIC Educational Resources Information Center

Theiss, Nancy Stearns, Ed.; And Others

Seventy-seven multidisciplinary activities for grades K-6 are contained in this revised edition of energy education lessons for Kentucky students. Section I introduces students to the topic of energy by emphasizing human interaction with the environment. It focuses on personal energy, food as the source of human energy, food chains, and the sun as…

Temporal stability in human interaction networks

NASA Astrophysics Data System (ADS)

Fabbri, Renato; Fabbri, Ricardo; Antunes, Deborah Christina; Pisani, Marilia Mello; de Oliveira, Osvaldo Novais

2017-11-01

This paper reports on stable (or invariant) properties of human interaction networks, with benchmarks derived from public email lists. Activity, recognized through messages sent, along time and topology were observed in snapshots in a timeline, and at different scales. Our analysis shows that activity is practically the same for all networks across timescales ranging from seconds to months. The principal components of the participants in the topological metrics space remain practically unchanged as different sets of messages are considered. The activity of participants follows the expected scale-free trace, thus yielding the hub, intermediary and peripheral classes of vertices by comparison against the Erdös-Rényi model. The relative sizes of these three sectors are essentially the same for all email lists and the same along time. Typically, < 15% of the vertices are hubs, 15%-45% are intermediary and > 45% are peripheral vertices. Similar results for the distribution of participants in the three sectors and for the relative importance of the topological metrics were obtained for 12 additional networks from Facebook, Twitter and ParticipaBR. These properties are consistent with the literature and may be general for human interaction networks, which has important implications for establishing a typology of participants based on quantitative criteria.

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.

Evidence for triclosan-induced activation of human and rodent xenobiotic nuclear receptors

EPA Science Inventory

The bacteriostat triclosan (2,4,40-trichloro-20-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 divergenc...

DIFFUSION-WEIGHTED IMAGING TRACTOGRAPHY-BASED PARCELLATION OF THE HUMAN PARIETAL CORTEX AND COMPARISON WITH HUMAN AND MACAQUE RESTING STATE FUNCTIONAL CONNECTIVITY

PubMed Central

Mars, Rogier B.; Jbabdi, Saad; Sallet, Jérôme; O’Reilly, Jill X.; Croxson, Paula L.; Olivier, Etienne; Noonan, MaryAnn P.; Bergmann, Caroline; Mitchell, Anna S.; Baxter, Mark G.; Behrens, Timothy E.J.; Johansen-Berg, Heidi; Tomassini, Valentina; Miller, Karla L.; Rushworth, Matthew F.S.

2011-01-01

Despite the prominence of parietal activity in human neuromaging investigations of sensorimotor and cognitive processes there remains uncertainty about basic aspects of parietal cortical anatomical organization. Descriptions of human parietal cortex draw heavily on anatomical schemes developed in other primate species but the validity of such comparisons has been questioned by claims that there are fundamental differences between the parietal cortex in humans and other primates. A scheme is presented for parcellation of human lateral parietal cortex into component regions on the basis of anatomical connectivity and the functional interactions of the resulting clusters with other brain regions. Anatomical connectivity was estimated using diffusion-weighted magnetic resonance image (MRI) based tractography and functional interactions were assessed by correlations in activity measured with functional MRI (fMRI) at rest. Resting state functional connectivity was also assessed directly in the rhesus macaque lateral parietal cortex in an additional experiment and the patterns found reflected known neuroanatomical connections. Cross-correlation in the tractography-based connectivity patterns of parietal voxels reliably parcellated human lateral parietal cortex into ten component clusters. The resting state functional connectivity of human superior parietal and intraparietal clusters with frontal and extrastriate cortex suggested correspondences with areas in macaque superior and intraparietal sulcus. Functional connectivity patterns with parahippocampal cortex and premotor cortex again suggested fundamental correspondences between inferior parietal cortex in humans and macaques. In contrast, the human parietal cortex differs in the strength of its interactions between the central inferior parietal lobule region and the anterior prefrontal cortex. PMID:21411650

Land Use and Climate Impacts on Fluvial Systems (LUCIFS): A PAGES - Focus 4 (PHAROS) research activity

NASA Astrophysics Data System (ADS)

Dearing, John; Hoffmann, Thomas

2010-05-01

LUCIFS is a global research program which is concerned with understanding past interactions between climate, human activity and fluvial systems. Its focus is on evaluating the geomorphic impact of humans on landscapes, with a strong emphasis on geomorphological and sedimentological perspectives on mid- to long-term man-landscape interactions. Of particular relevance are aspects of sediment redistribution systems such as non-linear behaviour, the role of system configuration, scale effects, and emergent properties Over the last decade the LUCIFS program has been investigating both contemporary and long-term river response to global change with the principal aims of i)quantifying land use and climate change impacts of river-borne fluxes of water, sediment, C, N and P; ii) identification of key controls on these fluxes at the catchment scale; and iii) identification of the feedback on both human society and biogeochemical cycles of long-term changes in the fluxes of these materials The major scientific tasks of the LUCIFS-program are: • synthesising results of regional case studies • identify regional gaps and encouraging new case studies • addressing research gaps and formulating new research questions • organising workshops and conferences In this paper we present the LUCIFS program within the new PAGES structure. LUCIFS is located in the Focus 4 (PHAROS) dealing with how a knowledge of human-climate-ecosystem interactions in the past can help inform understanding and management today. In conjunction with the other working groups HITE (Human Impacts on Terrestrial Ecosystems), LIMPACS (Human Impacts on Lake Ecosystems) and IHOPE (Integrated History of People on Earth) PHAROS aims to compare regional-scale reconstructions of environmental and climatic processes using natural archives, documentary and instrumental data, with evidence of past human activity obtained from historical, paleoecological and archaeological records.

Differential Antagonism of Human Innate Immune Responses by Tick-Borne Phlebovirus Nonstructural Proteins

PubMed Central

Rezelj, Veronica V.; Li, Ping; Chaudhary, Vidyanath; Elliott, Richard M.

2017-01-01

ABSTRACT In recent years, several newly discovered tick-borne viruses causing a wide spectrum of diseases in humans have been ascribed to the Phlebovirus genus of the Bunyaviridae family. The nonstructural protein (NSs) of bunyaviruses is the main virulence factor and interferon (IFN) antagonist. We studied the molecular mechanisms of IFN antagonism employed by the NSs proteins of human apathogenic Uukuniemi virus (UUKV) and those of Heartland virus (HRTV) and severe fever with thrombocytopenia syndrome virus (SFTSV), both of which cause severe disease. Using reporter assays, we found that UUKV NSs weakly inhibited the activation of the beta interferon (IFN-β) promoter and response elements. UUKV NSs weakly antagonized human IFN-β promoter activation through a novel interaction with mitochondrial antiviral-signaling protein (MAVS), confirmed by coimmunoprecipitation and confocal microscopy studies. HRTV NSs efficiently antagonized both IFN-β promoter activation and type I IFN signaling pathways through interactions with TBK1, preventing its phosphorylation. HRTV NSs exhibited diffused cytoplasmic localization. This is in comparison to the inclusion bodies formed by SFTSV NSs. HRTV NSs also efficiently interacted with STAT2 and impaired IFN-β-induced phosphorylation but did not affect STAT1 or its translocation to the nucleus. Our results suggest that a weak interaction between STAT1 and HRTV or SFTSV NSs may explain their inability to block type II IFN signaling efficiently, thus enabling the activation of proinflammatory responses that lead to severe disease. Our findings offer insights into how pathogenicity may be linked to the capacity of NSs proteins to block the innate immune system and illustrate the plethora of viral immune evasion strategies utilized by emerging phleboviruses. IMPORTANCE Since 2011, there has been a large expansion in the number of emerging tick-borne viruses that have been assigned to the Phlebovirus genus. Heartland virus (HRTV) and SFTS virus (SFTSV) were found to cause severe disease in humans, unlike other documented tick-borne phleboviruses such as Uukuniemi virus (UUKV). Phleboviruses encode nonstructural proteins (NSs) that enable them to counteract the human innate antiviral defenses. We assessed how these proteins interacted with the innate immune system. We found that UUKV NSs engaged with innate immune factors only weakly, at one early step. However, the viruses that cause more severe disease efficiently disabled the antiviral response by targeting multiple components at several stages across the innate immune induction and signaling pathways. Our results suggest a correlation between the efficiency of the virus protein/host interaction and severity of disease. PMID:28680969

Video-based convolutional neural networks for activity recognition from robot-centric videos

NASA Astrophysics Data System (ADS)

Ryoo, M. S.; Matthies, Larry

2016-05-01

In this evaluation paper, we discuss convolutional neural network (CNN)-based approaches for human activity recognition. In particular, we investigate CNN architectures designed to capture temporal information in videos and their applications to the human activity recognition problem. There have been multiple previous works to use CNN-features for videos. These include CNNs using 3-D XYT convolutional filters, CNNs using pooling operations on top of per-frame image-based CNN descriptors, and recurrent neural networks to learn temporal changes in per-frame CNN descriptors. We experimentally compare some of these different representatives CNNs while using first-person human activity videos. We especially focus on videos from a robots viewpoint, captured during its operations and human-robot interactions.

Modeling activity recognition of multi resident using label combination of multi label classification in smart home

NASA Astrophysics Data System (ADS)

Mohamed, Raihani; Perumal, Thinagaran; Sulaiman, Md Nasir; Mustapha, Norwati; Zainudin, M. N. Shah

2017-10-01

Pertaining to the human centric concern and non-obtrusive way, the ambient sensor type technology has been selected, accepted and embedded in the environment in resilient style. Human activities, everyday are gradually becoming complex and thus complicate the inferences of activities when it involving the multi resident in the same smart environment. Current works solutions focus on separate model between the resident, activities and interactions. Some study use data association and extra auxiliary of graphical nodes to model human tracking information in an environment and some produce separate framework to incorporate the auxiliary for interaction feature model. Thus, recognizing the activities and which resident perform the activity at the same time in the smart home are vital for the smart home development and future applications. This paper will cater the above issue by considering the simplification and efficient method using the multi label classification framework. This effort eliminates time consuming and simplifies a lot of pre-processing tasks comparing with previous approach. Applications to the multi resident multi label learning in smart home problems shows the LC (Label Combination) using Decision Tree (DT) as base classifier can tackle the above problems.

Polymorphism in Human Cytomegalovirus UL40 Impacts on Recognition of Human Leukocyte Antigen-E (HLA-E) by Natural Killer Cells*

PubMed Central

Heatley, Susan L.; Pietra, Gabriella; Lin, Jie; Widjaja, Jacqueline M. L.; Harpur, Christopher M.; Lester, Sue; Rossjohn, Jamie; Szer, Jeff; Schwarer, Anthony; Bradstock, Kenneth; Bardy, Peter G.; Mingari, Maria Cristina; Moretta, Lorenzo; Sullivan, Lucy C.; Brooks, Andrew G.

2013-01-01

Natural killer (NK) cell recognition of the nonclassical human leukocyte antigen (HLA) molecule HLA-E is dependent on the presentation of a nonamer peptide derived from the leader sequence of other HLA molecules to CD94-NKG2 receptors. However, human cytomegalovirus can manipulate this central innate interaction through the provision of a “mimic” of the HLA-encoded peptide derived from the immunomodulatory glycoprotein UL40. Here, we analyzed UL40 sequences isolated from 32 hematopoietic stem cell transplantation recipients experiencing cytomegalovirus reactivation. The UL40 protein showed a “polymorphic hot spot” within the region that encodes the HLA leader sequence mimic. Although all sequences that were identical to those encoded within HLA-I genes permitted the interaction between HLA-E and CD94-NKG2 receptors, other UL40 polymorphisms reduced the affinity of the interaction between HLA-E and CD94-NKG2 receptors. Furthermore, functional studies using NK cell clones expressing either the inhibitory receptor CD94-NKG2A or the activating receptor CD94-NKG2C identified UL40-encoded peptides that were capable of inhibiting target cell lysis via interaction with CD94-NKG2A, yet had little capacity to activate NK cells through CD94-NKG2C. The data suggest that UL40 polymorphisms may aid evasion of NK cell immunosurveillance by modulating the affinity of the interaction with CD94-NKG2 receptors. PMID:23335510

Polymorphism in human cytomegalovirus UL40 impacts on recognition of human leukocyte antigen-E (HLA-E) by natural killer cells.

PubMed

Heatley, Susan L; Pietra, Gabriella; Lin, Jie; Widjaja, Jacqueline M L; Harpur, Christopher M; Lester, Sue; Rossjohn, Jamie; Szer, Jeff; Schwarer, Anthony; Bradstock, Kenneth; Bardy, Peter G; Mingari, Maria Cristina; Moretta, Lorenzo; Sullivan, Lucy C; Brooks, Andrew G

2013-03-22

Natural killer (NK) cell recognition of the nonclassical human leukocyte antigen (HLA) molecule HLA-E is dependent on the presentation of a nonamer peptide derived from the leader sequence of other HLA molecules to CD94-NKG2 receptors. However, human cytomegalovirus can manipulate this central innate interaction through the provision of a "mimic" of the HLA-encoded peptide derived from the immunomodulatory glycoprotein UL40. Here, we analyzed UL40 sequences isolated from 32 hematopoietic stem cell transplantation recipients experiencing cytomegalovirus reactivation. The UL40 protein showed a "polymorphic hot spot" within the region that encodes the HLA leader sequence mimic. Although all sequences that were identical to those encoded within HLA-I genes permitted the interaction between HLA-E and CD94-NKG2 receptors, other UL40 polymorphisms reduced the affinity of the interaction between HLA-E and CD94-NKG2 receptors. Furthermore, functional studies using NK cell clones expressing either the inhibitory receptor CD94-NKG2A or the activating receptor CD94-NKG2C identified UL40-encoded peptides that were capable of inhibiting target cell lysis via interaction with CD94-NKG2A, yet had little capacity to activate NK cells through CD94-NKG2C. The data suggest that UL40 polymorphisms may aid evasion of NK cell immunosurveillance by modulating the affinity of the interaction with CD94-NKG2 receptors.

A real-time architecture for time-aware agents.

PubMed

Prouskas, Konstantinos-Vassileios; Pitt, Jeremy V

2004-06-01

This paper describes the specification and implementation of a new three-layer time-aware agent architecture. This architecture is designed for applications and environments where societies of humans and agents play equally active roles, but interact and operate in completely different time frames. The architecture consists of three layers: the April real-time run-time (ART) layer, the time aware layer (TAL), and the application agents layer (AAL). The ART layer forms the underlying real-time agent platform. An original online, real-time, dynamic priority-based scheduling algorithm is described for scheduling the computation time of agent processes, and it is shown that the algorithm's O(n) complexity and scalable performance are sufficient for application in real-time domains. The TAL layer forms an abstraction layer through which human and agent interactions are temporally unified, that is, handled in a common way irrespective of their temporal representation and scale. A novel O(n2) interaction scheduling algorithm is described for predicting and guaranteeing interactions' initiation and completion times. The time-aware predicting component of a workflow management system is also presented as an instance of the AAL layer. The described time-aware architecture addresses two key challenges in enabling agents to be effectively configured and applied in environments where humans and agents play equally active roles. It provides flexibility and adaptability in its real-time mechanisms while placing them under direct agent control, and it temporally unifies human and agent interactions.

Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1–AKT interaction

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

Fang, Xian-Ying; Chen, Wei; Fan, Jun-Ting

2013-02-15

In the present paper, we examined the effects of a natural cyclopeptide RA-V on human breast cancer cells and the underlying mechanisms. RA-V significantly inhibited the growth of human breast cancer MCF-7, MDA-MB-231 cells and murine breast cancer 4T1 cells. In addition, RA-V triggered mitochondrial apoptotic pathway which was indicated by the loss of mitochondrial membrane potential, the release of cytochrome c, and the activation of caspase cascade. Further study showed that RA-V dramatically inhibited phosphorylation of AKT and 3-phosphoinositide dependent protein kinase 1 (PDK1) in MCF-7 cells. Moreover, RA-V disrupted the interaction between PDK1 and AKT in MCF-7 cells.more » Furthermore, RA-V-induced apoptosis could be enhanced by phosphatidylinositol 3-kinase inhibitor or attenuated by over-expression of AKT in all the three kinds of breast cancer cells. Taken together, this study shows that RA-V, which can induce mitochondria-mediated apoptosis, exerts strong anti-tumor activity against human breast cancer. The underlying anti-cancer mechanism of RA-V is related to the blockage of the interaction between PDK1 and AKT. - Highlights: ► Plant cyclopeptide RA-V kills human breast cancer cells. ► RA-V triggered mitochondrial apoptotic pathway in human breast cancer cells. ► RA-V inhibited phosphorylation of AKT and PDK1 in breast cancer MCF-7 cells. ► Its mechanism is related to the blockage of the interaction between PDK1 and AKT.« less

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.

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

Prediction of Human Activity by Discovering Temporal Sequence Patterns.

PubMed

Li, Kang; Fu, Yun

2014-08-01

Early prediction of ongoing human activity has become more valuable in a large variety of time-critical applications. To build an effective representation for prediction, human activities can be characterized by a complex temporal composition of constituent simple actions and interacting objects. Different from early detection on short-duration simple actions, we propose a novel framework for long -duration complex activity prediction by discovering three key aspects of activity: Causality, Context-cue, and Predictability. The major contributions of our work include: (1) a general framework is proposed to systematically address the problem of complex activity prediction by mining temporal sequence patterns; (2) probabilistic suffix tree (PST) is introduced to model causal relationships between constituent actions, where both large and small order Markov dependencies between action units are captured; (3) the context-cue, especially interactive objects information, is modeled through sequential pattern mining (SPM), where a series of action and object co-occurrence are encoded as a complex symbolic sequence; (4) we also present a predictive accumulative function (PAF) to depict the predictability of each kind of activity. The effectiveness of our approach is evaluated on two experimental scenarios with two data sets for each: action-only prediction and context-aware prediction. Our method achieves superior performance for predicting global activity classes and local action units.

Future climate and fire interactions in the southeastern region of the United States

Treesearch

Robert J. Mitchell; Yongqiang Liu; Joseph J. O’Brien; Katherine J. Elliott; Gregory Starr; Chelcy Ford Miniat; J. Kevin Hiers

2014-01-01

Fire has a profound, though paradoxical influence on landscapes of the southeastern U.S.; it simultaneously maintains native biodiversity and ecosystem processes but also threatens silvicultural resources and human landscapes. Furthermore, since the majority of the southern landscape is heavily influenced by human activities, contemporary fire regimes are human managed...

Cyberpsychology: a human-interaction perspective based on cognitive modeling.

PubMed

Emond, Bruno; West, Robert L

2003-10-01

This paper argues for the relevance of cognitive modeling and cognitive architectures to cyberpsychology. From a human-computer interaction point of view, cognitive modeling can have benefits both for theory and model building, and for the design and evaluation of sociotechnical systems usability. Cognitive modeling research applied to human-computer interaction has two complimentary objectives: (1) to develop theories and computational models of human interactive behavior with information and collaborative technologies, and (2) to use the computational models as building blocks for the design, implementation, and evaluation of interactive technologies. From the perspective of building theories and models, cognitive modeling offers the possibility to anchor cyberpsychology theories and models into cognitive architectures. From the perspective of the design and evaluation of socio-technical systems, cognitive models can provide the basis for simulated users, which can play an important role in usability testing. As an example of application of cognitive modeling to technology design, the paper presents a simulation of interactive behavior with five different adaptive menu algorithms: random, fixed, stacked, frequency based, and activation based. Results of the simulation indicate that fixed menu positions seem to offer the best support for classification like tasks such as filing e-mails. This research is part of the Human-Computer Interaction, and the Broadband Visual Communication research programs at the National Research Council of Canada, in collaboration with the Carleton Cognitive Modeling Lab at Carleton University.

Interactions of landscape disturbances and climate change dictate ecological pattern and process: spatial modeling of wildfire, insect, and disease dynamics under future climates

Treesearch

Rachel A. Loehman; Robert E. Keane; Lisa M. Holsinger; Zhiwei Wu

2017-01-01

Context: Interactions among disturbances, climate, and vegetation influence landscape patterns and ecosystem processes. Climate changes, exotic invasions, beetle outbreaks, altered fire regimes, and human activities may interact to produce landscapes that appear and function beyond historical analogs. Objectives We used the mechanistic...

Effects of atorvastatin metabolites on induction of drug-metabolizing enzymes and membrane transporters through human pregnane X receptor

PubMed Central

Hoffart, E; Ghebreghiorghis, L; Nussler, AK; Thasler, WE; Weiss, TS; Schwab, M; Burk, O

2012-01-01

BACKGROUND AND PURPOSE Atorvastatin metabolites differ in their potential for drug interaction because of differential inhibition of drug-metabolizing enzymes and transporters. We here investigate whether they exert differential effects on the induction of these genes via activation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR). EXPERIMENTAL APPROACH Ligand binding to PXR or CAR was analysed by mammalian two-hybrid assembly and promoter/reporter gene assays. Additionally, surface plasmon resonance was used to analyse ligand binding to CAR. Primary human hepatocytes were treated with atorvastatin metabolites, and mRNA and protein expression of PXR-regulated genes was measured. Two-hybrid co-activator interaction and co-repressor release assays were utilized to elucidate the molecular mechanism of PXR activation. KEY RESULTS All atorvastatin metabolites induced the assembly of PXR and activated CYP3A4 promoter activity. Ligand binding to CAR could not be proven. In primary human hepatocytes, the para-hydroxy metabolite markedly reduced or abolished induction of cytochrome P450 and transporter genes. While significant differences in co-activator recruitment were not observed, para-hydroxy atorvastatin demonstrated only 50% release of co-repressors. CONCLUSIONS AND IMPLICATIONS Atorvastatin metabolites are ligands of PXR but not of CAR. Atorvastatin metabolites demonstrate differential induction of PXR target genes, which results from impaired release of co-repressors. Consequently, the properties of drug metabolites have to be taken into account when analysing PXR-dependent induction of drug metabolism and transport. The drug interaction potential of the active metabolite, para-hydroxy atorvastatin, might be lower than that of the parent compound. PMID:21913896

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.

INTEGRATING ECOLOGY AND SOCIOECONOMICS FOR WILDLIFE MANAGEMENT AND CONSERVATION

EPA Science Inventory

Many researchers have studied impacts of human activity on wildlife or human attitudes toward wildlife, but not both simultaneously. Understanding these interactions is critical to better understand the intricacies of real world conservation issues. The goal of my presentation ...

MERTK as negative regulator of human T cell activation

PubMed Central

Cabezón, Raquel; Carrera-Silva, E. Antonio; Flórez-Grau, Georgina; Errasti, Andrea E.; Calderón-Gómez, Elisabeth; Lozano, Juan José; España, Carolina; Ricart, Elena; Panés, Julián; Rothlin, Carla Vanina; Benítez-Ribas, Daniel

2015-01-01

The aim of this study was to test the hypothesis whether MERTK, which is up-regulated in human DCs treated with immunosuppressive agents, is directly involved in modulating T cell activation. MERTK is a member of the TAM family and contributes to regulating innate immune response to ACs by inhibiting DC activation in animal models. However, whether MERTK interacts directly with T cells has not been addressed. Here, we show that MERTK is highly expressed on dex-induced human tol-DCs and participates in their tolerogenic effect. Neutralization of MERTK in allogenic MLR, as well as autologous DC–T cell cultures, leads to increased T cell proliferation and IFN-γ production. Additionally, we identify a previously unrecognized noncell-autonomous regulatory function of MERTK expressed on DCs. Mer-Fc protein, used to mimic MERTK on DCs, suppresses naïve and antigen-specific memory T cell activation. This mechanism is mediated by the neutralization of the MERTK ligand PROS1. We find that MERTK and PROS1 are expressed in human T cells upon TCR activation and drive an autocrine proproliferative mechanism. Collectively, these results suggest that MERTK on DCs controls T cell activation and expansion through the competition for PROS1 interaction with MERTK in the T cells. In conclusion, this report identified MERTK as a potent suppressor of T cell response. PMID:25624460

Biochemical and biophysical investigations of the interaction between human glucokinase and pro-apoptotic BAD.

PubMed

Rexford, Alix; Zorio, Diego A R; Miller, Brian G

2017-01-01

The glycolytic enzyme glucokinase (GCK) and the pro-apoptotic protein BAD reportedly reside within a five-membered complex that localizes to the mitochondria of mammalian hepatocytes and pancreatic β-cells. Photochemical crosslinking studies using a synthetic analog of BAD's BH3 domain and in vitro transcription/translation experiments support a direct interaction between BAD and GCK. To investigate the biochemical and biophysical consequences of the BAD:GCK interaction, we developed a method for the production of recombinant human BAD. Consistent with published reports, recombinant BAD displays high affinity for Bcl-xL (KD = 7 nM), and phosphorylation of BAD at S118, within the BH3 domain, abolishes this interaction. Unexpectedly, we do not detect association of recombinant, full-length BAD with recombinant human pancreatic GCK over a range of protein concentrations using various biochemical methods including size-exclusion chromatography, chemical cross-linking, analytical ultracentrifugation, and isothermal titration calorimetry. Furthermore, fluorescence polarization assays and isothermal titration calorimetry detect no direct interaction between GCK and BAD BH3 peptides. Kinetic characterization of GCK in the presence of high concentrations of recombinant BAD show modest (<15%) increases in GCK activity, observable only at glucose concentrations well below the K0.5 value. GCK activity is unaffected by BAD BH3 peptides. These results raise questions as to the mechanism of action of stapled peptide analogs modeled after the BAD BH3 domain, which reportedly enhance the Vmax value of GCK and stimulate insulin release in BAD-deficient islets. Based on our results, we postulate that the BAD:GCK interaction, and any resultant regulatory effect(s) upon GCK activity, requires the participation of additional members of the mitochondrial complex.

RPA physically interacts with the human DNA glycosylase NEIL1 to regulate excision of oxidative DNA base damage in primer-template structures.

PubMed

Theriot, Corey A; Hegde, Muralidhar L; Hazra, Tapas K; Mitra, Sankar

2010-06-04

The human DNA glycosylase NEIL1, activated during the S-phase, has been shown to excise oxidized base lesions in single-strand DNA substrates. Furthermore, our previous work demonstrating functional interaction of NEIL1 with PCNA and flap endonuclease 1 (FEN1) suggested its involvement in replication-associated repair. Here we show interaction of NEIL1 with replication protein A (RPA), the heterotrimeric single-strand DNA binding protein that is essential for replication and other DNA transactions. The NEIL1 immunocomplex isolated from human cells contains RPA, and its abundance in the complex increases after exposure to oxidative stress. NEIL1 directly interacts with the large subunit of RPA (K(d) approximately 20 nM) via the common interacting interface (residues 312-349) in NEIL1's disordered C-terminal region. RPA inhibits the base excision activity of both wild-type NEIL1 (389 residues) and its C-terminal deletion CDelta78 mutant (lacking the interaction domain) for repairing 5-hydroxyuracil (5-OHU) in a primer-template structure mimicking the DNA replication fork. This inhibition is reduced when the damage is located near the primer-template junction. Contrarily, RPA moderately stimulates wild-type NEIL1 but not the CDelta78 mutant when 5-OHU is located within the duplex region. While NEIL1 is inhibited by both RPA and Escherichia coli single-strand DNA binding protein, only inhibition by RPA is relieved by PCNA. These results showing modulation of NEIL1's activity on single-stranded DNA substrate by RPA and PCNA support NEIL1's involvement in repairing the replicating genome. Copyright 2010 Elsevier B.V. All rights reserved.

Situated Meaning-Making of the Human Body: A Study of Elementary School Children's Reasons in Two Different Activities

ERIC Educational Resources Information Center

Lundin, Mattias; Jakobson, Britt

2014-01-01

In this text we compare children's expressions in drawings to their statements during interviews, for the purpose of understanding how different situations afford children to make meaning. In specific we study how two different activities interact and afford children to make meaning differently about the human body. The analytic attention is…

EADB: An Estrogenic Activity Database for Assessing Potential Endocrine Activity

EPA Science Inventory

Endocrine-active chemicals can potentially have adverse effects on both humans and wildlife. They can interfere with the body’s endocrine system through direct or indirect interactions with many protein targets. Estrogen receptors (ERs) are one of the major targets, and many ...

SIG -- The Role of Human-Computer Interaction in Next-Generation Control Rooms

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

Ronald L. Boring; Jacques Hugo; Christian Richard

2005-04-01

The purpose of this CHI Special Interest Group (SIG) is to facilitate the convergence between human-computer interaction (HCI) and control room design. HCI researchers and practitioners actively need to infuse state-of-the-art interface technology into control rooms to meet usability, safety, and regulatory requirements. This SIG outlines potential HCI contributions to instrumentation and control (I&C) and automation in control rooms as well as to general control room design.

Structure of the human protein kinase MPSK1 reveals an atypical activation loop architecture.

PubMed

Eswaran, Jeyanthy; Bernad, Antonio; Ligos, Jose M; Guinea, Barbara; Debreczeni, Judit E; Sobott, Frank; Parker, Sirlester A; Najmanovich, Rafael; Turk, Benjamin E; Knapp, Stefan

2008-01-01

The activation segment of protein kinases is structurally highly conserved and central to regulation of kinase activation. Here we report an atypical activation segment architecture in human MPSK1 comprising a beta sheet and a large alpha-helical insertion. Sequence comparisons suggested that similar activation segments exist in all members of the MPSK1 family and in MAST kinases. The consequence of this nonclassical activation segment on substrate recognition was studied using peptide library screens that revealed a preferred substrate sequence of X-X-P/V/I-phi-H/Y-T*-N/G-X-X-X (phi is an aliphatic residue). In addition, we identified the GTPase DRG1 as an MPSK1 interaction partner and specific substrate. The interaction domain in DRG1 was mapped to the N terminus, leading to recruitment and phosphorylation at Thr100 within the GTPase domain. The presented data reveal an atypical kinase structural motif and suggest a role of MPSK1 regulating DRG1, a GTPase involved in regulation of cellular growth.

Human mast cell and airway smooth muscle cell interactions: implications for asthma.

PubMed

Page, S; Ammit, A J; Black, J L; Armour, C L

2001-12-01

Asthma is characterized by inflammation, hyperresponsiveness, and remodeling of the airway. Human mast cells (HMCs) play a central role in all of these changes by releasing mediators that cause exaggerated bronchoconstriction, induce human airway smooth muscle (HASM) cell proliferation, and recruit and activate inflammatory cells. Moreover, the number of HMCs present on asthmatic HASM is increased compared with that on nonasthmatic HASM. HASM cells also have the potential to actively participate in the inflammatory process by synthesizing cytokines and chemokines and expressing surface molecules, which have the capacity to perpetuate the inflammatory mechanisms present in asthma. This review specifically examines how the mediators of HMCs have the capacity to modulate many functions of HASM; how the synthetic function of HASM, particularly through the release and expression of stem cell factor, has the potential to influence HMC number and activation in an extraordinarily potent and proinflammatory manner; and how these interactions between HMCs and HASM have potential consequences for airway structure and inflammation relevant to the disease process of asthma.

[The modification of structural and functional properties of human hemoglobin induced by nitroglycerin under different oxygen regime conditions].

PubMed

Artyukhov, V G; Kalaeva, E A; Putintseva, O V; Polyubez'eva, A I

2016-03-01

Human oxyhemoglobin exhibits high resistance to nitroglycerin during incubation of the protein with this compound for 0.3-3 h. Prolonged exposure (24 h) leads to activation of methemoglobin production. In the presence of nitroglycerin hemoglobin molecules undergo rapid oxidation during deoxygenation with formation of methemoglobin as the terminal product of human oxyhemoglobin interaction with nitroglycerin. The scheme of interaction processes of oxyhemoglobin with nitroglycerin in different conditions of oxygen regime is proposed. Partially deliganded hemoglobin plays the leading role in the initiation of hemoglobin oxidation processes.

The molecular basis for species-specific activation of human TRPA1 protein by protons involves poorly conserved residues within transmembrane domains 5 and 6.

PubMed

de la Roche, Jeanne; Eberhardt, Mirjam J; Klinger, Alexandra B; Stanslowsky, Nancy; Wegner, Florian; Koppert, Wolfgang; Reeh, Peter W; Lampert, Angelika; Fischer, Michael J M; Leffler, Andreas

2013-07-12

The surveillance of acid-base homeostasis is concerted by diverse mechanisms, including an activation of sensory afferents. Proton-evoked activation of rodent sensory neurons is mainly mediated by the capsaicin receptor TRPV1 and acid-sensing ion channels. In this study, we demonstrate that extracellular acidosis activates and sensitizes the human irritant receptor TRPA1 (hTRPA1). Proton-evoked membrane currents and calcium influx through hTRPA1 occurred at physiological acidic pH values, were concentration-dependent, and were blocked by the selective TRPA1 antagonist HC030031. Both rodent and rhesus monkey TRPA1 failed to respond to extracellular acidosis, and protons even inhibited rodent TRPA1. Accordingly, mouse dorsal root ganglion neurons lacking TRPV1 only responded to protons when hTRPA1 was expressed heterologously. This species-specific activation of hTRPA1 by protons was reversed in both mouse and rhesus monkey TRPA1 by exchange of distinct residues within transmembrane domains 5 and 6. Furthermore, protons seem to interact with an extracellular interaction site to gate TRPA1 and not via a modification of intracellular N-terminal cysteines known as important interaction sites for electrophilic TRPA1 agonists. Our data suggest that hTRPA1 acts as a sensor for extracellular acidosis in human sensory neurons and should thus be taken into account as a yet unrecognized transduction molecule for proton-evoked pain and inflammation. The species specificity of this property is unique among known endogenous TRPA1 agonists, possibly indicating that evolutionary pressure enforced TRPA1 to inherit the role as an acid sensor in human sensory neurons.

The Molecular Basis for Species-specific Activation of Human TRPA1 Protein by Protons Involves Poorly Conserved Residues within Transmembrane Domains 5 and 6*

PubMed Central

de la Roche, Jeanne; Eberhardt, Mirjam J.; Klinger, Alexandra B.; Stanslowsky, Nancy; Wegner, Florian; Koppert, Wolfgang; Reeh, Peter W.; Lampert, Angelika; Fischer, Michael J. M.; Leffler, Andreas

2013-01-01

The surveillance of acid-base homeostasis is concerted by diverse mechanisms, including an activation of sensory afferents. Proton-evoked activation of rodent sensory neurons is mainly mediated by the capsaicin receptor TRPV1 and acid-sensing ion channels. In this study, we demonstrate that extracellular acidosis activates and sensitizes the human irritant receptor TRPA1 (hTRPA1). Proton-evoked membrane currents and calcium influx through hTRPA1 occurred at physiological acidic pH values, were concentration-dependent, and were blocked by the selective TRPA1 antagonist HC030031. Both rodent and rhesus monkey TRPA1 failed to respond to extracellular acidosis, and protons even inhibited rodent TRPA1. Accordingly, mouse dorsal root ganglion neurons lacking TRPV1 only responded to protons when hTRPA1 was expressed heterologously. This species-specific activation of hTRPA1 by protons was reversed in both mouse and rhesus monkey TRPA1 by exchange of distinct residues within transmembrane domains 5 and 6. Furthermore, protons seem to interact with an extracellular interaction site to gate TRPA1 and not via a modification of intracellular N-terminal cysteines known as important interaction sites for electrophilic TRPA1 agonists. Our data suggest that hTRPA1 acts as a sensor for extracellular acidosis in human sensory neurons and should thus be taken into account as a yet unrecognized transduction molecule for proton-evoked pain and inflammation. The species specificity of this property is unique among known endogenous TRPA1 agonists, possibly indicating that evolutionary pressure enforced TRPA1 to inherit the role as an acid sensor in human sensory neurons. PMID:23709225

CD56 Is a Pathogen Recognition Receptor on Human Natural Killer Cells.

PubMed

Ziegler, Sabrina; Weiss, Esther; Schmitt, Anna-Lena; Schlegel, Jan; Burgert, Anne; Terpitz, Ulrich; Sauer, Markus; Moretta, Lorenzo; Sivori, Simona; Leonhardt, Ines; Kurzai, Oliver; Einsele, Hermann; Loeffler, Juergen

2017-07-21

Aspergillus (A.) fumigatus is an opportunistic fungal mold inducing invasive aspergillosis (IA) in immunocompromised patients. Although antifungal activity of human natural killer (NK) cells was shown in previous studies, the underlying cellular mechanisms and pathogen recognition receptors (PRRs) are still unknown. Using flow cytometry we were able to show that the fluorescence positivity of the surface receptor CD56 significantly decreased upon fungal contact. To visualize the interaction site of NK cells and A. fumigatus we used SEM, CLSM and dSTORM techniques, which clearly demonstrated that NK cells directly interact with A. fumigatus via CD56 and that CD56 is re-organized and accumulated at this interaction site time-dependently. The inhibition of the cytoskeleton showed that the receptor re-organization was an active process dependent on actin re-arrangements. Furthermore, we could show that CD56 plays a role in the fungus mediated NK cell activation, since blocking of CD56 surface receptor reduced fungal mediated NK cell activation and reduced cytokine secretion. These results confirmed the direct interaction of NK cells and A. fumigatus, leading to the conclusion that CD56 is a pathogen recognition receptor. These findings give new insights into the functional role of CD56 in the pathogen recognition during the innate immune response.

HYDRAULIC ANALYSIS ON STREAM-AQUIFER INTERACTION BY STORAGE FUNCTION MODELS

EPA Science Inventory

In the natural hydrologic cycle, surface and subsurface water in a watershed are closely related and interact with each other. However, their relatrionships are affected by human activities. For instance, as the impervious area of a basin spreads due to urbanization, rainfall r...

Touch increases autonomic coupling between romantic partners

PubMed Central

Chatel-Goldman, Jonas; Congedo, Marco; Jutten, Christian; Schwartz, Jean-Luc

2014-01-01

Interpersonal touch is of paramount importance in human social bonding and close relationships, allowing a unique channel for affect communication. So far the effect of touch on human physiology has been studied at an individual level. The present study aims at extending the study of affective touch from isolated individuals to truly interacting dyads. We have designed an ecological paradigm where romantic partners interact only via touch and we manipulate their empathic states. Simultaneously, we collected their autonomic activity (skin conductance, pulse, respiration). Fourteen couples participated to the experiment. We found that interpersonal touch increased coupling of electrodermal activity between the interacting partners, regardless the intensity and valence of the emotion felt. In addition, physical touch induced strong and reliable changes in physiological states within individuals. These results support an instrumental role of interpersonal touch for affective support in close relationships. Furthermore, they suggest that touch alone allows the emergence of a somatovisceral resonance between interacting individuals, which in turn is likely to form the prerequisites for emotional contagion and empathy. PMID:24734009

Neuroadaptive technology enables implicit cursor control based on medial prefrontal cortex activity.

PubMed

Zander, Thorsten O; Krol, Laurens R; Birbaumer, Niels P; Gramann, Klaus

2016-12-27

The effectiveness of today's human-machine interaction is limited by a communication bottleneck as operators are required to translate high-level concepts into a machine-mandated sequence of instructions. In contrast, we demonstrate effective, goal-oriented control of a computer system without any form of explicit communication from the human operator. Instead, the system generated the necessary input itself, based on real-time analysis of brain activity. Specific brain responses were evoked by violating the operators' expectations to varying degrees. The evoked brain activity demonstrated detectable differences reflecting congruency with or deviations from the operators' expectations. Real-time analysis of this activity was used to build a user model of those expectations, thus representing the optimal (expected) state as perceived by the operator. Based on this model, which was continuously updated, the computer automatically adapted itself to the expectations of its operator. Further analyses showed this evoked activity to originate from the medial prefrontal cortex and to exhibit a linear correspondence to the degree of expectation violation. These findings extend our understanding of human predictive coding and provide evidence that the information used to generate the user model is task-specific and reflects goal congruency. This paper demonstrates a form of interaction without any explicit input by the operator, enabling computer systems to become neuroadaptive, that is, to automatically adapt to specific aspects of their operator's mindset. Neuroadaptive technology significantly widens the communication bottleneck and has the potential to fundamentally change the way we interact with technology.

C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes.

PubMed

Tavano, Regina; Gabrielli, Luca; Lubian, Elisa; Fedeli, Chiara; Visentin, Silvia; Polverino De Laureto, Patrizia; Arrigoni, Giorgio; Geffner-Smith, Alessandra; Chen, Fangfang; Simberg, Dmitri; Morgese, Giulia; Benetti, Edmondo M; Wu, Linping; Moghimi, Seyed Moein; Mancin, Fabrizio; Papini, Emanuele

2018-05-23

Poly(2-methyl-2-oxazoline) (PMOXA) is an alternative promising polymer to poly(ethylene glycol) (PEG) for design and engineering of macrophage-evading nanoparticles (NPs). Although PMOXA-engineered NPs have shown comparable pharmacokinetics and in vivo performance to PEGylated stealth NPs in the murine model, its interaction with elements of the human innate immune system has not been studied. From a translational angle, we studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived organically modified silica NPs (PMOXA-coated NPs) of approximately 100 nm in diameter with human complement system, blood leukocytes, and macrophages and compared their performance with PEGylated and uncoated NP counterparts. Through detailed immunological and proteomic profiling, we show that PMOXA-coated NPs extensively trigger complement activation in human sera exclusively through the classical pathway. Complement activation is initiated by the sensing molecule C1q, where C1q binds with high affinity ( K d = 11 ± 1 nM) to NP surfaces independent of immunoglobulin binding. C1q-mediated complement activation accelerates PMOXA opsonization with the third complement protein (C3) through the amplification loop of the alternative pathway. This promoted NP recognition by human blood leukocytes and monocyte-derived macrophages. The macrophage capture of PMOXA-coated NPs correlates with sera donor variability in complement activation and opsonization but not with other major corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps.

Bear-human interactions at Glacier Bay National Park and Preserve: Conflict risk assessment

USGS Publications Warehouse

Smith, Tom S.; DeBruyn, Terry D.; Lewis, Tania; Yerxa, Rusty; Partridge, Steven T.

2003-01-01

Many bear-human conflicts have occurred in Alaska parks and refuges, resulting in area closures, property damage, human injury, and loss of life. Human activity in bear country has also had negative and substantial consequences for bears: disruption of their natural activity patterns, displacement from important habitats, injury, and death. It is unfortunate for both people and bears when conflicts occur. Fortunately, however, solutions exist for reducing, and in some instances eliminating, bear-human conflict. This article presents ongoing work at Glacier Bay National Park and Preserve by U.S. Geological Survey (USGS) and National Park Service scientists who are committed to finding solutions for the bear-human conflicts that periodically occurs there.

A Qualitative Model of Human Interaction with Complex Dynamic Systems

NASA Technical Reports Server (NTRS)

Hess, Ronald A.

1987-01-01

A qualitative model describing human interaction with complex dynamic systems is developed. The model is hierarchical in nature and consists of three parts: a behavior generator, an internal model, and a sensory information processor. The behavior generator is responsible for action decomposition, turning higher level goals or missions into physical action at the human-machine interface. The internal model is an internal representation of the environment which the human is assumed to possess and is divided into four submodel categories. The sensory information processor is responsible for sensory composition. All three parts of the model act in consort to allow anticipatory behavior on the part of the human in goal-directed interaction with dynamic systems. Human workload and error are interpreted in this framework, and the familiar example of an automobile commute is used to illustrate the nature of the activity in the three model elements. Finally, with the qualitative model as a guide, verbal protocols from a manned simulation study of a helicopter instrument landing task are analyzed with particular emphasis on the effect of automation on human-machine performance.

A qualitative model of human interaction with complex dynamic systems

NASA Technical Reports Server (NTRS)

Hess, Ronald A.

1987-01-01

A qualitative model describing human interaction with complex dynamic systems is developed. The model is hierarchical in nature and consists of three parts: a behavior generator, an internal model, and a sensory information processor. The behavior generator is responsible for action decomposition, turning higher level goals or missions into physical action at the human-machine interface. The internal model is an internal representation of the environment which the human is assumed to possess and is divided into four submodel categories. The sensory information processor is responsible for sensory composition. All three parts of the model act in consort to allow anticipatory behavior on the part of the human in goal-directed interaction with dynamic systems. Human workload and error are interpreted in this framework, and the familiar example of an automobile commute is used to illustrate the nature of the activity in the three model elements. Finally, with the qualitative model as a guide, verbal protocols from a manned simulation study of a helicopter instrument landing task are analyzed with particular emphasis on the effect of automation on human-machine performance.

Interactions among human behavior, social networks, and societal infrastructures: A Case Study in Computational Epidemiology

NASA Astrophysics Data System (ADS)

Barrett, Christopher L.; Bisset, Keith; Chen, Jiangzhuo; Eubank, Stephen; Lewis, Bryan; Kumar, V. S. Anil; Marathe, Madhav V.; Mortveit, Henning S.

Human behavior, social networks, and the civil infrastructures are closely intertwined. Understanding their co-evolution is critical for designing public policies and decision support for disaster planning. For example, human behaviors and day to day activities of individuals create dense social interactions that are characteristic of modern urban societies. These dense social networks provide a perfect fabric for fast, uncontrolled disease propagation. Conversely, people’s behavior in response to public policies and their perception of how the crisis is unfolding as a result of disease outbreak can dramatically alter the normally stable social interactions. Effective planning and response strategies must take these complicated interactions into account. In this chapter, we describe a computer simulation based approach to study these issues using public health and computational epidemiology as an illustrative example. We also formulate game-theoretic and stochastic optimization problems that capture many of the problems that we study empirically.

A Formal Investigation of Human Spatial Control Skills: Mathematical Formalization, Skill Development, and Skill Assessment

NASA Astrophysics Data System (ADS)

Li, Bin

Spatial control behaviors account for a large proportion of human everyday activities from normal daily tasks, such as reaching for objects, to specialized tasks, such as driving, surgery, or operating equipment. These behaviors involve intensive interactions within internal processes (i.e. cognitive, perceptual, and motor control) and with the physical world. This dissertation builds on a concept of interaction pattern and a hierarchical functional model. Interaction pattern represents a type of behavior synergy that humans coordinates cognitive, perceptual, and motor control processes. It contributes to the construction of the hierarchical functional model that delineates humans spatial control behaviors as the coordination of three functional subsystems: planning, guidance, and tracking/pursuit. This dissertation formalizes and validates these two theories and extends them for the investigation of human spatial control skills encompassing development and assessment. Specifically, this dissertation first presents an overview of studies in human spatial control skills encompassing definition, characteristic, development, and assessment, to provide theoretical evidence for the concept of interaction pattern and the hierarchical functional model. The following, the human experiments for collecting motion and gaze data and techniques to register and classify gaze data, are described. This dissertation then elaborates and mathematically formalizes the hierarchical functional model and the concept of interaction pattern. These theories then enables the construction of a succinct simulation model that can reproduce a variety of human performance with a minimal set of hypotheses. This validates the hierarchical functional model as a normative framework for interpreting human spatial control behaviors. The dissertation then investigates human skill development and captures the emergence of interaction pattern. The final part of the dissertation applies the hierarchical functional model for skill assessment and introduces techniques to capture interaction patterns both from the top down using their geometric features and from the bottom up using their dynamical characteristics. The validity and generality of the skill assessment is illustrated using two the remote-control flight and laparoscopic surgical training experiments.

Antagonist interaction with the human 5-HT7 receptor mediates the rapid and potent inhibition of non-G-protein-stimulated adenylate cyclase activity: a novel GPCR effect

PubMed Central

Klein, MT; Teitler, M

2011-01-01

BACKGROUND AND PURPOSE The human 5-hydroxytryptamine7 (h5-HT7) receptor is Gs-coupled and stimulates the production of the intracellular signalling molecule cAMP. Previously, we reported a novel property of the h5-HT7 receptor: pseudo-irreversible antagonists irreversibly inhibit forskolin-stimulated (non-receptor-mediated) cAMP production. Herein, we sought to determine if competitive antagonists also affect forskolin-stimulated activity and if this effect is common among other Gs-coupled receptors. EXPERIMENTAL APPROACH Recombinant cell lines expressing h5-HT7 receptors or other receptors of interest were briefly exposed to antagonists; cAMP production was then stimulated by forskolin and quantified by an immunocompetitive assay. KEY RESULTS In human embryonic kidney 293 cells stably expressing h5-HT7 receptors, all competitive antagonists inhibited nearly 100% of forskolin-stimulated cAMP production. This effect was insensitive to pertussis toxin, that is, not Gi/o-mediated. Potency to inhibit forskolin-stimulated activity strongly correlated with h5-HT7 binding affinity (r2= 0.91), indicating that the antagonists acted through h5-HT7 receptors to inhibit forskolin. Potency and maximal effects of clozapine, a prototypical competitive h5-HT7 antagonist, were unaffected by varying forskolin concentration. Antagonist interaction with h5-HT6, human β1, β2, and β3 adrenoceptors did not inhibit forskolin's activity. CONCLUSIONS AND IMPLICATIONS The inhibition of adenylate cyclase, as measured by forskolin's activity, is an underlying property of antagonist interaction with h5-HT7 receptors; however, this is not a common property of other Gs-coupled receptors. This phenomenon may be involved in the roles played by h5-HT7 receptors in human physiology. Development of h5-HT7 antagonists that do not elicit this effect would aid in the elucidation of its mechanisms and shed light on its possible physiological relevance. PMID:21198551

Intrinsic interactive reinforcement learning - Using error-related potentials for real world human-robot interaction.

PubMed

Kim, Su Kyoung; Kirchner, Elsa Andrea; Stefes, Arne; Kirchner, Frank

2017-12-14

Reinforcement learning (RL) enables robots to learn its optimal behavioral strategy in dynamic environments based on feedback. Explicit human feedback during robot RL is advantageous, since an explicit reward function can be easily adapted. However, it is very demanding and tiresome for a human to continuously and explicitly generate feedback. Therefore, the development of implicit approaches is of high relevance. In this paper, we used an error-related potential (ErrP), an event-related activity in the human electroencephalogram (EEG), as an intrinsically generated implicit feedback (rewards) for RL. Initially we validated our approach with seven subjects in a simulated robot learning scenario. ErrPs were detected online in single trial with a balanced accuracy (bACC) of 91%, which was sufficient to learn to recognize gestures and the correct mapping between human gestures and robot actions in parallel. Finally, we validated our approach in a real robot scenario, in which seven subjects freely chose gestures and the real robot correctly learned the mapping between gestures and actions (ErrP detection (90% bACC)). In this paper, we demonstrated that intrinsically generated EEG-based human feedback in RL can successfully be used to implicitly improve gesture-based robot control during human-robot interaction. We call our approach intrinsic interactive RL.

Towards the Verification of Human-Robot Teams

NASA Technical Reports Server (NTRS)

Fisher, Michael; Pearce, Edward; Wooldridge, Mike; Sierhuis, Maarten; Visser, Willem; Bordini, Rafael H.

2005-01-01

Human-Agent collaboration is increasingly important. Not only do high-profile activities such as NASA missions to Mars intend to employ such teams, but our everyday activities involving interaction with computational devices falls into this category. In many of these scenarios, we are expected to trust that the agents will do what we expect and that the agents and humans will work together as expected. But how can we be sure? In this paper, we bring together previous work on the verification of multi-agent systems with work on the modelling of human-agent teamwork. Specifically, we target human-robot teamwork. This paper provides an outline of the way we are using formal verification techniques in order to analyse such collaborative activities. A particular application is the analysis of human-robot teams intended for use in future space exploration.

The Interactive Minority Game: a Web-based investigation of human market interactions

NASA Astrophysics Data System (ADS)

Laureti, Paolo; Ruch, Peter; Wakeling, Joseph; Zhang, Yi-Cheng

2004-01-01

The unprecedented access offered by the World Wide Web brings with it the potential to gather huge amounts of data on human activities. Here we exploit this by using a toy model of financial markets, the Minority Game (MG), to investigate human speculative trading behaviour and information capacity. Hundreds of individuals have played a total of tens of thousands of game turns against computer-controlled agents in the Web-based Interactive Minority Game. The analytical understanding of the MG permits fine-tuning of the market situations encountered, allowing for investigation of human behaviour in a variety of controlled environments. In particular, our results indicate a transition in players’ decision-making, as the markets become more difficult, between deductive behaviour making use of short-term trends in the market, and highly repetitive behaviour that ignores entirely the market history, yet outperforms random decision-making.

A Re-Examination of Information Seeking Behaviour in the Context of Activity Theory

ERIC Educational Resources Information Center

Wilson, T. D.

2006-01-01

Introduction: Activity theory, developed in the USSR as a Marxist alternative to Western psychology, has been applied widely in educational studies and increasingly in human-computer interaction research. Argument: The key elements of activity theory, Motivation, Goal, Activity, Tools, Object, Outcome, Rules, Community and Division of labour are…

HA Antibody-Mediated FcγRIIIa Activity Is Both Dependent on FcR Engagement and Interactions between HA and Sialic Acids.

PubMed

Cox, Freek; Kwaks, Ted; Brandenburg, Boerries; Koldijk, Martin H; Klaren, Vincent; Smal, Bastiaan; Korse, Hans J W M; Geelen, Eric; Tettero, Lisanne; Zuijdgeest, David; Stoop, Esther J M; Saeland, Eirikur; Vogels, Ronald; Friesen, Robert H E; Koudstaal, Wouter; Goudsmit, Jaap

2016-01-01

Interactions with receptors for the Fc region of IgG (FcγRs) have been shown to contribute to the in vivo protection against influenza A viruses provided by broadly neutralizing antibodies (bnAbs) that bind to the viral hemagglutinin (HA) stem. In particular, Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) has been shown to contribute to protection by stem-binding bnAbs. Fc-mediated effector functions appear not to contribute to protection provided by strain-specific HA head-binding antibodies. We used a panel of anti-stem and anti-head influenza A and B monoclonal antibodies with identical human IgG1 Fc domains and investigated their ability to mediate ADCC-associated FcγRIIIa activation. Antibodies which do not interfere with sialic acid binding of HA can mediate FcγRIIIa activation. However, the FcγRIIIa activation was inhibited when a mutant HA, unable to bind sialic acids, was used. Antibodies which block sialic acid receptor interactions of HA interfered with FcγRIIIa activation. The inhibition of FcγRIIIa activation by HA head-binding and sialic acid receptor-blocking antibodies was confirmed in plasma samples of H5N1 vaccinated human subjects. Together, these results suggest that in addition to Fc-FcγR binding, interactions between HA and sialic acids on immune cells are required for optimal Fc-mediated effector functions by anti-HA antibodies.

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.

Activation of EGF Receptor Kinase by L1-mediated Homophilic Cell Interactions

PubMed Central

Islam, Rafique; Kristiansen, Lars V.; Romani, Susana; Garcia-Alonso, Luis; Hortsch, Michael

2004-01-01

Neural cell adhesion molecules (CAMs) are important players during neurogenesis and neurite outgrowth as well as axonal fasciculation and pathfinding. Some of these developmental processes entail the activation of cellular signaling cascades. Pharmacological and genetic evidence indicates that the neurite outgrowth-promoting activity of L1-type CAMs is at least in part mediated by the stimulation of neuronal receptor tyrosine kinases (RTKs), especially FGF and EGF receptors. It has long been suspected that neural CAMs might physically interact with RTKs, but their activation by specific cell adhesion events has not been directly demonstrated. Here we report that gain-of-function conditions of the Drosophila L1-type CAM Neuroglian result in profound sensory axon pathfinding defects in the developing Drosophila wing. This phenotype can be suppressed by decreasing the normal gene dosage of the Drosophila EGF receptor gene. Furthermore, in Drosophila S2 cells, cell adhesion mediated by human L1-CAM results in the specific activation of human EGF tyrosine kinase at cell contact sites and EGF receptors engage in a physical interaction with L1-CAM molecules. Thus L1-type CAMs are able to promote the adhesion-dependent activation of EGF receptor signaling in vitro and in vivo. PMID:14718570

Intracranial recordings and human memory.

PubMed

Johnson, Elizabeth L; Knight, Robert T

2015-04-01

Recent work involving intracranial recording during human memory performance provides superb spatiotemporal resolution on mnemonic processes. These data demonstrate that the cortical regions identified in neuroimaging studies of memory fall into temporally distinct networks and the hippocampal theta activity reported in animal memory literature also plays a central role in human memory. Memory is linked to activity at multiple interacting frequencies, ranging from 1 to 500Hz. High-frequency responses and coupling between different frequencies suggest that frontal cortex activity is critical to human memory processes, as well as a potential key role for the thalamus in neocortical oscillations. Future research will inform unresolved questions in the neuroscience of human memory and guide creation of stimulation protocols to facilitate function in the damaged brain. Copyright © 2014 Elsevier Ltd. All rights reserved.

Expression of exogenous human hepatic nuclear factor-1α by a lentiviral vector and its interactions with Plasmodium falciparum subtilisin-like protease 2.

PubMed

Liao, Shunyao; Liu, Yunqiang; Zheng, Bing; Cho, Pyo Yun; Song, Hyun Ok; Lee, Yun-Seok; Jung, Suk-Yul; Park, Hyun

2011-12-01

The onset, severity, and ultimate outcome of malaria infection are influenced by parasite-expressed virulence factors as well as by individual host responses to these determinants. In both humans and mice, liver injury follows parasite entry, persisting to the erythrocytic stage in the case of infection with the fatal strain of Plasmodium falciparum. Hepatic nuclear factor (HNF)-1α is a master regulator of not only the liver damage and adaptive responses but also diverse metabolic functions. In this study, we analyzed the expression of host HNF-1α in relation to malaria infection and evaluated its interaction with the 5'-untranslated region of subtilisin-like protease 2 (subtilase, Sub2). Recombinant human HNF-1α expressed by a lentiviral vector (LV HNF-1α) was introduced into mice. Interestingly, differences in the activity of the 5'-untranslated region of the Pf-Sub2 promoter were detected in 293T cells, and LV HNF-1α was observed to influence promoter activity, suggesting that host HNF-1α interacts with the Sub2 gene.

Anatomical connectivity influences both intra- and inter-brain synchronizations.

PubMed

Dumas, Guillaume; Chavez, Mario; Nadel, Jacqueline; Martinerie, Jacques

2012-01-01

Recent development in diffusion spectrum brain imaging combined to functional simulation has the potential to further our understanding of how structure and dynamics are intertwined in the human brain. At the intra-individual scale, neurocomputational models have already started to uncover how the human connectome constrains the coordination of brain activity across distributed brain regions. In parallel, at the inter-individual scale, nascent social neuroscience provides a new dynamical vista of the coupling between two embodied cognitive agents. Using EEG hyperscanning to record simultaneously the brain activities of subjects during their ongoing interaction, we have previously demonstrated that behavioral synchrony correlates with the emergence of inter-brain synchronization. However, the functional meaning of such synchronization remains to be specified. Here, we use a biophysical model to quantify to what extent inter-brain synchronizations are related to the anatomical and functional similarity of the two brains in interaction. Pairs of interacting brains were numerically simulated and compared to real data. Results show a potential dynamical property of the human connectome to facilitate inter-individual synchronizations and thus may partly account for our propensity to generate dynamical couplings with others.

Human agency beliefs influence behaviour during virtual social interactions.

PubMed

Caruana, Nathan; Spirou, Dean; Brock, Jon

2017-01-01

In recent years, with the emergence of relatively inexpensive and accessible virtual reality technologies, it is now possible to deliver compelling and realistic simulations of human-to-human interaction. Neuroimaging studies have shown that, when participants believe they are interacting via a virtual interface with another human agent, they show different patterns of brain activity compared to when they know that their virtual partner is computer-controlled. The suggestion is that users adopt an "intentional stance" by attributing mental states to their virtual partner. However, it remains unclear how beliefs in the agency of a virtual partner influence participants' behaviour and subjective experience of the interaction. We investigated this issue in the context of a cooperative "joint attention" game in which participants interacted via an eye tracker with a virtual onscreen partner, directing each other's eye gaze to different screen locations. Half of the participants were correctly informed that their partner was controlled by a computer algorithm ("Computer" condition). The other half were misled into believing that the virtual character was controlled by a second participant in another room ("Human" condition). Those in the "Human" condition were slower to make eye contact with their partner and more likely to try and guide their partner before they had established mutual eye contact than participants in the "Computer" condition. They also responded more rapidly when their partner was guiding them, although the same effect was also found for a control condition in which they responded to an arrow cue. Results confirm the influence of human agency beliefs on behaviour in this virtual social interaction context. They further suggest that researchers and developers attempting to simulate social interactions should consider the impact of agency beliefs on user experience in other social contexts, and their effect on the achievement of the application's goals.

The CCDC55 couples cannabinoid receptor CNR1 to a putative DISC1 schizophrenia pathway.

PubMed

Xie, J; Gizatullin, R; Vukojevic, V; Leopardi, R

2015-12-03

Our previous study suggested that the coiled coil domain-containing 55 gene (CCDC55), also named as NSRP1 (nuclear speckle splicing regulatory protein 1 (NSRP1)), was encompassed in a haplotype block spanning over the serotonin transporter (5-HTT) gene in patients with schizophrenia (SCZ). However, the neurobiological function of CCDC55 gene remains unknown. This study aims to uncover the potential role of CCDC55 in SCZ-associated molecular pathways. Using molecular cloning, sequencing and immune blotting to identify basic properties, yeast two-hybrid screening and glutathione S-transferase (GST) pull-down assay to test protein-protein interaction, and confocal laser scanning microscopy (CSLM) to show intracellular interaction of proteins. (i) CCDC55 is expressed as a nuclear protein in human neuronal cells; (ii) Protein-protein interaction analyses showed CCDC55 physically interacted with Ran binding protein 9 (RanBP9) and disrupted in schizophrenia 1 (DISC1); (iii) CCDC55 and RanBP9 co-localized in the nucleus of human neuronal cells; (iv) CCDC55 also interacted with the cannabinoid receptor 1 (CNR1), and with the brain cannabinoid receptor-interacting protein 1a (CNRIP1a); (v) CNR1 activation in differentiated human neuronal cells resulted in an altered RanBP9 localization. CCDC55 may be involved in a functional bridging between the CNR1 activation and the DISC1/RanBP9-associated pathways. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Interaction of atorvastatin with the human glial transporter SLC16A1.

PubMed

Sasaki, Shotaro; Futagi, Yuya; Ideno, Masaya; Kobayashi, Masaki; Narumi, Katsuya; Furugen, Ayako; Iseki, Ken

2016-10-05

Solute carrier (SLC) 16A1 is a pH-dependent carrier of 5-oxoproline, a derivative of the amino acid. SLC16A1 interacts with carboxylate group-containing substrates, which are also present in atorvastatin, and might be the reason for its ability to interact with atorvastatin. Does atorvastatin interact with the carrier? Does it also interact with the carrier via the substrate recognition site? This study was carried out to answer these questions. Polymerase chain reaction was used to determine the expression of SLC16A1 in normal human astrocytes. We induced SLC16A1 expression in a mammalian cell line and in Xenopus laevis oocytes. We used [(3)H] 5-oxoproline for direct measurement of SLC16A1-specific transport activity. SLC16A1 was clearly observed in normal human astrocytes. 3-Hydroxy-3-methyl-glutaryl-CoA reductase inhibitors inhibited the SLC16A1-specific transport of 5-oxoproline. Atorvastatin was the most potent inhibitor, with an inhibition constant of 40μM. The drug was a non-competitive inhibitor of SLC16A1. In the present study, we showed non-competitive inhibition of SLC16A1-specific transport activity by atorvastatin. However, the affinity between the drug and the carrier was extremely low. Therefore, the interaction of atorvastatin with SLC16A1 is unlikely to be a problem in clinical practice. Copyright © 2016. Published by Elsevier B.V.

A Multiscale Survival Process for Modeling Human Activity Patterns.

PubMed

Zhang, Tianyang; Cui, Peng; Song, Chaoming; Zhu, Wenwu; Yang, Shiqiang

2016-01-01

Human activity plays a central role in understanding large-scale social dynamics. It is well documented that individual activity pattern follows bursty dynamics characterized by heavy-tailed interevent time distributions. Here we study a large-scale online chatting dataset consisting of 5,549,570 users, finding that individual activity pattern varies with timescales whereas existing models only approximate empirical observations within a limited timescale. We propose a novel approach that models the intensity rate of an individual triggering an activity. We demonstrate that the model precisely captures corresponding human dynamics across multiple timescales over five orders of magnitudes. Our model also allows extracting the population heterogeneity of activity patterns, characterized by a set of individual-specific ingredients. Integrating our approach with social interactions leads to a wide range of implications.

CONTRIBUTION OF HOUSEHOLD ACTIVITIES TO THE HEALTH OF URBAN ECOSYSTEMS

EPA Science Inventory

With a majority of humans now living in urban and suburban areas, innovative methods are needed for land use planning to maintain healthy urban communities and ecosystems. As urban areas expand, an increasing number of human-environmental interactions take place, particularly al...

Identification of CENP-V as a novel microtubule-associating molecule that activates Src family kinases through SH3 domain interaction.

PubMed

Honda, Zen-Ichiro; Suzuki, Takeshi; Honda, Hiroaki

2009-12-01

The activation mechanisms of Src family kinases (SFKs) involve the dissociation of the intramolecular interaction between the Src homology (SH) 3 and kinase domain. This process is mediated by the intermolecular attack of outer ligands to the SH3 domain. By using a yeast two-hybrid screen, we isolated a relevant ligand involved in the activation mechanisms of SFKs. This molecule was found to be identical to a recently recognized kinetochore protein--designated as centromere protein (CENP)-V--which is required for the progression of mitosis. We show here that human CENP-V plays further roles in cell dynamics; the proline-rich region of human CENP-V associates with the SH3 domains of SFKs and potently activates SFKs, whereas another domain of CENP-V that possesses a highly conserved cysteine array confers the ability to associate with stabilized microtubules (MTs). Human CENP-V distributes to the cell protrusion and to the leading edge of migrating cells in response to external stimuli, and depletion of CENP-V by RNA interference significantly attenuates closure of a scratch wound. These findings indicate that human CENP-V is involved in directional cell motility as well as in the progression of mitosis, as a scaffolding molecule that links MTs and SFKs.

Regulation of human Nfu activity in Fe-S cluster delivery-characterization of the interaction between Nfu and the HSPA9/Hsc20 chaperone complex.

PubMed

Wachnowsky, Christine; Liu, Yushi; Yoon, Taejin; Cowan, J A

2018-01-01

Iron-sulfur cluster biogenesis is a complex, but highly regulated process that involves de novo cluster formation from iron and sulfide ions on a scaffold protein, and subsequent delivery to final targets via a series of Fe-S cluster-binding carrier proteins. The process of cluster release from the scaffold/carrier for transfer to the target proteins may be mediated by a dedicated Fe-S cluster chaperone system. In human cells, the chaperones include heat shock protein HSPA9 and the J-type chaperone Hsc20. While the role of chaperones has been somewhat clarified in yeast and bacterial systems, many questions remain over their functional roles in cluster delivery and interactions with a variety of human Fe-S cluster proteins. One such protein, Nfu, has recently been recognized as a potential interaction partner of the chaperone complex. Herein, we examined the ability of human Nfu to function as a carrier by interacting with the human chaperone complex. Human Nfu is shown to bind to both chaperone proteins with binding affinities similar to those observed for IscU binding to the homologous HSPA9 and Hsc20, while Nfu can also stimulate the ATPase activity of HSPA9. Additionally, the chaperone complex was able to promote Nfu function by enhancing the second-order rate constants for Fe-S cluster transfer to target proteins and providing directionality in cluster transfer from Nfu by eliminating promiscuous transfer reactions. Together, these data support a hypothesis in which Nfu can serve as an alternative carrier protein for chaperone-mediated cluster release and delivery in Fe-S cluster biogenesis and trafficking. © 2017 Federation of European Biochemical Societies.

Human-directed local autonomy for motion guidance and coordination in an intelligent manufacturing system

NASA Astrophysics Data System (ADS)

Alford, W. A.; Kawamura, Kazuhiko; Wilkes, Don M.

1997-12-01

This paper discusses the problem of integrating human intelligence and skills into an intelligent manufacturing system. Our center has jointed the Holonic Manufacturing Systems (HMS) Project, an international consortium dedicated to developing holonic systems technologies. One of our contributions to this effort is in Work Package 6: flexible human integration. This paper focuses on one activity, namely, human integration into motion guidance and coordination. Much research on intelligent systems focuses on creating totally autonomous agents. At the Center for Intelligent Systems (CIS), we design robots that interact directly with a human user. We focus on using the natural intelligence of the user to simplify the design of a robotic system. The problem is finding ways for the user to interact with the robot that are efficient and comfortable for the user. Manufacturing applications impose the additional constraint that the manufacturing process should not be disturbed; that is, frequent interacting with the user could degrade real-time performance. Our research in human-robot interaction is based on a concept called human directed local autonomy (HuDL). Under this paradigm, the intelligent agent selects and executes a behavior or skill, based upon directions from a human user. The user interacts with the robot via speech, gestures, or other media. Our control software is based on the intelligent machine architecture (IMA), an object-oriented architecture which facilitates cooperation and communication among intelligent agents. In this paper we describe our research testbed, a dual-arm humanoid robot and human user, and the use of this testbed for a human directed sorting task. We also discuss some proposed experiments for evaluating the integration of the human into the robot system. At the time of this writing, the experiments have not been completed.

Shear Forces during Blast, Not Abrupt Changes in Pressure Alone, Generate Calcium Activity in Human Brain Cells

DTIC Science & Technology

2012-06-29

the tissue-force interaction(s) and the cellular damage properties remain unresolved. Studies on a mechanical head model demonstrated high transient...that pressure transient. In vitro models of primary blast injury [5,18,19] are likewise limited by an absence of real-time, high spatial and temporal... models , as well as with human injuries in which expression of bTBI symptoms among different individuals that are exposed to the same blast is

The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions.

PubMed Central

Lehmann, J M; McKee, D D; Watson, M A; Willson, T M; Moore, J T; Kliewer, S A

1998-01-01

The cytochrome P-450 monooxygenase 3A4 (CYP3A4) is responsible for the oxidative metabolism of a wide variety of xenobiotics including an estimated 60% of all clinically used drugs. Although expression of the CYP3A4 gene is known to be induced in response to a variety of compounds, the mechanism underlying this induction, which represents a basis for drug interactions in patients, has remained unclear. We report the identification of a human (h) orphan nuclear receptor, termed the pregnane X receptor (PXR), that binds to a response element in the CYP3A4 promoter and is activated by a range of drugs known to induce CYP3A4 expression. Comparison of hPXR with the recently cloned mouse PXR reveals marked differences in their activation by certain drugs, which may account in part for the species-specific effects of compounds on CYP3A gene expression. These findings provide a molecular explanation for the ability of disparate chemicals to induce CYP3A4 levels and, furthermore, provide a basis for developing in vitro assays to aid in predicting whether drugs will interact in humans. PMID:9727070

The Neural Representations Underlying Human Episodic Memory.

PubMed

Xue, Gui

2018-06-01

A fundamental question of human episodic memory concerns the cognitive and neural representations and processes that give rise to the neural signals of memory. By integrating behavioral tests, formal computational models, and neural measures of brain activity patterns, recent studies suggest that memory signals not only depend on the neural processes and representations during encoding and retrieval, but also on the interaction between encoding and retrieval (e.g., transfer-appropriate processing), as well as on the interaction between the tested events and all other events in the episodic memory space (e.g., global matching). In addition, memory signals are also influenced by the compatibility of the event with the existing long-term knowledge (e.g., schema matching). These studies highlight the interactive nature of human episodic memory. Copyright © 2018 Elsevier Ltd. All rights reserved.

Interaction in Spoken Word Recognition Models: Feedback Helps.

PubMed

Magnuson, James S; Mirman, Daniel; Luthra, Sahil; Strauss, Ted; Harris, Harlan D

2018-01-01

Human perception, cognition, and action requires fast integration of bottom-up signals with top-down knowledge and context. A key theoretical perspective in cognitive science is the interactive activation hypothesis: forward and backward flow in bidirectionally connected neural networks allows humans and other biological systems to approximate optimal integration of bottom-up and top-down information under real-world constraints. An alternative view is that online feedback is neither necessary nor helpful; purely feed forward alternatives can be constructed for any feedback system, and online feedback could not improve processing and would preclude veridical perception. In the domain of spoken word recognition, the latter view was apparently supported by simulations using the interactive activation model, TRACE, with and without feedback: as many words were recognized more quickly without feedback as were recognized faster with feedback, However, these simulations used only a small set of words and did not address a primary motivation for interaction: making a model robust in noise. We conducted simulations using hundreds of words, and found that the majority were recognized more quickly with feedback than without. More importantly, as we added noise to inputs, accuracy and recognition times were better with feedback than without. We follow these simulations with a critical review of recent arguments that online feedback in interactive activation models like TRACE is distinct from other potentially helpful forms of feedback. We conclude that in addition to providing the benefits demonstrated in our simulations, online feedback provides a plausible means of implementing putatively distinct forms of feedback, supporting the interactive activation hypothesis.

Interaction in Spoken Word Recognition Models: Feedback Helps

PubMed Central

Magnuson, James S.; Mirman, Daniel; Luthra, Sahil; Strauss, Ted; Harris, Harlan D.

2018-01-01

Human perception, cognition, and action requires fast integration of bottom-up signals with top-down knowledge and context. A key theoretical perspective in cognitive science is the interactive activation hypothesis: forward and backward flow in bidirectionally connected neural networks allows humans and other biological systems to approximate optimal integration of bottom-up and top-down information under real-world constraints. An alternative view is that online feedback is neither necessary nor helpful; purely feed forward alternatives can be constructed for any feedback system, and online feedback could not improve processing and would preclude veridical perception. In the domain of spoken word recognition, the latter view was apparently supported by simulations using the interactive activation model, TRACE, with and without feedback: as many words were recognized more quickly without feedback as were recognized faster with feedback, However, these simulations used only a small set of words and did not address a primary motivation for interaction: making a model robust in noise. We conducted simulations using hundreds of words, and found that the majority were recognized more quickly with feedback than without. More importantly, as we added noise to inputs, accuracy and recognition times were better with feedback than without. We follow these simulations with a critical review of recent arguments that online feedback in interactive activation models like TRACE is distinct from other potentially helpful forms of feedback. We conclude that in addition to providing the benefits demonstrated in our simulations, online feedback provides a plausible means of implementing putatively distinct forms of feedback, supporting the interactive activation hypothesis. PMID:29666593

Robots As Intentional Agents: Using Neuroscientific Methods to Make Robots Appear More Social

PubMed Central

Wiese, Eva; Metta, Giorgio; Wykowska, Agnieszka

2017-01-01

Robots are increasingly envisaged as our future cohabitants. However, while considerable progress has been made in recent years in terms of their technological realization, the ability of robots to interact with humans in an intuitive and social way is still quite limited. An important challenge for social robotics is to determine how to design robots that can perceive the user’s needs, feelings, and intentions, and adapt to users over a broad range of cognitive abilities. It is conceivable that if robots were able to adequately demonstrate these skills, humans would eventually accept them as social companions. We argue that the best way to achieve this is using a systematic experimental approach based on behavioral and physiological neuroscience methods such as motion/eye-tracking, electroencephalography, or functional near-infrared spectroscopy embedded in interactive human–robot paradigms. This approach requires understanding how humans interact with each other, how they perform tasks together and how they develop feelings of social connection over time, and using these insights to formulate design principles that make social robots attuned to the workings of the human brain. In this review, we put forward the argument that the likelihood of artificial agents being perceived as social companions can be increased by designing them in a way that they are perceived as intentional agents that activate areas in the human brain involved in social-cognitive processing. We first review literature related to social-cognitive processes and mechanisms involved in human–human interactions, and highlight the importance of perceiving others as intentional agents to activate these social brain areas. We then discuss how attribution of intentionality can positively affect human–robot interaction by (a) fostering feelings of social connection, empathy and prosociality, and by (b) enhancing performance on joint human–robot tasks. Lastly, we describe circumstances under which attribution of intentionality to robot agents might be disadvantageous, and discuss challenges associated with designing social robots that are inspired by neuroscientific principles. PMID:29046651

Molecular interaction of novel benzothiazolyl triazolium analogues with calf thymus DNA and HSA-their biological investigation as potent antimicrobial agents.

PubMed

Maddili, Swetha K; Katla, Ramesh; Kannekanti, Vijaya Kumar; Bejjanki, Naveen Kumar; Tuniki, Balaraju; Zhou, Cheng-He; Gandham, Himabindu

2018-04-25

The binding behaviour between calf thymus DNA and synthesized benzothiazolyl triazolium derivatives as potent antimicrobial agents was explored by means of spectroscopic applications together with molecular docking study at the sub-domain IIA, binding site I of human serum albumin (HSA). Most of the synthesized derivatives presented significant antimicrobial inhibition when compared with the clinical Norfloxacin, Chloromycin, and Fluconazole. In particular, compound 5q presented efficient anti-Bacillus subtilis, anti-Escherichia coli, anti-Salmonella typhi, and anti-Psuedomonas aeruginosa activity with low MIC values of 2-8 μg/mL which were relatively superior to the reference drugs. The preliminarily investigation of interaction studies with calf thymus DNA demonstrated that the most active compound 5q could effectively intercalate into DNA to form 5q-DNA complex. Further investigations revealed that human serum albumin could effectively transport compound 5q while molecular modelling studies with good docking score showed that hydrophobic interactions as well as hydrogen bonds played a significant role in the interaction of compound 5q with HSA. In addition, the cytotoxic investigation carried out on four different cancerous cell lines (3 human cell lines and 1 murine cell lines) by MTT assay presented that compound 5n is active against MDA cell lines with IC 50 values less than 100 μg/mL. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Subunits of the Pyruvate Dehydrogenase Cluster of Mycoplasma pneumoniae Are Surface-Displayed Proteins that Bind and Activate Human Plasminogen

PubMed Central

Gründel, Anne; Friedrich, Kathleen; Pfeiffer, Melanie; Jacobs, Enno; Dumke, Roger

2015-01-01

The dual role of glycolytic enzymes in cytosol-located metabolic processes and in cell surface-mediated functions with an influence on virulence is described for various micro-organisms. Cell wall-less bacteria of the class Mollicutes including the common human pathogen Mycoplasma pneumoniae possess a reduced genome limiting the repertoire of virulence factors and metabolic pathways. After the initial contact of bacteria with cells of the respiratory epithelium via a specialized complex of adhesins and release of cell-damaging factors, surface-displayed glycolytic enzymes may facilitate the further interaction between host and microbe. In this study, we described detection of the four subunits of pyruvate dehydrogenase complex (PDHA-D) among the cytosolic and membrane-associated proteins of M. pneumoniae. Subunits of PDH were cloned, expressed and purified to produce specific polyclonal guinea pig antisera. Using colony blotting, fractionation of total proteins and immunofluorescence experiments, the surface localization of PDHA-C was demonstrated. All recombinant PDH subunits are able to bind to HeLa cells and human plasminogen. These interactions can be specifically blocked by the corresponding polyclonal antisera. In addition, an influence of ionic interactions on PDHC-binding to plasminogen as well as of lysine residues on the association of PDHA-D with plasminogen was confirmed. The PDHB subunit was shown to activate plasminogen and the PDHB-plasminogen complex induces degradation of human fibrinogen. Hence, our data indicate that the surface-associated PDH subunits might play a role in the pathogenesis of M. pneumoniae infections by interaction with human plasminogen. PMID:25978044

Membrane interaction and functional plasticity of inositol polyphosphate 5-phosphatases.

PubMed

Braun, Werner; Schein, Catherine H

2014-05-06

In this issue of Structure, Trésaugues and colleagues determined the interaction of membrane-bound phosphoinositides with three clinically significant human inositol polyphosphate 5-phosphatases (I5Ps). A comparison to the structures determined with soluble substrates revealed differences in the binding mode and suggested how the I5Ps and apurinic endonuclease (APE1) activities evolved from the same metal-binding active center. Copyright © 2014 Elsevier Ltd. All rights reserved.

SHOX interacts with the chondrogenic transcription factors SOX5 and SOX6 to activate the aggrecan enhancer.

PubMed

Aza-Carmona, Miriam; Shears, Debbie J; Yuste-Checa, Patricia; Barca-Tierno, Verónica; Hisado-Oliva, Alfonso; Belinchón, Alberta; Benito-Sanz, Sara; Rodríguez, J Ignacio; Argente, Jesús; Campos-Barros, Angel; Scambler, Peter J; Heath, Karen E

2011-04-15

SHOX (short stature homeobox-containing gene) encodes a transcription factor implicated in skeletal development. SHOX haploinsufficiency has been demonstrated in Leri-Weill dyschondrosteosis (LWD), a skeletal dysplasia associated with disproportionate short stature, as well as in a variable proportion of cases with idiopathic short stature (ISS). In order to gain insight into the SHOX signalling pathways, we performed a yeast two-hybrid screen to identify SHOX-interacting proteins. Two transcription factors, SOX5 and SOX6, were identified. Co-immunoprecipitation assays confirmed the existence of the SHOX-SOX5 and SHOX-SOX6 interactions in human cells, whereas immunohistochemical studies demonstrated the coexpression of these proteins in 18- and 32-week human fetal growth plates. The SHOX homeodomain and the SOX6 HMG domain were shown to be implicated in the SHOX-SOX6 interaction. Moreover, different SHOX missense mutations, identified in LWD and ISS patients, disrupted this interaction. The physiological importance of these interactions was investigated by studying the effect of SHOX on a transcriptional target of the SOX trio, Agc1, which encodes one of the main components of cartilage, aggrecan. Our results show that SHOX cooperates with SOX5/SOX6 and SOX9 in the activation of the upstream Agc1 enhancer and that SHOX mutations affect this activation. In conclusion, we have identified SOX5 and SOX6 as the first two SHOX-interacting proteins and have shown that this interaction regulates aggrecan expression, an essential factor in chondrogenesis and skeletal development.

Synthesis, spectroscopic characterization and in vitro cytotoxicities of new organometallic palladium complexes with biologically active β-diketones; Biological evaluation probing of the interaction mechanism with DNA/Protein and molecular docking

NASA Astrophysics Data System (ADS)

Karami, Kazem; Rafiee, Mina; Lighvan, Zohreh Mehri; Zakariazadeh, Mostafa; Faal, Ali Yeganeh; Esmaeili, Seyed-Alireza; Momtazi-Borojeni, Amir Abbas

2018-02-01

[Pd{(C,N)sbnd C6H4CH (CH3)NH}(CUR)] (3) and [Pd2{(C,N)sbnd C6H4CH(CH3)NH2}2(μ-N3CS2)] (4) [cur = 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dion] novel organometallic complexes with biologically active ligands have been prepared and characterized via elemental analysis, multinuclear spectroscopic techniques (1H, and 13C NMR and IR) and their biological activities, including antitumoral activity and DNA-protein interactions have been investigated. Fluorescence spectroscopy used to study the interaction of the complexes with BSA have shown the affinity of the complexes for these proteins with relatively high binding constant values and the changed secondary structure of BSA in the presence of the complexes. In the meantime, spectroscopy and competitive titration have been applied to investigate the interaction of complexes with Warfarin and Ibuprofen site markers for sites I and II, respectively, with BSA. The results have suggested that the locations of complexes 3 and 4 are sites II and I, respectively. UV-Vis spectroscopy, emission titration and helix melting methods have been used to study the interaction of these complexes with CT-DNA, indicating that complexes are bound to CT-DNA by intercalation binding mode. In addition, good cytotoxic activity against MCF-7 (human breast cancer) and JURKAT (human leukemia) cell line has been shown by both complexes whereas low cytotoxicity was exerted on normal peripheral blood mononuclear cells.

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.

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.

Potential herb-drug interaction of shexiang baoxin pill in vitro based on drug metabolism/transporter

PubMed Central

Shen, Zhijie; Wang, Yingjie; Guo, Wei; Yao, Yili; Wang, Xiaolong

2016-01-01

Many researches have proved functions of anti-oxidation, endothelial protection and pro-angiogenesis efficiency of Shexiang Baoxin Pill (SBP). This study aims to investigate potential for metabolism-based interaction on CYP450s and transporter based interaction on OATP1B1, BRCP and MDR1. Human primary hepatocytes were used in this study. Probe substrates of cytochrome P450 enzymes were incubated in human liver microsomes (HLMs) with or without SBP and IC50 values were estimated. Inhibitive potential of SBP on activities of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4 was evaluated. Inducible potential of SBP on activities of CYP1A2, 2B6 and 3A4 was accessed. Inhibitive potential of SBP on human OATP1B1 was evaluated using cell-based assay. Inhibitive potential of SBP on human MDR1 and BCRP was also evaluated using vesicles assay. MDR1 and BCRP vesicle kit were used to determine ATP dependent uptake activity when incubated with SBP. SBP was a competitive inhibitor of CYP2B6, 2C19, while neither inhibitory nor inductive potentials toward other CYP450s were detected. No significant MDR1 inhibitory potential was estimated, while only high concentration of SBP (500 μg/ml) could inhibit activity of BCRP. Probe substrates Estradiol-17 β-glucuronide was incubated in HEK293-OATP1B1 and HEK293-MOCK cell system with different concentration of SBP and estimated IC50 was 179 μg/mL, which demonstrated a moderate inhibition potential against OATP1B1. In conclusion, outcome of this study suggests that SBP plays an important role in inhibition of CYP450 isozymes (including CYP2B6 and 2C9) and transporter OATP1B1. Therefore, precautions should be taken when using SBP for CYP and OATP-related herb-drug interactions. PMID:28078025

Interaction with Machine Improvisation

NASA Astrophysics Data System (ADS)

Assayag, Gerard; Bloch, George; Cont, Arshia; Dubnov, Shlomo

We describe two multi-agent architectures for an improvisation oriented musician-machine interaction systems that learn in real time from human performers. The improvisation kernel is based on sequence modeling and statistical learning. We present two frameworks of interaction with this kernel. In the first, the stylistic interaction is guided by a human operator in front of an interactive computer environment. In the second framework, the stylistic interaction is delegated to machine intelligence and therefore, knowledge propagation and decision are taken care of by the computer alone. The first framework involves a hybrid architecture using two popular composition/performance environments, Max and OpenMusic, that are put to work and communicate together, each one handling the process at a different time/memory scale. The second framework shares the same representational schemes with the first but uses an Active Learning architecture based on collaborative, competitive and memory-based learning to handle stylistic interactions. Both systems are capable of processing real-time audio/video as well as MIDI. After discussing the general cognitive background of improvisation practices, the statistical modelling tools and the concurrent agent architecture are presented. Then, an Active Learning scheme is described and considered in terms of using different improvisation regimes for improvisation planning. Finally, we provide more details about the different system implementations and describe several performances with the system.

From 'automation' to 'autonomy': the importance of trust repair in human-machine interaction.

PubMed

de Visser, Ewart J; Pak, Richard; Shaw, Tyler H

2018-04-09

Modern interactions with technology are increasingly moving away from simple human use of computers as tools to the establishment of human relationships with autonomous entities that carry out actions on our behalf. In a recent commentary, Peter Hancock issued a stark warning to the field of human factors that attention must be focused on the appropriate design of a new class of technology: highly autonomous systems. In this article, we heed the warning and propose a human-centred approach directly aimed at ensuring that future human-autonomy interactions remain focused on the user's needs and preferences. By adapting literature from industrial psychology, we propose a framework to infuse a unique human-like ability, building and actively repairing trust, into autonomous systems. We conclude by proposing a model to guide the design of future autonomy and a research agenda to explore current challenges in repairing trust between humans and autonomous systems. Practitioner Summary: This paper is a call to practitioners to re-cast our connection to technology as akin to a relationship between two humans rather than between a human and their tools. To that end, designing autonomy with trust repair abilities will ensure future technology maintains and repairs relationships with their human partners.

Downregulation of Hsp27 (HSPB1) in MCF-7 human breast cancer cells induces upregulation of PTEN.

PubMed

Cayado-Gutiérrez, Niubys; Moncalero, Vera L; Rosales, Eliana M; Berón, Walter; Salvatierra, Edgardo E; Alvarez-Olmedo, Daiana; Radrizzani, Martín; Ciocca, Daniel R

2013-03-01

Hsp27 (HSPB1) is usually overexpressed in breast cancers affecting the disease outcome and the sensitivity of tumors to chemotherapy and radiotherapy. Hsp27 interacts with other proteins such as β-catenin, histone deacetylase HDAC6, transcription factor STAT2 and procaspase-3. Phosphatase and tensin homologue (PTEN) is a tumor suppressor gene that is deleted in many human tumors. The PI3K/Akt signaling pathway is negatively regulated by PTEN. Hsp27 is described as a key component of the Akt signaling cascade: Akt, BAD, Forkhead transcription factors, Hsp27, mitogen-activated protein kinase kinase-3 and -6. Here, we have examined whether the downregulation of Hsp27 by siHsp27 affects the PTEN levels in the MCF-7 human breast cancer cell line. PTEN was detected with two different antibodies using western blots and immunocytochemistry. p-Akt was also evaluated by western blot. In addition, Hsp27 and PTEN were immunoprecipitated to know whether these proteins interact. Intracellular colocalization studies were carried out by confocal microscopy. A significant reduction in the Hsp27 levels was noted in the siHsp27 transfected cells. These Hsp27 downregulated cells showed a significant increased expression of PTEN. The MW 76 and 55 kDa PTEN forms were upregulated as revealed by two different antibodies. The phosphatase activity of PTEN seems to be active because p-Akt levels were reduced. Hsp27 immunoprecipitation was bringing PTEN and vice versa, these two proteins seem to interact at cytoplasmic level by FRET. Downregulation of Hsp27 stabilized PTEN protein levels. Chaperone-assisted E3 ligase C terminus of Hsc70-interacting protein (CHIP) levels were not significantly influenced by Hsp27 downregulation. In conclusion, we report a novel function of Hsp27 modulating the PTEN levels in human breast cancer cells suggesting an interaction between these two molecules.

Low-affinity FcγR interactions can decide the fate of novel human IgG-sensitised red blood cells and platelets.

PubMed

Armour, Kathryn L; Smith, Cheryl S; Turner, Craig P; Kirton, Christopher M; Wilkes, Anthony M; Hadley, Andrew G; Ghevaert, Cedric; Williamson, Lorna M; Clark, Michael R

2014-03-01

G1Δnab is a mutant human IgG1 constant region with a lower ability to interact with FcγR than the natural IgG constant regions. Radiolabelled RBCs and platelets sensitised with specific G1Δnab Abs were cleared more slowly from human circulation than IgG1-sensitised counterparts. However, non-destructive splenic retention of G1Δnab-coated RBCs required investigation and plasma radioactivities now suggest this also occurred for platelets sensitised with an IgG1/G1Δnab mixture. In vitro assays with human cells showed that G1Δnab-sensitised RBCs did not cause FcγRI-mediated monocyte activation, FcγRIIIa-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) or macrophage phagocytosis although they did adhere to macrophages. Thus, FcγRII was implicated in the adhesion despite the Δnab mutation reducing the already low-affinity binding to this receptor class. Additional contacts via P-selectin enhance the interaction of sensitised platelets with monocytes and this system provided evidence of FcγRII-dependent activation by G1Δnab. These results emphasise the physiological relevance of low-affinity interactions: It appears that FcγRII interactions of G1Δnab allowed splenic retention of G1Δnab-coated RBCs with inhibitory FcγRIIb binding preventing RBC destruction and that FcγRIIb engagement by G1Δnab on IgG1/G1Δnab-sensitised platelets overcame activation by IgG1. Considering therapeutic blocking Abs, G1Δnab offers lower FcγR binding and a greater bias towards inhibition than IgG2 and IgG4 constant regions. © 2013 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interaction of Mycoplasma hominis PG21 with Human Dendritic Cells: Interleukin-23-Inducing Mycoplasmal Lipoproteins and Inflammasome Activation of the Cell.

PubMed

Goret, J; Béven, L; Faustin, B; Contin-Bordes, C; Le Roy, C; Claverol, S; Renaudin, H; Bébéar, C; Pereyre, S

2017-08-01

Mycoplasma hominis lacks a cell wall, and lipoproteins anchored to the extracellular side of the plasma membrane are in direct contact with the host components. A Triton X-114 extract of M. hominis enriched with lipoproteins was shown to stimulate the production of interleukin-23 (IL-23) by human dendritic cells (hDCs). The inflammasome activation of the host cell has never been reported upon M. hominis infection. We studied here the interaction between M. hominis PG21 and hDCs by analyzing both the inflammation-inducing mycoplasmal lipoproteins and the inflammasome activation of the host cell. IL-23-inducing lipoproteins were determined using a sequential extraction strategy with two nondenaturing detergents, Sarkosyl and Triton X-114, followed by SDS-PAGE separation and mass spectrometry identification. The activation of the hDC inflammasome was assessed using PCR array and enzyme-linked immunosorbent assay (ELISA). We defined a list of 24 lipoproteins that could induce the secretion of IL-23 by hDCs, 5 with a molecular mass between 20 and 35 kDa and 19 with a molecular mass between 40 and 100 kDa. Among them, lipoprotein MHO_4720 was identified as potentially bioactive, and a synthetic lipopeptide corresponding to the N-terminal part of the lipoprotein was subsequently shown to induce IL-23 release by hDCs. Regarding the hDC innate immune response, inflammasome activation with caspase-dependent production of IL-1β was observed. After 24 h of coincubation of hDCs with M. homini s, downregulation of the NLRP3-encoding gene and of the adaptor PYCARD-encoding gene was noticed. Overall, this study provides insight into both protagonists of the interaction of M. hominis and hDCs. IMPORTANCE Mycoplasma hominis is a human urogenital pathogen involved in gynecologic and opportunistic infections. M. hominis lacks a cell wall, and its membrane contains many lipoproteins that are anchored to the extracellular side of the plasma membrane. In the present study, we focused on the interaction between M. hominis and human dendritic cells and examined both sides of the interaction, the mycoplasmal lipoproteins involved in the activation of the host cell and the immune response of the cell. On the mycoplasmal side, we showed for the first time that M. hominis lipoproteins with high molecular mass were potentially bioactive. On the cell side, we reported an activation of the inflammasome, which is involved in the innate immune response. Copyright © 2017 American Society for Microbiology.

Influence of human ascitic fluid on the in vitro antibacterial activity of moxifloxacin.

PubMed

Miglioli, P A; Cappellari, G; Cavallaro, A; Cardaioli, C; Sossai, P; Fille, M; Allerberger, F

2005-08-01

We investigated the in vitro influence of HAF on the antibacterial activity of moxifloxacin against Escherichia coli ATCC 10798, Escherichia coli K-12, Proteus rettgeri (Sanelli), Staphylococcus aureus ATCC 25923, Staphylococcus aureus NCTC 1808 and Staphylococcus epidermidis ATCC 12228. Human ascitic fluid was obtained from 6 cirrhotic patients by paracentesis. The interaction effect was evaluated by the checkerboard technique. Our results indicate the ability of human ascitic fluid to reduce minimum inhibitory concentrations of moxifloxacin against Gram-negative bacteria, but not against Gram-positives.

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.

Emergence of Chiral Phases in Active Torque Dipole Systems

NASA Astrophysics Data System (ADS)

Fialho, Ana; Tjhung, Elsen; Cates, Michael; Marenduzzo, Davide

The common description of active particles as active force dipoles fails to take into account that active processes in biological systems often exhibit chiral asymmetries, generating active chiral processes and torque dipoles. Examples of such systems include cytoskeleton filaments which interact with motor proteins and beating cilia and flagella. In particular, the generation of active torques by the actomyosin cytoskeleton has been linked to the break of chiral symmetry at a cellular level. This phenomenon could constitute the primary determinant for the break of left-right symmetry in many living organisms, e.g. the position of the human heart within the human body. In order to account for the effects of chirality, we consider active torque dipoles which generate a chiral active stress. We characterize quasi-1D and 2D systems of torque dipoles, using a combination of linear stability analysis and numerical simulations (Lattice Boltzmann). Our results show that activity drives a spontaneous breaking of chiral symmetry, leading to the self-assembly of a chiral phase, in the absence of any thermodynamic interactions favoring cholesteric ordering. At high values of activity, we also observe labyrinthine patterns where the activity-induced chiral ordering is highly frustrated.

Physical human-robot interaction of an active pelvis orthosis: toward ergonomic assessment of wearable robots.

PubMed

d'Elia, Nicolò; Vanetti, Federica; Cempini, Marco; Pasquini, Guido; Parri, Andrea; Rabuffetti, Marco; Ferrarin, Maurizio; Molino Lova, Raffaele; Vitiello, Nicola

2017-04-14

In human-centered robotics, exoskeletons are becoming relevant for addressing needs in the healthcare and industrial domains. Owing to their close interaction with the user, the safety and ergonomics of these systems are critical design features that require systematic evaluation methodologies. Proper transfer of mechanical power requires optimal tuning of the kinematic coupling between the robotic and anatomical joint rotation axes. We present the methods and results of an experimental evaluation of the physical interaction with an active pelvis orthosis (APO). This device was designed to effectively assist in hip flexion-extension during locomotion with a minimum impact on the physiological human kinematics, owing to a set of passive degrees of freedom for self-alignment of the human and robotic hip flexion-extension axes. Five healthy volunteers walked on a treadmill at different speeds without and with the APO under different levels of assistance. The user-APO physical interaction was evaluated in terms of: (i) the deviation of human lower-limb joint kinematics when wearing the APO with respect to the physiological behavior (i.e., without the APO); (ii) relative displacements between the APO orthotic shells and the corresponding body segments; and (iii) the discrepancy between the kinematics of the APO and the wearer's hip joints. The results show: (i) negligible interference of the APO in human kinematics under all the experimented conditions; (ii) small (i.e., < 1 cm) relative displacements between the APO cuffs and the corresponding body segments (called stability); and (iii) significant increment in the human-robot kinematics discrepancy at the hip flexion-extension joint associated with speed and assistance level increase. APO mechanics and actuation have negligible interference in human locomotion. Human kinematics was not affected by the APO under all tested conditions. In addition, under all tested conditions, there was no relevant relative displacement between the orthotic cuffs and the corresponding anatomical segments. Hence, the physical human-robot coupling is reliable. These facts prove that the adopted mechanical design of passive degrees of freedom allows an effective human-robot kinematic coupling. We believe that this analysis may be useful for the definition of evaluation metrics for the ergonomics assessment of wearable robots.

Alisol B 23-acetate from the rhizomes of Alisma orientale is a natural agonist of the human pregnane X receptor.

PubMed

Kanno, Yuichiro; Yatsu, Tomofumi; Yamashita, Naoya; Zhao, Shuai; Li, Wei; Imai, Miyuki; Kashima, Manami; Inouye, Yoshio; Nemoto, Kiyomitsu; Koike, Kazuo

2017-03-15

Pregnane X receptor (PXR) is a key regulator of the induction of drug metabolizing enzymes. PXR has been studied for its importance in drug-drug or herb-drug interactions, and it is also a molecular target for the treatment of inflammatory and metabolic diseases. This study aims to determine new natural PXR-ligands from traditional plant medicines. The PXR activation activity was measured by a mammalian one hybrid assay of PXR. Identification of the active compound from Alisma rhizome (the rhizomes of Alisma orientale) was carried out by bioassay-guided fractionation method. The transcriptional activity of the liver-enriched nuclear receptors was measured by the luciferase reporter assay. The interaction between the SRC-1 and PXR was measured by a mammalian 2-hybrid assay. The expression of endogenous CYP3A4 mRNA in both cultured hPXR-overexpressing hepatoma cells and human primary hepatocytes were measured by quantitative RT-PCR method. The extract of Alisma rhizome showed the most potent activation activity by screening of a library of medicinal plant extracts. Alisol B 23-acetate (ABA) was identified to be the active compound of Alisma rhizome. ABA caused a concentration-dependent increase on the PXR-dependent transactivation of a luciferase reporter gene, but did not affect the ligand binding activity of the liver-enriched nuclear receptors, such as CAR, LXR, FXR, PPARα, PPARδ and PPARγ, emphasizing that ABA is a potent and specific agonist of PXR. With ABA treatment, the direct interaction between the ligand-binding domain of PXR and the receptor interaction domain of SRC1 was observed. ABA also induced the expression of endogenous CYP3A4 mRNA in both cultured hPXR-overexpressing hepatoma cells and human primary hepatocytes. Since the rhizomes of Alisma orientale are used for a wide range of ailments in traditional Chinese medicine and Japanese Kampo medicine, this study could possibly extend into the clinical usage of these medicines via the mechanism of PXR activation. Copyright © 2017 Elsevier GmbH. All rights reserved.

The Relationship Between Consciousness, Interaction, and Language Learning.

ERIC Educational Resources Information Center

van Lier, Leo

1998-01-01

Examines the relationship between consciousness, language learning, and social interaction from an ecological perspective. Argues that consciousness and language are integral parts of the human ecology, that is, they can be defined in terms of social activity and relationships among people, as well as in terms of mental operations or cerebral…

Mapping of the binding sites involved in PSP94-CRISP-3 interaction by molecular dissection of the complex.

PubMed

Breed, Ananya A; Gomes, Amanda; Roy, Binita Sur; Mahale, Smita D; Pathak, Bhakti R

2013-04-01

Human Prostate Secretory Protein of 94 amino acids (PSP94) has been shown to bind human CRISP-3 (cysteine-rich secretory protein 3) with very high affinity. CRISP-3 belongs to the CRISP family of proteins having a PR-1 (pathogenesis related protein 1) domain at its N-terminal and ion channel regulatory (ICR) domain at its C-terminal connected by a hinge region. Functional significance of this complex is not yet known. In order to identify the residues and/or regions involved in PSP94-CRISP-3 interaction, site-directed mutagenesis was employed. Effect of the mutations on the interaction was studied by co-immunoprecipitation (Co-IP). For PSP94, amino acids Y(3), F(4), P(56) and the C-terminal β-strand were found to be crucial for interacting with CRISP-3. A disulfide bond between the two domains of PSP94 (C(37)A-C(73)A) was also important for this interaction. In case of CRISP-3, the N-terminal domain alone could not maintain a strong interaction with PSP94 but it required presence of the hinge region and not the C-terminal domain. Apart from CRISP-3, CRISP-2 was also found to interact with human PSP94. Based on our findings the most likely model of PSP94-CRISP-3 complex has been proposed. The terminal β-strands of PSP94 contact the first α-helix and the hinge region of CRISP-3. Involvement of the hinge region of CRISPs in interaction with PSP94 may affect the domain movement of CRISPs essential for the ion-channel regulatory activity resulting in inhibition of this activity. Copyright © 2013 Elsevier B.V. All rights reserved.

Cloning, overexpression, purification of bacteriocin enterocin-B and structural analysis, interaction determination of enterocin-A, B against pathogenic bacteria and human cancer cells.

PubMed

Ankaiah, Dasari; Palanichamy, Esakkiraj; Antonyraj, Christian Bharathi; Ayyanna, Repally; Perumal, Venkatesh; Ahamed, Syed Ibrahim Basheer; Arul, Venkatesan

2018-05-02

In this present study, a gene (ent-B) encoding the bacteriocin enterocin-B was cloned, overexpressed and purified from Enterococcus faecium por1. The molecular weight of the bacteriocin enterocin-B was observed around 7.2 kDa and exhibited antimicrobial activity against several human pathogenic bacteria. The antimicrobial activity of cloned enterocin-B was increased effectively by combining with another bacteriocin enterocin-A from the same microorganism. Protein-protein docking and molecular dynamics simulation studies revealed that the bacteriocin enterocin-B is interacting with enterocin-A and formation of a heterodimer (enterocin A + B). The heterodimer of bacteriocin enterocin-A + B exhibited potential anti-bacterial, anti-biofilm activity against Staphylococcus aureus, Acinetobacter baumannii, Listeria monocytogenes and Escherichia coli. The bacteriocin enterocin-B, A and heterodimer of bacteriocin enterocin A + B showed no haemolysis on human RBC cells. This is the first report that the cell growth inhibitory activity of the bacteriocin enterocin B against HeLa, HT-29 and AGS human cancer cells and this cell growth inhibitory activity was significantly increased when cancer cells treated with the heterodimer of bacteriocins enterocin-A + B. The cell growth inhibitory activity of the bacteriocin enterocin-B and the heterodimer of bacteriocin enterocin-A + B were not observed in non-cancerous INT-407 cells (intestinal epithelial cells). Copyright © 2018. Published by Elsevier B.V.

c-Jun binds the N terminus of human TAF(II)250 to derepress RNA polymerase II transcription in vitro.

PubMed

Lively, T N; Ferguson, H A; Galasinski, S K; Seto, A G; Goodrich, J A

2001-07-06

c-Jun is an oncoprotein that activates transcription of many genes involved in cell growth and proliferation. We studied the mechanism of transcriptional activation by human c-Jun in a human RNA polymerase II transcription system composed of highly purified recombinant and native transcription factors. Transcriptional activation by c-Jun depends on the TATA-binding protein (TBP)-associated factor (TAF) subunits of transcription factor IID (TFIID). Protein-protein interaction assays revealed that c-Jun binds with high specificity to the largest subunit of human TFIID, TAF(II)250. The region of TAF(II)250 bound by c-Jun lies in the N-terminal 163 amino acids. This same region of TAF(II)250 binds to TBP and represses its interaction with TATA boxes, thereby decreasing DNA binding by TFIID. We hypothesized that c-Jun is capable of derepressing the effect of the TAF(II)250 N terminus on TFIID-driven transcription. In support of this hypothesis, we found that c-Jun increased levels of TFIID-driven transcription in vitro when added at high concentrations to a DNA template lacking activator protein 1 (AP-1) sites. Moreover, c-Jun blocked the repression of TBP DNA binding caused by the N terminus of TAF(II)250. In addition to revealing a mechanism by which c-Jun activates transcription, our studies provide the first evidence that an activator can bind directly to the N terminus of TAF(II)250 to derepress RNA polymerase II transcription in vitro.

76 FR 12966 - Proposed Information Collection Activity; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Administration for Children and Families Proposed Information Collection Activity; Comment Request Title: Measurement Development: Quality of Caregiver-Child... child care settings, specifically the quality of caregiver-child interaction for infants and toddlers in...

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

PubMed

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

2014-06-15

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

A high-resolution map of the three-dimensional chromatin interactome in human cells.

PubMed

Jin, Fulai; Li, Yan; Dixon, Jesse R; Selvaraj, Siddarth; Ye, Zhen; Lee, Ah Young; Yen, Chia-An; Schmitt, Anthony D; Espinoza, Celso A; Ren, Bing

2013-11-14

A large number of cis-regulatory sequences have been annotated in the human genome, but defining their target genes remains a challenge. One strategy is to identify the long-range looping interactions at these elements with the use of chromosome conformation capture (3C)-based techniques. However, previous studies lack either the resolution or coverage to permit a whole-genome, unbiased view of chromatin interactions. Here we report a comprehensive chromatin interaction map generated in human fibroblasts using a genome-wide 3C analysis method (Hi-C). We determined over one million long-range chromatin interactions at 5-10-kb resolution, and uncovered general principles of chromatin organization at different types of genomic features. We also characterized the dynamics of promoter-enhancer contacts after TNF-α signalling in these cells. Unexpectedly, we found that TNF-α-responsive enhancers are already in contact with their target promoters before signalling. Such pre-existing chromatin looping, which also exists in other cell types with different extracellular signalling, is a strong predictor of gene induction. Our observations suggest that the three-dimensional chromatin landscape, once established in a particular cell type, is relatively stable and could influence the selection or activation of target genes by a ubiquitous transcription activator in a cell-specific manner.

Targeting Signal Transducers and Activators of Transcription-3 (STAT3) as a Novel Strategy in Sensitizing Breast Cancer to EGFR-Targeted Therapy

DTIC Science & Technology

2009-06-01

Osman, F. The human glutathione S-transferase P1 ( GSTP1 ) gene is transactivated by cyclic AMP (cAMP) via a cAMP response element (CRE) proximal to the...transcription start site. Chem-Biol. Interactions 133, 320-321, 2001. 4. Lo, H.-W. and Ali-Osman, F. Cyclic AMP mediated GSTP1 gene activation in...tumor cells involves the interaction of activated CREB-1 with the GSTP1 CRE: a novel mechanism of cellular GSTP1 gene regulation. Journal of Cellular

Suppression of RIP3-dependent Necroptosis by Human Cytomegalovirus

PubMed Central

Omoto, Shinya; Guo, Hongyan; Talekar, Ganesh R.; Roback, Linda; Kaiser, William J.; Mocarski, Edward S.

2015-01-01

Necroptosis is an alternate programmed cell death pathway that is unleashed by caspase-8 compromise and mediated by receptor-interacting protein kinase 3 (RIP3). Murine cytomegalovirus (CMV) and herpes simplex virus (HSV) encode caspase-8 inhibitors that prevent apoptosis together with competitors of RIP homotypic interaction motif (RHIM)-dependent signal transduction to interrupt the necroptosis. Here, we show that pro-necrotic murine CMV M45 mutant virus drives virus-induced necroptosis during nonproductive infection of RIP3-expressing human fibroblasts, whereas WT virus does not. Thus, M45-encoded RHIM competitor, viral inhibitor of RIP activation, sustains viability of human cells like it is known to function in infected mouse cells. Importantly, human CMV is shown to block necroptosis induced by either TNF or M45 mutant murine CMV in RIP3-expressing human cells. Human CMV blocks TNF-induced necroptosis after RIP3 activation and phosphorylation of the mixed lineage kinase domain-like (MLKL) pseudokinase. An early, IE1-regulated viral gene product acts on a necroptosis step that follows MLKL phosphorylation prior to membrane leakage. This suppression strategy is distinct from RHIM signaling competition by murine CMV or HSV and interrupts an execution process that has not yet been fully elaborated. PMID:25778401

Antimicrobial activity of human pancreatic juice and its interaction with antibiotics.

PubMed Central

Minelli, E B; Benini, A; Bassi, C; Abbas, H; Falconi, M; Locatelli, F; de Marco, R; Pederzoli, P

1996-01-01

Pancreatic juice (PJ) should be a factor of variability in the antimicrobial activity of antibiotics eliminated by the pancreas during pancreatic infections. We studied its effects on the activity of antimicrobial drugs with different mechanisms of action. Samples of pure PJ were collected from 16 patients with stabilized external pancreatic fistulas. The antimicrobial activity of the juice at different concentrations (from 1.25 to 100%) alone and in combination with mezlocillin, imipenem, ceftriaxone, gentamicin, ofloxacin, and ciprofloxacin was studied by a microbiological method (continuous turbidimetric recording of bacterial growth). The human PJ showed dose-dependent antimicrobial activity that increased directly with the concentration. The activity of the antibiotics at bactericidal concentrations were not modified by the PJ, while the combination with subinhibitory concentrations produced the following variable and different effects: (i) additivity with mezlocillin, ceftriaxone, gentamicin, and ciprofloxacin and autonomy (no interaction) with imipenem and ofloxacin against Providencia rettgeri and (ii) additivity with ceftriaxone, ofloxacin, gentamicin, imipenem, and mezlocillin and autonomy with ciprofloxacin against Escherichia coli. In the presence of PJ, fluoroquinolones showed constant positive effects, while beta-lactams showed more variable antimicrobial activity. Antibiotic concentrations and PJ pharmacodynamics are the main factors determining the final effect of the interaction in vitro. These results may be useful in choosing antibiotics for the treatment of pancreatic infections when they are supplemented with the pharmacokinetic data for each drug. PMID:8878588

Marine mammal harvests and other interactions with humans.

PubMed

Hovelsrud, Grete K; McKenna, Meghan; Huntington, Henry P

2008-03-01

The Arctic is currently undergoing rapid social and environmental changes, and while the peoples of the north have a long history of adapting, the current changes in climate pose unprecedented challenges to the marine mammal-human interactions in the Arctic regions. Arctic marine mammals have been and remain an important resource for many of the indigenous and nonindigenous people of the north. Changes in climate are likely to bring about profound changes to the environment in which these animals live and subsequently to the hunting practices and livelihoods of the people who hunt them. Climate change will lead to reduction in the sea ice extent and thickness and will likely increase shipping through the Northern Sea Route and the Northwest Passage and oil and gas activities in Arctic areas previously inaccessible. Such activities will lead to more frequent interactions between humans and marine mammals. These activities may also change the distribution of marine mammals, affecting the hunters. This paper has three parts. First, an overview of marine mammal harvesting activities in the different circumpolar regions provides a snapshot of current practices and conditions. Second, case studies of selected Arctic regions, indigenous groups, and species provide insight into the manner in which climate change is already impacting marine mammal harvesting activities in the Arctic. Third, we describe how climate change is likely to affect shipping and oil and gas exploration and production activities in the Arctic and describe the possible implications of these changes for the marine mammal populations. We conclude that many of the consequences of climate change are likely to be negative for marine mammal hunters and for marine mammals. Lack of adequate baseline data, however, makes it difficult to identify specific causal mechanisms and thus to develop appropriate conservation measures. Nonetheless, the future of Arctic marine mammals and human uses of them depends on addressing this challenge successfully.

Awake canine fMRI predicts dogs' preference for praise vs food.

PubMed

Cook, Peter F; Prichard, Ashley; Spivak, Mark; Berns, Gregory S

2016-12-01

Dogs are hypersocial with humans, and their integration into human social ecology makes dogs a unique model for studying cross-species social bonding. However, the proximal neural mechanisms driving dog-human social interaction are unknown. We used functional magnetic resonance imaging in 15 awake dogs to probe the neural basis for their preferences for social interaction and food reward. In a first experiment, we used the ventral caudate as a measure of intrinsic reward value and compared activation to conditioned stimuli that predicted food, praise or nothing. Relative to the control stimulus, the caudate was significantly more active to the reward-predicting stimuli and showed roughly equal or greater activation to praise vs food in 13 of 15 dogs. To confirm that these differences were driven by the intrinsic value of social praise, we performed a second imaging experiment in which the praise was withheld on a subset of trials. The difference in caudate activation to the receipt of praise, relative to its withholding, was strongly correlated with the differential activation to the conditioned stimuli in the first experiment. In a third experiment, we performed an out-of-scanner choice task in which the dog repeatedly selected food or owner in a Y-maze. The relative caudate activation to food- and praise-predicting stimuli in Experiment 1 was a strong predictor of each dog's sequence of choices in the Y-maze. Analogous to similar neuroimaging studies of individual differences in human social reward, our findings demonstrate a neural mechanism for preference in domestic dogs that is stable within, but variable between, individuals. Moreover, the individual differences in the caudate responses indicate the potentially higher value of social than food reward for some dogs and may help to explain the apparent efficacy of social interaction in dog training. © The Author (2016). Published by Oxford University Press.

Small Molecule Inhibition of cAMP Response Element Binding Protein in Human Acute Myeloid Leukemia Cells

PubMed Central

Mitton, Bryan; Chae, Hee-Don; Hsu, Katie; Dutta, Ritika; Aldana-Masangkay, Grace; Ferrari, Roberto; Davis, Kara; Tiu, Bruce C.; Kaul, Arya; Lacayo, Norman; Dahl, Gary; Xie, Fuchun; Li, Bingbing X.; Breese, Marcus R.; Landaw, Elliot M.; Nolan, Garry; Pellegrini, Matteo; Romanov, Sergei; Xiao, Xiangshu; Sakamoto, Kathleen M.

2016-01-01

The transcription factor CREB (cAMP Response Element Binding Protein) is overexpressed in the majority of acute myeloid leukemia (AML) patients, and this is associated with a worse prognosis. Previous work revealed that CREB overexpression augmented AML cell growth, while CREB knockdown disrupted key AML cell functions in vitro. In contrast, CREB knockdown had no effect on long-term hematopoietic stem cell activity in mouse transduction/transplantation assays. Together, these studies position CREB as a promising drug target for AML. To test this concept, a small molecule inhibitor of CREB, XX-650-23, was developed. This molecule blocks a critical interaction between CREB and its required co-activator CBP (CREB Binding Protein), leading to disruption of CREB-driven gene expression. Inhibition of CBP-CREB interaction induced apoptosis and cell cycle arrest in AML cells, and prolonged survival in vivo in mice injected with human AML cells. XX-650-23 had little toxicity on normal human hematopoietic cells and tissues in mice. To understand the mechanism of XX-650-23, we performed RNA-seq, ChIP-seq and Cytometry Time of Flight with human AML cells. Our results demonstrate that small molecule inhibition of CBP-CREB interaction mostly affects apoptotic, cell cycle, and survival pathways, which may represent a novel approach for AML therapy. PMID:27211267

Interaction studies reveal specific recognition of an anti-inflammatory polyphosphorhydrazone dendrimer by human monocytes.

PubMed

Ledall, Jérémy; Fruchon, Séverine; Garzoni, Matteo; Pavan, Giovanni M; Caminade, Anne-Marie; Turrin, Cédric-Olivier; Blanzat, Muriel; Poupot, Rémy

2015-11-14

Dendrimers are nano-materials with perfectly defined structure and size, and multivalency properties that confer substantial advantages for biomedical applications. Previous work has shown that phosphorus-based polyphosphorhydrazone (PPH) dendrimers capped with azabisphosphonate (ABP) end groups have immuno-modulatory and anti-inflammatory properties leading to efficient therapeutic control of inflammatory diseases in animal models. These properties are mainly prompted through activation of monocytes. Here, we disclose new insights into the molecular mechanisms underlying the anti-inflammatory activation of human monocytes by ABP-capped PPH dendrimers. Following an interdisciplinary approach, we have characterized the physicochemical and biological behavior of the lead ABP dendrimer with model and cell membranes, and compared this experimental set of data to predictive computational modelling studies. The behavior of the ABP dendrimer was compared to the one of an isosteric analog dendrimer capped with twelve azabiscarboxylate (ABC) end groups instead of twelve ABP end groups. The ABC dendrimer displayed no biological activity on human monocytes, therefore it was considered as a negative control. In detail, we show that the ABP dendrimer can bind both non-specifically and specifically to the membrane of human monocytes. The specific binding leads to the internalization of the ABP dendrimer by human monocytes. On the contrary, the ABC dendrimer only interacts non-specifically with human monocytes and is not internalized. These data indicate that the bioactive ABP dendrimer is recognized by specific receptor(s) at the surface of human monocytes.

Human osteocalcin and bone sialoprotein mediating osteomimicry of prostate cancer cells: role of cAMP-dependent protein kinase A signaling pathway.

PubMed

Huang, Wen-Chin; Xie, Zhihui; Konaka, Hiroyuki; Sodek, Jaro; Zhau, Haiyen E; Chung, Leland W K

2005-03-15

Osteocalcin and bone sialoprotein are the most abundant noncollagenous bone matrix proteins expressed by osteoblasts. Surprisingly, osteocalcin and bone sialoprotein are also expressed by malignant but not normal prostate epithelial cells. The purpose of this study is to investigate how osteocalcin and bone sialoprotein expression is regulated in prostate cancer cells. Our investigation revealed that (a) human osteocalcin and bone sialoprotein promoter activities in an androgen-independent prostate cancer cell line of LNCaP lineage, C4-2B, were markedly enhanced 7- to 12-fold in a concentration-dependent manner by conditioned medium collected from prostate cancer and bone stromal cells. (b) Deletion analysis of human osteocalcin and bone sialoprotein promoter regions identified cyclic AMP (cAMP)-responsive elements (CRE) as the critical determinants for conditioned medium-mediated osteocalcin and bone sialoprotein gene expression in prostate cancer cells. Consistent with these results, the protein kinase A (PKA) pathway activators forskolin and dibutyryl cAMP and the PKA pathway inhibitor H-89, respectively, increased or repressed human osteocalcin and bone sialoprotein promoter activities. (c) Electrophoretic mobility shift assay showed that conditioned medium-mediated stimulation of human osteocalcin and bone sialoprotein promoter activities occurs through increased interaction between CRE and CRE-binding protein. (d) Conditioned medium was found to induce human osteocalcin and bone sialoprotein promoter activities via increased CRE/CRE-binding protein interaction in a cell background-dependent manner, with marked stimulation in selected prostate cancer but not bone stromal cells. Collectively, these results suggest that osteocalcin and bone sialoprotein expression is coordinated and regulated through cAMP-dependent PKA signaling, which may define the molecular basis of the osteomimicry exhibited by prostate cancer cells.

Cognition in action: imaging brain/body dynamics in mobile humans.

PubMed

Gramann, Klaus; Gwin, Joseph T; Ferris, Daniel P; Oie, Kelvin; Jung, Tzyy-Ping; Lin, Chin-Teng; Liao, Lun-De; Makeig, Scott

2011-01-01

We have recently developed a mobile brain imaging method (MoBI), that allows for simultaneous recording of brain and body dynamics of humans actively behaving in and interacting with their environment. A mobile imaging approach was needed to study cognitive processes that are inherently based on the use of human physical structure to obtain behavioral goals. This review gives examples of the tight coupling between human physical structure with cognitive processing and the role of supraspinal activity during control of human stance and locomotion. Existing brain imaging methods for actively behaving participants are described and new sensor technology allowing for mobile recordings of different behavioral states in humans is introduced. Finally, we review recent work demonstrating the feasibility of a MoBI system that was developed at the Swartz Center for Computational Neuroscience at the University of California, San Diego, demonstrating the range of behavior that can be investigated with this method.

The Human Performance Envelope: Past Research, Present Activities and Future Directions

NASA Technical Reports Server (NTRS)

Edwards, Tamsyn

2017-01-01

Air traffic controllers (ATCOs) must maintain a consistently high level of human performance in order to maintain flight safety and efficiency. In current control environments, performance-influencing factors such as workload, fatigue and situation awareness can co-occur, and interact, to effect performance. However, multifactor influences and the association with performance are under-researched. This study utilized a high fidelity human in the loop enroute air traffic control simulation to investigate the relationship between workload, situation awareness and ATCO performance. The study aimed to replicate and extend Edwards, Sharples, Wilson and Kirwans (2012) previous study and confirm multifactor interactions with a participant sample of ex-controllers. The study also aimed to extend Edwards et als previous research by comparing multifactor relationships across 4 automation conditions. Results suggest that workload and SA may interact to produce a cumulative impact on controller performance, although the effect of the interaction on performance may be dependent on the context and amount of automation present. Findings have implications for human-automation teaming in air traffic control, and the potential prediction and support of ATCO performance.

Vestibular influences on autonomic cardiovascular control in humans

NASA Technical Reports Server (NTRS)

Biaggioni, I.; Costa, F.; Kaufmann, H.; Robertson, D. (Principal Investigator)

1998-01-01

There is substantial evidence that anatomical connections exist between vestibular and autonomic nuclei. Animal studies have shown functional interactions between the vestibular and autonomic systems. The nature of these interactions, however, is complex and has not been fully defined. Vestibular stimulation has been consistently found to reduce blood pressure in animals. Given the potential interaction between vestibular and autonomic pathways this finding could be explained by a reduction in sympathetic activity. However, rather than sympathetic inhibition, vestibular stimulation has consistently been shown to increase sympathetic outflow in cardiac and splanchnic vascular beds in most experimental models. Several clinical observations suggest that a link between vestibular and autonomic systems may also exist in humans. However, direct evidence for vestibular/autonomic interactions in humans is sparse. Motion sickness has been found to induce forearm vasodilation and reduce baroreflex gain, and head down neck flexion induces transient forearm and calf vasoconstriction. On the other hand, studies using optokinetic stimulation have found either very small, variable, or inconsistent changes in heart rate and blood pressure, despite substantial symptoms of motion sickness. Furthermore, caloric stimulation severe enough to produce nystagmus, dizziness, and nausea had no effect on sympathetic nerve activity measured directly with microneurography. No effect was observed on heart rate, blood pressure, or plasma norepinephrine. Several factors may explain the apparent discordance of these results, but more research is needed before we can define the potential importance of vestibular input to cardiovascular regulation and orthostatic tolerance in humans.

Potential for drug interactions mediated by polymorphic flavin-containing monooxygenase 3 in human livers.

PubMed

Shimizu, Makiko; Shiraishi, Arisa; Sato, Ayumi; Nagashima, Satomi; Yamazaki, Hiroshi

2015-02-01

Human flavin-containing monooxygenase 3 (FMO3) in the liver catalyzes a variety of oxygenations of nitrogen- and sulfur-containing medicines and xenobiotic substances. Because of growing interest in drug interactions mediated by polymorphic FMO3, benzydamine N-oxygenation by human FMO3 was investigated as a model reaction. Among the 41 compounds tested, trimethylamine, methimazole, itopride, and tozasertib (50 μM) suppressed benzydamine N-oxygenation at a substrate concentration of 50 μM by approximately 50% after co-incubation. Suppression of N-oxygenation of benzydamine, trimethylamine, itopride, and tozasertib and S-oxygenation of methimazole and sulindac sulfide after co-incubation with the other five of these six substrates was compared using FMO3 proteins recombinantly expressed in bacterial membranes. Apparent competitive inhibition by methimazole (0-50 μM) of sulindac sulfide S-oxygenation was observed with FMO3 proteins. Sulindac sulfide S-oxygenation activity of Arg205Cys variant FMO3 protein was likely to be suppressed more by methimazole than wild-type or Val257Met variant FMO3 protein was. These results suggest that genetic polymorphism in the human FMO3 gene may lead to changes of drug interactions for N- or S-oxygenations of xenobiotics and endogenous substances and that a probe battery system of benzydamine N-oxygenation and sulindac sulfide S-oxygenation activities is recommended to clarify the drug interactions mediated by FMO3. Copyright © 2014 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Molecular analysis of human papillomavirus virus-like particle activated Langerhans cells in vitro.

PubMed

Woodham, Andrew W; Raff, Adam B; Da Silva, Diane M; Kast, W Martin

2015-01-01

Langerhans cells (LC) are the resident antigen-presenting cells in human epithelium, and are therefore responsible for initiating immune responses against human papillomaviruses (HPV) entering the epithelial and mucosal layers in vivo. Upon proper pathogenic stimulation, LC become activated causing an internal signaling cascade that results in the up-regulation of co-stimulatory molecules and the release of inflammatory cytokines. Activated LC then migrate to lymph nodes where they interact with antigen-specific T cells and initiate an adaptive T-cell response. However, HPV manipulates LC in a suppressive manner that alters these normal maturation responses. Here, in vitro LC activation assays for the detection of phosphorylated signaling intermediates, the up-regulation of activation-associated surface markers, and the release of inflammatory cytokines in response to HPV particles are described.

Epstein-Barr virus nuclear antigen 3C targets p53 and modulates its transcriptional and apoptotic activities

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

Yi Fuming; Saha, Abhik; Murakami, Masanao

The p53 tumor suppressor gene is one of the most commonly mutated genes in human cancers and the corresponding encoded protein induces apoptosis or cell-cycle arrest at the G1/S checkpoint in response to DNA damage. To date, previous studies have shown that antigens encoded by human tumor viruses such as SV40 large T antigen, adenovirus E1A and HPV E6 interact with p53 and disrupt its functional activity. In a similar fashion, we now show that EBNA3C, one of the EBV latent antigens essential for the B-cell immortalization in vitro, interacts directly with p53. Additionally, we mapped the interaction of EBNA3Cmore » with p53 to the C-terminal DNA-binding and the tetramerization domain of p53, and the region of EBNA3C responsible for binding to p53 was mapped to the N-terminal domain of EBNA3C (residues 130-190), previously shown to interact with a number of important cell-cycle components, specifically SCF{sup Skp2}, cyclin A, and cMyc. Furthermore, we demonstrate that EBNA3C substantially represses the transcriptional activity of p53 in luciferase based reporter assays, and rescues apoptosis induced by ectopic p53 expression in SAOS-2 (p53{sup -/-}) cells. Interestingly, we also show that the DNA-binding ability of p53 is diminished in the presence of EBNA3C. Thus, the interaction between the p53 and EBNA3C provides new insights into the mechanism(s) by which the EBNA3C oncoprotein can alter cellular gene expression in EBV associated human cancers.« less

Triggering social interactions: chimpanzees respond to imitation by a humanoid robot and request responses from it.

PubMed

Davila-Ross, Marina; Hutchinson, Johanna; Russell, Jamie L; Schaeffer, Jennifer; Billard, Aude; Hopkins, William D; Bard, Kim A

2014-05-01

Even the most rudimentary social cues may evoke affiliative responses in humans and promote social communication and cohesion. The present work tested whether such cues of an agent may also promote communicative interactions in a nonhuman primate species, by examining interaction-promoting behaviours in chimpanzees. Here, chimpanzees were tested during interactions with an interactive humanoid robot, which showed simple bodily movements and sent out calls. The results revealed that chimpanzees exhibited two types of interaction-promoting behaviours during relaxed or playful contexts. First, the chimpanzees showed prolonged active interest when they were imitated by the robot. Second, the subjects requested 'social' responses from the robot, i.e. by showing play invitations and offering toys or other objects. This study thus provides evidence that even rudimentary cues of a robotic agent may promote social interactions in chimpanzees, like in humans. Such simple and frequent social interactions most likely provided a foundation for sophisticated forms of affiliative communication to emerge.

Interactions of polyphenols with carbohydrates, lipids and proteins.

PubMed

Jakobek, Lidija

2015-05-15

Polyphenols are secondary metabolites in plants, investigated intensively because of their potential positive effects on human health. Their bioavailability and mechanism of positive effects have been studied, in vitro and in vivo. Lately, a high number of studies takes into account the interactions of polyphenols with compounds present in foods, like carbohydrates, proteins or lipids, because these food constituents can have significant effects on the activity of phenolic compounds. This paper reviews the interactions between phenolic compounds and lipids, carbohydrates and proteins and their impact on polyphenol activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

The B-subdomain of the Xenopus laevis XFIN KRAB-AB domain is responsible for its weaker transcriptional repressor activity compared to human ZNF10/Kox1.

PubMed

Born, Nadine; Thiesen, Hans-Jürgen; Lorenz, Peter

2014-01-01

The Krüppel-associated box (KRAB) domain interacts with the nuclear hub protein TRIM28 to initiate or mediate chromatin-dependent processes like transcriptional repression, imprinting or suppression of endogenous retroviruses. The prototype KRAB domain initially identified in ZNF10/KOX1 encompasses two subdomains A and B that are found in hundreds of zinc finger transcription factors studied in human and murine genomes. Here we demonstrate for the first time transcriptional repressor activity of an amphibian KRAB domain. After sequence correction, the updated KRAB-AB domain of zinc finger protein XFIN from the frog Xenopus laevis was found to confer transcriptional repression in reporter assays in Xenopus laevis A6 kidney cells as well as in human HeLa, but not in the minnow Pimephales promelas fish cell line EPC. Binding of the XFIN KRAB-AB domain to human TRIM28 was demonstrated in a classical co-immunoprecipitation approach and visualized in a single-cell compartmentalization assay. XFIN-AB displayed reduced potency in repression as well as lower strength of interaction with TRIM28 compared to ZNF10 KRAB-AB. KRAB-B subdomain swapping between the two KRAB domains indicated that it was mainly the KRAB-B subdomain of XFIN that was responsible for its lower capacity in repression and binding to human TRIM28. In EPC fish cells, ZNF10 and XFIN KRAB repressor activity could be partially restored to low levels by adding exogenous human TRIM28. In contrast to XFIN, we did not find any transcriptional repression activity for the KRAB-like domain of human PRDM9 in HeLa cells. PRDM9 is thought to harbor an evolutionary older domain related to KRAB whose homologs even occur in invertebrates. Our results support the notion that functional bona fide KRAB domains which confer transcriptional repression and interact with TRIM28 most likely co-evolved together with TRIM28 at the beginning of tetrapode evolution.

Structures of closed and open conformations of dimeric human ATM

PubMed Central

Baretić, Domagoj; Pollard, Hannah K.; Fisher, David I.; Johnson, Christopher M.; Santhanam, Balaji; Truman, Caroline M.; Kouba, Tomas; Fersht, Alan R.; Phillips, Christopher; Williams, Roger L.

2017-01-01

ATM (ataxia-telangiectasia mutated) is a phosphatidylinositol 3-kinase–related protein kinase (PIKK) best known for its role in DNA damage response. ATM also functions in oxidative stress response, insulin signaling, and neurogenesis. Our electron cryomicroscopy (cryo-EM) suggests that human ATM is in a dynamic equilibrium between closed and open dimers. In the closed state, the PIKK regulatory domain blocks the peptide substrate–binding site, suggesting that this conformation may represent an inactive or basally active enzyme. The active site is held in this closed conformation by interaction with a long helical hairpin in the TRD3 (tetratricopeptide repeats domain 3) domain of the symmetry-related molecule. The open dimer has two protomers with only a limited contact interface, and it lacks the intermolecular interactions that block the peptide-binding site in the closed dimer. This suggests that the open conformation may be more active. The ATM structure shows the detailed topology of the regulator-interacting N-terminal helical solenoid. The ATM conformational dynamics shown by the structures represent an important step in understanding the enzyme regulation. PMID:28508083

The immune-neuro-endocrine interactions.

PubMed

Tomaszewska, D; Przekop, F

1997-06-01

This article reviews data concerning the interactions between immune, endocrine and neural systems in physiological, pathophysiological and stress conditions in animals and humans. Numerous studies have provided evidence that these systems interact with each other in maintaining homeostasis. This interaction may be classified as follows: immune, endocrine and neural cell products coexist in lymphoid, endocrine and neural tissue. Endocrine and neural mediators modulate immune system activity. Immune, endocrine and neural cells express receptors for cytokines, hormones, neuropeptides and transmitters.

Report of the panel on the land surface: Process of change, section 5

NASA Technical Reports Server (NTRS)

Adams, John B.; Barron, Eric E.; Bloom, Arthur A.; Breed, Carol; Dohrenwend, J.; Evans, Diane L.; Farr, Thomas T.; Gillespie, Allan R.; Isaks, B. L.; Williams, Richard S.

1991-01-01

The panel defined three main areas of study that are central to the Solid Earth Science (SES) program: climate interactions with the Earth's surface, tectonism as it affects the Earth's surface and climate, and human activities that modify the Earth's surface. Four foci of research are envisioned: process studies with an emphasis on modern processes in transitional areas; integrated studies with an emphasis on long term continental climate change; climate-tectonic interactions; and studies of human activities that modify the Earth's surface, with an emphasis on soil degradation. The panel concluded that there is a clear requirement for global coverage by high resolution stereoscopic images and a pressing need for global topographic data in support of studies of the land surface.

Exploring Contemporary Issues in Genetics & Society: Karyotyping, Biological Sex, & Gender

ERIC Educational Resources Information Center

Brown, Julie C.

2013-01-01

In this two-part activity, high school biology students examine human karyotyping, sex-chromosome-linked disorders, and the relationship between biological sex and gender. Through interactive simulations and a structured discussion lab, students create a human karyotype and diagnose chromosomal disorders in hypothetical patients, as well as…

Paradoxical Expectation: Oscillatory Brain Activity Reveals Social Interaction Impairment in Schizophrenia.

PubMed

Billeke, Pablo; Armijo, Alejandra; Castillo, Daniel; López, Tamara; Zamorano, Francisco; Cosmelli, Diego; Aboitiz, Francisco

2015-09-15

People with schizophrenia show social impairments that are related to functional outcomes. We tested the hypothesis that social interaction impairments in people with schizophrenia are related to alterations in the predictions of others' behavior and explored their underlying neurobiological mechanisms. Electroencephalography was performed in 20 patients with schizophrenia and 25 well-matched control subjects. Participants played as proposers in the repeated version of the Ultimatum Game believing that they were playing with another human or with a computer. The power of oscillatory brain activity was obtained by means of the wavelet transform. We performed a trial-by-trial correlation between the oscillatory activity and the risk of the offer. Control subjects adapted their offers when playing with computers and tended to maintain their offers when playing with humans, as such revealing learning and bargaining strategies, respectively. People with schizophrenia presented the opposite pattern of behavior in both games. During the anticipation of others' responses, the power of alpha oscillations correlated with the risk of the offers made, in a different way in both games. Patients with schizophrenia presented a greater correlation in computer games than in human games; control subjects showed the opposite pattern. The alpha activity correlated with positive symptoms. Our results reveal an alteration in social interaction in patients with schizophrenia that is related to oscillatory brain activity, suggesting maladjustment of expectation when patients face social and nonsocial agents. This alteration is related to psychotic symptoms and could guide further therapies for improving social functioning in patients with schizophrenia. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Sustained activation of SMAD3/SMAD4 by FOXM1 promotes TGF-β–dependent cancer metastasis

PubMed Central

Xue, Jianfei; Lin, Xia; Chiu, Wen-Tai; Chen, Yao-Hui; Yu, Guanzhen; Liu, Mingguang; Feng, Xin-Hua; Sawaya, Raymond; Medema, René H.; Hung, Mien-Chie; Huang, Suyun

2014-01-01

A key feature of TGF-β signaling activation in cancer cells is the sustained activation of SMAD complexes in the nucleus; however, the drivers of SMAD activation are poorly defined. Here, using human and mouse breast cancer cell lines, we found that oncogene forkhead box M1 (FOXM1) interacts with SMAD3 to sustain activation of the SMAD3/SMAD4 complex in the nucleus. FOXM1 prevented the E3 ubiquitin-protein ligase transcriptional intermediary factor 1 γ (TIF1γ) from binding SMAD3 and monoubiquitinating SMAD4, which stabilized the SMAD3/SMAD4 complex. Loss of FOXM1 abolished TGF-β–induced SMAD3/SMAD4 formation. Moreover, the interaction of FOXM1 and SMAD3 promoted TGF-β/SMAD3–mediated transcriptional activity and target gene expression. We found that FOXM1/SMAD3 interaction was required for TGF-β–induced breast cancer invasion, which was the result of SMAD3/SMAD4-dependent upregulation of the transcription factor SLUG. Importantly, the function of FOXM1 in TGF-β–induced invasion was not dependent on FOXM1’s transcriptional activity. Knockdown of SMAD3 diminished FOXM1-induced metastasis. Furthermore, FOXM1 levels correlated with activated TGF-β signaling and metastasis in human breast cancer specimens. Together, our data indicate that FOXM1 promotes breast cancer metastasis by increasing nuclear retention of SMAD3 and identify crosstalk between FOXM1 and TGF-β/SMAD3 pathways. This study highlights the critical interaction of FOXM1 and SMAD3 for controlling TGF-β signaling during metastasis. PMID:24382352

Distinct Neurocognitive Strategies for Comprehensions of Human and Artificial Intelligence

PubMed Central

Ge, Jianqiao; Han, Shihui

2008-01-01

Although humans have inevitably interacted with both human and artificial intelligence in real life situations, it is unknown whether the human brain engages homologous neurocognitive strategies to cope with both forms of intelligence. To investigate this, we scanned subjects, using functional MRI, while they inferred the reasoning processes conducted by human agents or by computers. We found that the inference of reasoning processes conducted by human agents but not by computers induced increased activity in the precuneus but decreased activity in the ventral medial prefrontal cortex and enhanced functional connectivity between the two brain areas. The findings provide evidence for distinct neurocognitive strategies of taking others' perspective and inhibiting the process referenced to the self that are specific to the comprehension of human intelligence. PMID:18665211

Social Mimicry Enhances Mu-Suppression During Action Observation.

PubMed

Hogeveen, Jeremy; Chartrand, Tanya L; Obhi, Sukhvinder S

2015-08-01

During social interactions, there is a tendency for people to mimic the gestures and mannerisms of others, which increases liking and rapport. Psychologists have extensively studied the antecedents and consequences of mimicry at the social level, but the neural basis of this behavior remains unclear. Many researchers have speculated that mimicry is related to activity in the human mirror system (HMS), a network of parietofrontal regions that are involved in both action execution and observation. However, activity of the HMS during reciprocal social interactions involving mimicry has not been demonstrated. Here, we took an electroencephalographic (EEG) index of mirror activity-mu-suppression during action observation-in a pretest/post-test design with 1 of 3 intervening treatments: 1) social interaction in which the participant was mimicked, 2) social interaction without mimicry, or 3) an innocuous computer task, not involving another human agent. The change in mu-suppression from pre- to post-test varied as a function of the intervening treatment, with participants who had been mimicked showing an increase in mu-suppression during the post-treatment action observation session. We propose that this specific modulation of HMS activity as a function of mimicry constitutes the first direct evidence for mirror system involvement in real social mimicry. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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.

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

Fronto-parietal coding of goal-directed actions performed by artificial agents.

PubMed

Kupferberg, Aleksandra; Iacoboni, Marco; Flanagin, Virginia; Huber, Markus; Kasparbauer, Anna; Baumgartner, Thomas; Hasler, Gregor; Schmidt, Florian; Borst, Christoph; Glasauer, Stefan

2018-03-01

With advances in technology, artificial agents such as humanoid robots will soon become a part of our daily lives. For safe and intuitive collaboration, it is important to understand the goals behind their motor actions. In humans, this process is mediated by changes in activity in fronto-parietal brain areas. The extent to which these areas are activated when observing artificial agents indicates the naturalness and easiness of interaction. Previous studies indicated that fronto-parietal activity does not depend on whether the agent is human or artificial. However, it is unknown whether this activity is modulated by observing grasping (self-related action) and pointing actions (other-related action) performed by an artificial agent depending on the action goal. Therefore, we designed an experiment in which subjects observed human and artificial agents perform pointing and grasping actions aimed at two different object categories suggesting different goals. We found a signal increase in the bilateral inferior parietal lobule and the premotor cortex when tool versus food items were pointed to or grasped by both agents, probably reflecting the association of hand actions with the functional use of tools. Our results show that goal attribution engages the fronto-parietal network not only for observing a human but also a robotic agent for both self-related and social actions. The debriefing after the experiment has shown that actions of human-like artificial agents can be perceived as being goal-directed. Therefore, humans will be able to interact with service robots intuitively in various domains such as education, healthcare, public service, and entertainment. © 2017 Wiley Periodicals, Inc.

Monoamine receptor interaction profiles of 4-thio-substituted phenethylamines (2C-T drugs).

PubMed

Luethi, Dino; Trachsel, Daniel; Hoener, Marius C; Liechti, Matthias E

2018-05-15

4-Thio-substituted phenethylamines (2C-T drugs) are potent psychedelics with poorly defined pharmacological properties. Because of their psychedelic effects, 2C-T drugs are sometimes sold as new psychoactive substances (NPSs). The aim of the present study was to characterize the monoamine receptor and transporter interaction profiles of a series of 2C-T drugs. We determined the binding affinities of 2C-T drugs at monoamine receptors and transporters in human cells that were transfected with the respective receptors or transporters. We also investigated the functional activation of serotonergic 5-hydroxytryptamine 2A (5-HT 2A ) and 5-HT 2B receptors, activation of human trace amine-associated receptor 1 (TAAR 1 ), and inhibition of monoamine uptake transporters. 2C-T drugs had high affinity for 5-HT 2A and 5-HT 2C receptors (1-54 nM and 40-350 nM, respectively). With activation potencies of 1-53 nM and 44-370 nM, the drugs were potent 5-HT 2A receptor and 5-HT 2B receptor, respectively, partial agonists. An exception to this were the benzylthiophenethylamines, which did not potently activate the 5-HT 2B receptor (EC 50  > 3000 nM). Furthermore, the compounds bound to serotonergic 5-HT 1A and adrenergic receptors. The compounds had high affinity for the rat TAAR 1 (5-68 nM) and interacted with the mouse but not human TAAR 1 . The 2C-T drugs did not potently interact with monoamine transporters (K i  > 4000 nM). The receptor binding profile of 2C-T drugs predicts psychedelic effects that are mediated by potent 5-HT 2 receptor interactions. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.' Copyright © 2017 Elsevier Ltd. All rights reserved.

Interaction vs. observation: distinctive modes of social cognition in human brain and behavior? A combined fMRI and eye-tracking study.

PubMed

Tylén, Kristian; Allen, Micah; Hunter, Bjørk K; Roepstorff, Andreas

2012-01-01

Human cognition has usually been approached on the level of individual minds and brains, but social interaction is a challenging case. Is it best thought of as a self-contained individual cognitive process aiming at an "understanding of the other," or should it rather be approached as an collective, inter-personal process where individual cognitive components interact on a moment-to-moment basis to form coupled dynamics? In a combined fMRI and eye-tracking study we directly contrasted these models of social cognition. We found that the perception of situations affording social contingent responsiveness (e.g., someone offering or showing you an object) elicited activations in regions of the right posterior temporal sulcus and yielded greater pupil dilation corresponding to a model of coupled dynamics (joint action). In contrast, the social-cognitive perception of someone "privately" manipulating an object elicited activation in medial prefrontal cortex, the right inferior frontal gyrus and right inferior parietal lobus, regions normally associated with Theory of Mind and with the mirror neuron system. Our findings support a distinction in social cognition between social observation and social interaction, and demonstrate that simple ostensive cues may shift participants' experience, behavior, and brain activity between these modes. The identification of a distinct, interactive mode has implications for research on social cognition, both in everyday life and in clinical conditions.

Antiviral activity of human oligoadenylate synthetases-like (OASL) is mediated by enhancing retinoic acid-inducible gene I (RIG-I) signaling

PubMed Central

Zhu, Jianzhong; Zhang, Yugen; Ghosh, Arundhati; Cuevas, Rolando A.; Forero, Adriana; Dhar, Jayeeta; Ibsen, Mikkel Søes; Schmid-Burgk, Jonathan Leo; Schmidt, Tobias; Ganapathiraju, Madhavi K.; Fujita, Takashi; Hartmann, Rune; Barik, Sailen; Hornung, Veit; Coyne, Carolyn B.; Sarkar, Saumendra N.

2014-01-01

SUMMARY Virus infection is sensed in the cytoplasm by retinoic acid-inducible gene I (RIG-I, also known as DDX58), which requires RNA and polyubiquitin binding to induce type I interferon (IFN), and activate cellular innate immunity. We show that the human IFN-inducible oligoadenylate synthetases-like (OASL) protein had antiviral activity and mediated RIG-I activation by mimicking polyubiquitin. Loss of OASL expression reduced RIG-I signaling and enhanced virus replication in human cells. Conversely, OASL expression suppressed replication of a number of viruses in a RIG-I-dependent manner and enhanced RIG-I-mediated IFN induction. OASL interacted and colocalized with RIG-I, and through its C-terminal ubiquitin-like domain specifically enhanced RIG-I signaling. Bone marrow derived macrophages from mice deficient for Oasl2 showed that among the two mouse orthologs of human OASL; Oasl2 is functionally similar to human OASL. Our findings show a mechanism by which human OASL contributes to host antiviral responses by enhancing RIG-I activation. PMID:24931123

Animal-Assisted Activities for Students with Disabilities: Obtaining Stakeholders' Approval and Planning Strategies for Teachers

ERIC Educational Resources Information Center

Baumgartner, Erin; Cho, Jeong-il

2014-01-01

Animal-human interactions have been found to have positive influences on children across the world. In particular, research supports the benefits of animal-assisted activities in addressing students' social and behavioral problems within the classroom environment. The general information about animal-assisted activities provided in this…

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

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.

1,2,3,4-Tetrahydroisoquinolines as inhibitors of HIV-1 integrase and human LEDGF/p75 interaction.

PubMed

George, Anu; Gopi Krishna Reddy, Alavala; Satyanarayana, Gedu; Raghavendra, Nidhanapati K

2018-06-01

Alkaloids are a class of organic compounds with a wide range of biological properties, including anti-HIV activity. The 1,2,3,4-tetrahydroisoquinoline is a ubiquitous structural motif of many alkaloids. Using a short and an efficient route for synthesis, a series of 1,2,3,4-tetrahydroisoquinolines/isoquinolines was developed. These compounds have been analysed for their ability to inhibit an important interaction between HIV-1 integrase enzyme (IN) and human LEDGF/p75 protein (p75) which assists in the viral integration into the active genes. A lead compound 6d is found to inhibit the LEDGF/p75-IN interaction in vitro with an IC 50 of ~10 μm. Molecular docking analysis of the isoquinoline 6d reveals its interactions with the LEDGF/p75-binding residues of IN. Based on an order of addition experiment, the binding of 6d or LEDGF/p75 to IN is shown to be mutually exclusive. Also, the activity of 6d in vitro is found to be unaffected by the presence of a non-specific DNA. As reported earlier for the inhibitors of LEDGF/p75-IN interaction, 6d exhibits a potent inhibition of both the early and late stages of HIV-1 replication. Compound 6d differing from the known inhibitors in the chemical moieties and interactions with CCD could potentially be explored further for developing small molecule inhibitors of LEDGF/p75-IN interaction having a higher potency. © 2018 John Wiley & Sons A/S.

Vitamin D and prebiotics may benefit the intestinal microbacteria and improve glucose homeostasis in prediabetes and type 2 diabetes.

PubMed

Barengolts, Elena

2013-01-01

To review the role of human large bowel microbacteria (microbiota) in the glucose homeostasis, to address vitamin D (VD) and prebiotics interactions with microbiota, and to summarize recent randomized clinical trials (RCTs) of VD and prebiotics supplementation in prediabetes (PreDM) and type 2 diabetes mellitus (T2DM). Primary literature was reviewed in the following areas: composition and activity of human microbiota associated with PreDM and T2DM, interactions between microbiota and glucose homeostasis, the interaction of microbiota with VD/prebiotics, and RCTs of VD/prebiotics in subjects with PreDM or T2DM. The human microbiota is comprised of 100 trillion bacteria with an aggregate genome that is 150-fold larger than the human genome. Data from the animal models and human studies reveal that an "obesogenic" diet results into the initial event of microbiota transformation from symbiosis to dysbiosis. The microbial antigens, such as Gram(-) bacteria and lipopolysaccharide (LPS), translocate to the host interior and trigger increased energy harvesting and Toll-like receptor (TLR) activation with subsequent inflammatory pathways signaling. The "double hit" of steatosis (ectopic fat accumulation) and "-itis" (inflammation) and contribution of "corisks" (e.g., vitamin D deficiency [VDD]) are required to activate molecular signaling, including impaired insulin signaling and secretion, that ends with T2DM and associated diseases. Dietary changes (e.g., prebiotics, VD supplementation) may ameliorate this process if initiated prior to the process becoming irreversible. Emerging evidence suggests an important role of microbiota in glucose homeostasis. VD supplementation and prebiotics may be useful in managing PreDM and T2DM.

Characterization of the interactions between protein and carbon black.

PubMed

Chen, Tzu-Tao; Chuang, Kai-Jen; Chiang, Ling-Ling; Chen, Chun-Chao; Yeh, Chi-Tai; Wang, Liang-Shun; Gregory, Clive; Jones, Tim; BéruBé, Kelly; Lee, Chun-Nin; Chuang, Hsiao-Chi; Cheng, Tsun-Jen

2014-01-15

A considerable amount of studies have been conducted to investigate the interactions of biological fluids with nanoparticle surfaces, which exhibit a high affinity for proteins and particles. However, the mechanisms underlying these interactions have not been elucidated, particularly as they relate to human health. Using bovine serum albumin (BSA) and mice bronchoalveolar lavage fluid (BALF) as models for protein-particle conjugates, we characterized the physicochemical modifications of carbon blacks (CB) with 23nm or 65nm in diameter after protein treatment. Adsorbed BALF-containing proteins were quantified and identified by pathways, biological analyses and protein classification. Significant modifications of the physicochemistry of CB were induced by the addition of BSA. Enzyme modulators and hydrolase predominately interacted with CB, with protein-to-CB interactions that were associated with the coagulation pathways. Additionally, our results revealed that an acute-phase response could be activated by these proteins. With regard to human health, the present study revealed that the CB can react with proteins (∼55kDa and 70kDa) after inhalation and may modify the functional structures of lung proteins, leading to the activation of acute-inflammatory responses in the lungs. Copyright © 2013 Elsevier B.V. All rights reserved.

The great outdoors: how a green exercise environment can benefit all

PubMed Central

2013-01-01

The studies of human and environment interactions usually consider the extremes of environment on individuals or how humans affect the environment. It is well known that physical activity improves both physiological and psychological well-being, but further evidence is required to ascertain how different environments influence and shape health. This review considers the declining levels of physical activity, particularly in the Western world, and how the environment may help motivate and facilitate physical activity. It also addresses the additional physiological and mental health benefits that appear to occur when exercise is performed in an outdoor environment. However, people’s connectedness to nature appears to be changing and this has important implications as to how humans are now interacting with nature. Barriers exist, and it is important that these are considered when discussing how to make exercise in the outdoors accessible and beneficial for all. The synergistic combination of exercise and exposure to nature and thus the ‘great outdoors’ could be used as a powerful tool to help fight the growing incidence of both physical inactivity and non-communicable disease. PMID:23849478

The great outdoors: how a green exercise environment can benefit all.

PubMed

Gladwell, Valerie F; Brown, Daniel K; Wood, Carly; Sandercock, Gavin R; Barton, Jo L

2013-01-03

The studies of human and environment interactions usually consider the extremes of environment on individuals or how humans affect the environment. It is well known that physical activity improves both physiological and psychological well-being, but further evidence is required to ascertain how different environments influence and shape health. This review considers the declining levels of physical activity, particularly in the Western world, and how the environment may help motivate and facilitate physical activity. It also addresses the additional physiological and mental health benefits that appear to occur when exercise is performed in an outdoor environment. However, people's connectedness to nature appears to be changing and this has important implications as to how humans are now interacting with nature. Barriers exist, and it is important that these are considered when discussing how to make exercise in the outdoors accessible and beneficial for all. The synergistic combination of exercise and exposure to nature and thus the 'great outdoors' could be used as a powerful tool to help fight the growing incidence of both physical inactivity and non-communicable disease.

Interactive activation and mutual constraint satisfaction in perception and cognition.

PubMed

McClelland, James L; Mirman, Daniel; Bolger, Donald J; Khaitan, Pranav

2014-08-01

In a seminal 1977 article, Rumelhart argued that perception required the simultaneous use of multiple sources of information, allowing perceivers to optimally interpret sensory information at many levels of representation in real time as information arrives. Building on Rumelhart's arguments, we present the Interactive Activation hypothesis-the idea that the mechanism used in perception and comprehension to achieve these feats exploits an interactive activation process implemented through the bidirectional propagation of activation among simple processing units. We then examine the interactive activation model of letter and word perception and the TRACE model of speech perception, as early attempts to explore this hypothesis, and review the experimental evidence relevant to their assumptions and predictions. We consider how well these models address the computational challenge posed by the problem of perception, and we consider how consistent they are with evidence from behavioral experiments. We examine empirical and theoretical controversies surrounding the idea of interactive processing, including a controversy that swirls around the relationship between interactive computation and optimal Bayesian inference. Some of the implementation details of early versions of interactive activation models caused deviation from optimality and from aspects of human performance data. More recent versions of these models, however, overcome these deficiencies. Among these is a model called the multinomial interactive activation model, which explicitly links interactive activation and Bayesian computations. We also review evidence from neurophysiological and neuroimaging studies supporting the view that interactive processing is a characteristic of the perceptual processing machinery in the brain. In sum, we argue that a computational analysis, as well as behavioral and neuroscience evidence, all support the Interactive Activation hypothesis. The evidence suggests that contemporary versions of models based on the idea of interactive activation continue to provide a basis for efforts to achieve a fuller understanding of the process of perception. Copyright © 2014 Cognitive Science Society, Inc.

Tax posttranslational modifications and interaction with calreticulin in MT-2 cells and human peripheral blood mononuclear cells of human T cell lymphotropic virus type-I-associated myelopathy/tropical spastic paraparesis patients.

PubMed

Medina, Fernando; Quintremil, Sebastian; Alberti, Carolina; Barriga, Andres; Cartier, Luis; Puente, Javier; Ramírez, Eugenio; Ferreira, Arturo; Tanaka, Yuetsu; Valenzuela, Maria Antonieta

2014-04-01

The human retrovirus human T cell lymphotropic virus type-I (HTLV-1) is the etiologic agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Axonal degeneration in HAM/TSP patients occurs without neuron infection, with the secreted viral Tax protein proposed to be involved. We previously found that Tax secreted into the culture medium of MT-2 cells (HTLV-1-infected cell line) produced neurite retraction in neuroblastoma cells differentiated to neuronal type. To assess the relevance of Tax posttranslational modifications on this effect, we addressed the question of whether Tax secreted by MT-2 cells and peripheral blood mononuclear cells (PBMCs) of HTLV-1-infected subjects is modified. The interaction of Tax with calreticulin (CRT) that modulates intracellular Tax localization and secretion has been described. We studied Tax localization and modifications in MT-2 cells and its interaction with CRT. Intracellular Tax in MT-2 cells was assessed by flow cytometry, corresponding mainly to a 71-kDa protein followed by western blot. This protein reported as a chimera with gp21 viral protein-confirmed by mass spectrometry-showed no ubiquitination or SUMOylation. The Tax-CRT interaction was determined by confocal microscopy and coimmunoprecipitation. Extracellular Tax from HAM/TSP PBMCs is ubiquitinated according to western blot, and its interaction with CRT was shown by coimmunoprecipitation. A positive correlation between Tax and CRT secretion was observed in HAM/TSP PBMCs and asymptomatic carriers. For both proteins inhibitors and activators of secretion showed secretion through the endoplasmic reticulum-Golgi complex. Tax, present in PBMC culture medium, produced neurite retraction in differentiated neuroblastoma cells. These results suggest that Tax, whether ubiquitinated or not, is active for neurite retraction.

Membrane Estrogen and HER-2 Receptors in Human Breast Cancer

DTIC Science & Technology

2002-07-01

activation of G-proteins, adenylate cyclase, inositol phosphate, calcium homeostasis and/or MAP kinase. These interactions may promote phosphorylation of ER...of breast cancer cells and interact with transmembrane HER-2 growth factor receptors. Expression of HER-2 receptors occurs in many breast cancers...reports of significant cross-talk and interaction between erb B (HER) pathways and estrogen receptor signaling (3,24,27,34-36). It is generally held

Evidence for the Activation of Sensorimotor Information during Visual Word Recognition: The Body-Object Interaction Effect

ERIC Educational Resources Information Center

Siakaluk, Paul D.; Pexman, Penny M.; Aguilera, Laura; Owen, William J.; Sears, Christopher R.

2008-01-01

We examined the effects of sensorimotor experience in two visual word recognition tasks. Body-object interaction (BOI) ratings were collected for a large set of words. These ratings assess perceptions of the ease with which a human body can physically interact with a word's referent. A set of high BOI words (e.g., "mask") and a set of low BOI…

Motor contagion during human-human and human-robot interaction.

PubMed

Bisio, Ambra; Sciutti, Alessandra; Nori, Francesco; Metta, Giorgio; Fadiga, Luciano; Sandini, Giulio; Pozzo, Thierry

2014-01-01

Motor resonance mechanisms are known to affect humans' ability to interact with others, yielding the kind of "mutual understanding" that is the basis of social interaction. However, it remains unclear how the partner's action features combine or compete to promote or prevent motor resonance during interaction. To clarify this point, the present study tested whether and how the nature of the visual stimulus and the properties of the observed actions influence observer's motor response, being motor contagion one of the behavioral manifestations of motor resonance. Participants observed a humanoid robot and a human agent move their hands into a pre-specified final position or put an object into a container at various velocities. Their movements, both in the object- and non-object- directed conditions, were characterized by either a smooth/curvilinear or a jerky/segmented trajectory. These trajectories were covered with biological or non-biological kinematics (the latter only by the humanoid robot). After action observation, participants were requested to either reach the indicated final position or to transport a similar object into another container. Results showed that motor contagion appeared for both the interactive partner except when the humanoid robot violated the biological laws of motion. These findings suggest that the observer may transiently match his/her own motor repertoire to that of the observed agent. This matching might mediate the activation of motor resonance, and modulate the spontaneity and the pleasantness of the interaction, whatever the nature of the communication partner.

Motor Contagion during Human-Human and Human-Robot Interaction

PubMed Central

Bisio, Ambra; Sciutti, Alessandra; Nori, Francesco; Metta, Giorgio; Fadiga, Luciano; Sandini, Giulio; Pozzo, Thierry

2014-01-01

Motor resonance mechanisms are known to affect humans' ability to interact with others, yielding the kind of “mutual understanding” that is the basis of social interaction. However, it remains unclear how the partner's action features combine or compete to promote or prevent motor resonance during interaction. To clarify this point, the present study tested whether and how the nature of the visual stimulus and the properties of the observed actions influence observer's motor response, being motor contagion one of the behavioral manifestations of motor resonance. Participants observed a humanoid robot and a human agent move their hands into a pre-specified final position or put an object into a container at various velocities. Their movements, both in the object- and non-object- directed conditions, were characterized by either a smooth/curvilinear or a jerky/segmented trajectory. These trajectories were covered with biological or non-biological kinematics (the latter only by the humanoid robot). After action observation, participants were requested to either reach the indicated final position or to transport a similar object into another container. Results showed that motor contagion appeared for both the interactive partner except when the humanoid robot violated the biological laws of motion. These findings suggest that the observer may transiently match his/her own motor repertoire to that of the observed agent. This matching might mediate the activation of motor resonance, and modulate the spontaneity and the pleasantness of the interaction, whatever the nature of the communication partner. PMID:25153990

Opinion formation in a social network: The role of human activity

NASA Astrophysics Data System (ADS)

Grabowski, Andrzej

2009-03-01

The model of opinion formation in human population based on social impact theory is investigated numerically. On the basis of a database received from the on-line game server, we examine the structure of social network and human dynamics. We calculate the activity of individuals, i.e. the relative time devoted daily to interactions with others in the artificial society. We study the influence of correlation between the activity of an individual and its connectivity on the process of opinion formation. We find that such correlations have a significant influence on the temperature of the phase transition and the effect of the mass media, modeled as an external stimulation acting on the social network.

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

Distinct Functional Interactions between Actin Isoforms and Nonsarcomeric Myosins

PubMed Central

Müller, Mirco; Diensthuber, Ralph P.; Chizhov, Igor; Claus, Peter; Heissler, Sarah M.; Preller, Matthias; Taft, Manuel H.; Manstein, Dietmar J.

2013-01-01

Despite their near sequence identity, actin isoforms cannot completely replace each other in vivo and show marked differences in their tissue-specific and subcellular localization. Little is known about isoform-specific differences in their interactions with myosin motors and other actin-binding proteins. Mammalian cytoplasmic β- and γ-actin interact with nonsarcomeric conventional myosins such as the members of the nonmuscle myosin-2 family and myosin-7A. These interactions support a wide range of cellular processes including cytokinesis, maintenance of cell polarity, cell adhesion, migration, and mechano-electrical transduction. To elucidate differences in the ability of isoactins to bind and stimulate the enzymatic activity of individual myosin isoforms, we characterized the interactions of human skeletal muscle α-actin, cytoplasmic β-actin, and cytoplasmic γ-actin with human myosin-7A and nonmuscle myosins-2A, -2B and -2C1. In the case of nonmuscle myosins-2A and -2B, the interaction with either cytoplasmic actin isoform results in 4-fold greater stimulation of myosin ATPase activity than was observed in the presence of α-skeletal muscle actin. Nonmuscle myosin-2C1 is most potently activated by β-actin and myosin-7A by γ-actin. Our results indicate that β- and γ-actin isoforms contribute to the modulation of nonmuscle myosin-2 and myosin-7A activity and thereby to the spatial and temporal regulation of cytoskeletal dynamics. FRET-based analyses show efficient copolymerization abilities for the actin isoforms in vitro. Experiments with hybrid actin filaments show that the extent of actomyosin coupling efficiency can be regulated by the isoform composition of actin filaments. PMID:23923011

JAB1 regulates unphosphorylated STAT3 DNA-binding activity through protein–protein interaction in human colon cancer cells

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

Nishimoto, Arata, E-mail: anishimo@yamaguchi-u.ac.jp; Kugimiya, Naruji; Hosoyama, Toru

2013-08-30

Highlights: •JAB1 interacted with unphosphorylated STAT3 in the nucleus. •JAB1 knockdown tended to increase nuclear STAT3 expression. •JAB1 knockdown significantly decreased unphosphorylated STAT3 DNA-binding activity. •JAB1 knockdown significantly decreased MDR1, NANOG, and VEGF expressions. •Nuclear JAB1, but not nuclear STAT3, correlated with STAT3 DNA-binding activity. -- Abstract: Recent studies have revealed that unphosphorylated STAT3 forms a dimer, translocates to the nucleus, binds to the STAT3 binding site, and activates the transcription of STAT3 target genes, thereby playing an important role in oncogenesis in addition to phosphorylated STAT3. Among signaling steps of unphosphorylated STAT3, nuclear translocation and target DNA-binding are themore » critical steps for its activation. Therefore, elucidating the regulatory mechanism of these signaling steps of unphosphorylated STAT3 is a potential step in the discovery of a novel cancer drug. However, the mechanism of unphosphorylated STAT3 binding to the promoter of target genes remains unclear. In this study, we focused on Jun activation domain-binding protein 1 (JAB1) as a candidate protein that regulates unphosphorylated STAT3 DNA-binding activity. Initially, we observed that both unphosphorylated STAT3 and JAB1 existed in the nucleus of human colon cancer cell line COLO205 at the basal state (no cytokine stimulation). On the other hand, phosphorylated STAT3 did not exist in the nucleus of COLO205 cells at the basal state. Immunoprecipitation using nuclear extract of COLO205 cells revealed that JAB1 interacted with unphosphorylated STAT3. To investigate the effect of JAB1 on unphosphorylated STAT3 activity, RNAi studies were performed. Although JAB1 knockdown tended to increase nuclear STAT3 expression, it significantly decreased unphosphorylated STAT3 DNA-binding activity. Subsequently, JAB1 knockdown significantly decreased the expression levels of MDR1, NANOG, and VEGF, which are STAT3 target genes. Furthermore, the expression level of nuclear JAB1, but not nuclear STAT3, correlated with unphosphorylated STAT3 DNA-binding activity between COLO205 and LoVo cells. Taken together, these results suggest that nuclear JAB1 positively regulates unphosphorylated STAT3 DNA-binding activity through protein–protein interaction in human colon cancer cell line COLO205.« less

The social brain: allowing humans to boldly go where no other species has been

PubMed Central

Frith, Uta; Frith, Chris

2010-01-01

The biological basis of complex human social interaction and communication has been illuminated through a coming together of various methods and disciplines. Among these are comparative studies of other species, studies of disorders of social cognition and developmental psychology. The use of neuroimaging and computational models has given weight to speculations about the evolution of social behaviour and culture in human societies. We highlight some networks of the social brain relevant to two-person interactions and consider the social signals between interacting partners that activate these networks. We make a case for distinguishing between signals that automatically trigger interaction and cooperation and ostensive signals that are used deliberately. We suggest that this ostensive signalling is needed for ‘closing the loop’ in two-person interactions, where the partners each know that they have the intention to communicate. The use of deliberate social signals can serve to increase reputation and trust and facilitates teaching. This is likely to be a critical factor in the steep cultural ascent of mankind. PMID:20008394

[Interaction of the bodies and institutions of the Russian Inspectorate for the protection of consumer rights and human welfare on sanitary-and-epidemiological examinations and issuing sanitary-and-epidemiological opinions].

PubMed

Safonkina, S G

2009-01-01

The paper describes problems in the organization of the interaction of the Russian Inspectorate for the Protection of Consumer Rights and Human Welfare in Moscow and the Center for Hygiene and Epidemiology in Moscow to perform sanitary-and-epidemiological examinations and to issue sanitary-and-epidemiological opinions. The goals of setting up a one-window service and measures required for its effective work are defined. Positive results of one-window activities are shown.

Species-specific calls evoke asymmetric activity in the monkey's temporal poles.

PubMed

Poremba, Amy; Malloy, Megan; Saunders, Richard C; Carson, Richard E; Herscovitch, Peter; Mishkin, Mortimer

2004-01-29

It has often been proposed that the vocal calls of monkeys are precursors of human speech, in part because they provide critical information to other members of the species who rely on them for survival and social interactions. Both behavioural and lesion studies suggest that monkeys, like humans, use the auditory system of the left hemisphere preferentially to process vocalizations. To investigate the pattern of neural activity that might underlie this particular form of functional asymmetry in monkeys, we measured local cerebral metabolic activity while the animals listened passively to species-specific calls compared with a variety of other classes of sound. Within the superior temporal gyrus, significantly greater metabolic activity occurred on the left side than on the right, only in the region of the temporal pole and only in response to monkey calls. This functional asymmetry was absent when these regions were separated by forebrain commissurotomy, suggesting that the perception of vocalizations elicits concurrent interhemispheric interactions that focus the auditory processing within a specialized area of one hemisphere.

Toward Multimodal Human-Robot Interaction to Enhance Active Participation of Users in Gait Rehabilitation.

PubMed

Gui, Kai; Liu, Honghai; Zhang, Dingguo

2017-11-01

Robotic exoskeletons for physical rehabilitation have been utilized for retraining patients suffering from paraplegia and enhancing motor recovery in recent years. However, users are not voluntarily involved in most systems. This paper aims to develop a locomotion trainer with multiple gait patterns, which can be controlled by the active motion intention of users. A multimodal human-robot interaction (HRI) system is established to enhance subject's active participation during gait rehabilitation, which includes cognitive HRI (cHRI) and physical HRI (pHRI). The cHRI adopts brain-computer interface based on steady-state visual evoked potential. The pHRI is realized via admittance control based on electromyography. A central pattern generator is utilized to produce rhythmic and continuous lower joint trajectories, and its state variables are regulated by cHRI and pHRI. A custom-made leg exoskeleton prototype with the proposed multimodal HRI is tested on healthy subjects and stroke patients. The results show that voluntary and active participation can be effectively involved to achieve various assistive gait patterns.

Chitosan derivatives targeting lipid bilayers: Synthesis, biological activity and interaction with model membranes.

PubMed

Martins, Danubia Batista; Nasário, Fábio Domingues; Silva-Gonçalves, Laiz Costa; de Oliveira Tiera, Vera Aparecida; Arcisio-Miranda, Manoel; Tiera, Marcio José; Dos Santos Cabrera, Marcia Perez

2018-02-01

The antimicrobial activity of chitosan and derivatives to human and plant pathogens represents a high-valued prospective market. Presently, two low molecular weight derivatives, endowed with hydrophobic and cationic character at different ratios were synthesized and characterized. They exhibit antimicrobial activity and increased performance in relation to the intermediate and starting compounds. However, just the derivative with higher cationic character showed cytotoxicity towards human cervical carcinoma cells. Considering cell membranes as targets, the mode of action was investigated through the interaction with model lipid vesicles mimicking bacterial, tumoral and erythrocyte membranes. Intense lytic activity and binding are demonstrated for both derivatives in anionic bilayers. The less charged compound exhibits slightly improved selectivity towards bacterial model membranes, suggesting that balancing its hydrophobic/hydrophilic character may improve efficiency. Observing the aggregation of vesicles, we hypothesize that the "charge cluster mechanism", ascribed to some antimicrobial peptides, could be applied to these chitosan derivatives. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interaction of rocuronium with human liver cytochromes P450.

PubMed

Anzenbacherova, Eva; Spicakova, Alena; Jourova, Lenka; Ulrichova, Jitka; Adamus, Milan; Bachleda, Petr; Anzenbacher, Pavel

2015-02-01

Rocuronium is a neuromuscular blocking agent acting as a competitive antagonist of acetylcholine. Results of an inhibition of eight individual liver microsomal cytochromes P450 (CYP) are presented. As the patients are routinely premedicated with diazepam, possible interaction of diazepam with rocuronium has been also studied. Results indicated that rocuronium interacts with human liver microsomal CYPs by binding to the substrate site. Next, concentration dependent inhibition of liver microsomal CYP3A4 down to 42% (at rocuronium concentration 189 μM) was found. This effect has been confirmed with two CYP3A4 substrates, testosterone (formation of 6β-hydroxytestosterone) and diazepam (temazepam formation). CYP2C9 and CYP2C19 activities were inhibited down to 75-80% (at the same rocuronium concentration). Activities of other microsomal CYPs have not been inhibited by rocuronium. To prove the possibility of rocuronium interaction with other drugs (diazepam), the effect of rocuronium on formation of main diazepam metabolites, temazepam (by CYP3A4) and desmethyldiazepam, (also known as nordiazepam; formed by CYP2C19) in primary culture of human hepatocytes has been examined. Rocuronium has caused inhibition of both reactions by 20 and 15%, respectively. The results open a possibility that interactions of rocuronium with drugs metabolized by CYP3A4 (and possibly also CYP2C19) may be observed. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

Prehistoric Human-environment Interactions and Their Impact on Aquatic Ecosystems

NASA Astrophysics Data System (ADS)

Mackay, H.; Henderson, A. C. G.; van Hardenbroek, M.; Cavers, G.; Crone, A.; Davies, K. L.; Fonville, T. R.; Head, K.; Langdon, P. G.; Matton, R.; McCormick, F.; Murray, E.; Whitehouse, N. J.; Brown, A. G.

2017-12-01

One of the first widespread human-environment interactions in Scotland and Ireland occurred 3000 years ago when communities first inhabited wetlands, building artificial islands in lakes called crannogs. The reason behind the development and intermittent occupation of crannogs is unclear. We don't know if they were a response to changes in environment or if they were driven by societal influences. Furthermore, the impact of the construction, settlement and human activities on lake ecosystems is unknown, but is a key example of early anthropogenic signatures on the environment. Our research characterises the prehistoric human-environment interactions associated with crannogs by analysing geochemical and biological signals preserved within the crannog and wetland sediments. Records of anthropogenic activities and environmental change have been produced using lipid biomarkers of faecal matter, sedimentary DNA, and the remains of beetles, aquatic invertebrates (chironomids), siliceous algae (diatoms) and pollen. Results of these analyses reveal settlement occupations occurred in phases from the Iron Age to the Medieval Period. The main effects of occupation on the wetland ecosystems are nutrient-driven increases in productivity and shifts in aquatic species from clear water taxa to those associated with more eutrophic conditions. Crannog abandonment reduces nutrient inputs and therefore levels of aquatic productivity, as evidenced by decreases in the abundance of siliceous algae. Despite returns to pre-settlement nutrient and productivity levels, the lake ecosystems do not recover to their previous ecological state: dominant aquatic invertebrate and siliceous algae taxa shift in response to elevated levels of macrophytes within the lakes. Whilst these phase changes in lake ecosystems highlight their adaptive capacity to environmental change, the temporary human interactions associated with crannogs had persisting environmental impacts that shaped the long-term structure of the aquatic ecosystems.

Lateralized interactive social content and valence processing within the human amygdala

PubMed Central

Vrtička, Pascal; Sander, David; Vuilleumier, Patrik

2013-01-01

In the past, the amygdala has generally been conceptualized as a fear-processing module. Recently, however, it has been proposed to respond to all stimuli that are relevant with respect to the current needs, goals, and values of an individual. This raises the question of whether the human amygdala may differentiate between separate kinds of relevance. A distinction between emotional (vs. neutral) and social (vs. non-social) relevance is supported by previous studies showing that the human amygdala preferentially responds to both emotionally and socially significant information, and these factors might even display interactive encoding properties. However, no investigation has yet probed a full 2 (positive vs. negative valence) × 2 (social vs. non-social content) processing pattern, with neutral images as an additional baseline. Applying such an extended orthogonal factorial design, our fMRI study demonstrates that the human amygdala is (1) more strongly activated for neutral social vs. non-social information, (2) activated at a similar level when viewing social positive or negative images, but (3) displays a valence effect (negative vs. positive) for non-social images. In addition, this encoding pattern is not influenced by cognitive or behavioral emotion regulation mechanisms, and displays a hemispheric lateralization with more pronounced effects on the right side. Finally, the same valence × social content interaction was found in three additional cortical regions, namely the right fusiform gyrus, right anterior superior temporal gyrus, and medial orbitofrontal cortex. Overall, these findings suggest that valence and social content processing represent distinct kinds of relevance that interact within the human amygdala as well as in a more extensive cortical network, likely subserving a key role in relevance detection. PMID:23346054

An expanded One Health model: integrating social science and One Health to inform study of the human-animal interface.

PubMed

Woldehanna, Sara; Zimicki, Susan

2015-03-01

Zoonotic disease emergence is not a purely biological process mediated only by ecologic factors; opportunities for transmission of zoonoses from animals to humans also depend on how people interact with animals. While exposure is conditioned by the type of animal and the location in which interactions occur, these in turn are influenced by human activity. The activities people engage in are determined by social as well as contextual factors including gender, age, socio-economic status, occupation, social norms, settlement patterns and livelihood systems, family and community dynamics, as well as national and global influences. This paper proposes an expanded "One Health" conceptual model for human-animal exposure that accounts for social as well as epidemiologic factors. The expanded model informed a new study approach to document the extent of human exposure to animals and explore the interplay of social and environmental factors that influence risk of transmission at the individual and community level. The approach includes a formative phase using qualitative and participatory methods, and a representative, random sample survey to quantify exposure to animals in a variety of settings. The paper discusses the different factors that were considered in developing the approach, including the range of animals asked about and the parameters of exposure that are included, as well as factors to be considered in local adaptation of the generic instruments. Illustrative results from research using this approach in Lao PDR are presented to demonstrate the effect of social factors on how people interact with animals. We believe that the expanded model can be similarly operationalized to explore the interactions of other social and policy-level determinants that may influence transmission of zoonoses. Copyright © 2014 Elsevier Ltd. All rights reserved.

Understanding the interaction between human serum albumin and anti-bacterial/ anti-cancer compounds.

PubMed

Rehman, Md Tabish; Khan, Asad U

2015-01-01

Human serum albumin (HSA) is the most important carrier of exogenous and endogenous molecules in human plasma. Understanding and characterizing the interaction of drugs with HSA has attracted enormous research interests from decades. The nature and magnitude of these bindings have direct consequence on drug delivery, pharmacokinetics, pharmacodynamics, therapeutic efficacy and drug designing. An overview of HSA and antibacterial/ anti-cancer ligands interaction is the need of the hour as these drugs together constitute more than half of the total drug consumption in the world. In this review, the information on the number of binding sites, binding strength, the nature of binding interactions and the location of binding sites of such drugs on the HSA are summarised. The effect of such drugs on the overall conformation, stability and function of HSA is also reviewed. This review will help to gain useful insights into the significance of the binding of anti-bacterial and anti-cancer drugs with plasma protein and the effect of binding on its overall distribution and pharmacological activities.

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.

Dynamic phenomena and human activity in an artificial society

NASA Astrophysics Data System (ADS)

Grabowski, A.; Kruszewska, N.; Kosiński, R. A.

2008-12-01

We study dynamic phenomena in a large social network of nearly 3×104 individuals who interact in the large virtual world of a massive multiplayer online role playing game. On the basis of a database received from the online game server, we examine the structure of the friendship network and human dynamics. To investigate the relation between networks of acquaintances in virtual and real worlds, we carried out a survey among the players. We show that, even though the virtual network did not develop as a growing graph of an underlying network of social acquaintances in the real world, it influences it. Furthermore we find very interesting scaling laws concerning human dynamics. Our research shows how long people are interested in a single task and how much time they devote to it. Surprisingly, exponent values in both cases are close to -1 . We calculate the activity of individuals, i.e., the relative time daily devoted to interactions with others in the artificial society. Our research shows that the distribution of activity is not uniform and is highly correlated with the degree of the node, and that such human activity has a significant influence on dynamic phenomena, e.g., epidemic spreading and rumor propagation, in complex networks. We find that spreading is accelerated (an epidemic) or decelerated (a rumor) as a result of superspreaders’ various behavior.

ActiveDriverDB: human disease mutations and genome variation in post-translational modification sites of proteins

PubMed Central

Krassowski, Michal; Paczkowska, Marta; Cullion, Kim; Huang, Tina; Dzneladze, Irakli; Ouellette, B F Francis; Yamada, Joseph T; Fradet-Turcotte, Amelie

2018-01-01

Abstract Interpretation of genetic variation is needed for deciphering genotype-phenotype associations, mechanisms of inherited disease, and cancer driver mutations. Millions of single nucleotide variants (SNVs) in human genomes are known and thousands are associated with disease. An estimated 21% of disease-associated amino acid substitutions corresponding to missense SNVs are located in protein sites of post-translational modifications (PTMs), chemical modifications of amino acids that extend protein function. ActiveDriverDB is a comprehensive human proteo-genomics database that annotates disease mutations and population variants through the lens of PTMs. We integrated >385,000 published PTM sites with ∼3.6 million substitutions from The Cancer Genome Atlas (TCGA), the ClinVar database of disease genes, and human genome sequencing projects. The database includes site-specific interaction networks of proteins, upstream enzymes such as kinases, and drugs targeting these enzymes. We also predicted network-rewiring impact of mutations by analyzing gains and losses of kinase-bound sequence motifs. ActiveDriverDB provides detailed visualization, filtering, browsing and searching options for studying PTM-associated mutations. Users can upload mutation datasets interactively and use our application programming interface in pipelines. Integrative analysis of mutations and PTMs may help decipher molecular mechanisms of phenotypes and disease, as exemplified by case studies of TP53, BRCA2 and VHL. The open-source database is available at https://www.ActiveDriverDB.org. PMID:29126202

Stability of human interferon-beta 1: oligomeric human interferon-beta 1 is inactive but is reactivated by monomerization.

PubMed

Utsumi, J; Yamazaki, S; Kawaguchi, K; Kimura, S; Shimizu, H

1989-10-05

Human interferon-beta 1 is extremely stable is a low ionic strength solution of pH 2 such as 10 mM HCl at 37 degrees C. However, the presence of 0.15 M NaCl led to a remarkable loss of antiviral activity. The molecular-sieve high-performance liquid chromatography revealed that, whereas completely active human interferon-beta 1 eluted as a 25 kDa species (monomeric form), the inactivated preparation eluted primarily as a 90 kDa species (oligomeric form). The specific activity (units per mg protein) of the oligomeric form was approx. 10% of that of the monomeric form. This observation shows that oligomeric human interferon-beta 1 is apparently in an inactive form. When the oligomeric eluate was resolved by polyacrylamide gel containing sodium dodecyl sulphate (SDS), it appeared to be monomeric under non-reducing conditions. Monomerization of the oligomeric human interferon-beta 1 by treatment with 1% SDS, fully regenerated its antiviral activity. These results suggest that the inactivation of the human interferon-beta 1 preparation was caused by its oligomerization via hydrophobic interactions without the formation of intermolecular disulphide bonds. These oligomers can be dissociated by SDS to restore biological activity.

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.

Bursty communication patterns facilitate spreading in a threshold-based epidemic dynamics.

PubMed

Takaguchi, Taro; Masuda, Naoki; Holme, Petter

2013-01-01

Records of social interactions provide us with new sources of data for understanding how interaction patterns affect collective dynamics. Such human activity patterns are often bursty, i.e., they consist of short periods of intense activity followed by long periods of silence. This burstiness has been shown to affect spreading phenomena; it accelerates epidemic spreading in some cases and slows it down in other cases. We investigate a model of history-dependent contagion. In our model, repeated interactions between susceptible and infected individuals in a short period of time is needed for a susceptible individual to contract infection. We carry out numerical simulations on real temporal network data to find that bursty activity patterns facilitate epidemic spreading in our model.

Active muscle response using feedback control of a finite element human arm model.

PubMed

Östh, Jonas; Brolin, Karin; Happee, Riender

2012-01-01

Mathematical human body models (HBMs) are important research tools that are used to study the human response in car crash situations. Development of automotive safety systems requires the implementation of active muscle response in HBM, as novel safety systems also interact with vehicle occupants in the pre-crash phase. In this study, active muscle response was implemented using feedback control of a nonlinear muscle model in the right upper extremity of a finite element (FE) HBM. Hill-type line muscle elements were added, and the active and passive properties were assessed. Volunteer tests with low impact loading resulting in elbow flexion motions were performed. Simulations of posture maintenance in a gravity field and the volunteer tests were successfully conducted. It was concluded that feedback control of a nonlinear musculoskeletal model can be used to obtain posture maintenance and human-like reflexive responses in an FE HBM.

Mammalian EAK-7 activates alternative mTOR signaling to regulate cell proliferation and migration.

PubMed

Nguyen, Joe Truong; Ray, Connor; Fox, Alexandra Lucienne; Mendonça, Daniela Baccelli; Kim, Jin Koo; Krebsbach, Paul H

2018-05-01

Nematode EAK-7 (enhancer-of- akt -1-7) regulates dauer formation and controls life span; however, the function of the human ortholog mammalian EAK-7 (mEAK-7) is unknown. We report that mEAK-7 activates an alternative mechanistic/mammalian target of rapamycin (mTOR) signaling pathway in human cells, in which mEAK-7 interacts with mTOR at the lysosome to facilitate S6K2 activation and 4E-BP1 repression. Despite interacting with mTOR and mammalian lethal with SEC13 protein 8 (mLST8), mEAK-7 does not interact with other mTOR complex 1 (mTORC1) or mTOR complex 2 (mTORC2) components; however, it is essential for mTOR signaling at the lysosome. This phenomenon is distinguished by S6 and 4E-BP1 activity in response to nutrient stimulation. Conventional S6K1 phosphorylation is uncoupled from S6 phosphorylation in response to mEAK-7 knockdown. mEAK-7 recruits mTOR to the lysosome, a crucial compartment for mTOR activation. Loss of mEAK-7 results in a marked decrease in lysosomal localization of mTOR, whereas overexpression of mEAK-7 results in enhanced lysosomal localization of mTOR. Deletion of the carboxyl terminus of mEAK-7 significantly decreases mTOR interaction. mEAK-7 knockdown decreases cell proliferation and migration, whereas overexpression of mEAK-7 enhances these cellular effects. Constitutively activated S6K rescues mTOR signaling in mEAK-7-knocked down cells. Thus, mEAK-7 activates an alternative mTOR signaling pathway through S6K2 and 4E-BP1 to regulate cell proliferation and migration.

The Differential Interactions of Peroxisome Proliferator-Activated Receptor [gamma] Ligands with Tyr473 Is a Physical Basis for Their Unique Biological Activities

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

Einstein, Monica; Akiyama, Taro E.; Castriota, Gino A.

2008-08-01

Despite their proven antidiabetic efficacy, widespread use of peroxisome proliferator-activated receptor (PPAR){gamma} agonists has been limited by adverse cardiovascular effects. To overcome this shortcoming, selective PPAR{gamma} modulators (SPPAR{gamma}Ms) have been identified that have antidiabetic efficacy comparable with full agonists with improved tolerability in preclinical species. The results of structural studies support the proposition that SPPAR{gamma}Ms interact with PPAR{gamma} differently from full agonists, thereby providing a physical basis for their novel activities. Herein, we describe a novel PPAR{gamma} ligand, SPPAR{gamma}M2. This compound was a partial agonist in a cell-based transcriptional activity assay, with diminished adipogenic activity and an attenuated gene signaturemore » in cultured human adipocytes. X-ray cocrystallography studies demonstrated that, unlike rosiglitazone, SPPAR{gamma}M2 did not interact with the Tyr473 residue located within helix 12 of the ligand binding domain (LBD). Instead, SPPAR{gamma}M2 was found to bind to and activate human PPAR{gamma} in which the Tyr473 residue had been mutated to alanine (hPPAR{gamma}Y473A), with potencies similar to those observed with the wild-type receptor (hPPAR{gamma}WT). In additional studies, we found that the intrinsic binding and functional potencies of structurally distinct SPPAR{gamma}Ms were not diminished by the Y473A mutation, whereas those of various thiazolidinedione (TZD) and non-TZD PPAR{gamma} full agonists were reduced in a correlative manner. These results directly demonstrate the important role of Tyr473 in mediating the interaction of full agonists but not SPPAR{gamma}Ms with the PPAR{gamma} LBD, thereby providing a precise molecular determinant for their differing pharmacologies.« less

Human L-ficolin, a recognition molecule of the lectin activation pathway of complement, activates complement by binding to pneumolysin, the major toxin of Streptococcus pneumoniae.

PubMed

Ali, Youssif M; Kenawy, Hany I; Muhammad, Adnan; Sim, Robert B; Andrew, Peter W; Schwaeble, Wilhelm J

2013-01-01

The complement system is an essential component of the immune response, providing a critical line of defense against different pathogens including S. pneumoniae. Complement is activated via three distinct pathways: the classical (CP), the alternative (AP) and the lectin pathway (LP). The role of Pneumolysin (PLY), a bacterial toxin released by S. pneumoniae, in triggering complement activation has been studied in vitro. Our results demonstrate that in both human and mouse sera complement was activated via the CP, initiated by direct binding of even non-specific IgM and IgG3 to PLY. Absence of CP activity in C1q(-/-) mouse serum completely abolished any C3 deposition. However, C1q depleted human serum strongly opsonized PLY through abundant deposition of C3 activation products, indicating that the LP may have a vital role in activating the human complement system on PLY. We identified that human L-ficolin is the critical LP recognition molecule that drives LP activation on PLY, while all of the murine LP recognition components fail to bind and activate complement on PLY. This work elucidates the detailed interactions between PLY and complement and shows for the first time a specific role of the LP in PLY-mediated complement activation in human serum.

Human L-ficolin, a Recognition Molecule of the Lectin Activation Pathway of Complement, Activates Complement by Binding to Pneumolysin, the Major Toxin of Streptococcus pneumoniae

PubMed Central

Ali, Youssif M.; Kenawy, Hany I.; Muhammad, Adnan; Sim, Robert B.

2013-01-01

The complement system is an essential component of the immune response, providing a critical line of defense against different pathogens including S. pneumoniae. Complement is activated via three distinct pathways: the classical (CP), the alternative (AP) and the lectin pathway (LP). The role of Pneumolysin (PLY), a bacterial toxin released by S. pneumoniae, in triggering complement activation has been studied in vitro. Our results demonstrate that in both human and mouse sera complement was activated via the CP, initiated by direct binding of even non-specific IgM and IgG3 to PLY. Absence of CP activity in C1q−/− mouse serum completely abolished any C3 deposition. However, C1q depleted human serum strongly opsonized PLY through abundant deposition of C3 activation products, indicating that the LP may have a vital role in activating the human complement system on PLY. We identified that human L-ficolin is the critical LP recognition molecule that drives LP activation on PLY, while all of the murine LP recognition components fail to bind and activate complement on PLY. This work elucidates the detailed interactions between PLY and complement and shows for the first time a specific role of the LP in PLY-mediated complement activation in human serum. PMID:24349316

Interactions between glutamate, dopamine, and the neuronal signature of response inhibition in the human striatum.

PubMed

Lorenz, Robert C; Gleich, Tobias; Buchert, Ralph; Schlagenhauf, Florian; Kühn, Simone; Gallinat, Jürgen

2015-10-01

Response inhibition is a basic mechanism in cognitive control and dysfunctional in major psychiatric disorders. The neuronal mechanisms are in part driven by dopamine in the striatum. Animal data suggest a regulatory role of glutamate on the level of the striatum. We used a trimodal imaging procedure of the human striatum including F18-DOPA positron emission tomography, proton magnetic resonance spectroscopy, and functional magnetic resonance imaging of a stop signal task. We investigated dopamine synthesis capacity and glutamate concentration in vivo and their relation to functional properties of response inhibition. A mediation analysis revealed a significant positive association between dopamine synthesis capacity and inhibition-related neural activity in the caudate nucleus. This relationship was significantly mediated by striatal glutamate concentration. Furthermore, stop signal reaction time was inversely related to striatal activity during inhibition. The data show, for the first time in humans, an interaction between dopamine, glutamate, and the neural signature of response inhibition in the striatum. This finding stresses the importance of the dopamine-glutamate interaction for behavior and may facilitate the understanding of psychiatric disorders characterized by impaired response inhibition. © 2015 Wiley Periodicals, Inc.

Diverse Phytochemicals and Bioactivities in the Ancient Fruit and Modern Functional Food Pomegranate (Punica granatum).

PubMed

Wu, Sheng; Tian, Li

2017-09-25

Having served as a symbolic fruit since ancient times, pomegranate ( Punica granatum ) has also gained considerable recognition as a functional food in the modern era. A large body of literature has linked pomegranate polyphenols, particularly anthocyanins (ATs) and hydrolyzable tannins (HTs), to the health-promoting activities of pomegranate juice and fruit extracts. However, it remains unclear as to how, and to what extent, the numerous phytochemicals in pomegranate may interact and exert cooperative activities in humans. In this review, we examine the structural and analytical information of the diverse phytochemicals that have been identified in different pomegranate tissues, to establish a knowledge base for characterization of metabolite profiles, discovery of novel phytochemicals, and investigation of phytochemical interactions in pomegranate. We also assess recent findings on the function and molecular mechanism of ATs as well as urolithins, the intestinal microbial derivatives of pomegranate HTs, on human nutrition and health. A better understanding of the structural diversity of pomegranate phytochemicals as well as their bioconversions and bioactivities in humans will facilitate the interrogation of their synergistic/antagonistic interactions and accelerate their applications in dietary-based cancer chemoprevention and treatment in the future.

Toward a Mechanistic Understanding of Environmentally Forced Zoonotic Disease Emergence: Sin Nombre Hantavirus

PubMed Central

Carver, Scott; Mills, James N.; Parmenter, Cheryl A.; Parmenter, Robert R.; Richardson, Kyle S.; Harris, Rachel L.; Douglass, Richard J.; Kuenzi, Amy J.; Luis, Angela D.

2015-01-01

Understanding the environmental drivers of zoonotic reservoir and human interactions is crucial to understanding disease risk, but these drivers are poorly predicted. We propose a mechanistic understanding of human–reservoir interactions, using hantavirus pulmonary syndrome as a case study. Crucial processes underpinning the disease's incidence remain poorly studied, including the connectivity among natural and peridomestic deer mouse host activity, virus transmission, and human exposure. We found that disease cases were greatest in arid states and declined exponentially with increasing precipitation. Within arid environments, relatively rare climatic conditions (e.g., El Niño) are associated with increased rainfall and reservoir abundance, producing more frequent virus transmission and host dispersal. We suggest that deer mice increase their occupancy of peridomestic structures during spring–summer, amplifying intraspecific transmission and human infection risk. Disease incidence in arid states may increase with predicted climatic changes. Mechanistic approaches incorporating reservoir behavior, reservoir–human interactions, and pathogen spillover could enhance our understanding of global hantavirus ecology, with applications to other directly transmitted zoonoses. PMID:26955081

The human mirror neuron system: A link between action observation and social skills

PubMed Central

Pineda, Jaime A.; Ramachandran, Vilayanur S.

2007-01-01

The discovery of the mirror neuron system (MNS) has led researchers to speculate that this system evolved from an embodied visual recognition apparatus in monkey to a system critical for social skills in humans. It is accepted that the MNS is specialized for processing animate stimuli, although the degree to which social interaction modulates the firing of mirror neurons has not been investigated. In the current study, EEG mu wave suppression was used as an index of MNS activity. Data were collected while subjects viewed four videos: (1) Visual White Noise: baseline, (2) Non-interacting: three individuals tossed a ball up in the air to themselves, (3) Social Action, Spectator: three individuals tossed a ball to each other and (4) Social Action, Interactive: similar to video 3 except occasionally the ball would be thrown off the screen toward the viewer. The mu wave was modulated by the degree of social interaction, with the Non-interacting condition showing the least suppression, followed by the Social Action, Spectator condition and the Social Action, Interactive condition showing the most suppression. These data suggest that the human MNS is specialized not only for processing animate stimuli, but specifically stimuli with social relevance. PMID:18985120

Insight into the interaction mechanism of human SGLT2 with its inhibitors: 3D-QSAR studies, homology modeling, and molecular docking and molecular dynamics simulations.

PubMed

Dong, Lili; Feng, Ruirui; Bi, Jiawei; Shen, Shengqiang; Lu, Huizhe; Zhang, Jianjun

2018-03-06

Human sodium-dependent glucose co-transporter 2 (hSGLT2) is a crucial therapeutic target in the treatment of type 2 diabetes. In this study, both comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were applied to generate three-dimensional quantitative structure-activity relationship (3D-QSAR) models. In the most accurate CoMFA-based and CoMSIA-based QSAR models, the cross-validated coefficients (r 2 cv ) were 0.646 and 0.577, respectively, while the non-cross-validated coefficients (r 2 ) were 0.997 and 0.991, respectively, indicating that both models were reliable. In addition, we constructed a homology model of hSGLT2 in the absence of a crystal structure. Molecular docking was performed to explore the bonding mode of inhibitors to the active site of hSGLT2. Molecular dynamics (MD) simulations and binding free energy calculations using MM-PBSA and MM-GBSA were carried out to further elucidate the interaction mechanism. With regards to binding affinity, we found that hydrogen-bond interactions of Asn51 and Glu75, located in the active site of hSGLT2, with compound 40 were critical. Hydrophobic and electrostatic interactions were shown to enhance activity, in agreement with the results obtained from docking and 3D-QSAR analysis. Our study results shed light on the interaction mode between inhibitors and hSGLT2 and may aid in the development of C-aryl glucoside SGLT2 inhibitors.

Purification and characterization of an inhibitor (soluble tumor necrosis factor receptor) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients

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

Gatanaga, Tetsuya; Whang, Chenduen; Cappuccini, F.

1990-11-01

Serum ultrafiltrates (SUF) from human patients with different types of cancer contain a blocking factor (BF) that inhibits the cytolytic activity of human tumor necrosis factor {alpha} (TNF-{alpha}) in vitro. BF is a protein with a molecular mass of 28kDa on reducing sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE). The active material was purified to homogeneity by a combination of affinity chromatography, PAGE, and high-pressure liquid chromatography. Amino acid sequence analysis revealed that BF is derived from the membrane TNF receptor. Purified BF blocks the lytic activity of recombinant human and mouse TNF-{alpha} and recombinant human lymphotoxin activity of TNF-{alpha} andmore » recombinant human lymphotoxin on murine L929 cells in vitro. However, BF inhibits the lytic activity of TNF-{alpha} more effectively than it does that of lymphotoxin. The BF also inhibits the necrotizing activity of recombinant human TNF-{alpha} when coinjected into established cutaneous Meth A tumors in BALB/c mice. The BF may have an important role in (i) the regulation and control of TNF-{alpha} and lymphotoxin activity in cancer patients, (ii) interaction between the tumor and the host antitumor mechanisms, and (iii) use of systemically administered TNF-{alpha} in clinical trials with human cancer patients.« less

Generating a Reduced Gravity Environment on Earth

NASA Technical Reports Server (NTRS)

Dungan, Larry K.; Cunningham, Tom; Poncia, Dina

2010-01-01

Since the 1950s several reduced gravity simulators have been designed and utilized in preparing humans for spaceflight and in reduced gravity system development. The Active Response Gravity Offload System (ARGOS) is the newest and most realistic gravity offload simulator. ARGOS provides three degrees of motion within the test area and is scalable for full building deployment. The inertia of the overhead system is eliminated by an active motor and control system. This presentation will discuss what ARGOS is, how it functions, and the unique challenges of interfacing to the human. Test data and video for human and robotic systems will be presented. A major variable in the human machine interaction is the interface of ARGOS to the human. These challenges along with design solutions will be discussed.

Cholinergic modulation of cognition: Insights from human pharmacological functional neuroimaging

PubMed Central

Bentley, Paul; Driver, Jon; Dolan, Raymond J.

2011-01-01

Evidence from lesion and cortical-slice studies implicate the neocortical cholinergic system in the modulation of sensory, attentional and memory processing. In this review we consider findings from sixty-three healthy human cholinergic functional neuroimaging studies that probe interactions of cholinergic drugs with brain activation profiles, and relate these to contemporary neurobiological models. Consistent patterns that emerge are: (1) the direction of cholinergic modulation of sensory cortex activations depends upon top-down influences; (2) cholinergic hyperstimulation reduces top-down selective modulation of sensory cortices; (3) cholinergic hyperstimulation interacts with task-specific frontoparietal activations according to one of several patterns, including: suppression of parietal-mediated reorienting; decreasing ‘effort’-associated activations in prefrontal regions; and deactivation of a ‘resting-state network’ in medial cortex, with reciprocal recruitment of dorsolateral frontoparietal regions during performance-challenging conditions; (4) encoding-related activations in both neocortical and hippocampal regions are disrupted by cholinergic blockade, or enhanced with cholinergic stimulation, while the opposite profile is observed during retrieval; (5) many examples exist of an ‘inverted-U shaped’ pattern of cholinergic influences by which the direction of functional neural activation (and performance) depends upon both task (e.g. relative difficulty) and subject (e.g. age) factors. Overall, human cholinergic functional neuroimaging studies both corroborate and extend physiological accounts of cholinergic function arising from other experimental contexts, while providing mechanistic insights into cholinergic-acting drugs and their potential clinical applications. PMID:21708219

Structural Dynamics Investigation of Human Family 1 & 2 Cystatin-Cathepsin L1 Interaction: A Comparison of Binding Modes.

PubMed

Nandy, Suman Kumar; Seal, Alpana

2016-01-01

Cystatin superfamily is a large group of evolutionarily related proteins involved in numerous physiological activities through their inhibitory activity towards cysteine proteases. Despite sharing the same cystatin fold, and inhibiting cysteine proteases through the same tripartite edge involving highly conserved N-terminal region, L1 and L2 loop; cystatins differ widely in their inhibitory affinity towards C1 family of cysteine proteases and molecular details of these interactions are still elusive. In this study, inhibitory interactions of human family 1 & 2 cystatins with cathepsin L1 are predicted and their stability and viability are verified through protein docking & comparative molecular dynamics. An overall stabilization effect is observed in all cystatins on complex formation. Complexes are mostly dominated by van der Waals interaction but the relative participation of the conserved regions varied extensively. While van der Waals contacts prevail in L1 and L2 loop, N-terminal segment chiefly acts as electrostatic interaction site. In fact the comparative dynamics study points towards the instrumental role of L1 loop in directing the total interaction profile of the complex either towards electrostatic or van der Waals contacts. The key amino acid residues surfaced via interaction energy, hydrogen bonding and solvent accessible surface area analysis for each cystatin-cathepsin L1 complex influence the mode of binding and thus control the diverse inhibitory affinity of cystatins towards cysteine proteases.

Identification of Odorant-Receptor Interactions by Global Mapping of the Human Odorome

PubMed Central

Audouze, Karine; Tromelin, Anne; Le Bon, Anne Marie; Belloir, Christine; Petersen, Rasmus Koefoed; Kristiansen, Karsten; Brunak, Søren; Taboureau, Olivier

2014-01-01

The human olfactory system recognizes a broad spectrum of odorants using approximately 400 different olfactory receptors (hORs). Although significant improvements of heterologous expression systems used to study interactions between ORs and odorant molecules have been made, screening the olfactory repertoire of hORs remains a tremendous challenge. We therefore developed a chemical systems level approach based on protein-protein association network to investigate novel hOR-odorant relationships. Using this new approach, we proposed and validated new bioactivities for odorant molecules and OR2W1, OR51E1 and OR5P3. As it remains largely unknown how human perception of odorants influence or prevent diseases, we also developed an odorant-protein matrix to explore global relationships between chemicals, biological targets and disease susceptibilities. We successfully experimentally demonstrated interactions between odorants and the cannabinoid receptor 1 (CB1) and the peroxisome proliferator-activated receptor gamma (PPARγ). Overall, these results illustrate the potential of integrative systems chemical biology to explore the impact of odorant molecules on human health, i.e. human odorome. PMID:24695519

Anthropology and Geosciences: Training and Collaboration Advancing Interdisciplinary Research of Human-environment Interaction

NASA Astrophysics Data System (ADS)

Brondizio, E.; Moran, E.

2005-05-01

Over the past thirteen years the Anthropological Center for Training and Research on Global Environmental Change (ACT) at Indiana University has pioneered the use of anthropological and environmental research approaches to address issues of land use change, and population-environment interaction, particularly in the Amazon. Our research and training objectives focus on how particular local populations manage resources and how those activities may be studied by integrating time-tested ethnographic methods, survey instruments, ecological field studies, and the spatial and temporal perspectives of remote sensing and Geographical Information Systems. The globalization of the environment crisis bears the risk of the research and training at universities being purely global or large scale in nature. This would fail to take into account the highly variable local causes of human activities or to discover sustainable solutions to the use, conservation, and restoration of human ecosystems. Our approach combines institutional and international collaboration, formal and hands-on laboratory and field activities developed within an interdisciplinary environment, but based on the strength of disciplinary programs. Over the past years, we have particularly emphasized collaboration between American and Brazilian scholars and students and intense work with local farmers and communities both during data collection and field research, as well as in returning data and results using different formats. In this paper, we address our experience, the challenges and advantages of theoretical and methodological development for students approaching interdisciplinary problems, innovations in linking levels of analysis, and new opportunities for international and collaborative training and research on human-environment interaction.

Nanoparticle-allergen interactions mediate human allergic responses: protein corona characterization and cellular responses.

PubMed

Radauer-Preiml, Isabella; Andosch, Ancuela; Hawranek, Thomas; Luetz-Meindl, Ursula; Wiederstein, Markus; Horejs-Hoeck, Jutta; Himly, Martin; Boyles, Matthew; Duschl, Albert

2016-01-16

Engineered nanomaterials (ENMs) interact with different biomolecules as soon as they are in contact, resulting in the formation of a biomolecule 'corona'. Hence, the 'corona' defines the biological identity of the ENMs and could affect the response of the immune system to ENM exposure. With up to 40 % of the world population suffering from type I allergy, a possible modulation of allergen effects by binding to ENMs is highly relevant with respect to work place and consumer safety. Therefore, the aim of this present study was to gain an insight into the interactions of gold nanoparticles with different seasonally and perennially occurring outdoor and indoor allergens. Gold nanoparticles (AuNPs) were conjugated with the major allergens of birch pollen (Bet v 1), timothy grass pollen (Phl p 5) and house dust mite (Der p 1). The AuNP-allergen conjugates were characterized by means of TEM negative staining, dynamic light scattering (DLS), z-potential measurements and hyperspectral imaging. Furthermore, 3D models were constructed, based on the characterization data, to visualize the interaction between the allergens and the AuNPs surface. Differences in the activation of human basophil cells derived from birch/grass pollen- and house dust mite-allergic patients in response to free allergen and AuNP-allergen conjugates were determined using the basophil activation assay (BAT). Potential allergen corona replacement during BAT was controlled for using Western blotting. The protease activity of AuNP-Der p 1 conjugates compared to free Der p 1 was assessed, by an enzymatic activity assay and a cellular assay pertaining to lung type II alveolar epithelial cell tight junction integrity. The formation of a stable corona was found for all three allergens used. Our data suggest, that depending on the allergen, different effects are observed after binding to ENMs, including enhanced allergic responses against Der p 1 and also, for some patients, against Bet v 1. Moreover elevated protease activity of AuNP-Der p 1 conjugates compared to free Der p 1 was found. In summary, this study presents that conjugation of allergens to ENMs can modulate the human allergic response, and that protease activity can be increased. Graphical Abstract Cross-linking of IgE receptors and degranulation of human basophils due to epitope alignment of nanoparticle-coated allergens.

Population Growth. Understanding Global Change: Earth Science and Human Impacts. Global Change Instruction Program.

ERIC Educational Resources Information Center

Jacobsen, Judith E.

The Global Change Instruction Program was designed by college professors to fill a need for interdisciplinary materials on the emerging science of global change. This instructional module concentrates on interactions between population growth and human activities that produce global change. The materials are designed for undergraduate students…

Information Work Analysis: An Approach to Research on Information Interactions and Information Behaviour in Context

ERIC Educational Resources Information Center

Huvila, Isto

2008-01-01

Introduction: A work roles and role theory-based approach to conceptualise human information activity, denoted information work analysis is discussed. The present article explicates the approach and its special characteristics and benefits in comparison to earlier methods of analysing human information work. Method: The approach is discussed in…

An Activity and Theory for Applying Human Systems Approach to Industrial Arts.

ERIC Educational Resources Information Center

Mietus, Walter S.

A human systems approach that emphasizes knowing the parts of a phenomenon, their order, and particularly their interactions needs to be adopted by industrial arts. A student-based theoretical framework that incorporates systems and subsystems in industrial arts has been presented by Donald Maley. The theoretical base includes 10 organismic…

Automation effects in a stereotypical multiloop manual control system. [for aircraft

NASA Technical Reports Server (NTRS)

Hess, R. A.; Mcnally, B. D.

1984-01-01

The increasing reliance of state-of-the art, high performance aircraft on high authority stability and command augmentation systems, in order to obtain satisfactory performance and handling qualities, has made critical the achievement of a better understanding of human capabilities, limitations, and preferences during interactions with complex dynamic systems that involve task allocation between man and machine. An analytical and experimental study has been undertaken to investigate human interaction with a simple, multiloop dynamic system in which human activity was systematically varied by changing the levels of automation. Task definition has led to a control loop structure which parallels that for any multiloop manual control system, and may therefore be considered a stereotype.

Phosphorylated STAT5 directly facilitates parvovirus B19 DNA replication in human erythroid progenitors through interaction with the MCM complex.

PubMed

Ganaie, Safder S; Zou, Wei; Xu, Peng; Deng, Xuefeng; Kleiboeker, Steve; Qiu, Jianming

2017-05-01

Productive infection of human parvovirus B19 (B19V) exhibits high tropism for burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) progenitor cells in human bone marrow and fetal liver. This exclusive restriction of the virus replication to human erythroid progenitor cells is partly due to the intracellular factors that are essential for viral DNA replication, including erythropoietin signaling. Efficient B19V replication also requires hypoxic conditions, which upregulate the signal transducer and activator of transcription 5 (STAT5) pathway, and phosphorylated STAT5 is essential for virus replication. In this study, our results revealed direct involvement of STAT5 in B19V DNA replication. Consensus STAT5-binding elements were identified adjacent to the NS1-binding element within the minimal origins of viral DNA replication in the B19V genome. Phosphorylated STAT5 specifically interacted with viral DNA replication origins both in vivo and in vitro, and was actively recruited within the viral DNA replication centers. Notably, STAT5 interacted with minichromosome maintenance (MCM) complex, suggesting that STAT5 directly facilitates viral DNA replication by recruiting the helicase complex of the cellular DNA replication machinery to viral DNA replication centers. The FDA-approved drug pimozide dephosphorylates STAT5, and it inhibited B19V replication in ex vivo expanded human erythroid progenitors. Our results demonstrated that pimozide could be a promising antiviral drug for treatment of B19V-related diseases.

Psychosocial and Psychophysiological Effects of Human-Animal Interactions: The Possible Role of Oxytocin

PubMed Central

Beetz, Andrea; Uvnäs-Moberg, Kerstin; Julius, Henri; Kotrschal, Kurt

2012-01-01

During the last decade it has become more widely accepted that pet ownership and animal assistance in therapy and education may have a multitude of positive effects on humans. Here, we review the evidence from 69 original studies on human-animal interactions (HAI) which met our inclusion criteria with regard to sample size, peer-review, and standard scientific research design. Among the well-documented effects of HAI in humans of different ages, with and without special medical, or mental health conditions are benefits for: social attention, social behavior, interpersonal interactions, and mood; stress-related parameters such as cortisol, heart rate, and blood pressure; self-reported fear and anxiety; and mental and physical health, especially cardiovascular diseases. Limited evidence exists for positive effects of HAI on: reduction of stress-related parameters such as epinephrine and norepinephrine; improvement of immune system functioning and pain management; increased trustworthiness of and trust toward other persons; reduced aggression; enhanced empathy and improved learning. We propose that the activation of the oxytocin system plays a key role in the majority of these reported psychological and psychophysiological effects of HAI. Oxytocin and HAI effects largely overlap, as documented by research in both, humans and animals, and first studies found that HAI affects the oxytocin system. As a common underlying mechanism, the activation of the oxytocin system does not only provide an explanation, but also allows an integrative view of the different effects of HAI. PMID:22866043

Humpback Dolphin (Genus Sousa) Behavioural Responses to Human Activities.

PubMed

Piwetz, Sarah; Lundquist, David; Würsig, Bernd

2015-01-01

Humpback dolphins (genus Sousa) use shallow, near-shore waters throughout their range. This coastal distribution makes them vulnerable to recreational and commercial disturbances, especially near heavily populated and industrialized areas. Most research focusing on Sousa and human activities has emphasized direct impacts and threats, involving injury and death, with relatively little focus on indirect effects on dolphins, such as changes in behaviour that may lead to deleterious effects. Understanding behaviour is important in resolving human-wildlife conflict and is an important component of conservation. This chapter gives an overview of animal behavioural responses to human activity with examples from diverse taxa; reviews the scientific literature on behavioural responses of humpback dolphins to human activity throughout their range, including marine vessel traffic, dolphin tourism, cetacean-fishery interactions, noise pollution, and habitat alteration; and highlights information and data gaps for future humpback dolphin research to better inform behaviour-based management decisions that contribute to conservation efforts. © 2015 Elsevier Ltd All rights reserved.

DHM simulation in virtual environments: a case-study on control room design.

PubMed

Zamberlan, M; Santos, V; Streit, P; Oliveira, J; Cury, R; Negri, T; Pastura, F; Guimarães, C; Cid, G

2012-01-01

This paper will present the workflow developed for the application of serious games in the design of complex cooperative work settings. The project was based on ergonomic studies and development of a control room among participative design process. Our main concerns were the 3D human virtual representation acquired from 3D scanning, human interaction, workspace layout and equipment designed considering ergonomics standards. Using Unity3D platform to design the virtual environment, the virtual human model can be controlled by users on dynamic scenario in order to evaluate the new work settings and simulate work activities. The results obtained showed that this virtual technology can drastically change the design process by improving the level of interaction between final users and, managers and human factors team.

THERAPIST: Towards an Autonomous Socially Interactive Robot for Motor and Neurorehabilitation Therapies for Children

PubMed Central

Calderita, Luis Vicente; Manso, Luis J; Bustos, Pablo; Fernández, Fernando; Bandera, Antonio

2014-01-01

Background Neurorehabilitation therapies exploiting the use-dependent plasticity of our neuromuscular system are devised to help patients who suffer from injuries or diseases of this system. These therapies take advantage of the fact that the motor activity alters the properties of our neurons and muscles, including the pattern of their connectivity, and thus their functionality. Hence, a sensor-motor treatment where patients makes certain movements will help them (re)learn how to move the affected body parts. But these traditional rehabilitation processes are usually repetitive and lengthy, reducing motivation and adherence to the treatment, and thus limiting the benefits for the patients. Objective Our goal was to create innovative neurorehabilitation therapies based on THERAPIST, a socially assistive robot. THERAPIST is an autonomous robot that is able to find and execute plans and adapt them to new situations in real-time. The software architecture of THERAPIST monitors and determines the course of action, learns from previous experiences, and interacts with people using verbal and non-verbal channels. THERAPIST can increase the adherence of the patient to the sessions using serious games. Data are recorded and can be used to tailor patient sessions. Methods We hypothesized that pediatric patients would engage better in a therapeutic non-physical interaction with a robot, facilitating the design of new therapies to improve patient motivation. We propose RoboCog, a novel cognitive architecture. This architecture will enhance the effectiveness and time-of-response of complex multi-degree-of-freedom robots designed to collaborate with humans, combining two core elements: a deep and hybrid representation of the current state, own, and observed; and a set of task-dependent planners, working at different levels of abstraction but connected to this central representation through a common interface. Using RoboCog, THERAPIST engages the human partner in an active interactive process. But RoboCog also endows the robot with abilities for high-level planning, monitoring, and learning. Thus, THERAPIST engages the patient through different games or activities, and adapts the session to each individual. Results RoboCog successfully integrates a deliberative planner with a set of modules working at situational or sensorimotor levels. This architecture also allows THERAPIST to deliver responses at a human rate. The synchronization of the multiple interaction modalities results from a unique scene representation or model. THERAPIST is now a socially interactive robot that, instead of reproducing the phrases or gestures that the developers decide, maintains a dialogue and autonomously generate gestures or expressions. THERAPIST is able to play simple games with human partners, which requires humans to perform certain movements, and also to capture the human motion, for later analysis by clinic specialists. Conclusions The initial hypothesis was validated by our experimental studies showing that interaction with the robot results in highly attentive and collaborative attitudes in pediatric patients. We also verified that RoboCog allows the robot to interact with patients at human rates. However, there remain many issues to overcome. The development of novel hands-off rehabilitation therapies will require the intersection of multiple challenging directions of research that we are currently exploring. PMID:28582242

Flower Garden Banks (northwest Gulf of Mexico): Environmental characteristics and human interaction. Final report

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

Deslarzes, K.J.P.

1998-10-01

This report is a multidisciplinary update of various topics concerning the Banks -- oceanography, meteorology, commercial fishing, recreation, military activities, hydrocarbon development, and potential environmental impacts. The area surrounding the Flower Garden Banks is increasingly active with oil and gas development.

Role of human pregnane X receptor in tamoxifen- and 4-hydroxytamoxifen-mediated CYP3A4 induction in primary human hepatocytes and LS174T cells.

PubMed

Sane, Rucha S; Buckley, Donna J; Buckley, Arthur R; Nallani, Srikanth C; Desai, Pankaj B

2008-05-01

Previously we observed that the antiestrogens tamoxifen and 4-hydroxytamoxifen (4OHT) induce CYP3A4 in primary human hepatocytes and activate human pregnane X receptor (PXR) in cell-based reporter assays. Given the complex cross-talk between nuclear receptors, tissue-specific expression of CYP3A4, and the potential for tamoxifen and 4OHT to interact with a myriad of receptors, this study was undertaken to gain mechanistic insights into the inductive effects of tamoxifen and 4OHT. First, we observed that transfection of the primary cultures of human hepatocytes with PXR-specific small interfering RNA reduced the PXR mRNA expression and the extent of CYP3A4 induction by tamoxifen and 4OHT by 50%. Second, in LS174T colon carcinoma cells, which were observed to have significantly lower PXR expression relative to human hepatocytes, neither tamoxifen nor 4OHT induced CYP3A4. Third, N-desmethyltamoxifen, which did not induce CYP3A4 in human hepatocytes, also did not activate PXR in LS174T cells. We then used cell-based reporter assay to evaluate the effects of other receptors such as glucocorticoid receptor GR alpha and estrogen receptor ER alpha on the transcriptional activation of PXR. The cotransfection of GR alpha in LS174T cells augmented PXR activation by tamoxifen and 4OHT. On the other hand, the presence of ER alpha inhibited PXR-mediated basal activation of CYP3A4 promoter, possibly via competing for common cofactors such as steroid receptor coactivator 1 and glucocorticoid receptor interacting protein 1. Collectively, our findings suggest that the CYP3A4 induction by tamoxifen and 4OHT is primarily mediated by PXR but the overall stoichiometry of other nuclear receptors and transcription cofactors also contributes to the extent of the inductive effect.

Estrogen Modification of Human Glutamate Dehydrogenases Is Linked to Enzyme Activation State*

PubMed Central

Borompokas, Nikolas; Papachatzaki, Maria-Martha; Kanavouras, Konstantinos; Mastorodemos, Vasileios; Zaganas, Ioannis; Spanaki, Cleanthe; Plaitakis, Andreas

2010-01-01

Mammalian glutamate dehydrogenase (GDH) is a housekeeping enzyme central to the metabolism of glutamate. Its activity is potently inhibited by GTP (IC50 = 0.1–0.3 μm) and thought to be controlled by the need of the cell in ATP. Estrogens are also known to inhibit mammalian GDH, but at relatively high concentrations. Because, in addition to this housekeeping human (h) GDH1, humans have acquired via a duplication event an hGDH2 isoform expressed in human cortical astrocytes, we tested here the interaction of estrogens with the two human isoenzymes. The results showed that, under base-line conditions, diethylstilbestrol potently inhibited hGDH2 (IC50 = 0.08 ± 0.01 μm) and with ∼18-fold lower affinity hGDH1 (IC50 = 1.67 ± 0.06 μm; p < 0.001). Similarly, 17β-estradiol showed a ∼18-fold higher affinity for hGDH2 (IC50 = 1.53 ± 0.24 μm) than for hGDH1 (IC50 = 26.94 ± 1.07 μm; p < 0.001). Also, estriol and progesterone were more potent inhibitors of hGDH2 than hGDH1. Structure/function analyses revealed that the evolutionary R443S substitution, which confers low basal activity, was largely responsible for sensitivity of hGDH2 to estrogens. Inhibition of both human GDHs by estrogens was inversely related to their state of activation induced by ADP, with the slope of this correlation being steeper for hGDH2 than for hGDH1. Also, the study of hGDH1 and hGDH2 mutants displaying different states of activation revealed that the affinity of estrogen for these enzymes correlated inversely (R = 0.99; p = 0.0001) with basal catalytic activity. Because astrocytes are known to synthesize estrogens, these hormones, by interacting potently with hGDH2 in its closed state, may contribute to regulation of glutamate metabolism in brain. PMID:20628048

On inclusion of water resource management in Earth system models - Part 1: Problem definition and representation of water demand

NASA Astrophysics Data System (ADS)

Nazemi, A.; Wheater, H. S.

2015-01-01

Human activities have caused various changes to the Earth system, and hence the interconnections between human activities and the Earth system should be recognized and reflected in models that simulate Earth system processes. One key anthropogenic activity is water resource management, which determines the dynamics of human-water interactions in time and space and controls human livelihoods and economy, including energy and food production. There are immediate needs to include water resource management in Earth system models. First, the extent of human water requirements is increasing rapidly at the global scale and it is crucial to analyze the possible imbalance between water demands and supply under various scenarios of climate change and across various temporal and spatial scales. Second, recent observations show that human-water interactions, manifested through water resource management, can substantially alter the terrestrial water cycle, affect land-atmospheric feedbacks and may further interact with climate and contribute to sea-level change. Due to the importance of water resource management in determining the future of the global water and climate cycles, the World Climate Research Program's Global Energy and Water Exchanges project (WRCP-GEWEX) has recently identified gaps in describing human-water interactions as one of the grand challenges in Earth system modeling (GEWEX, 2012). Here, we divide water resource management into two interdependent elements, related firstly to water demand and secondly to water supply and allocation. In this paper, we survey the current literature on how various components of water demand have been included in large-scale models, in particular land surface and global hydrological models. Issues of water supply and allocation are addressed in a companion paper. The available algorithms to represent the dominant demands are classified based on the demand type, mode of simulation and underlying modeling assumptions. We discuss the pros and cons of available algorithms, address various sources of uncertainty and highlight limitations in current applications. We conclude that current capability of large-scale models to represent human water demands is rather limited, particularly with respect to future projections and coupled land-atmospheric simulations. To fill these gaps, the available models, algorithms and data for representing various water demands should be systematically tested, intercompared and improved. In particular, human water demands should be considered in conjunction with water supply and allocation, particularly in the face of water scarcity and unknown future climate.

Computer-aided active-site-directed modeling of the Herpes Simplex Virus 1 and human thymidine kinase

NASA Astrophysics Data System (ADS)

Folkers, Gerd; Trumpp-Kallmeyer, Susanne; Gutbrod, Oliver; Krickl, Sabine; Fetzer, Jürgen; Keil, Günther M.

1991-10-01

Thymidine kinase (TK), which is induced by Herpes Simplex Virus 1 (HSV1), plays a key role in the antiviral activity of guanine derivatives such as aciclovir (ACV). In contrast, ACV shows only low affinity to the corresponding host cell enzyme. In order to define the differences in substrate binding of the two enzymes on molecular level, models for the three-dimensional (3-D) structures of the active sites of HSV1-TK and human TK were developed. The reconstruction of the active sites started from primary and secondary structure analysis of various kinases. The results were validated to homologous enzymes with known 3-D structures. The models predict that both enzymes consist of a central core β-sheet structure, connected by loops and α-helices very similar to the overall structure of other nucleotide binding enzymes. The phosphate binding is made up of a highly conserved glycine-rich loop at the N-terminus of the proteins and a conserved region at the C-terminus. The thymidine recognition site was found about 100 amino acids downstream from the phosphate binding loop. The differing substrate specificity of human and HSV1-TK can be explained by amino-acid substitutions in the homologous regions. To achieve a better understanding of the structure of the active site and how the thymidine kinase proteins interact with their substrates, the corresponding complexes of thymidine and dihydroxypropoxyguanine (DHPG) with HSV1 and human TK were built. For the docking of the guanine derivative, the X-ray structure of Elongation Factor Tu (EF-Tu), co-crystallized with guanosine diphosphate, was taken as reference. Fitting of thymidine into the active sites was done with respect to similar interactions found in thymidylate kinase. To complement the analysis of the 3-D structures of the two kinases and the substrate enzyme interactions, site-directed mutagenesis of the thymidine recognition site of HSV1-TK has been undertaken, changing Asp162 in the thymidine recognition site into Asn. First investigations reveal that the enzymatic activity of the mutant protein is destroyed.

The brain in time: insights from neuromagnetic recordings.

PubMed

Hari, Riitta; Parkkonen, Lauri; Nangini, Cathy

2010-03-01

The millisecond time resolution of magnetoencephalography (MEG) is instrumental for investigating the brain basis of sensory processing, motor planning, cognition, and social interaction. We review the basic principles, recent progress, and future potential of MEG in noninvasive tracking of human brain activity. Cortical activation sequences from tens to hundreds of milliseconds can be followed during, e.g., perception, motor action, imitation, and language processing by recording both spontaneous and evoked brain signals. Moreover, tagging of sensory input can be used to reveal neuronal mechanisms of binaural interaction and perception of ambiguous images. The results support the emerging ideas of multiple, hierarchically organized temporal scales in human brain function. Instrumentation and data analysis methods are rapidly progressing, enabling attempts to decode the four-dimensional spatiotemporal signal patterns to reveal correlates of behavior and mental contents.

The Homeostatic Interaction Between Anodal Transcranial Direct Current Stimulation and Motor Learning in Humans is Related to GABAA Activity.

PubMed

Amadi, Ugwechi; Allman, Claire; Johansen-Berg, Heidi; Stagg, Charlotte J

2015-01-01

The relative timing of plasticity-induction protocols is known to be crucial. For example, anodal transcranial direct current stimulation (tDCS), which increases cortical excitability and typically enhances plasticity, can impair performance if it is applied before a motor learning task. Such timing-dependent effects have been ascribed to homeostatic plasticity, but the specific synaptic site of this interaction remains unknown. We wished to investigate the synaptic substrate, and in particular the role of inhibitory signaling, underpinning the behavioral effects of anodal tDCS in homeostatic interactions between anodal tDCS and motor learning. We used transcranial magnetic stimulation (TMS) to investigate cortical excitability and inhibitory signaling following tDCS and motor learning. Each subject participated in four experimental sessions and data were analyzed using repeated measures ANOVAs and post-hoc t-tests as appropriate. As predicted, we found that anodal tDCS prior to the motor task decreased learning rates. This worsening of learning after tDCS was accompanied by a correlated increase in GABAA activity, as measured by TMS-assessed short interval intra-cortical inhibition (SICI). This provides the first direct demonstration in humans that inhibitory synapses are the likely site for the interaction between anodal tDCS and motor learning, and further, that homeostatic plasticity at GABAA synapses has behavioral relevance in humans. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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.

[Effect of new peptide bioregulators livagen and epitalon on enkephalin-degrading enzymes in human serum].

PubMed

Kost, N V; Sokolov, O Iu; Gabaeva, M V; Zolotarev, Iu A; Malinin, V V; Khavinson, V Kh

2003-01-01

The effect of new peptide bioregulators--Livagen (Lys-Glu-Asp-Ala) and Epitalon (Ala-Glu-Asp-Gly)--on endogenous opioid system was studied, particularly, their ability to change the activity of enkephalin-degrading enzymes from serum and interact with opioid receptors of the brain membrane fraction. Enkephalinase activity was assayed in vitro by the rate of 3H-Leu-enkephalin hydrolysis in the presence of the tested peptides. Livagen and Epitalon inhibited enkephalin-degrading enzymes from human serum. Livagen proved to be more efficient also as compared to well-known peptidase inhibitors such as puromycin, leupeptin, and D-PAM. The dose-inhibitory effect curves for Livagen and Epitalon were plotted; their IC50 equaled 20 and 500 microM, respectively. The interaction between the peptides and opioid receptors was estimated using a radioreceptor method with [3H][D-Ala2, D-Leu5]-enkephalin. No interaction was observed between the tested peptides and mu- or delta-opioid receptors of the membrane fraction from the rat brain.

Effect of Culverts on Predator-Prey Interactions in a Tropical Stream.

NASA Astrophysics Data System (ADS)

Hein, C. L.; Kikkert, D. A.; Crowl, T. A.

2005-05-01

As part of a biocomplexity project in Puerto Rico, we use river and road networks as a platform to understand the interactions between stream biota, the physical environment, and human activity. Specifically, we ask if humans affect aquatic organisms through road building and recreational activities. Culverts have been documented to impede or slow migration of aquatic biota. This is especially important in these streams because all of the freshwater, stream species have diadramous life cycles. If culverts do act as bottlenecks to shrimp migrations, we expect altered predator-prey interactions downstream through density-dependent predation dynamics. In order to determine how roads may affect predation rates on upstream migrating shrimp, we parameterized functional response curves for mountain mullet (Agonostomus monticola) consuming shrimp (Xiphocaris sp.) using artificial mesocosm experiments. We then used data obtained from underwater videography to determine how culverts decrease the rate and number of shrimp moving upstream. These data were combined in a predator-prey model to quantify the effects of culverts on localized shrimp densities and fish predation.

New activity pattern in human interactive dynamics

NASA Astrophysics Data System (ADS)

Formentin, Marco; Lovison, Alberto; Maritan, Amos; Zanzotto, Giovanni

2015-09-01

We investigate the response function of human agents as demonstrated by written correspondence, uncovering a new pattern for how the reactive dynamics of individuals is distributed across the set of each agent’s contacts. In long-term empirical data on email, we find that the set of response times considered separately for the messages to each different correspondent of a given writer, generate a family of heavy-tailed distributions, which have largely the same features for all agents, and whose characteristic times grow exponentially with the rank of each correspondent. We furthermore show that this new behavioral pattern emerges robustly by considering weighted moving averages of the priority-conditioned response-time probabilities generated by a basic prioritization model. Our findings clarify how the range of priorities in the inputs from one’s environment underpin and shape the dynamics of agents embedded in a net of reactive relations. These newly revealed activity patterns might be universal, being present in other general interactive environments, and constrain future models of communication and interaction networks, affecting their architecture and evolution.

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

Togi, Sumihito; Nakasuji, Misa; Muromoto, Ryuta

Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA), which interacts with cellular proteins, plays a central role in modification of viral and/or cellular gene expression. Here, we show that LANA associates with glucocorticoid receptor (GR), and that LANA enhances the transcriptional activity of GR. Co-immunoprecipitation revealed a physical interaction between LANA and GR in transiently transfected 293T and HeLa cells. In human B-lymphoma cells, LANA overexpression enhanced GR activity and cell growth suppression following glucocorticoid stimulation. Furthermore, confocal microscopy showed that activated GR was bound to LANA and accumulated in the nucleus, leading to an increase in binding of activatedmore » GR to the glucocorticoid response element of target genes. Taken together, KSHV-derived LANA acts as a transcriptional co-activator of GR. Our results might suggest a careful use of glucocorticoids in the treatment of patients with KSHV-related malignancies such as Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. - Highlights: • KSHV-LANA enhances the transcriptional activity of GR in 293T and HeLa cells. • KSHV-LANA physically associates with GR. • KSHV-LANA enhances GR activation and cell growth suppression in human B-lymphocytes. • KSHV-LANA influences the nuclear retention and DNA binding activity of GR.« less

Proteomic Interaction Patterns between Human Cyclins, the Cyclin-Dependent Kinase Ortholog pUL97 and Additional Cytomegalovirus Proteins

PubMed Central

Steingruber, Mirjam; Kraut, Alexandra; Socher, Eileen; Sticht, Heinrich; Reichel, Anna; Stamminger, Thomas; Amin, Bushra; Couté, Yohann; Hutterer, Corina; Marschall, Manfred

2016-01-01

The human cytomegalovirus (HCMV)-encoded cyclin-dependent kinase (CDK) ortholog pUL97 associates with human cyclin B1 and other types of cyclins. Here, the question was addressed whether cyclin interaction of pUL97 and additional viral proteins is detectable by mass spectrometry-based approaches. Proteomic data were validated by coimmunoprecipitation (CoIP), Western blot, in vitro kinase and bioinformatic analyses. Our findings suggest that: (i) pUL97 shows differential affinities to human cyclins; (ii) pUL97 inhibitor maribavir (MBV) disrupts the interaction with cyclin B1, but not with other cyclin types; (iii) cyclin H is identified as a new high-affinity interactor of pUL97 in HCMV-infected cells; (iv) even more viral phosphoproteins, including all known substrates of pUL97, are detectable in the cyclin-associated complexes; and (v) a first functional validation of pUL97-cyclin B1 interaction, analyzed by in vitro kinase assay, points to a cyclin-mediated modulation of pUL97 substrate preference. In addition, our bioinformatic analyses suggest individual, cyclin-specific binding interfaces for pUL97-cyclin interaction, which could explain the different strengths of interactions and the selective inhibitory effect of MBV on pUL97-cyclin B1 interaction. Combined, the detection of cyclin-associated proteins in HCMV-infected cells suggests a complex pattern of substrate phosphorylation and a role of cyclins in the fine-modulation of pUL97 activities. PMID:27548200

The juxtamembrane regions of human receptor tyrosine kinases exhibit conserved interaction sites with anionic lipids

PubMed Central

Hedger, George; Sansom, Mark S. P.; Koldsø, Heidi

2015-01-01

Receptor tyrosine kinases (RTKs) play a critical role in diverse cellular processes and their activity is regulated by lipids in the surrounding membrane, including PIP2 (phosphatidylinositol-4,5-bisphosphate) in the inner leaflet, and GM3 (monosialodihexosylganglioside) in the outer leaflet. However, the precise details of the interactions at the molecular level remain to be fully characterised. Using a multiscale molecular dynamics simulation approach, we comprehensively characterise anionic lipid interactions with all 58 known human RTKs. Our results demonstrate that the juxtamembrane (JM) regions of RTKs are critical for inducing clustering of anionic lipids, including PIP2, both in simple asymmetric bilayers, and in more complex mixed membranes. Clustering is predominantly driven by interactions between a conserved cluster of basic residues within the first five positions of the JM region, and negatively charged lipid headgroups. This highlights a conserved interaction pattern shared across the human RTK family. In particular predominantly the N-terminal residues of the JM region are involved in the interactions with PIP2, whilst residues within the distal JM region exhibit comparatively less lipid specificity. Our results suggest that JM–lipid interactions play a key role in RTK structure and function, and more generally in the nanoscale organisation of receptor-containing cell membranes. PMID:25779975

Decoding ensemble activity from neurophysiological recordings in the temporal cortex.

PubMed

Kreiman, Gabriel

2011-01-01

We study subjects with pharmacologically intractable epilepsy who undergo semi-chronic implantation of electrodes for clinical purposes. We record physiological activity from tens to more than one hundred electrodes implanted in different parts of neocortex. These recordings provide higher spatial and temporal resolution than non-invasive measures of human brain activity. Here we discuss our efforts to develop hardware and algorithms to interact with the human brain by decoding ensemble activity in single trials. We focus our discussion on decoding visual information during a variety of visual object recognition tasks but the same technologies and algorithms can also be directly applied to other cognitive phenomena.

Kinematic design to improve ergonomics in human machine interaction.

PubMed

Schiele, André; van der Helm, Frans C T

2006-12-01

This paper introduces a novel kinematic design paradigm for ergonomic human machine interaction. Goals for optimal design are formulated generically and applied to the mechanical design of an upper-arm exoskeleton. A nine degree-of-freedom (DOF) model of the human arm kinematics is presented and used to develop, test, and optimize the kinematic structure of an human arm interfacing exoskeleton. The resulting device can interact with an unprecedented portion of the natural limb workspace, including motions in the shoulder-girdle, shoulder, elbow, and the wrist. The exoskeleton does not require alignment to the human joint axes, yet is able to actuate each DOF of our redundant limb unambiguously and without reaching into singularities. The device is comfortable to wear and does not create residual forces if misalignments exist. Implemented in a rehabilitation robot, the design features of the exoskeleton could enable longer lasting training sessions, training of fully natural tasks such as activities of daily living and shorter dress-on and dress-off times. Results from inter-subject experiments with a prototype are presented, that verify usability over the entire workspace of the human arm, including shoulder and shoulder girdle.

Arsenic: A Review of the Element's Toxicity, Plant Interactions, and Potential Methods of Remediation.

PubMed

Hettick, Bryan E; Cañas-Carrell, Jaclyn E; French, Amanda D; Klein, David M

2015-08-19

Arsenic is a naturally occurring element with a long history of toxicity. Sites of contamination are found worldwide as a result of both natural processes and anthropogenic activities. The broad scope of arsenic toxicity to humans and its unique interaction with the environment have led to extensive research into its physicochemical properties and toxic behavior in biological systems. The purpose of this review is to compile the results of recent studies concerning the metalloid and consider the chemical and physical properties of arsenic in the broad context of human toxicity and phytoremediation. Areas of focus include arsenic's mechanisms of human toxicity, interaction with plant systems, potential methods of remediation, and protocols for the determination of metals in experimentation. This assessment of the literature indicates that controlling contamination of water sources and plants through effective remediation and management is essential to successfully addressing the problems of arsenic toxicity and contamination.

Displacement of Drugs from Human Serum Albumin: From Molecular Interactions to Clinical Significance.

PubMed

Rimac, Hrvoje; Debeljak, Željko; Bojić, Mirza; Miller, Larisa

2017-01-01

Human serum albumin (HSA) is the most abundant protein in human serum. It has numerous functions, one of which is transport of small hydrophobic molecules, including drugs, toxins, nutrients, hormones and metabolites. HSA has the ability to interact with a wide variety of structurally different compounds. This promiscuous, nonspecific affinity can lead to sudden changes in concentrations caused by displacement, when two or more compounds compete for binding to the same molecular site. It is important to consider drug combinations and their binding to HSA when defining dosing regimens, as this can directly influence drug's free, active concentration in blood. In present paper we review drug interactions with potential for displacement from HSA, situations in which they are likely to occur and their clinical significance. We also offer guidelines in designing drugs with decreased binding to HSA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Understanding social collaboration between actors and technology in an automated and digitised deep mining environment.

PubMed

Sanda, M-A; Johansson, J; Johansson, B; Abrahamsson, L

2011-10-01

The purpose of this article is to develop knowledge and learning on the best way to automate organisational activities in deep mines that could lead to the creation of harmony between the human, technical and the social system, towards increased productivity. The findings showed that though the introduction of high-level technological tools in the work environment disrupted the social relations developed over time amongst the employees in most situations, the technological tools themselves became substitute social collaborative partners to the employees. It is concluded that, in developing a digitised mining production system, knowledge of the social collaboration between the humans (miners) and the technology they use for their work must be developed. By implication, knowledge of the human's subject-oriented and object-oriented activities should be considered as an important integral resource for developing a better technological, organisational and human interactive subsystem when designing the intelligent automation and digitisation systems for deep mines. STATEMENT OF RELEVANCE: This study focused on understanding the social collaboration between humans and the technologies they use to work in underground mines. The learning provides an added knowledge in designing technologies and work organisations that could better enhance the human-technology interactive and collaborative system in the automation and digitisation of underground mines.

Attentional Preference and Experience: II. An Exploratory Longitudinal Study of the Effects of Visual Familiarity and Responsiveness.

ERIC Educational Resources Information Center

Uzgiris, Ina C.; Hunt, J. McV.

The human infant is now considered capable of active informational interaction with the environment. This study tested certain hypotheses concerning the nature of that interaction. These hypotheses, developed partly from Piaget's work, are (1) that repeated visual encounters with a stimulus pattern leads first to attentional preference for that…

Interactive effects of disturbance and nitrogen availability on phosphorus dynamics of southern Appalachian forests

Treesearch

Corinne E. Block; Jennifer D. Knoepp; Jennifer M. Fraterrigo

2013-01-01

Understanding the main and interactive effects of chronically altered resource availability and disturbance on phosphorus (P) availability is increasingly important in light of the rapid pace at which human activities are altering these processes and potentially introducing P limitation. We measured P pools and fluxes in eighteen mixed forest stands at three elevations...

Meeting Active Start Guidelines in the ADC-Boykin Program: Infants

ERIC Educational Resources Information Center

Adalbjornsson, Carola F.; Rudisill, Mary E.; Wall, Sarah J.; Howard, Candice H.

2004-01-01

Contrary to past thinking, at birth, infants are capable of exploring their environment and interacting with other humans. They become aware of and learn about their world by observing, exploring, playing, and interacting with their caregivers. Motor skills play a major role in this process, which is achieved by allowing infants to move around,…

Prediction of in vivo drug-drug interactions based on mechanism-based inhibition from in vitro data: inhibition of 5-fluorouracil metabolism by (E)-5-(2-Bromovinyl)uracil.

PubMed

Kanamitsu, S I; Ito, K; Okuda, H; Ogura, K; Watabe, T; Muro, K; Sugiyama, Y

2000-04-01

The fatal drug-drug interaction between sorivudine, an antiviral drug, and 5-fluorouracil (5-FU) has been shown to be caused by a mechanism-based inhibition. In this interaction, sorivudine is converted by gut flora to (E)-5-(2-bromovinyl)uracil (BVU), which is metabolically activated by dihydropyrimidine dehydrogenase (DPD), and the activated BVU irreversibly binds to DPD itself, thereby inactivating it. In an attempt to predict this interaction in vivo from in vitro data, inhibition of 5-FU metabolism by BVU was investigated by using rat and human hepatic cytosol and human recombinant DPD. Whichever enzyme was used, increased inhibition was observed that depended on the preincubation time of BVU and enzyme in the presence of NADPH and BVU concentration. The kinetic parameters obtained for inactivation represented by k(inact) and K'(app) were 2.05 +/- 1.52 min(-1), 69.2 +/- 60.8 microM (rat hepatic cytosol), 2.39 +/- 0.13 min(-1), 48.6 +/- 11.8 microM (human hepatic cytosol), and 0.574 +/- 0.121 min(-1), 2.20 +/- 0.57 microM (human recombinant DPD). The drug-drug interaction in vivo was predicted quantitatively based on a physiologically based pharmacokinetic model, using pharmacokinetic parameters obtained from the literature and kinetic parameters for the enzyme inactivation obtained in the in vitro studies. In rats, DPD was predicted to be completely inactivated by administration of BVU and the area under the curve of 5-FU was predicted to increase 11-fold, which agreed well with the reported data. In humans, a 5-fold increase in the area under the curve of 5-FU was predicted after administration of sorivudine, 150 mg/day for 5 days. Mechanism-based inhibition of drug metabolism is supposed to be very dangerous. We propose that such in vitro studies should be carried out during the drug-developing phase so that in vivo drug-drug interactions can be predicted.

LINE-1 silencing by retinoblastoma proteins is effected through the nucleosomal and remodeling deacetylase multiprotein complex.

PubMed

Montoya-Durango, Diego E; Ramos, Kenneth A; Bojang, Pasano; Ruiz, Lorell; Ramos, Irma N; Ramos, Kenneth S

2016-01-25

Long Interspersed Nuclear Element-1 (L1) is an oncogenic mammalian retroelement silenced early in development via tightly controlled epigenetic mechanisms. We have previously shown that the regulatory region of human and murine L1s interact with retinoblastoma (RB) proteins to effect retroelement silencing. The present studies were conducted to identify the corepressor complex responsible for RB-mediated silencing of L1. Chromatin immunoprecipitation and silencing RNA technology were used to identify the repressor complex that silences L1 in human and murine cells. Components of the Nucleosomal and Remodeling Deacetylase (NuRD) multiprotein complex specifically enriched the L1 5'-untranslated DNA sequence in human and murine cells. Genetic ablation of RB proteins in murine cells destabilized interactions within the NuRD macromolecular complex and mediated nuclear rearrangement of Mi2-β, an ATP-dependent helicase subunit with nucleosome remodeling activity. Depletion of Mi2-β, RbAP46 and HDAC2 reduced the repressor activity of the NuRD complex and reactivated a synthetic L1 reporter in human cells. Epigenetic reactivation of L1 in RB-null cells by DNA damage was markedly enhanced compared to wild type cells. RB proteins stabilize interactions of the NuRD corepressor complex within the L1 promoter to effect L1 silencing. L1 retroelements may serve as a scaffold on which RB builds heterochromatic regions that regulate chromatin function.

Interaction studies reveal specific recognition of an anti-inflammatory polyphosphorhydrazone dendrimer by human monocytes

NASA Astrophysics Data System (ADS)

Ledall, Jérémy; Fruchon, Séverine; Garzoni, Matteo; Pavan, Giovanni M.; Caminade, Anne-Marie; Turrin, Cédric-Olivier; Blanzat, Muriel; Poupot, Rémy

2015-10-01

Dendrimers are nano-materials with perfectly defined structure and size, and multivalency properties that confer substantial advantages for biomedical applications. Previous work has shown that phosphorus-based polyphosphorhydrazone (PPH) dendrimers capped with azabisphosphonate (ABP) end groups have immuno-modulatory and anti-inflammatory properties leading to efficient therapeutic control of inflammatory diseases in animal models. These properties are mainly prompted through activation of monocytes. Here, we disclose new insights into the molecular mechanisms underlying the anti-inflammatory activation of human monocytes by ABP-capped PPH dendrimers. Following an interdisciplinary approach, we have characterized the physicochemical and biological behavior of the lead ABP dendrimer with model and cell membranes, and compared this experimental set of data to predictive computational modelling studies. The behavior of the ABP dendrimer was compared to the one of an isosteric analog dendrimer capped with twelve azabiscarboxylate (ABC) end groups instead of twelve ABP end groups. The ABC dendrimer displayed no biological activity on human monocytes, therefore it was considered as a negative control. In detail, we show that the ABP dendrimer can bind both non-specifically and specifically to the membrane of human monocytes. The specific binding leads to the internalization of the ABP dendrimer by human monocytes. On the contrary, the ABC dendrimer only interacts non-specifically with human monocytes and is not internalized. These data indicate that the bioactive ABP dendrimer is recognized by specific receptor(s) at the surface of human monocytes.Dendrimers are nano-materials with perfectly defined structure and size, and multivalency properties that confer substantial advantages for biomedical applications. Previous work has shown that phosphorus-based polyphosphorhydrazone (PPH) dendrimers capped with azabisphosphonate (ABP) end groups have immuno-modulatory and anti-inflammatory properties leading to efficient therapeutic control of inflammatory diseases in animal models. These properties are mainly prompted through activation of monocytes. Here, we disclose new insights into the molecular mechanisms underlying the anti-inflammatory activation of human monocytes by ABP-capped PPH dendrimers. Following an interdisciplinary approach, we have characterized the physicochemical and biological behavior of the lead ABP dendrimer with model and cell membranes, and compared this experimental set of data to predictive computational modelling studies. The behavior of the ABP dendrimer was compared to the one of an isosteric analog dendrimer capped with twelve azabiscarboxylate (ABC) end groups instead of twelve ABP end groups. The ABC dendrimer displayed no biological activity on human monocytes, therefore it was considered as a negative control. In detail, we show that the ABP dendrimer can bind both non-specifically and specifically to the membrane of human monocytes. The specific binding leads to the internalization of the ABP dendrimer by human monocytes. On the contrary, the ABC dendrimer only interacts non-specifically with human monocytes and is not internalized. These data indicate that the bioactive ABP dendrimer is recognized by specific receptor(s) at the surface of human monocytes. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03884g

Interaction of human biliverdin reductase with Akt/protein kinase B and phosphatidylinositol-dependent kinase 1 regulates glycogen synthase kinase 3 activity: a novel mechanism of Akt activation

PubMed Central

Miralem, Tihomir; Lerner-Marmarosh, Nicole; Gibbs, Peter E. M.; Jenkins, Jermaine L.; Heimiller, Chelsea; Maines, Mahin D.

2016-01-01

Biliverdin reductase A (BVR) and Akt isozymes have overlapping pleiotropic functions in the insulin/PI3K/MAPK pathway. Human BVR (hBVR) also reduces the hemeoxygenase activity product biliverdin to bilirubin and is directly activated by insulin receptor kinase (IRK). Akt isoenzymes (Akt1–3) are downstream of IRK and are activated by phosphatidylinositol-dependent kinase 1 (PDK1) phosphorylating T308 before S473 autophosphorylation. Akt (RxRxxSF) and PDK1 (RFxFPxFS) binding motifs are present in hBVR. Phosphorylation of glycogen synthase kinase 3 (GSK3) isoforms α/β by Akts inhibits their activity; nonphosphorylated GSK3β inhibits activation of various genes. We examined the role of hBVR in PDK1/Akt1/GSK3 signaling and Akt1 in hBVR phosphorylation. hBVR activates phosphorylation of Akt1 at S473 independent of hBVR’s kinase competency. hBVR and Akt1 coimmunoprecipitated, and in-cell Förster resonance energy transfer (FRET) and glutathione S-transferase pulldown analyses identified Akt1 pleckstrin homology domain as the interactive domain. hBVR activates phosphorylation of Akt1 at S473 independent of hBVR’s kinase competency. Site-directed mutagenesis, mass spectrometry, and kinetic analyses identified S230 in hBVR 225RNRYLSF sequence as the Akt1 target. Underlined amino acids are the essential residues of the signaling motifs. In cells, hBVR-activated Akt1 increased both GSK3α/β and forkhead box of the O class transcription class 3 (FoxO3) phosphorylation and inhibited total GSK3 activity; depletion of hBVR released inhibition and stimulated glucose uptake. Immunoprecipitation analysis showed that PDK1 and hBVR interact through hBVR’s PDK1 binding 161RFGFPAFS motif and formation of the PDK1/hBVR/Akt1 complex. sihBVR blocked complex formation. Findings identify hBVR as a previously unknown coactivator of Akt1 and as a key mediator of Akt1/GSK3 pathway, as well as define a key role for hBVR in Akt1 activation by PDK1.—Miralem, T., Lerner-Marmarosh, N., Gibbs, P. E. M., Jenkins, J. L., Heimiller, C., Maines, M. D. Interaction of human biliverdin reductase with Akt/protein kinase B and phosphatidylinositol-dependent kinase 1 regulates glycogen synthase kinase 3 activity: a novel mechanism of Akt activation. PMID:27166089

Interaction of human biliverdin reductase with Akt/protein kinase B and phosphatidylinositol-dependent kinase 1 regulates glycogen synthase kinase 3 activity: a novel mechanism of Akt activation.

PubMed

Miralem, Tihomir; Lerner-Marmarosh, Nicole; Gibbs, Peter E M; Jenkins, Jermaine L; Heimiller, Chelsea; Maines, Mahin D

2016-08-01

Biliverdin reductase A (BVR) and Akt isozymes have overlapping pleiotropic functions in the insulin/PI3K/MAPK pathway. Human BVR (hBVR) also reduces the hemeoxygenase activity product biliverdin to bilirubin and is directly activated by insulin receptor kinase (IRK). Akt isoenzymes (Akt1-3) are downstream of IRK and are activated by phosphatidylinositol-dependent kinase 1 (PDK1) phosphorylating T(308) before S(473) autophosphorylation. Akt (RxRxxSF) and PDK1 (RFxFPxFS) binding motifs are present in hBVR. Phosphorylation of glycogen synthase kinase 3 (GSK3) isoforms α/β by Akts inhibits their activity; nonphosphorylated GSK3β inhibits activation of various genes. We examined the role of hBVR in PDK1/Akt1/GSK3 signaling and Akt1 in hBVR phosphorylation. hBVR activates phosphorylation of Akt1 at S(473) independent of hBVR's kinase competency. hBVR and Akt1 coimmunoprecipitated, and in-cell Förster resonance energy transfer (FRET) and glutathione S-transferase pulldown analyses identified Akt1 pleckstrin homology domain as the interactive domain. hBVR activates phosphorylation of Akt1 at S(473) independent of hBVR's kinase competency. Site-directed mutagenesis, mass spectrometry, and kinetic analyses identified S(230) in hBVR (225)RNRYLSF sequence as the Akt1 target. Underlined amino acids are the essential residues of the signaling motifs. In cells, hBVR-activated Akt1 increased both GSK3α/β and forkhead box of the O class transcription class 3 (FoxO3) phosphorylation and inhibited total GSK3 activity; depletion of hBVR released inhibition and stimulated glucose uptake. Immunoprecipitation analysis showed that PDK1 and hBVR interact through hBVR's PDK1 binding (161)RFGFPAFS motif and formation of the PDK1/hBVR/Akt1 complex. sihBVR blocked complex formation. Findings identify hBVR as a previously unknown coactivator of Akt1 and as a key mediator of Akt1/GSK3 pathway, as well as define a key role for hBVR in Akt1 activation by PDK1.-Miralem, T., Lerner-Marmarosh, N., Gibbs, P. E. M., Jenkins, J. L., Heimiller, C., Maines, M. D. Interaction of human biliverdin reductase with Akt/protein kinase B and phosphatidylinositol-dependent kinase 1 regulates glycogen synthase kinase 3 activity: a novel mechanism of Akt activation. © FASEB.

Autolytic activity of human calpain 7 is enhanced by ESCRT-III-related protein IST1 through MIT-MIM interaction.

PubMed

Osako, Yohei; Maemoto, Yuki; Tanaka, Ryohei; Suzuki, Hironori; Shibata, Hideki; Maki, Masatoshi

2010-11-01

Calpain 7, a mammalian ortholog of yeast Cpl1/Rim13 and fungal PalB, is an atypical calpain that lacks a penta-EF-hand domain. Previously, we reported that a region containing a tandem repeat of microtubule-interacting and transport (MIT) domains in calpain 7 interacts with a subset of endosomal sorting complex required for transport (ESCRT)-III-related proteins, suggesting involvement of calpain 7 in the ESCRT system. Although yeast and fungal calpains are thought to be involved in alkaline adaptation via limited proteolysis of specific transcription factors, proteolytic activity of calpain 7 has not been demonstrated yet. In this study, we investigated the interaction between calpain 7 and a newly reported ESCRT-III family member, increased sodium tolerance-1 (IST1), which possesses two different types of MIT-interacting motifs (MIM1 and MIM2). We found that glutathione-S-transferase (GST)-fused tandem MIT domains of calpain 7 (calpain 7MIT) pulled down FLAG-tagged IST1 expressed in HEK293T cells. Coimmunoprecipitation assays with various deletion or point mutants of epitope-tagged calpain 7 and IST1 revealed that both repetitive MIT domains and MIMs are required for efficient interaction. Direct MIT-MIM binding was confirmed by a pulldown experiment with GST-fused IST1 MIM and purified recombinant calpain 7MIT. Furthermore, we found that the GST-MIM protein enhances the autolysis of purified Strep-tagged monomeric green fluorescent protein (mGFP)-fused calpain 7 (mGFP-calpain 7-Strep). The autolysis was almost completely abolished by 10 mmN-ethylmaleimide but only partially inhibited by 1 mm leupeptin or E-64. The putative catalytic Cys290-substituted mutant (mGFP-calpain 7(C290S)-Strep) showed no autolytic activity. These results demonstrate for the first time that human calpain 7 is proteolytically active, and imply that calpain 7 is activated in the ESCRT system. © 2010 The Authors Journal compilation © 2010 FEBS.

Human 15-LOX-1 active site mutations alter inhibitor binding and decrease potency.

PubMed

Armstrong, Michelle; van Hoorebeke, Christopher; Horn, Thomas; Deschamps, Joshua; Freedman, J Cody; Kalyanaraman, Chakrapani; Jacobson, Matthew P; Holman, Theodore

2016-11-01

Human 15-lipoxygenase-1 (h15-LOX-1 or h12/15-LOX) reacts with polyunsaturated fatty acids and produces bioactive lipid derivatives that are implicated in many important human diseases. One such disease is stroke, which is the fifth leading cause of death and the first leading cause of disability in America. The discovery of h15-LOX-1 inhibitors could potentially lead to novel therapeutics in the treatment of stroke, however, little is known about the inhibitor/active site interaction. This study utilizes site-directed mutagenesis, guided in part by molecular modeling, to gain a better structural understanding of inhibitor interactions within the active site. We have generated eight mutants (R402L, R404L, F414I, F414W, E356Q, Q547L, L407A, I417A) of h15-LOX-1 to determine whether these active site residues interact with two h15-LOX-1 inhibitors, ML351 and an ML094 derivative, compound 18. IC 50 values and steady-state inhibition kinetics were determined for the eight mutants, with four of the mutants affecting inhibitor potency relative to wild type h15-LOX-1 (F414I, F414W, E356Q and L407A). The data indicate that ML351 and compound 18, bind in a similar manner in the active site to an aromatic pocket close to F414 but have subtle differences in their specific binding modes. This information establishes the binding mode for ML094 and ML351 and will be leveraged to develop next-generation inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of Coal Fly Ash Particulate Matter on the Antimicrobial Activity of Airway Surface Liquid

PubMed Central

Vargas Buonfiglio, Luis G.; Mudunkotuwa, Imali A.; Abou Alaiwa, Mahmoud H.; Vanegas Calderón, Oriana G.; Borcherding, Jennifer A.; Gerke, Alicia K.; Zabner, Joseph; Grassian, Vicki H.

2017-01-01

Background: Sustained exposure to ambient particulate matter (PM) is a global cause of mortality. Coal fly ash (CFA) is a byproduct of coal combustion and is a source of anthropogenic PM with worldwide health relevance. The airway epithelia are lined with fluid called airway surface liquid (ASL), which contains antimicrobial proteins and peptides (AMPs). Cationic AMPs bind negatively charged bacteria to exert their antimicrobial activity. PM arriving in the airways could potentially interact with AMPs in the ASL to affect their antimicrobial activity. Objectives: We hypothesized that PM can interact with ASL AMPs to impair their antimicrobial activity. Methods: We exposed pig and human airway explants, pig and human ASL, and the human cationic AMPs β-defensin-3, LL-37, and lysozyme to CFA or control. Thereafter, we assessed the antimicrobial activity of exposed airway samples using both bioluminescence and standard colony-forming unit assays. We investigated PM-AMP electrostatic interaction by attenuated total reflection Fourier-transform infrared spectroscopy and measuring the zeta potential. We also studied the adsorption of AMPs on PM. Results: We found increased bacterial survival in CFA-exposed airway explants, ASL, and AMPs. In addition, we report that PM with a negative surface charge can adsorb cationic AMPs and form negative particle–protein complexes. Conclusion: We propose that when CFA arrives at the airway, it rapidly adsorbs AMPs and creates negative complexes, thereby decreasing the functional amount of AMPs capable of killing pathogens. These results provide a novel translational insight into an early mechanism for how ambient PM increases the susceptibility of the airways to bacterial infection. https://doi.org/10.1289/EHP876 PMID:28696208

The HOX genes are expressed, in vivo, in human tooth germs: in vitro cAMP exposure of dental pulp cells results in parallel HOX network activation and neuronal differentiation.

PubMed

D'Antò, Vincenzo; Cantile, Monica; D'Armiento, Maria; Schiavo, Giulia; Spagnuolo, Gianrico; Terracciano, Luigi; Vecchione, Raffaela; Cillo, Clemente

2006-03-01

Homeobox-containing genes play a crucial role in odontogenesis. After the detection of Dlx and Msx genes in overlapping domains along maxillary and mandibular processes, a homeobox odontogenic code has been proposed to explain the interaction between different homeobox genes during dental lamina patterning. No role has so far been assigned to the Hox gene network in the homeobox odontogenic code due to studies on specific Hox genes and evolutionary considerations. Despite its involvement in early patterning during embryonal development, the HOX gene network, the most repeat-poor regions of the human genome, controls the phenotype identity of adult eukaryotic cells. Here, according to our results, the HOX gene network appears to be active in human tooth germs between 18 and 24 weeks of development. The immunohistochemical localization of specific HOX proteins mostly concerns the epithelial tooth germ compartment. Furthermore, only a few genes of the network are active in embryonal retromolar tissues, as well as in ectomesenchymal dental pulp cells (DPC) grown in vitro from adult human molar. Exposure of DPCs to cAMP induces the expression of from three to nine total HOX genes of the network in parallel with phenotype modifications with traits of neuronal differentiation. Our observations suggest that: (i) by combining its component genes, the HOX gene network determines the phenotype identity of epithelial and ectomesenchymal cells interacting in the generation of human tooth germ; (ii) cAMP treatment activates the HOX network and induces, in parallel, a neuronal-like phenotype in human primary ectomesenchymal dental pulp cells. 2005 Wiley-Liss, Inc.

New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) II: Albumin Suppresses Angiotensin Converting Enzyme (ACE) Activity in Human

PubMed Central

Fagyas, Miklós; Úri, Katalin; Siket, Ivetta M.; Fülöp, Gábor Á.; Csató, Viktória; Daragó, Andrea; Boczán, Judit; Bányai, Emese; Szentkirályi, István Elek; Maros, Tamás Miklós; Szerafin, Tamás; Édes, István; Papp, Zoltán; Tóth, Attila

2014-01-01

About 8% of the adult population is taking angiotensin-converting enzyme (ACE) inhibitors to treat cardiovascular disease including hypertension, myocardial infarction and heart failure. These drugs decrease mortality by up to one-fifth in these patients. We and others have reported previously that endogenous inhibitory substances suppress serum ACE activity, in vivo, similarly to the ACE inhibitor drugs. Here we have made an effort to identify this endogenous ACE inhibitor substance. ACE was crosslinked with interacting proteins in human sera. The crosslinked products were immunoprecipitated and subjected to Western blot. One of the crosslinked products was recognized by both anti-ACE and anti-HSA (human serum albumin) antibodies. Direct ACE-HSA interaction was confirmed by binding assays using purified ACE and HSA. HSA inhibited human purified (circulating) and human recombinant ACE with potencies (IC50) of 5.7±0.7 and 9.5±1.1 mg/mL, respectively. Effects of HSA on the tissue bound native ACE were tested on human saphenous vein samples. Angiotensin I evoked vasoconstriction was inhibited by HSA in this vascular tissue (maximal force with HSA: 6.14±1.34 mN, without HSA: 13.54±2.63 mN), while HSA was without effects on angiotensin II mediated constrictions (maximal force with HSA: 18.73±2.17 mN, without HSA: 19.22±3.50 mN). The main finding of this study is that HSA was identified as a potent physiological inhibitor of the ACE. The enzymatic activity of ACE appears to be almost completely suppressed by HSA when it is present in its physiological concentration. These data suggest that angiotensin I conversion is limited by low physiological ACE activities, in vivo. PMID:24691203

Neural correlates of trust.

PubMed

Krueger, Frank; McCabe, Kevin; Moll, Jorge; Kriegeskorte, Nikolaus; Zahn, Roland; Strenziok, Maren; Heinecke, Armin; Grafman, Jordan

2007-12-11

Trust is a critical social process that helps us to cooperate with others and is present to some degree in all human interaction. However, the underlying brain mechanisms of conditional and unconditional trust in social reciprocal exchange are still obscure. Here, we used hyperfunctional magnetic resonance imaging, in which two strangers interacted online with one another in a sequential reciprocal trust game while their brains were simultaneously scanned. By designing a nonanonymous, alternating multiround game, trust became bidirectional, and we were able to quantify partnership building and maintenance. Using within- and between-brain analyses, an examination of functional brain activity supports the hypothesis that the preferential activation of different neuronal systems implements these two trust strategies. We show that the paracingulate cortex is critically involved in building a trust relationship by inferring another person's intentions to predict subsequent behavior. This more recently evolved brain region can be differently engaged to interact with more primitive neural systems in maintaining conditional and unconditional trust in a partnership. Conditional trust selectively activated the ventral tegmental area, a region linked to the evaluation of expected and realized reward, whereas unconditional trust selectively activated the septal area, a region linked to social attachment behavior. The interplay of these neural systems supports reciprocal exchange that operates beyond the immediate spheres of kinship, one of the distinguishing features of the human species.

Neural correlates of trust

PubMed Central

Krueger, Frank; McCabe, Kevin; Moll, Jorge; Kriegeskorte, Nikolaus; Zahn, Roland; Strenziok, Maren; Heinecke, Armin; Grafman, Jordan

2007-01-01

Trust is a critical social process that helps us to cooperate with others and is present to some degree in all human interaction. However, the underlying brain mechanisms of conditional and unconditional trust in social reciprocal exchange are still obscure. Here, we used hyperfunctional magnetic resonance imaging, in which two strangers interacted online with one another in a sequential reciprocal trust game while their brains were simultaneously scanned. By designing a nonanonymous, alternating multiround game, trust became bidirectional, and we were able to quantify partnership building and maintenance. Using within- and between-brain analyses, an examination of functional brain activity supports the hypothesis that the preferential activation of different neuronal systems implements these two trust strategies. We show that the paracingulate cortex is critically involved in building a trust relationship by inferring another person's intentions to predict subsequent behavior. This more recently evolved brain region can be differently engaged to interact with more primitive neural systems in maintaining conditional and unconditional trust in a partnership. Conditional trust selectively activated the ventral tegmental area, a region linked to the evaluation of expected and realized reward, whereas unconditional trust selectively activated the septal area, a region linked to social attachment behavior. The interplay of these neural systems supports reciprocal exchange that operates beyond the immediate spheres of kinship, one of the distinguishing features of the human species. PMID:18056800

Insights into the mechanism of human papillomavirus E2-induced procaspase-8 activation and cell death

NASA Astrophysics Data System (ADS)

Singh, Nitu; Senapati, Sanjib; Bose, Kakoli

2016-02-01

High-risk human papillomavirus (HR-HPV) E2 protein, the master regulator of viral life cycle, induces apoptosis of host cell that is independent of its virus-associated regulatory functions. E2 protein of HR-HPV18 has been found to be involved in novel FADD-independent activation of caspase-8, however, the molecular basis of this unique non-death-fold E2-mediated apoptosis is poorly understood. Here, with an interdisciplinary approach that involves in silico, mutational, biochemical and biophysical probes, we dissected and characterized the E2-procasapse-8 binding interface. Our data demonstrate direct non-homotypic interaction of HPV18 E2 transactivation domain (TAD) with α2/α5 helices of procaspase-8 death effector domain-B (DED-B). The observed interaction mimics the homotypic DED-DED complexes, wherein the conserved hydrophobic motif of procaspase-8 DED-B (F122/L123) occupies a groove between α2/α3 helices of E2 TAD. This interaction possibly drives DED oligomerization leading to caspase-8 activation and subsequent cell death. Furthermore, our data establish a model for E2-induced apoptosis in HR-HPV types and provide important clues for designing E2 analogs that might modulate procaspase-8 activation and hence apoptosis.

Imbalanced Oxidative Stress Causes Chlamydial Persistence during Non-Productive Human Herpes Virus Co-Infection

PubMed Central

Prusty, Bhupesh K.; Böhme, Linda; Bergmann, Birgit; Siegl, Christine; Krause, Eva; Mehlitz, Adrian; Rudel, Thomas

2012-01-01

Both human herpes viruses and Chlamydia are highly prevalent in the human population and are detected together in different human disorders. Here, we demonstrate that co-infection with human herpes virus 6 (HHV6) interferes with the developmental cycle of C. trachomatis and induces persistence. Induction of chlamydial persistence by HHV6 is independent of productive virus infection, but requires the interaction and uptake of the virus by the host cell. On the other hand, viral uptake is strongly promoted under co-infection conditions. Host cell glutathione reductase activity was suppressed by HHV6 causing NADPH accumulation, decreased formation of reduced glutathione and increased oxidative stress. Prevention of oxidative stress restored infectivity of Chlamydia after HHV6-induced persistence. We show that co-infection with Herpes simplex virus 1 or human Cytomegalovirus also induces chlamydial persistence by a similar mechanism suggesting that Chlamydia -human herpes virus co-infections are evolutionary shaped interactions with a thus far unrecognized broad significance. PMID:23077614

Monoamine transporter and receptor interaction profiles in vitro predict reported human doses of novel psychoactive stimulants and psychedelics.

PubMed

Luethi, Dino; Liechti, Matthias E

2018-05-29

Pharmacological profiles of new psychoactive substances (NPSs) can be established rapidly in vitro and provide information on potential psychoactive effects in humans. The present study investigated whether specific in vitro monoamine transporter and receptor interactions can predict effective psychoactive doses in humans. We correlated previously assessed in vitro data of stimulants and psychedelics with human doses that are reported on the Internet and in books. For stimulants, dopamine and norepinephrine transporter inhibition potency was positively correlated with human doses, whereas serotonin transporter inhibition potency was inversely correlated with human doses. Serotonin 5-hydroxytryptamine-2A (5-HT2A) and 5-HT2C receptor affinity was significantly correlated with psychedelic doses, but 5-HT1A receptor affinity and 5-HT2A and 5-HT2B receptor activation potency were not. The rapid assessment of in vitro pharmacological profiles of NPSs can help to predict psychoactive doses and effects in humans and facilitate the appropriate scheduling of NPSs.

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

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

Using Activity Theory to Understand Learning Design Requirements of Patient Self-Management Environments

ERIC Educational Resources Information Center

Schaffer, Scott P.; Reyes, Lisette; Kim, Hannah; Collins, Bart

2010-01-01

Learning designs aimed at supporting transformational change could significantly benefit from the adoption of socio-historical and socio-cultural analysis approaches. Such systemic perspectives are gaining more importance in education as they facilitate understanding of complex interactions between learning environments and human activity. The…

Integrating Science, Mathematics, and Sociology in an Inquiry-Based Study of Changing Population Density.

ERIC Educational Resources Information Center

Schlenker, Richard M.; Schlenker, Karl R.

2000-01-01

Presents a five-activity sequence designed to help students understand the effects of population doubling. Activities consider the effects of population doubling on human interactions, drinking water supplies, and food supply. Students also develop graphs of data and write research papers. (WRM)

Human Urinary Composition Controls Antibacterial Activity of Siderocalin* ♦

PubMed Central

Shields-Cutler, Robin R.; Crowley, Jan R.; Hung, Chia S.; Stapleton, Ann E.; Aldrich, Courtney C.; Marschall, Jonas; Henderson, Jeffrey P.

2015-01-01

During Escherichia coli urinary tract infections, cells in the human urinary tract release the antimicrobial protein siderocalin (SCN; also known as lipocalin 2, neutrophil gelatinase-associated lipocalin/NGAL, or 24p3). SCN can interfere with E. coli iron acquisition by sequestering ferric iron complexes with enterobactin, the conserved E. coli siderophore. Here, we find that human urinary constituents can reverse this relationship, instead making enterobactin critical for overcoming SCN-mediated growth restriction. Urinary control of SCN activity exhibits wide ranging individual differences. We used these differences to identify elevated urinary pH and aryl metabolites as key biochemical host factors controlling urinary SCN activity. These aryl metabolites are well known products of intestinal microbial metabolism. Together, these results identify an innate antibacterial immune interaction that is critically dependent upon individualistic chemical features of human urine. PMID:25861985

Physical interaction of human T-cell leukemia virus type 1 Tax with cyclin-dependent kinase 4 stimulates the phosphorylation of retinoblastoma protein.

PubMed

Haller, Kerstin; Wu, Yalin; Derow, Elisabeth; Schmitt, Iris; Jeang, Kuan-Teh; Grassmann, Ralph

2002-05-01

The Tax oncoprotein of human T-cell leukemia virus type 1 (HTLV-1) induces leukemia in transgenic mice and permanent T-cell growth in vitro. In transformed lymphocytes, it acts as an essential growth factor. Tax stimulates the cell cycle in the G(1) phase by activating the cyclin-dependent kinase (CDK) CDK4 and CDK6 holoenzyme complexes. Here we show that Tax directly interacts with CDK4. This binding to CDK4 was specific, since Tax did not bind to either CDK2 or CDK1. The interaction with CDK4/cyclin D complexes was observed in vitro, in transfected fibroblasts, in HTLV-1-infected T cells, and in adult T-cell leukemia-derived cultures. Binding studies with several point and deletion mutants indicated that the N terminus of Tax mediates the interaction with CDK4. The Tax/CDK complex represented an active holoenzyme which capably phosphorylates the Rb protein in vitro and is resistant to repression by the inhibitor p21(CIP). Binding-deficient Tax mutants failed to activate CDK4, indicating that direct association with Tax is required for enhanced kinase activity. Tax also increased the association of CDK4 with its positive cyclin regulatory subunit. Thus, protein-protein contact between Tax and the components of the cyclin D/CDK complexes provides a further mechanistic explanation for the mitogenic and immortalizing effects of this HTLV-1 oncoprotein.

Physical Interaction of Human T-Cell Leukemia Virus Type 1 Tax with Cyclin-Dependent Kinase 4 Stimulates the Phosphorylation of Retinoblastoma Protein

PubMed Central

Haller, Kerstin; Wu, Yalin; Derow, Elisabeth; Schmitt, Iris; Jeang, Kuan-Teh; Grassmann, Ralph

2002-01-01

The Tax oncoprotein of human T-cell leukemia virus type 1 (HTLV-1) induces leukemia in transgenic mice and permanent T-cell growth in vitro. In transformed lymphocytes, it acts as an essential growth factor. Tax stimulates the cell cycle in the G1 phase by activating the cyclin-dependent kinase (CDK) CDK4 and CDK6 holoenzyme complexes. Here we show that Tax directly interacts with CDK4. This binding to CDK4 was specific, since Tax did not bind to either CDK2 or CDK1. The interaction with CDK4/cyclin D complexes was observed in vitro, in transfected fibroblasts, in HTLV-1-infected T cells, and in adult T-cell leukemia-derived cultures. Binding studies with several point and deletion mutants indicated that the N terminus of Tax mediates the interaction with CDK4. The Tax/CDK complex represented an active holoenzyme which capably phosphorylates the Rb protein in vitro and is resistant to repression by the inhibitor p21CIP. Binding-deficient Tax mutants failed to activate CDK4, indicating that direct association with Tax is required for enhanced kinase activity. Tax also increased the association of CDK4 with its positive cyclin regulatory subunit. Thus, protein-protein contact between Tax and the components of the cyclin D/CDK complexes provides a further mechanistic explanation for the mitogenic and immortalizing effects of this HTLV-1 oncoprotein. PMID:11971966

Observing real-time social interaction via telecommunication methods in budgerigars (Melopsittacus undulatus).

PubMed

Ikkatai, Yuko; Okanoya, Kazuo; Seki, Yoshimasa

2016-07-01

Humans communicate with one another not only face-to-face but also via modern telecommunication methods such as television and video conferencing. We readily detect the difference between people actively communicating with us and people merely acting via a broadcasting system. We developed an animal model of this novel communication method seen in humans to determine whether animals also make this distinction. We built a system for two animals to interact via audio-visual equipment in real-time, to compare behavioral differences between two conditions, an "interactive two-way condition" and a "non-interactive (one-way) condition." We measured birds' responses to stimuli which appeared in these two conditions. We used budgerigars, which are small, gregarious birds, and found that the frequency of vocal interaction with other individuals did not differ between the two conditions. However, body synchrony between the two birds was observed more often in the interactive condition, suggesting budgerigars recognized the difference between these interactive and non-interactive conditions on some level. Copyright © 2016 Elsevier B.V. All rights reserved.

Implications of rapid environmental change for polar bear behavior and sociality

USGS Publications Warehouse

Atwood, Todd C.

2017-01-01

Historically, the Arctic sea ice has functioned as a structural barrier that has limited the nature and extent of interactions between humans and polar bears (Ursus maritimus). However, declining sea ice extent, brought about by global climate change, is increasing the potential for human-polar bear interactions. Loss of sea ice habitat is driving changes to both human and polar bear behavior—it is facilitating increases in human activities (e.g., offshore oil and gas exploration and extraction, trans-Arctic shipping, recreation), while also causing the displacement of bears from preferred foraging habitat (i.e., sea ice over biologically productive shallow) to land in some portions of their range. The end result of these changes is that polar bears are spending greater amounts of time in close proximity to people. Coexistence between humans and polar bears will require imposing mechanisms to manage further development, as well as mitigation strategies that reduce the burden to local communities.

Music and social bonding: “self-other” merging and neurohormonal mechanisms

PubMed Central

Tarr, Bronwyn; Launay, Jacques; Dunbar, Robin I. M.

2014-01-01

It has been suggested that a key function of music during its development and spread amongst human populations was its capacity to create and strengthen social bonds amongst interacting group members. However, the mechanisms by which this occurs have not been fully discussed. In this paper we review evidence supporting two thus far independently investigated mechanisms for this social bonding effect: self-other merging as a consequence of inter-personal synchrony, and the release of endorphins during exertive rhythmic activities including musical interaction. In general, self-other merging has been experimentally investigated using dyads, which provide limited insight into large-scale musical activities. Given that music can provide an external rhythmic framework that facilitates synchrony, explanations of social bonding during group musical activities should include reference to endorphins, which are released during synchronized exertive movements. Endorphins (and the endogenous opioid system (EOS) in general) are involved in social bonding across primate species, and are associated with a number of human social behaviors (e.g., laughter, synchronized sports), as well as musical activities (e.g., singing and dancing). Furthermore, passively listening to music engages the EOS, so here we suggest that both self-other merging and the EOS are important in the social bonding effects of music. In order to investigate possible interactions between these two mechanisms, future experiments should recreate ecologically valid examples of musical activities. PMID:25324805

GNIP1 E3 ubiquitin ligase is a novel player in regulating glycogen metabolism in skeletal muscle.

PubMed

Montori-Grau, Marta; Pedreira-Casahuga, Robert; Boyer-Díaz, Zoé; Lassot, Iréna; García-Martínez, Celia; Orozco, Anna; Cebrià, Judith; Osorio-Conles, Oscar; Chacón, Matilde R; Vendrell, Joan; Vázquez-Carrera, Manuel; Desagher, Solange; Jiménez-Chillarón, Josep Carles; Gómez-Foix, Anna Ma

2018-06-01

Glycogenin-interacting protein 1 (GNIP1) is a tripartite motif (TRIM) protein with E3 ubiquitin ligase activity that interacts with glycogenin. These data suggest that GNIP1 could play a major role in the control of glycogen metabolism. However, direct evidence based on functional analysis remains to be obtained. The aim of this study was 1) to define the expression pattern of glycogenin-interacting protein/Tripartite motif containing protein 7 (GNIP/TRIM7) isoforms in humans, 2) to test their ubiquitin E3 ligase activity, and 3) to analyze the functional effects of GNIP1 on muscle glucose/glycogen metabolism both in human cultured cells and in vivo in mice. We show that GNIP1 was the most abundant GNIP/TRIM7 isoform in human skeletal muscle, whereas in cardiac muscle only TRIM7 was expressed. GNIP1 and TRIM7 had autoubiquitination activity in vitro and were localized in the Golgi apparatus and cytosol respectively in LHCN-M2 myoblasts. GNIP1 overexpression increased glucose uptake in LHCN-M2 myotubes. Overexpression of GNIP1 in mouse muscle in vivo increased glycogen content, glycogen synthase (GS) activity and phospho-GSK-3α/β (Ser21/9) and phospho-Akt (Ser473) content, whereas decreased GS phosphorylation in Ser640. These modifications led to decreased blood glucose levels, lactate levels and body weight, without changing whole-body insulin or glucose tolerance in mouse. GNIP1 is an ubiquitin ligase with a markedly glycogenic effect in skeletal muscle. Copyright © 2018 Elsevier Inc. All rights reserved.

Insights into the Membrane Interactions of the Saposin-Like Proteins Na-SLP-1 and Ac-SLP-1 from Human and Dog Hookworm

PubMed Central

Willis, Charlene; Wang, Conan K.; Osman, Asiah; Simon, Anne; Pickering, Darren; Mulvenna, Jason; Riboldi-Tunicliffe, Alan; Jones, Malcolm K.; Loukas, Alex; Hofmann, Andreas

2011-01-01

Saposin-like proteins (SAPLIPs) from soil-transmitted helminths play pivotal roles in host-pathogen interactions and have a high potential as targets for vaccination against parasitic diseases. We have identified two non-orthologous SAPLIPs from human and dog hookworm, Na-SLP-1 and Ac-SLP-1, and solved their three-dimensional crystal structures. Both proteins share the property of membrane binding as monitored by liposome co-pelleting assays and monolayer adsorption. Neither SAPLIP displayed any significant haemolytic or bactericidal activity. Based on the structural information, as well as the results from monolayer adsorption, we propose models of membrane interactions for both SAPLIPs. Initial membrane contact of the monomeric Na-SLP-1 is most likely by electrostatic interactions between the membrane surface and a prominent basic surface patch. In case of the dimeric Ac-SLP-1, membrane interactions are most likely initiated by a unique tryptophan residue that has previously been implicated in membrane interactions in other SAPLIPs. PMID:21991310

Insights into the membrane interactions of the saposin-like proteins Na-SLP-1 and Ac-SLP-1 from human and dog hookworm.

PubMed

Willis, Charlene; Wang, Conan K; Osman, Asiah; Simon, Anne; Pickering, Darren; Mulvenna, Jason; Riboldi-Tunicliffe, Alan; Jones, Malcolm K; Loukas, Alex; Hofmann, Andreas

2011-01-01

Saposin-like proteins (SAPLIPs) from soil-transmitted helminths play pivotal roles in host-pathogen interactions and have a high potential as targets for vaccination against parasitic diseases. We have identified two non-orthologous SAPLIPs from human and dog hookworm, Na-SLP-1 and Ac-SLP-1, and solved their three-dimensional crystal structures. Both proteins share the property of membrane binding as monitored by liposome co-pelleting assays and monolayer adsorption. Neither SAPLIP displayed any significant haemolytic or bactericidal activity. Based on the structural information, as well as the results from monolayer adsorption, we propose models of membrane interactions for both SAPLIPs. Initial membrane contact of the monomeric Na-SLP-1 is most likely by electrostatic interactions between the membrane surface and a prominent basic surface patch. In case of the dimeric Ac-SLP-1, membrane interactions are most likely initiated by a unique tryptophan residue that has previously been implicated in membrane interactions in other SAPLIPs.

Human HOX Proteins Use Diverse and Context-Dependent Motifs to Interact with TALE Class Cofactors.

PubMed

Dard, Amélie; Reboulet, Jonathan; Jia, Yunlong; Bleicher, Françoise; Duffraisse, Marilyne; Vanaker, Jean-Marc; Forcet, Christelle; Merabet, Samir

2018-03-13

HOX proteins achieve numerous functions by interacting with the TALE class PBX and MEIS cofactors. In contrast to this established partnership in development and disease, how HOX proteins could interact with PBX and MEIS remains unclear. Here, we present a systematic analysis of HOX/PBX/MEIS interaction properties, scanning all paralog groups with human and mouse HOX proteins in vitro and in live cells. We demonstrate that a previously characterized HOX protein motif known to be critical for HOX-PBX interactions becomes dispensable in the presence of MEIS in all except the two most anterior paralog groups. We further identify paralog-specific TALE-binding sites that are used in a highly context-dependent manner. One of these binding sites is involved in the proliferative activity of HOXA7 in breast cancer cells. Together these findings reveal an extraordinary level of interaction flexibility between HOX proteins and their major class of developmental cofactors. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Building a framework to manage trust in automation

NASA Astrophysics Data System (ADS)

Metcalfe, J. S.; Marathe, A. R.; Haynes, B.; Paul, V. J.; Gremillion, G. M.; Drnec, K.; Atwater, C.; Estepp, J. R.; Lukos, J. R.; Carter, E. C.; Nothwang, W. D.

2017-05-01

All automations must, at some point in their lifecycle, interface with one or more humans. Whether operators, end-users, or bystanders, human responses can determine the perceived utility and acceptance of an automation. It has been long believed that human trust is a primary determinant of human-automation interactions and further presumed that calibrating trust can lead to appropriate choices regarding automation use. However, attempts to improve joint system performance by calibrating trust have not yet provided a generalizable solution. To address this, we identified several factors limiting the direct integration of trust, or metrics thereof, into an active mitigation strategy. The present paper outlines our approach to addressing this important issue, its conceptual underpinnings, and practical challenges encountered in execution. Among the most critical outcomes has been a shift in focus from trust to basic interaction behaviors and their antecedent decisions. This change in focus inspired the development of a testbed and paradigm that was deployed in two experiments of human interactions with driving automation that were executed in an immersive, full-motion simulation environment. Moreover, by integrating a behavior and physiology-based predictor within a novel consequence-based control system, we demonstrated that it is possible to anticipate particular interaction behaviors and influence humans towards more optimal choices about automation use in real time. Importantly, this research provides a fertile foundation for the development and integration of advanced, wearable technologies for sensing and inferring critical state variables for better integration of human elements into otherwise fully autonomous systems.

Interaction vs. observation: distinctive modes of social cognition in human brain and behavior? A combined fMRI and eye-tracking study

PubMed Central

Tylén, Kristian; Allen, Micah; Hunter, Bjørk K.; Roepstorff, Andreas

2012-01-01

Human cognition has usually been approached on the level of individual minds and brains, but social interaction is a challenging case. Is it best thought of as a self-contained individual cognitive process aiming at an “understanding of the other,” or should it rather be approached as an collective, inter-personal process where individual cognitive components interact on a moment-to-moment basis to form coupled dynamics? In a combined fMRI and eye-tracking study we directly contrasted these models of social cognition. We found that the perception of situations affording social contingent responsiveness (e.g., someone offering or showing you an object) elicited activations in regions of the right posterior temporal sulcus and yielded greater pupil dilation corresponding to a model of coupled dynamics (joint action). In contrast, the social-cognitive perception of someone “privately” manipulating an object elicited activation in medial prefrontal cortex, the right inferior frontal gyrus and right inferior parietal lobus, regions normally associated with Theory of Mind and with the mirror neuron system. Our findings support a distinction in social cognition between social observation and social interaction, and demonstrate that simple ostensive cues may shift participants' experience, behavior, and brain activity between these modes. The identification of a distinct, interactive mode has implications for research on social cognition, both in everyday life and in clinical conditions. PMID:23267322

Toward flexible and wearable human-interactive health-monitoring devices.

PubMed

Takei, Kuniharu; Honda, Wataru; Harada, Shingo; Arie, Takayuki; Akita, Seiji

2015-03-11

This Progress Report introduces flexible wearable health-monitoring devices that interact with a person by detecting from and stimulating the body. Interactive health-monitoring devices should be highly flexible and attach to the body without awareness like a bandage. This type of wearable health-monitoring device will realize a new class of electronics, which will be applicable not only to health monitoring, but also to other electrical devices. However, to realize wearable health-monitoring devices, many obstacles must be overcome to economically form the active electrical components on a flexible substrate using macroscale fabrication processes. In particular, health-monitoring sensors and curing functions need to be integrated. Here recent developments and advancements toward flexible health-monitoring devices are presented, including conceptual designs of human-interactive devices. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The metal chaperone Atox1 regulates the activity of the human copper transporter ATP7B by modulating domain dynamics.

PubMed

Yu, Corey H; Yang, Nan; Bothe, Jameson; Tonelli, Marco; Nokhrin, Sergiy; Dolgova, Natalia V; Braiterman, Lelita; Lutsenko, Svetlana; Dmitriev, Oleg Y

2017-11-03

The human transporter ATP7B delivers copper to the biosynthetic pathways and maintains copper homeostasis in the liver. Mutations in ATP7B cause the potentially fatal hepatoneurological disorder Wilson disease. The activity and intracellular localization of ATP7B are regulated by copper, but the molecular mechanism of this regulation is largely unknown. We show that the copper chaperone Atox1, which delivers copper to ATP7B, and the group of the first three metal-binding domains (MBD1-3) are central to the activity regulation of ATP7B. Atox1-Cu binding to ATP7B changes domain dynamics and interactions within the MBD1-3 group and activates ATP hydrolysis. To understand the mechanism linking Atox1-MBD interactions and enzyme activity, we have determined the MBD1-3 conformational space using small angle X-ray scattering and identified changes in MBD dynamics caused by apo -Atox1 and Atox1-Cu by solution NMR. The results show that copper transfer from Atox1 decreases domain interactions within the MBD1-3 group and increases the mobility of the individual domains. The N-terminal segment of MBD1-3 was found to interact with the nucleotide-binding domain of ATP7B, thus physically coupling the domains involved in copper binding and those involved in ATP hydrolysis. Taken together, the data suggest a regulatory mechanism in which Atox1-mediated copper transfer activates ATP7B by releasing inhibitory constraints through increased freedom of MBD1-3 motions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

A Perspective on Computational Human Performance Models as Design Tools

NASA Technical Reports Server (NTRS)

Jones, Patricia M.

2010-01-01

The design of interactive systems, including levels of automation, displays, and controls, is usually based on design guidelines and iterative empirical prototyping. A complementary approach is to use computational human performance models to evaluate designs. An integrated strategy of model-based and empirical test and evaluation activities is particularly attractive as a methodology for verification and validation of human-rated systems for commercial space. This talk will review several computational human performance modeling approaches and their applicability to design of display and control requirements.

Human interactions with sirenians (manatees and dugongs)

USGS Publications Warehouse

Bonde, Robert K.; Flint, Mark

2017-01-01

There are three extant sirenian species of the Trichechidae family and one living Dugongidae family member. Given their close ties to coastal and often urbanized habitats, sirenians are exposed to many types of anthropogenic activities that result in challenges to their well-being, poor health, and even death. In the wild, they are exposed to direct and indirect local pressures as well as subject to large-scale stressors such as global climate change acting on regions or entire genetic stocks. In captivity, they are subject to husbandry and management practices based on our collective knowledge, or in some cases lack thereof, of their needs and welfare. It is therefore reasonable to consider that their current imperiled status is very closely linked to our actions. In this chapter, we identify and define human interactions that may impact dugongs and manatees, including hunting, fisheries, boat interactions, negative interactions with man-made structures, disease and contaminants, and global climate change. We examine techniques used to investigate these impacts and the influence of sirenian biology and of changing human behaviors on potential outcomes. We examine how this differs for dugongs and manatees in the wild and for those held in captivity. Finally, we provide possible mitigation strategies and ways to assess the efforts we are making to improve the welfare of individuals and to conserve these species. This chapter identifies how the welfare of these species is intrinsically linked to the human interactions these animals experience, and how the nature of these interactions has changed with societal shifts. We proffer suggested ways to minimize negative impacts. Current knowledge should be used to minimize negative human interactions and impacts, to promote positive impacts, and to protect these animals for the future.

Interaction between synaptic inhibition and glial-potassium dynamics leads to diverse seizure transition modes in biophysical models of human focal seizures.

PubMed

Y Ho, E C; Truccolo, Wilson

2016-10-01

How focal seizures initiate and evolve in human neocortex remains a fundamental problem in neuroscience. Here, we use biophysical neuronal network models of neocortical patches to study how the interaction between inhibition and extracellular potassium ([K (+)] o ) dynamics may contribute to different types of focal seizures. Three main types of propagated focal seizures observed in recent intracortical microelectrode recordings in humans were modelled: seizures characterized by sustained (∼30-60 Hz) gamma local field potential (LFP) oscillations; seizures where the onset in the propagated site consisted of LFP spikes that later evolved into rhythmic (∼2-3 Hz) spike-wave complexes (SWCs); and seizures where a brief stage of low-amplitude fast-oscillation (∼10-20 Hz) LFPs preceded the SWC activity. Our findings are fourfold: (1) The interaction between elevated [K (+)] o (due to abnormal potassium buffering by glial cells) and the strength of synaptic inhibition plays a predominant role in shaping these three types of seizures. (2) Strengthening of inhibition leads to the onset of sustained narrowband gamma seizures. (3) Transition into SWC seizures is obtained either by the weakening of inhibitory synapses, or by a transient strengthening followed by an inhibitory breakdown (e.g. GABA depletion). This reduction or breakdown of inhibition among fast-spiking (FS) inhibitory interneurons increases their spiking activity and leads them eventually into depolarization block. Ictal spike-wave discharges in the model are then sustained solely by pyramidal neurons. (4) FS cell dynamics are also critical for seizures where the evolution into SWC activity is preceded by low-amplitude fast oscillations. Different levels of elevated [K (+)] o were important for transitions into and maintenance of sustained gamma oscillations and SWC discharges. Overall, our modelling study predicts that the interaction between inhibitory interneurons and [K (+)] o glial buffering under abnormal conditions may explain different types of ictal transitions and dynamics during propagated seizures in human focal epilepsy.

MD-2 residues tyrosine 42, arginine 69, aspartic acid 122, and leucine 125 provide species specificity for lipid IVA.

PubMed

Meng, Jianmin; Drolet, Joshua R; Monks, Brian G; Golenbock, Douglas T

2010-09-03

Lipopolysaccharide (LPS) activates the innate immune response through the Toll-like receptor 4 (TLR4).MD-2 complex. A synthetic lipid A precursor, lipid IV(A), induces an innate immune response in mice but not in humans. Both TLR4 and MD-2 are required for the agonist activity of lipid IV(A) in mice, with TLR4 interacting through specific surface charges at the dimerization interface. In this study, we used site-directed mutagenesis to identify the MD-2 residues that determine lipid IV(A) species specificity. A single mutation of murine MD-2 at the hydrophobic pocket entrance, E122K, substantially reduced the response to lipid IV(A). Combining the murine MD-2 E122K with the murine TLR4 K367E/S386K/R434Q mutations completely abolished the response to lipid IV(A), effectively converting the murine cellular response to a human-like response. In human cells, however, simultaneous mutations of K122E, K125L, Y41F, and R69G on human MD-2 were required to promote a response to lipid IV(A). Combining the human MD-2 quadruple mutations with the human TLR4 E369K/Q436R mutations completely converted the human MD-2/human TLR4 receptor to a murine-like receptor. Because MD-2 residues 122 and 125 reside at the dimerization interface near the pocket entrance, surface charge differences here directly affect receptor dimerization. In comparison, residues 42 and 69 reside at the MD-2/TLR4 interaction surface opposite the dimerization interface. Surface charge differences there likely affect the binding angle and/or rigidity between MD-2 and TLR4, exerting an indirect influence on receptor dimerization and activation. Thus, surface charge differences at the two MD-2/TLR4 interfaces determine the species-specific activation of lipid IV(A).

Molecular and Cellular Mechanisms of Sperm-Oocyte Interactions Opinions Relative to in Vitro Fertilization (IVF)

PubMed Central

Anifandis, George; Messini, Christina; Dafopoulos, Konstantinos; Sotiriou, Sotiris; Messinis, Ioannis

2014-01-01

One of the biggest prerequisites for pregnancy is the fertilization step, where a human haploid spermatozoon interacts and penetrates one haploid oocyte in order to produce the diploid zygote. Although fertilization is defined by the presence of two pronuclei and the extraction of the second polar body the process itself requires preparation of both gametes for fertilization to take place at a specific time. These preparations include a number of consecutive biochemical and molecular events with the help of specific molecules and with the consequential interaction between the two gametes. These events take place at three different levels and in a precise order, where the moving spermatozoon penetrates (a) the outer vestments of the oocyte, known as the cumulus cell layer; (b) the zona pellucida (ZP); where exocytosis of the acrosome contents take place and (c) direct interaction of the spermatozoon with the plasma membrane of the oocyte, which involves a firm adhesion of the head of the spermatozoon with the oocyte plasma membrane that culminates with the fusion of both sperm and oocyte membranes (Part I). After the above interactions, a cascade of molecular signal transductions is initiated which results in oocyte activation. Soon after the entry of the first spermatozoon into the oocyte and oocyte activation, the oocyte’s coat (the ZP) and the oocyte’s plasma membrane seem to change quickly in order to initiate a fast block to a second spermatozoon (Part II). Sometimes, two spermatozoa fuse with one oocyte, an incidence of 1%–2%, resulting in polyploid fetuses that account for up to 10%–20% of spontaneously aborted human conceptuses. The present review aims to focus on the first part of the human sperm and oocyte interactions, emphasizing the latest molecular and cellular mechanisms controlling this process. PMID:25054321

Molecular and cellular mechanisms of sperm-oocyte interactions opinions relative to in vitro fertilization (IVF).

PubMed

Anifandis, George; Messini, Christina; Dafopoulos, Konstantinos; Sotiriou, Sotiris; Messinis, Ioannis

2014-07-22

One of the biggest prerequisites for pregnancy is the fertilization step, where a human haploid spermatozoon interacts and penetrates one haploid oocyte in order to produce the diploid zygote. Although fertilization is defined by the presence of two pronuclei and the extraction of the second polar body the process itself requires preparation of both gametes for fertilization to take place at a specific time. These preparations include a number of consecutive biochemical and molecular events with the help of specific molecules and with the consequential interaction between the two gametes. These events take place at three different levels and in a precise order, where the moving spermatozoon penetrates (a) the outer vestments of the oocyte, known as the cumulus cell layer; (b) the zona pellucida (ZP); where exocytosis of the acrosome contents take place and (c) direct interaction of the spermatozoon with the plasma membrane of the oocyte, which involves a firm adhesion of the head of the spermatozoon with the oocyte plasma membrane that culminates with the fusion of both sperm and oocyte membranes (Part I). After the above interactions, a cascade of molecular signal transductions is initiated which results in oocyte activation. Soon after the entry of the first spermatozoon into the oocyte and oocyte activation, the oocyte's coat (the ZP) and the oocyte's plasma membrane seem to change quickly in order to initiate a fast block to a second spermatozoon (Part II). Sometimes, two spermatozoa fuse with one oocyte, an incidence of 1%-2%, resulting in polyploid fetuses that account for up to 10%-20% of spontaneously aborted human conceptuses. The present review aims to focus on the first part of the human sperm and oocyte interactions, emphasizing the latest molecular and cellular mechanisms controlling this process.

[The interface of public healthcare with the health of the oceans: proliferation of disease, socio-economic impacts and beneficial relationships].

PubMed

de Moura, Jailson Fulgencio; Cardozo, Marcelo; Belo, Mariana Soares da Silva Peixoto; Hacon, Sandra; Siciliano, Salvatore

2011-08-01

Over the past decades, human activities have had a heavy impact on the marine environment, causing alterations in ecological processes. The relationship between the health of the oceans, human activities and public healthcare is already generally accepted, though the mechanisms involved are still under scientific scrutiny. These relationships include a focus on climate change, toxic algal blooms, microbial and chemical contamination in marine waters and bioinvasion by exotic species. Moreover, there is the beneficial effect of the oceans on human health and wellbeing, such as natural products for the human diet, the development of biomedicine, or simply the satisfaction derived from human recreation, sports and other interactions of humans with oceans. The importance of appreciating the link between public healthcare and the health of the oceans is especially important due to the growing number of people living in coastal areas, mainly in tropical and subtropical regions. The backcloth to this is risk-related human activities that pose a danger to marine environmental health and the increase in the vulnerability of humans and biodiversity and socio-environmental iniquity.

Requirements for psychological models to support design: Towards ecological task analysis

NASA Technical Reports Server (NTRS)

Kirlik, Alex

1991-01-01

Cognitive engineering is largely concerned with creating environmental designs to support skillful and effective human activity. A set of necessary conditions are proposed for psychological models capable of supporting this enterprise. An analysis of the psychological nature of the design product is used to identify a set of constraints that models must meet if they can usefully guide design. It is concluded that cognitive engineering requires models with resources for describing the integrated human-environment system, and that these models must be capable of describing the activities underlying fluent and effective interaction. These features are required in order to be able to predict the cognitive activity that will be required given various design concepts, and to design systems that promote the acquisition of fluent, skilled behavior. These necessary conditions suggest that an ecological approach can provide valuable resources for psychological modeling to support design. Relying heavily on concepts from Brunswik's and Gibson's ecological theories, ecological task analysis is proposed as a framework in which to predict the types of cognitive activity required to achieve productive behavior, and to suggest how interfaces can be manipulated to alleviate certain types of cognitive demands. The framework is described in terms, and illustrated with an example from the previous research on modeling skilled human-environment interaction.

Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis.

PubMed

Lee, Soung-Hoon; Seo, Seol Hwa; Lee, Dong-Hwan; Pi, Long-Quan; Lee, Won-Soo; Choi, Kang-Yell

2017-11-01

The Wnt/β-catenin pathway has been implicated in hair follicle development and hair regeneration in adults. We discovered that CXXC-type zinc finger protein 5 (CXXC5) is a negative regulator of the Wnt/β-catenin pathway involved in hair regrowth and wound-induced hair follicle neogenesis via an interaction with Dishevelled. CXXC5 was upregulated in miniaturized hair follicles and arrector pili muscles in human balding scalps. The inhibitory effects of CXXC5 on alkaline phosphatase activity and cell proliferation were demonstrated using human hair follicle dermal papilla cells. Moreover, CXXC5 -/- mice displayed accelerated hair regrowth, and treatment with valproic acid, a glycogen synthase kinase 3β inhibitor that activates the Wnt/β-catenin pathway, further induced hair regrowth in the CXXC5 -/- mice. Disrupting the CXXC5-Dishevelled interaction with a competitor peptide activated the Wnt/β-catenin pathway and accelerated hair regrowth and wound-induced hair follicle neogenesis. Overall, these findings suggest that the CXXC5-Dishevelled interaction is a potential target for the treatment of hair loss. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Interferon-γ converts human microvascular pericytes into negative regulators of alloimmunity through induction of indoleamine 2,3-dioxygenase 1

PubMed Central

Liu, Rebecca; Manes, Thomas D.; Qin, Lingfeng; Tietjen, Gregory T.; Broecker, Verena; Fang, Caodi; Xie, Catherine; Chen, Ping-Min; Kirkiles-Smith, Nancy C.; Jane-Wit, Dan; Pober, Jordan S.

2018-01-01

Early acute rejection of human allografts is mediated by circulating alloreactive host effector memory T cells (TEM). TEM infiltration typically occurs across graft postcapillary venules and involves sequential interactions with graft-derived endothelial cells (ECs) and pericytes (PCs). While the role of ECs in allograft rejection has been extensively studied, contributions of PCs to this process are largely unknown. This study aimed to characterize the effects and mechanisms of interactions between human PCs and allogeneic TEM. We report that unstimulated PCs, like ECs, can directly present alloantigen to TEM, but while IFN-γ–activated ECs (γ-ECs) show increased ability to stimulate alloreactive T cells, IFN-γ–activated PCs (γ-PCs) instead suppress TEM proliferation but not cytokine production or signaling. RNA sequencing analysis of PCs, γ-PCs, ECs, and γ-ECs reveal induction of indoleamine 2,3-dioxygenase 1 (IDO1) in γ-PCs to significantly higher levels than in γ-ECs that correlates with tryptophan depletion in vitro. Consistently, shRNA knockdown of IDO1 markedly reduces γ-PC–mediated immunoregulatory effects. Furthermore, human PCs express IDO1 in a skin allograft rejection humanized mouse model and in human renal allografts with acute T cell–mediated rejection. We conclude that immunosuppressive properties of human PCs are not intrinsic but instead result from IFN-γ–induced IDO1-mediated tryptophan depletion. PMID:29515027

TXNIP links redox circuitry to glucose control.

PubMed

Muoio, Deborah M

2007-06-01

Thioredoxin-interacting protein (TXNIP) binds and inhibits the reducing activity of thioredoxin. A new study (Parikh et al., 2007) implicates this redox rheostat as a negative regulator of peripheral glucose metabolism in humans. Investigators combined human physiology, genomic screening, and cell-based genetic studies to highlight TNXIP as a potential culprit in the pathogenesis of type 2 diabetes.

The Interactive Effects of Elevated CO2 and Ozone on Leaf Thermotolerance in Field-Grown Glycine Max (Soybean)

USDA-ARS?s Scientific Manuscript database

Human activity is increasing atmospheric CO2, which is increasing both mean global temperatures and acute heat stress (heat waves). Laboratory studies have shown that elevated CO2 can increase tolerance of photosynthesis to acute heat stress in C3 plants. However, human-caused increases in ground-...

How Learning Techniques Initiate Simulation of Human Mind

ERIC Educational Resources Information Center

Girija, C.

2014-01-01

The simulation of human mind often helps in the understanding of abstract concept by representing it in a realistic model and simplistic way so that a learner develops an understanding of the key concepts. Bian (1873) and James (1890) in their work suggested that thoughts and body activity result from interactions among neurons within the brain.…

A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2

NASA Astrophysics Data System (ADS)

Breitkopf, Susanne B.; Yang, Xuemei; Begley, Michael J.; Kulkarni, Meghana; Chiu, Yu-Hsin; Turke, Alexa B.; Lauriol, Jessica; Yuan, Min; Qi, Jie; Engelman, Jeffrey A.; Hong, Pengyu; Kontaridis, Maria I.; Cantley, Lewis C.; Perrimon, Norbert; Asara, John M.

2016-02-01

Using a series of immunoprecipitation (IP) - tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway.

Quantifying over-activity in bipolar and schizophrenia patients in a human open field paradigm.

PubMed

Perry, William; Minassian, Arpi; Henry, Brook; Kincaid, Meegin; Young, Jared W; Geyer, Mark A

2010-06-30

It has been suggested that a cardinal symptom of mania is over-activity and exaggerated goal-directed behavior. Nevertheless, few attempts have been made to quantify this behavior objectively in a laboratory environment. Having a methodology to assess over-activity reliably might be useful in distinguishing manic bipolar disorder (BD) from schizophrenia (SCZ) during highly activated states. In the current study, quantifiable measures of object interaction were assessed using a multivariate approach. Additionally, symptom correlates of over-activity were assessed. Patients admitted to an acute care psychiatric hospital for either BD with mania or SCZ (paranoid and non-paranoid subtypes) as well as non-patient comparison (NC) participants were assessed in an open field setting referred to as the human Behavioral Pattern Monitor (hBPM). Activity and interactions with novel and engaging objects were recorded for 15min via a concealed video camera and rated for exploratory behavior. Both BD and SCZ patients spent more time near the objects and exhibited more overall walking compared to NC. In contrast, BD patients exhibited greater physical contact with objects (number of object interactions and time spent with objects) relative to SCZ patients or NC participants, as well as more perseverative and socially disinhibited behaviors, indicating a unique pattern of over-activity and goal-directed behavior. Further analyses revealed a distinction between SCZ patients according to their subtype. The current study extends our methodology for quantifying exploration and over-activity in a controlled laboratory setting and aids in assessing the overlap and distinguishing characteristics of BD and SCZ.

Activation of duck RIG-I by TRIM25 is independent of anchored ubiquitin.

PubMed

Miranzo-Navarro, Domingo; Magor, Katharine E

2014-01-01

Retinoic acid inducible gene I (RIG-I) is a viral RNA sensor crucial in defense against several viruses including measles, influenza A and hepatitis C. RIG-I activates type-I interferon signalling through the adaptor for mitochondrial antiviral signaling (MAVS). The E3 ubiquitin ligase, tripartite motif containing protein 25 (TRIM25), activates human RIG-I through generation of anchored K63-linked polyubiquitin chains attached to lysine 172, or alternatively, through the generation of unanchored K63-linked polyubiquitin chains that interact non-covalently with RIG-I CARD domains. Previously, we identified RIG-I of ducks, of interest because ducks are the host and natural reservoir of influenza viruses, and showed it initiates innate immune signaling leading to production of interferon-beta (IFN-β). We noted that K172 is not conserved in RIG-I of ducks and other avian species, or mouse. Because K172 is important for both mechanisms of activation of human RIG-I, we investigated whether duck RIG-I was activated by TRIM25, and if other residues were the sites for attachment of ubiquitin. Here we show duck RIG-I CARD domains are ubiquitinated for activation, and ubiquitination depends on interaction with TRIM25, as a splice variant that cannot interact with TRIM25 is not ubiquitinated, and cannot be activated. We expressed GST-fusion proteins of duck CARD domains and characterized TRIM25 modifications of CARD domains by mass spectrometry. We identified two sites that are ubiquitinated in duck CARD domains, K167 and K193, and detected K63 linked polyubiquitin chains. Site directed mutagenesis of each site alone, does not alter the ubiquitination profile of the duck CARD domains. However, mutation of both sites resulted in loss of all attached ubiquitin and polyubiquitin chains. Remarkably, the double mutant duck RIG-I CARD still interacts with TRIM25, and can still be activated. Our results demonstrate that anchored ubiquitin chains are not necessary for TRIM25 activation of duck RIG-I.

How Do Small Things Make a Big Difference? Activities to Teach about Human-Microbe Interactions

ERIC Educational Resources Information Center

Jasti, Chandana; Hug, Barbara; Waters, Jillian L.; Whitaker, Rachel J.

2014-01-01

Recent scientific studies are providing increasing evidence for how microbes living in and on us are essential to our good health. However, many students still think of microbes only as germs that harm us. The classroom activities presented here are designed to shift student thinking on this topic. In these guided inquiry activities, students…

[Lights, art, science - action!].

PubMed

Lopes, Thelma

2005-01-01

The article offers some reflections on the main interactions between theater, science, and technology down through the history of theater. Based on our experience at "Science in the Spotlight", part of the Casa de Oswaldo Cruz's Museum of Life, we discuss how these interactions can be part of a science museum's daily activities. We use the word 'science' in its broad sense, encompassing not only the natural but human sciences as well; likewise, we use the word 'technology' as it relates to applied science. Art and science are understood here as creative processes, as ways of representing the world and expressing human knowledge.

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

Interaction of galectin-3 with MUC1 on cell surface promotes EGFR dimerization and activation in human epithelial cancer cells.

PubMed

Piyush, Tushar; Chacko, Anisha R; Sindrewicz, Paulina; Hilkens, John; Rhodes, Jonathan M; Yu, Lu-Gang

2017-11-01

Epidermal growth factor receptor (EGFR) is an important regulator of epithelial cell growth and survival in normal and cancerous tissues and is a principal therapeutic target for cancer treatment. EGFR is associated in epithelial cells with the heavily glycosylated transmembrane mucin protein MUC1, a natural ligand of galectin-3 that is overexpressed in cancer. This study reveals that the expression of cell surface MUC1 is a critical enhancer of EGF-induced EGFR activation in human breast and colon cancer cells. Both the MUC1 extracellular and intracellular domains are involved in EGFR activation but the predominant influence comes from its extracellular domain. Binding of galectin-3 to the MUC1 extracellular domain induces MUC1 cell surface polarization and increases MUC1-EGFR association. This leads to a rapid increase of EGFR homo-/hetero-dimerization and subsequently increased, and also prolonged, EGFR activation and signalling. This effect requires both the galectin-3 C-terminal carbohydrate recognition domain and its N-terminal ligand multi-merization domain. Thus, interaction of galectin-3 with MUC1 on cell surface promotes EGFR dimerization and activation in epithelial cancer cells. As MUC1 and galectin-3 are both commonly overexpressed in most types of epithelial cancers, their interaction and impact on EGFR activation likely makes important contribution to EGFR-associated tumorigenesis and cancer progression and may also influence the effectiveness of EGFR-targeted cancer therapy.

A Scalable Approach for Discovering Conserved Active Subnetworks across Species

PubMed Central

Verfaillie, Catherine M.; Hu, Wei-Shou; Myers, Chad L.

2010-01-01

Overlaying differential changes in gene expression on protein interaction networks has proven to be a useful approach to interpreting the cell's dynamic response to a changing environment. Despite successes in finding active subnetworks in the context of a single species, the idea of overlaying lists of differentially expressed genes on networks has not yet been extended to support the analysis of multiple species' interaction networks. To address this problem, we designed a scalable, cross-species network search algorithm, neXus (Network - cross(X)-species - Search), that discovers conserved, active subnetworks based on parallel differential expression studies in multiple species. Our approach leverages functional linkage networks, which provide more comprehensive coverage of functional relationships than physical interaction networks by combining heterogeneous types of genomic data. We applied our cross-species approach to identify conserved modules that are differentially active in stem cells relative to differentiated cells based on parallel gene expression studies and functional linkage networks from mouse and human. We find hundreds of conserved active subnetworks enriched for stem cell-associated functions such as cell cycle, DNA repair, and chromatin modification processes. Using a variation of this approach, we also find a number of species-specific networks, which likely reflect mechanisms of stem cell function that have diverged between mouse and human. We assess the statistical significance of the subnetworks by comparing them with subnetworks discovered on random permutations of the differential expression data. We also describe several case examples that illustrate the utility of comparative analysis of active subnetworks. PMID:21170309

Learning dictionaries of sparse codes of 3D movements of body joints for real-time human activity understanding.

PubMed

Qi, Jin; Yang, Zhiyong

2014-01-01

Real-time human activity recognition is essential for human-robot interactions for assisted healthy independent living. Most previous work in this area is performed on traditional two-dimensional (2D) videos and both global and local methods have been used. Since 2D videos are sensitive to changes of lighting condition, view angle, and scale, researchers begun to explore applications of 3D information in human activity understanding in recently years. Unfortunately, features that work well on 2D videos usually don't perform well on 3D videos and there is no consensus on what 3D features should be used. Here we propose a model of human activity recognition based on 3D movements of body joints. Our method has three steps, learning dictionaries of sparse codes of 3D movements of joints, sparse coding, and classification. In the first step, space-time volumes of 3D movements of body joints are obtained via dense sampling and independent component analysis is then performed to construct a dictionary of sparse codes for each activity. In the second step, the space-time volumes are projected to the dictionaries and a set of sparse histograms of the projection coefficients are constructed as feature representations of the activities. Finally, the sparse histograms are used as inputs to a support vector machine to recognize human activities. We tested this model on three databases of human activities and found that it outperforms the state-of-the-art algorithms. Thus, this model can be used for real-time human activity recognition in many applications.

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."

Human brain networks function in connectome-specific harmonic waves.

PubMed

Atasoy, Selen; Donnelly, Isaac; Pearson, Joel

2016-01-21

A key characteristic of human brain activity is coherent, spatially distributed oscillations forming behaviour-dependent brain networks. However, a fundamental principle underlying these networks remains unknown. Here we report that functional networks of the human brain are predicted by harmonic patterns, ubiquitous throughout nature, steered by the anatomy of the human cerebral cortex, the human connectome. We introduce a new technique extending the Fourier basis to the human connectome. In this new frequency-specific representation of cortical activity, that we call 'connectome harmonics', oscillatory networks of the human brain at rest match harmonic wave patterns of certain frequencies. We demonstrate a neural mechanism behind the self-organization of connectome harmonics with a continuous neural field model of excitatory-inhibitory interactions on the connectome. Remarkably, the critical relation between the neural field patterns and the delicate excitation-inhibition balance fits the neurophysiological changes observed during the loss and recovery of consciousness.

Upregulation and Identification of Antibiotic Activity of a Marine-Derived Streptomyces sp. via Co-Cultures with Human Pathogens.

PubMed

Sung, Anne A; Gromek, Samantha M; Balunas, Marcy J

2017-08-11

Marine natural product drug discovery has begun to play an important role in the treatment of disease, with several recently approved drugs. In addition, numerous microbial natural products have been discovered from members of the order Actinomycetales, particularly in the genus Streptomyces , due to their metabolic diversity for production of biologically active secondary metabolites. However, many secondary metabolites cannot be produced under laboratory conditions because growth conditions in flask culture differ from conditions in the natural environment. Various experimental conditions (e.g., mixed fermentation) have been attempted to increase yields of previously described metabolites, cause production of previously undetected metabolites, and increase antibiotic activity. Adult ascidians-also known as tunicates-are sessile marine invertebrates, making them vulnerable to predation and therefore are hypothesized to use host-associated bacteria that produce biologically active secondary metabolites for chemical defense. A marine-derived Streptomyces sp. strain PTY087I2 was isolated from a Panamanian tunicate and subsequently co-cultured with human pathogens including Bacillus subtilis , methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa , followed by extraction. Co-culture of Streptomyces sp. PTY087I2 with each of these human pathogens resulted in increased production of three antibiotics: granaticin, granatomycin D, and dihydrogranaticin B, as well as several analogues seen via molecular networking. In addition, co-cultures resulted in strongly enhanced biological activity against the Gram positive human pathogens used in these experiments. Expanded utilization of co-culture experiments to allow for competitive interactions may enhance metabolite production and further our understanding of these microbial interactions.

Interspecies Variation in the Functional Consequences of Mutation of Cytochrome c

PubMed Central

Josephs, Tracy M.; Hibbs, Moira E.; Ong, Lily; Morison, Ian M.; Ledgerwood, Elizabeth C.

2015-01-01

The naturally occurring human cytochrome c variant (G41S) is associated with a mild autosomal dominant thrombocytopenia (Thrombocytopenia Cargeeg) caused by dysregulation of platelet production. The molecular basis of the platelet production defect is unknown. Despite high conservation of cytochrome c between human and mouse (91.4% identity), introducing the G41S mutation into mouse cytochrome c in a knockin mouse (Cycs G41S/G41S) did not recapitulate the low platelet phenotype of Thrombocytopenia Cargeeg. While investigating the cause of this disparity we found a lack of conservation of the functional impact of cytochrome c mutations on caspase activation across species. Mutation of cytochrome c at residue 41 has distinct effects on the ability of cytochrome c to activate caspases depending on the species of both the cytochrome c and its binding partner Apaf-1. In contrast to our previous results showing the G41S mutation increases the ability of human cytochrome c to activate caspases, here we find this activity is decreased in mouse G41S cytochrome c. Additionally unlike wildtype human cytochrome c, G41S cytochrome c is unable to activate caspases in Xenopus embryo extracts. Taken together these results demonstrate a previously unreported species-specific component to the interaction of cytochrome c with Apaf-1. This suggests that the electrostatic interaction between cytochrome c and Apaf-1 is not the sole determinant of binding, with additional factors controlling binding specificity and affinity. These results have important implications for studies of the effects of cytochrome c mutations on the intrinsic apoptosis pathway. PMID:26086723

Effect of microgravity & space radiation on microbes.

PubMed

Senatore, Giuliana; Mastroleo, Felice; Leys, Natalie; Mauriello, Gianluigi

2018-06-01

One of the new challenges facing humanity is to reach increasingly further distant space targets. It is therefore of upmost importance to understand the behavior of microorganisms that will unavoidably reach the space environment together with the human body and equipment. Indeed, microorganisms could activate their stress defense mechanisms, modifying properties related to human pathogenesis. The host-microbe interactions, in fact, could be substantially affected under spaceflight conditions and the study of microorganisms' growth and activity is necessary for predicting these behaviors and assessing precautionary measures during spaceflight. This review gives an overview of the effects of microgravity and space radiation on microorganisms both in real and simulated conditions.

Safe Operations of Unmanned Systems for Reconnaissance in Complex Environments-Army Technology Objective (SOURCE ATO) Field Experimentation Observations and Soldier Feedback

DTIC Science & Technology

2012-07-01

intent during mission activities. Autonomous assets will have interactions with humans in several different relationships that could benefit from...RDRL HRM CN R SPENCER DCSFDI HF HQ USASOC BLDG E2929 FORT BRAGG NC 28310-5000 1 ARMY RSCH LABORATORY – HRED HUMAN RSRCH AND ENGRNG...A. William Evans, III Human Research and Engineering Directorate, ARL Approved for public release

Epigenetic Regulation of Chermokine Expression in Prostate Cancer

DTIC Science & Technology

2008-12-01

Chemotactic potential of CXCL14 for human DC Recently, we demonstrated that CXCL14 and CXCL14-positive HNSCC ( Head and Neck Squamouse Cell...insights into the functional interaction between DC and neoplastic cells, we proposed to analyze the effects of PCa on the chemotaxis of human DC in...vitro and in vivo. Our Specific Aims were: 1. Characterize chemotactic activity of CXCL14 towards human DC in vitro. 2. Examine whether restoration of

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

Bone morphogenetic protein and Notch signalling crosstalk in poor-prognosis, mesenchymal-subtype colorectal cancer.

PubMed

Irshad, Shazia; Bansal, Mukesh; Guarnieri, Paolo; Davis, Hayley; Al Haj Zen, Ayman; Baran, Brygida; Pinna, Claudia Maria Assunta; Rahman, Haseeb; Biswas, Sujata; Bardella, Chiara; Jeffery, Rosemary; Wang, Lai Mun; East, James Edward; Tomlinson, Ian; Lewis, Annabelle; Leedham, Simon John

2017-06-01

The functional role of bone morphogenetic protein (BMP) signalling in colorectal cancer (CRC) is poorly defined, with contradictory results in cancer cell line models reflecting the inherent difficulties of assessing a signalling pathway that is context-dependent and subject to genetic constraints. By assessing the transcriptional response of a diploid human colonic epithelial cell line to BMP ligand stimulation, we generated a prognostic BMP signalling signature, which was applied to multiple CRC datasets to investigate BMP heterogeneity across CRC molecular subtypes. We linked BMP and Notch signalling pathway activity and function in human colonic epithelial cells, and normal and neoplastic tissue. BMP induced Notch through a γ-secretase-independent interaction, regulated by the SMAD proteins. In homeostasis, BMP/Notch co-localization was restricted to cells at the top of the intestinal crypt, with more widespread interaction in some human CRC samples. BMP signalling was downregulated in the majority of CRCs, but was conserved specifically in mesenchymal-subtype tumours, where it interacts with Notch to induce an epithelial-mesenchymal transition (EMT) phenotype. In intestinal homeostasis, BMP-Notch pathway crosstalk is restricted to differentiating cells through stringent pathway segregation. Conserved BMP activity and loss of signalling stringency in mesenchymal-subtype tumours promotes a synergistic BMP-Notch interaction, and this correlates with poor patient prognosis. BMP signalling heterogeneity across CRC subtypes and cell lines can account for previous experimental contradictions. Crosstalk between the BMP and Notch pathways will render mesenchymal-subtype CRC insensitive to γ-secretase inhibition unless BMP activation is concomitantly addressed. © 2017 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Social interaction, languaging and the operational conditions for the emergence of observing.

PubMed

Raimondi, Vincenzo

2014-01-01

In order to adequately understand the foundations of human social interaction, we need to provide an explanation of our specific mode of living based on linguistic activity and the cultural practices with which it is interwoven. To this end, we need to make explicit the constitutive conditions for the emergence of the phenomena which relate to language and joint activity starting from their operational-relational matrix. The approach presented here challenges the inadequacy of mentalist models to explain the relation between language and interaction. Recent empirical studies concerning joint attention and language acquisition have led scholars such as Tomasello et al. (2005) to postulate the existence of a universal human "sociocognitive infrastructure" that drives joint social activities and is biologically inherited. This infrastructure would include the skill of precocious intention-reading, and is meant to explain human linguistic development and cultural learning. However, the cognitivist and functionalist assumptions on which this model relies have resulted in controversial hypotheses (i.e., intention-reading as the ontogenetic precursor of language) which take a contentious conception of mind and language for granted. By challenging this model, I will show that we should instead turn ourselves towards a constitutive explanation of language within a "bio-logical" understanding of interactivity. This is possible only by abandoning the cognitivist conception of organism and traditional views of language. An epistemological shift must therefore be proposed, based on embodied, enactive and distributed approaches, and on Maturana's work in particular. The notions of languaging and observing that will be discussed in this article will allow for a bio-logically grounded, theoretically parsimonious alternative to mentalist and spectatorial approaches, and will guide us towards a wider understanding of our sociocultural mode of living.

A Failure to Communicate

PubMed Central

Kronert, William A.; Melkani, Girish C.; Melkani, Anju; Bernstein, Sanford I.

2015-01-01

Our molecular modeling studies suggest a charge-dependent interaction between residues Glu-497 in the relay domain and Arg-712 in the converter domain of human β-cardiac myosin. To test the significance of this putative interaction, we generated transgenic Drosophila expressing indirect flight muscle myosin with charge reversal mutations in the relay (E496R) or converter (R713E). Each mutation yielded dramatic reductions in myosin Ca-ATPase activity (∼80%) as well as in basal (∼67%) and actin-activated (∼84%) Mg-ATPase activity. E496R myosin-induced in vitro actin-sliding velocity was reduced by 71% and R713E myosin permitted no actin motility. Indirect flight muscles of late pupae from each mutant displayed disrupted myofibril assembly, with adults having severely abnormal myofibrils and no flight ability. To understand the molecular basis of these defects, we constructed a putative compensatory mutant that expresses myosin with both E496R and R713E. Intriguingly, ATPase values were restored to ∼73% of wild-type and actin-sliding velocity increased to 40%. The double mutation suppresses myofibril assembly defects in pupal indirect flight muscles and dramatically reduces myofibril disruption in young adults. Although sarcomere organization is not sustained in older flies and flight ability is not restored in homozygotes, young heterozygotes fly well. Our results indicate that this charge-dependent interaction between the myosin relay and converter domains is essential to the mechanochemical cycle and sarcomere assembly. Furthermore, the same inter-domain interaction is disrupted when modeling human β-cardiac myosin heavy chain cardiomyopathy mutations E497D or R712L, implying that abolishing this salt bridge is one cause of the human disease. PMID:26446785

Social interaction, languaging and the operational conditions for the emergence of observing

PubMed Central

Raimondi, Vincenzo

2014-01-01

In order to adequately understand the foundations of human social interaction, we need to provide an explanation of our specific mode of living based on linguistic activity and the cultural practices with which it is interwoven. To this end, we need to make explicit the constitutive conditions for the emergence of the phenomena which relate to language and joint activity starting from their operational-relational matrix. The approach presented here challenges the inadequacy of mentalist models to explain the relation between language and interaction. Recent empirical studies concerning joint attention and language acquisition have led scholars such as Tomasello et al. (2005) to postulate the existence of a universal human “sociocognitive infrastructure” that drives joint social activities and is biologically inherited. This infrastructure would include the skill of precocious intention-reading, and is meant to explain human linguistic development and cultural learning. However, the cognitivist and functionalist assumptions on which this model relies have resulted in controversial hypotheses (i.e., intention-reading as the ontogenetic precursor of language) which take a contentious conception of mind and language for granted. By challenging this model, I will show that we should instead turn ourselves towards a constitutive explanation of language within a “bio-logical” understanding of interactivity. This is possible only by abandoning the cognitivist conception of organism and traditional views of language. An epistemological shift must therefore be proposed, based on embodied, enactive and distributed approaches, and on Maturana’s work in particular. The notions of languaging and observing that will be discussed in this article will allow for a bio-logically grounded, theoretically parsimonious alternative to mentalist and spectatorial approaches, and will guide us towards a wider understanding of our sociocultural mode of living. PMID:25177308

Believing androids - fMRI activation in the right temporo-parietal junction is modulated by ascribing intentions to non-human agents.

PubMed

Özdem, Ceylan; Wiese, Eva; Wykowska, Agnieszka; Müller, Hermann; Brass, Marcel; Van Overwalle, Frank

2017-10-01

Attributing mind to interaction partners has been shown to increase the social relevance we ascribe to others' actions and to modulate the amount of attention dedicated to them. However, it remains unclear how the relationship between higher-order mind attribution and lower-level attention processes is established in the brain. In this neuroimaging study, participants saw images of an anthropomorphic robot that moved its eyes left- or rightwards to signal the appearance of an upcoming stimulus in the same (valid cue) or opposite location (invalid cue). Independently, participants' beliefs about the intentionality underlying the observed eye movements were manipulated by describing the eye movements as under human control or preprogrammed. As expected, we observed a validity effect behaviorally and neurologically (increased response times and activation in the invalid vs. valid condition). More importantly, we observed that this effect was more pronounced for the condition in which the robot's behavior was believed to be controlled by a human, as opposed to be preprogrammed. This interaction effect between cue validity and belief was, however, only found at the neural level and was manifested as a significant increase of activation in bilateral anterior temporoparietal junction.

Human PrimPol activity is enhanced by RPA.

PubMed

Martínez-Jiménez, María I; Lahera, Antonio; Blanco, Luis

2017-04-10

Human PrimPol is a primase belonging to the AEP superfamily with the unique ability to synthesize DNA primers de novo, and a non-processive DNA polymerase able to bypass certain DNA lesions. PrimPol facilitates both mitochondrial and nuclear replication fork progression either acting as a conventional TLS polymerase, or repriming downstream of blocking lesions. In vivo assays have shown that PrimPol is rapidly recruited to sites of DNA damage by interaction with the human replication protein A (RPA). In agreement with previous findings, we show here that the higher affinity of RPA for ssDNA inhibits PrimPol activities in short ssDNA templates. In contrast, once the amount of ssDNA increases up to a length in which both proteins can simultaneously bind ssDNA, as expected during replicative stress conditions, PrimPol and RPA functionally interact, and their binding capacities are mutually enhanced. When using M13 ssDNA as template, RPA stimulated both the primase and polymerase activities of PrimPol, either alone or in synergy with Polε. These new findings supports the existence of a functional PrimPol/RPA association that allows repriming at the exposed ssDNA regions formed in the leading strand upon replicase stalling.

DHM and serious games: a case-study oil and gas laboratories.

PubMed

Santos, V; Zamberlan, M; Streit, P; Oliveira, J; Guimarães, C; Pastura, F; Cid, G

2012-01-01

The aim in this paper is to present a research on the application of serious games for the design of laboratories in the oil and gas industries. The focus is in human virtual representation acquired from 3D scanning, human interaction, workspace layout and equipment designed considering ergonomics standards. The laboratory studies were simulated in Unity3D platform, which allows the users to control the DHM1 on the dynamic virtual scenario, in order to simulate work activities. This methodology can change the design process by improving the level of interaction between final users, managers and human factor teams. That helps to better visualize future work settings and improve the level of participation between all stakeholders.

Identification of the hydrophobic strand in the A–B loop of leptin as major binding site III: implications for large-scale preparation of potent recombinant human and ovine leptin antagonists

PubMed Central

Niv-Spector, Leonora; Gonen-Berger, Dana; Gourdou, Isabelle; Biener, Eva; Gussakovsky, Eugene E.; Benomar, Yackir; Ramanujan, Krishnan V.; Taouis, Mohammed; Herman, Brian; Callebaut, Isabelle; Djiane, Jean; Gertler, Arieh

2005-01-01

Interaction of leptin with its receptors resembles that of interleukin-6 and granulocyte colony-stimulating factor, which interact with their receptors through binding sites I–III. Site III plays a pivotal role in receptors' dimerization or tetramerization and subsequent activation. Leptin's site III also mediates the formation of an active multimeric complex through its interaction with the IGD (immunoglobulin-like domain) of LEPRs (leptin receptors). Using a sensitive hydrophobic cluster analysis of leptin's and LEPR's sequences, we identified hydrophobic stretches in leptin's A–B loop (amino acids 39–42) and in the N-terminal end of LEPR's IGD (amino acids 325–328) that are predicted to participate in site III and to interact with each other in a β-sheet-like configuration. To verify this hypothesis, we prepared and purified to homogeneity (as verified by SDS/PAGE, gel filtration and reverse-phase chromatography) several alanine muteins of amino acids 39–42 in human and ovine leptins. CD analyses revealed that those mutations hardly affect the secondary structure. All muteins acted as true antagonists, i.e. they bound LEPR with an affinity similar to the wild-type hormone, had no agonistic activity and specifically inhibited leptin action in several leptin-responsive in vitro bioassays. Alanine mutagenesis of LEPR's IGD (amino acids 325–328) drastically reduced its biological but not binding activity, indicating the importance of this region for interaction with leptin's site III. FRET (fluorescence resonance energy transfer) microscopy experiments have documented that the transient FRET signalling occurring upon exposure to leptin results not from binding of the ligand, but from ligand-induced oligomerization of LEPRs mediated by leptin's site III. PMID:15952938

Interaction of 8-anilinonaphthalene 1-sulphonate (ANS) and human matrix metalloproteinase 7 (MMP-7) as examined by MMP-7 activity and ANS fluorescence.

PubMed

Samukange, Vimbai; Yasukawa, Kiyoshi; Inouye, Kuniyo

2012-05-01

Human matrix metalloproteinase 7 (MMP-7) is the smallest matrix metalloproteinase. It plays important roles in tumour invasion and metastasis. 8-Anilinonaphthalene 1-sulphonate (ANS) is a fluorescent probe widely used for the analysis of proteins. It emits large fluorescence energy when its anilinonaphthalene group binds with hydrophobic regions of protein. In this study, we analysed the interaction of ANS and MMP-7. At pH 4.5-9.5, ANS inhibited MMP-7 activity in the hydrolysis of (7-methoxycoumarin-4-yl)acetyl-L-Pro-L-Leu-Gly-L-Leu-[N(3)-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl]-L-Ala-L-Arg-NH(2). The inhibition was a non-competitive manner and depended on the time for pre-incubation of ANS and MMP-7. At pH 4.5-9.5, the fluorescence of ANS was not changed by the addition of MMP-7. At pH 3.5, MMP-7 lacked activity, and the fluorescence of ANS was increased by the addition of MMP-7. These results suggest that at pH 4.5-9.5, the sulphonic group of ANS binds with MMP-7 through electrostatic interaction, whereas at pH 3.5, the anilinonaphthalene group of ANS binds with MMP-7 through hydrophobic interaction.

Modeling the interaction of binary and ternary mixtures of estradiol with bisphenol A and bisphenol A F in an in vitro estrogen mediated transcriptional activation assay (T47D-KBluc).

EPA Science Inventory

Humans are concurrently exposed to xenoestrogens and to physiological levels of endogenous estrogens. Endogenous estrogen levels vary from low levels in infants to high levels during pregnancy and in young women. However, few studies have addressed how xenoestrogens interact with...

Culture, Urbanism and Changing Human Biology.

PubMed

Schell, L M

2014-04-03

Anthropologists have long known that human activity driven by culture changes the environment. This is apparent in the archaeological record and through the study of the modern environment. Perhaps the largest change since the paleolithic era is the organization of human populations in cities. New environments can reshape human biology through evolution as shown by the evolution of the hominid lineage. Evolution is not the only process capable of reshaping our biology. Some changes in our human biology are adaptive and evolutionary while others are pathological. What changes in human biology may be wrought by the modern urban environment? One significant new change in the environment is the introduction of pollutants largely through urbanization. Pollutants can affect human biology in myriad ways. Evidence shows that human growth, reproduction, and cognitive functioning can be altered by some pollutants, and altered in different ways depending on the pollutant. Thus, pollutants have significance for human biologists and anthropologists generally. Further, they illustrate the bio-cultural interaction characterizing human change. Humans adapt by changing the environment, a cultural process, and then change biologically to adjust to that new environment. This ongoing, interactive process is a fundamental characteristic of human change over the millennia.

Culture, Urbanism and Changing Human Biology

PubMed Central

Schell, L.M.

2014-01-01

Anthropologists have long known that human activity driven by culture changes the environment. This is apparent in the archaeological record and through the study of the modern environment. Perhaps the largest change since the paleolithic era is the organization of human populations in cities. New environments can reshape human biology through evolution as shown by the evolution of the hominid lineage. Evolution is not the only process capable of reshaping our biology. Some changes in our human biology are adaptive and evolutionary while others are pathological. What changes in human biology may be wrought by the modern urban environment? One significant new change in the environment is the introduction of pollutants largely through urbanization. Pollutants can affect human biology in myriad ways. Evidence shows that human growth, reproduction, and cognitive functioning can be altered by some pollutants, and altered in different ways depending on the pollutant. Thus, pollutants have significance for human biologists and anthropologists generally. Further, they illustrate the bio-cultural interaction characterizing human change. Humans adapt by changing the environment, a cultural process, and then change biologically to adjust to that new environment. This ongoing, interactive process is a fundamental characteristic of human change over the millennia. PMID:25598655

Interaction between the Staphylococcus aureus extracellular adherence protein Eap and its subdomains with platelets.

PubMed

Palankar, Raghavendra; Binsker, Ulrike; Haracska, Bianca; Wesche, Jan; Greinacher, Andreas; Hammerschmidt, Sven

2018-04-18

S. aureus associated bacteremia can lead to severe infections with high risk of mortality (e.g. sepsis, infective endocarditis). Many virulence factors and adhesins of S. aureus are known to directly interact with platelets. Extracellular adherence protein, Eap, one of the most important virulence factors in S. aureus mediated infections is a multi-tandem domain protein and has been shown to interact with almost all cell types in the human circulatory system. By using amine reactive fluorescent N-hydroxysuccinimidyl (NHS)-ester dyes and by direct detection with primary fluorescently conjugated anti-histidine (His-tag) antibodies against detect N-terminal His6, we show Eap subdomain Eap D 3 D 4 specifically interacts and rapidly activates human platelets. Furthermore, we validate our finding by using site directed directional immobilization of Eap D 3 D 4 through N-terminal His 6 on nickel (II)-nitrilotriacetic acid (Ni-NTA) functionalized bacteriomimetic microbead arrays to visualize real-time platelet activation through calcium release assay. These methods offer an easily adoptable protocols for screening of S.aureus derived virulence factors and adhesins with platelets. Copyright © 2018 Elsevier GmbH. All rights reserved.

Human Research Program Integrated Research Plan: December 20, 2007, Interim Baseline

NASA Technical Reports Server (NTRS)

2008-01-01

The Human Research Program (HRP) delivers human health and performance countermeasures, knowledge, technologies, and tools to enable safe, reliable, and productive human space exploration. This Integrated Research Plan (IRP) describes the program s research activities that are intended to address the needs of human space exploration and serve HRP customers. The timescale of human space exploration is envisioned to take many decades. The IRP illustrates the program s research plan through the timescale of early lunar missions of extended duration. The document serves several purposes for the Human Research Program: The IRP provides a means to assure that the most significant risks to human space explorers are being adequately mitigated and/or addressed, The IRP shows the relationship of research activities to expected outcomes and need dates, The IRP shows the interrelationships among research activities that may interact to produce products that are integrative or cross defined research disciplines, The IRP illustrates the non-deterministic nature of research and technology activities by showing expected decision points and potential follow-on activities, The IRP shows the assignments of responsibility within the program organization and, as practical, the intended solicitation approach, The IRP shows the intended use of research platforms such as the International Space Station, NASA Space Radiation Laboratory, and various space flight analogs. The IRP does not show all budgeted activities of the Human research program, as some of these are enabling functions, such as management, facilities and infrastructure

Activation of β Catenin and Yap1 in Human Hepatoblastoma and Induction of Hepatocarcinogenesis in Mice

PubMed Central

Cigliano, Antonio; Zhou, Lili; Singh, Sucha; Jiang, Lijie; Fan, Biao; Terracciano, Luigi; Armeanu-Ebinger, Sorin; Ribback, Silvia; Dombrowski, Frank; Evert, Matthias; Chen, Xin; Monga, Satdarshan P. S.

2014-01-01

Background & Aims Aberrant activation of βcatenin and Yes-associated protein 1 (Yap1) signaling pathways have been associated with development of multiple tumor types. Yap functions as a transcriptional co-activator by interacting with TEAD DNA binding proteins. We investigated the interactions among these pathways during hepatic tumorigenesis. Methods We used immunohistochemical analysis to determine expression of β-catenin and Yap1 in liver cancer specimens collected from patients in Europe and the US, consisting of 104 hepatocellular carcinoma (HCC), 62 intrahepatic cholangiocarcinoma (ICC), and 94 hepatoblastoma samples. We assessed βcatenin and Yap1 signaling and interactions in hepatoblastoma cell lines ((HuH6, HepG2, HepT1, HC-AFW1, HepG2, and HC-AFW1); proteins were knocked down with small interfering (si)RNAs and effects on proliferation and cell death were measured. Sleeping beauty-mediated hydrodynamic transfection was used to overexpress constitutively active forms of β catenin ( N90-βcatenin) and Yap1 (YapS127A) in livers of mice; tissues were collected and histologic and immunohistochemical analyses were performed. Results We observed nuclear localization of βcatenin and Yap1 in 79% of hepatoblastoma samples, but not in most HCC or ICC tissues. Yap1 and β catenin co-precipitated in hepatoblastoma but not HCC cells. siRNA-mediated knockdown of Yap1 or β catenin in hepatoblastoma cells reduced proliferation in an additive manner. Knockdown of Yap1 reduced its ability to co-activate transcription with βcatenin; βcatenin inhibitors inactivated Yap1. Overexpression of constitutively active forms of Yap1 and βcatenin in mouse liver led to rapid tumorigenesis, with 100% mortality by 11 weeks. Tumors cells expressed both proteins, and human hepatoblastoma cells expressed common targets of their 2 signaling pathways. Yap1 binding of TEAD factors was required for tumorigenesis in mice. Conclusions β catenin and the transcriptional regulator Yap1 interact physically and are activated in most human hepatoblastoma tissues; overexpression of activated forms of these proteins in livers of mice leads to rapid tumor development. Further analysis of these mice will allow further studies of these pathways in hepatoblastoma pathogenesis and could lead to the identification of new therapeutic targets. PMID:24837480

On the applicability of brain reading for predictive human-machine interfaces in robotics.

PubMed

Kirchner, Elsa Andrea; Kim, Su Kyoung; Straube, Sirko; Seeland, Anett; Wöhrle, Hendrik; Krell, Mario Michael; Tabie, Marc; Fahle, Manfred

2013-01-01

The ability of today's robots to autonomously support humans in their daily activities is still limited. To improve this, predictive human-machine interfaces (HMIs) can be applied to better support future interaction between human and machine. To infer upcoming context-based behavior relevant brain states of the human have to be detected. This is achieved by brain reading (BR), a passive approach for single trial EEG analysis that makes use of supervised machine learning (ML) methods. In this work we propose that BR is able to detect concrete states of the interacting human. To support this, we show that BR detects patterns in the electroencephalogram (EEG) that can be related to event-related activity in the EEG like the P300, which are indicators of concrete states or brain processes like target recognition processes. Further, we improve the robustness and applicability of BR in application-oriented scenarios by identifying and combining most relevant training data for single trial classification and by applying classifier transfer. We show that training and testing, i.e., application of the classifier, can be carried out on different classes, if the samples of both classes miss a relevant pattern. Classifier transfer is important for the usage of BR in application scenarios, where only small amounts of training examples are available. Finally, we demonstrate a dual BR application in an experimental setup that requires similar behavior as performed during the teleoperation of a robotic arm. Here, target recognition processes and movement preparation processes are detected simultaneously. In summary, our findings contribute to the development of robust and stable predictive HMIs that enable the simultaneous support of different interaction behaviors.

On the Applicability of Brain Reading for Predictive Human-Machine Interfaces in Robotics

PubMed Central

Kirchner, Elsa Andrea; Kim, Su Kyoung; Straube, Sirko; Seeland, Anett; Wöhrle, Hendrik; Krell, Mario Michael; Tabie, Marc; Fahle, Manfred

2013-01-01

The ability of today's robots to autonomously support humans in their daily activities is still limited. To improve this, predictive human-machine interfaces (HMIs) can be applied to better support future interaction between human and machine. To infer upcoming context-based behavior relevant brain states of the human have to be detected. This is achieved by brain reading (BR), a passive approach for single trial EEG analysis that makes use of supervised machine learning (ML) methods. In this work we propose that BR is able to detect concrete states of the interacting human. To support this, we show that BR detects patterns in the electroencephalogram (EEG) that can be related to event-related activity in the EEG like the P300, which are indicators of concrete states or brain processes like target recognition processes. Further, we improve the robustness and applicability of BR in application-oriented scenarios by identifying and combining most relevant training data for single trial classification and by applying classifier transfer. We show that training and testing, i.e., application of the classifier, can be carried out on different classes, if the samples of both classes miss a relevant pattern. Classifier transfer is important for the usage of BR in application scenarios, where only small amounts of training examples are available. Finally, we demonstrate a dual BR application in an experimental setup that requires similar behavior as performed during the teleoperation of a robotic arm. Here, target recognition processes and movement preparation processes are detected simultaneously. In summary, our findings contribute to the development of robust and stable predictive HMIs that enable the simultaneous support of different interaction behaviors. PMID:24358125

Human induced coastal changes and their impact on the coastal urban landscape. The case of Heraklion, Crete

NASA Astrophysics Data System (ADS)

Rempis, Nikolaos; Alexandrakis, George; Kampanis, Nikolaos

2017-04-01

Coastal zone is a vital part of human society due to sea activities. Α variety of activities and uses are present and are further developing in the coastal and marine are. Coastal ecosystems and landscape are under severe pressure due to population growth and continuous expansion of human activities and supplemented from the effects of climate change (e.g. coastal flooding, erosion). Heraklion is the largest urban center in Crete. Its suburban and coastal area receives intensive urban sprawl pressures, changing the urban landscape and resulting negative impacts on the human and natural environment. The saturation of coastal area of Heraklion creates the need for new development interventions (e.g. new marina, coastal protection, urban regeneration). This study examine the impacts of the new programmed coastal development intervention in the coastal landscape of Heraklion. A decision analytic approach was implemented, based on the need of stakeholders for the protection and further development of coastal area of Heraklion. In this direction, local authorities have proposed the realization of several development interventions which include a new marina, expansion of bathing beaches and coastal regeneration project in a large beach. The results indicate that the realization of any coastal development projects, also increases the negative effects that are related to land-sea interaction. The negative effects are a result of the interaction between different human activities but also between human activities and the environment. The development of the marina in the selected location, increases the pressure on the sea area as the navigation will increase, but also increases the pressure on land space, as traffic flows will change, creating new pressures in urban areas. The extension of bathing beaches implies larger number of bathers, thus creating greater needs for infrastructures in land area for their service. Coastal protection projects, as planned, will upgrade the inland section of the city coastal walls and upgrade them as tourist attraction.

IFN-γ Stimulated Human Umbilical-Tissue-Derived Cells Potently Suppress NK Activation and Resist NK-Mediated Cytotoxicity In Vitro

PubMed Central

Noone, Cariosa; Kihm, Anthony; O'Dea, Shirley; Mahon, Bernard P.

2013-01-01

Umbilical cord tissue represents a unique source of cells with potential for cell therapy applications for multiple diseases. Human umbilical tissue-derived cells (hUTC) are a developmentally early stage, homogenous population of cells that are HLA-ABC dim, HLA-DR negative, and lack expression of co-stimulatory molecules in the unactivated state. The lack of HLA-DR and co-stimulatory molecule expression on unactivated hUTC may account for their reduced immunogenicity, facilitating their use in allogeneic settings. However, such approaches could be confounded by host innate cells such as natural killer (NK) cells. Here, we evaluate in vitro NK cell interactions with hUTC and compare them with human mesenchymal stem cells (MSC). Our investigations show that hUTC suppress NK activation, through prostaglandin-E2 secretion in a contact-independent manner. Prestimulation of hUTC or human MSC with interferon gamma (IFN-γ) induced expression of the tryptophan degrading enzyme indoleamine 2, 3 dioxygenase, facilitating enhanced suppression. However, resting NK cells of different killer immunoglobulin-like receptor haplotypes did not kill hUTC or MSC; only activated NK cells had the ability to kill nonstimulated hUTC and, to a lesser extent, MSC. The cell killing process involved signaling through the NKG2D receptor and the perforin/granzyme pathway; this was supported by CD54 (ICAM-1) expression by hUTC. IFN-γ-stimulated hUTC or hMSC were less susceptible to NK killing; in this case, protection was associated with elevated HLA-ABC expression. These data delineate the different mechanisms in a two-way interaction between NK cells and two distinct cell therapies, hUTC or hMSC, and how these interactions may influence their clinical applications. PMID:23795941

Structural comparison of cytochromes P450 2A6, 2A13, and 2E1 with pilocarpine

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

DeVore, Natasha M.; Meneely, Kathleen M.; Bart, Aaron G.

2013-11-20

Human xenobiotic-metabolizing cytochrome P450 (CYP) enzymes can each bind and monooxygenate a diverse set of substrates, including drugs, often producing a variety of metabolites. Additionally, a single ligand can interact with multiple CYP enzymes, but often the protein structural similarities and differences that mediate such overlapping selectivity are not well understood. Even though the CYP superfamily has a highly canonical global protein fold, there are large variations in the active site size, topology, and conformational flexibility. We have determined how a related set of three human CYP enzymes bind and interact with a common inhibitor, the muscarinic receptor agonist drugmore » pilocarpine. Pilocarpine binds and inhibits the hepatic CYP2A6 and respiratory CYP2A13 enzymes much more efficiently than the hepatic CYP2E1 enzyme. To elucidate key residues involved in pilocarpine binding, crystal structures of CYP2A6 (2.4 {angstrom}), CYP2A13 (3.0 {angstrom}), CYP2E1 (2.35 {angstrom}), and the CYP2A6 mutant enzyme, CYP2A6 I208S/I300F/G301A/S369G (2.1 {angstrom}) have been determined with pilocarpine in the active site. In all four structures, pilocarpine coordinates to the heme iron, but comparisons reveal how individual residues lining the active sites of these three distinct human enzymes interact differently with the inhibitor pilocarpine.« less

Simulation-Based Design for Wearable Robotic Systems: An Optimization Framework for Enhancing a Standing Long Jump.

PubMed

Ong, Carmichael F; Hicks, Jennifer L; Delp, Scott L

2016-05-01

Technologies that augment human performance are the focus of intensive research and development, driven by advances in wearable robotic systems. Success has been limited by the challenge of understanding human-robot interaction. To address this challenge, we developed an optimization framework to synthesize a realistic human standing long jump and used the framework to explore how simulated wearable robotic devices might enhance jump performance. A planar, five-segment, seven-degree-of-freedom model with physiological torque actuators, which have variable torque capacity depending on joint position and velocity, was used to represent human musculoskeletal dynamics. An active augmentation device was modeled as a torque actuator that could apply a single pulse of up to 100 Nm of extension torque. A passive design was modeled as rotational springs about each lower limb joint. Dynamic optimization searched for physiological and device actuation patterns to maximize jump distance. Optimization of the nominal case yielded a 2.27 m jump that captured salient kinematic and kinetic features of human jumps. When the active device was added to the ankle, knee, or hip, jump distance increased to between 2.49 and 2.52 m. Active augmentation of all three joints increased the jump distance to 3.10 m. The passive design increased jump distance to 3.32 m by adding torques of 135, 365, and 297 Nm to the ankle, knee, and hip, respectively. Dynamic optimization can be used to simulate a standing long jump and investigate human-robot interaction. Simulation can aid in the design of performance-enhancing technologies.

Structural Dynamics Investigation of Human Family 1 & 2 Cystatin-Cathepsin L1 Interaction: A Comparison of Binding Modes

PubMed Central

Nandy, Suman Kumar; Seal, Alpana

2016-01-01

Cystatin superfamily is a large group of evolutionarily related proteins involved in numerous physiological activities through their inhibitory activity towards cysteine proteases. Despite sharing the same cystatin fold, and inhibiting cysteine proteases through the same tripartite edge involving highly conserved N-terminal region, L1 and L2 loop; cystatins differ widely in their inhibitory affinity towards C1 family of cysteine proteases and molecular details of these interactions are still elusive. In this study, inhibitory interactions of human family 1 & 2 cystatins with cathepsin L1 are predicted and their stability and viability are verified through protein docking & comparative molecular dynamics. An overall stabilization effect is observed in all cystatins on complex formation. Complexes are mostly dominated by van der Waals interaction but the relative participation of the conserved regions varied extensively. While van der Waals contacts prevail in L1 and L2 loop, N-terminal segment chiefly acts as electrostatic interaction site. In fact the comparative dynamics study points towards the instrumental role of L1 loop in directing the total interaction profile of the complex either towards electrostatic or van der Waals contacts. The key amino acid residues surfaced via interaction energy, hydrogen bonding and solvent accessible surface area analysis for each cystatin-cathepsin L1 complex influence the mode of binding and thus control the diverse inhibitory affinity of cystatins towards cysteine proteases. PMID:27764212

Trajectory data analyses for pedestrian space-time activity study.

PubMed

Qi, Feng; Du, Fei

2013-02-25

It is well recognized that human movement in the spatial and temporal dimensions has direct influence on disease transmission(1-3). An infectious disease typically spreads via contact between infected and susceptible individuals in their overlapped activity spaces. Therefore, daily mobility-activity information can be used as an indicator to measure exposures to risk factors of infection. However, a major difficulty and thus the reason for paucity of studies of infectious disease transmission at the micro scale arise from the lack of detailed individual mobility data. Previously in transportation and tourism research detailed space-time activity data often relied on the time-space diary technique, which requires subjects to actively record their activities in time and space. This is highly demanding for the participants and collaboration from the participants greatly affects the quality of data(4). Modern technologies such as GPS and mobile communications have made possible the automatic collection of trajectory data. The data collected, however, is not ideal for modeling human space-time activities, limited by the accuracies of existing devices. There is also no readily available tool for efficient processing of the data for human behavior study. We present here a suite of methods and an integrated ArcGIS desktop-based visual interface for the pre-processing and spatiotemporal analyses of trajectory data. We provide examples of how such processing may be used to model human space-time activities, especially with error-rich pedestrian trajectory data, that could be useful in public health studies such as infectious disease transmission modeling. The procedure presented includes pre-processing, trajectory segmentation, activity space characterization, density estimation and visualization, and a few other exploratory analysis methods. Pre-processing is the cleaning of noisy raw trajectory data. We introduce an interactive visual pre-processing interface as well as an automatic module. Trajectory segmentation(5) involves the identification of indoor and outdoor parts from pre-processed space-time tracks. Again, both interactive visual segmentation and automatic segmentation are supported. Segmented space-time tracks are then analyzed to derive characteristics of one's activity space such as activity radius etc. Density estimation and visualization are used to examine large amount of trajectory data to model hot spots and interactions. We demonstrate both density surface mapping(6) and density volume rendering(7). We also include a couple of other exploratory data analyses (EDA) and visualizations tools, such as Google Earth animation support and connection analysis. The suite of analytical as well as visual methods presented in this paper may be applied to any trajectory data for space-time activity studies.

Severe necroinflammatory reaction caused by natural killer cell-mediated Fas/Fas ligand interaction and dendritic cells in human hepatocyte chimeric mouse.

PubMed

Okazaki, Akihito; Hiraga, Nobuhiko; Imamura, Michio; Hayes, C Nelson; Tsuge, Masataka; Takahashi, Shoichi; Aikata, Hiroshi; Abe, Hiromi; Miki, Daiki; Ochi, Hidenori; Tateno, Chise; Yoshizato, Katsutoshi; Ohdan, Hideki; Chayama, Kazuaki

2012-08-01

The necroinflammatory reaction plays a central role in hepatitis B virus (HBV) elimination. Cluster of differentiation (CD)8-positive cytotoxic T lymphocytes (CTLs) are thought to be a main player in the elimination of infected cells, and a recent report suggests that natural killer (NK) cells also play an important role. Here, we demonstrate the elimination of HBV-infected hepatocytes by NK cells and dendritic cells (DCs) using urokinase-type plasminogen activator/severe combined immunodeficiency mice, in which the livers were highly repopulated with human hepatocytes. After establishing HBV infection, we injected human peripheral blood mononuclear cells (PBMCs) into the mice and analyzed liver pathology and infiltrating human immune cells with flow cytometry. Severe hepatocyte degeneration was observed only in HBV-infected mice transplanted with human PBMCs. We provide the first direct evidence that massive liver cell death can be caused by Fas/Fas ligand (FasL) interaction provided by NK cells activated by DCs. Treatment of mice with anti-Fas antibody completely prevented severe hepatocyte degeneration. Furthermore, severe hepatocyte death can be prevented by depletion of DCs, whereas depletion of CD8-positive CTLs did not disturb the development of massive liver cell apoptosis. Our findings provide the first direct evidence that DC-activated NK cells induce massive HBV-infected hepatocyte degeneration through the Fas/FasL system and may indicate new therapeutic implications for acute severe/fulminant hepatitis B. Copyright © 2012 American Association for the Study of Liver Diseases.

Phosphorylated STAT5 directly facilitates parvovirus B19 DNA replication in human erythroid progenitors through interaction with the MCM complex

PubMed Central

Ganaie, Safder S.; Zou, Wei; Xu, Peng; Deng, Xuefeng; Kleiboeker, Steve

2017-01-01

Productive infection of human parvovirus B19 (B19V) exhibits high tropism for burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) progenitor cells in human bone marrow and fetal liver. This exclusive restriction of the virus replication to human erythroid progenitor cells is partly due to the intracellular factors that are essential for viral DNA replication, including erythropoietin signaling. Efficient B19V replication also requires hypoxic conditions, which upregulate the signal transducer and activator of transcription 5 (STAT5) pathway, and phosphorylated STAT5 is essential for virus replication. In this study, our results revealed direct involvement of STAT5 in B19V DNA replication. Consensus STAT5-binding elements were identified adjacent to the NS1-binding element within the minimal origins of viral DNA replication in the B19V genome. Phosphorylated STAT5 specifically interacted with viral DNA replication origins both in vivo and in vitro, and was actively recruited within the viral DNA replication centers. Notably, STAT5 interacted with minichromosome maintenance (MCM) complex, suggesting that STAT5 directly facilitates viral DNA replication by recruiting the helicase complex of the cellular DNA replication machinery to viral DNA replication centers. The FDA-approved drug pimozide dephosphorylates STAT5, and it inhibited B19V replication in ex vivo expanded human erythroid progenitors. Our results demonstrated that pimozide could be a promising antiviral drug for treatment of B19V-related diseases. PMID:28459842

Deregulated activation of oncoprotein kinase Tpl2/Cot in HTLV-I-transformed T cells.

PubMed

Babu, Geetha; Waterfield, Michael; Chang, Mikyoung; Wu, Xuefeng; Sun, Shao-Cong

2006-05-19

Protein kinase Tpl2/Cot is encoded by a protooncogene that is cis-activated by retroviral insertion in murine T cell lymphomas. It has remained unclear whether this oncoprotein kinase is mutated or post-translationally activated in human cancer cells. We have shown here that Tpl2/Cot is constitutively activated in human leukemia cell lines transformed by the human T cell leukemia virus type I (HTLV-I). The kinase activity of Tpl2/Cot is normally suppressed through its physical interaction with an inhibitor, the NF-kappaB1 precursor protein p105. Interestingly, a large pool of Tpl2/Cot is liberated from p105 and exhibits constitutive kinase activity in HTLV-I-transformed T cells. In contrast to its labile property in normal cells, the pathologically activated Tpl2/Cot is remarkably stable. Further, whereas the physiological activation of Tpl2/Cot involves its long isoform, the HTLV-activated Tpl2/Cot is predominantly the short isoform. We have also shown that the HTLV-I-encoded Tax protein is able to activate Tpl2/Cot in transfected cells. Finally, Tpl2/Cot participates in the activation of NF-kappaB by Tax. These findings indicate that deregulated activation of Tpl2/Cot may occur in human cancer cells.

Functional Aspects of Fish Mucosal Lectins-Interaction with Non-Self.

PubMed

Brinchmann, Monica Fengsrud; Patel, Deepti Manjari; Pinto, Nevil; Iversen, Martin Haugmo

2018-05-09

Mucosal surfaces are of key importance in protecting animals against external threats including pathogens. In the mucosal surfaces, host molecules interact with non-self to prevent infection and disease. Interestingly, both inhibition and stimulation of uptake hinder infection. In this review, the current knowledgebase on teleost mucosal lectins’ ability to interact with non-self is summarised with a focus on agglutination, growth inhibition, opsonisation, cell adhesion, and direct killing activities. Further research on lectins is essential, both to understand the immune system of fishes, since they rely more on the innate immune system than mammals, and also to explore these molecules’ antibiotic and antiparasitic activities against veterinary and human pathogens.

The interplay between individual social behavior and clinical symptoms in small clustered groups.

PubMed

Poletti, Piero; Visintainer, Roberto; Lepri, Bruno; Merler, Stefano

2017-07-26

Mixing patterns of human populations play a crucial role in shaping the spreading paths of infectious diseases. The diffusion of mobile and wearable devices able to record close proximity interactions represents a great opportunity for gathering detailed data on social interactions and mixing patterns in human populations. The aim of this study is to investigate how social interactions are affected by the onset of symptomatic conditions and to what extent the heterogeneity in human behavior can reflect a different risk of infection. We study the relation between individuals' social behavior and the onset of different symptoms, by making use of data collected in 2009 among students sharing a dormitory in a North America university campus. The dataset combines Bluetooth proximity records between study participants with self-reported daily records on their health state. Specifically, we investigate whether individuals' social activity significantly changes during different symptomatic conditions, including those defining Influenza-like illness, and highlight to what extent possible heterogeneities in social behaviors among individuals with similar age and daily routines may be responsible for a different risk of infection for influenza. Our results suggest that symptoms associated with Influenza-like illness can be responsible of a reduction of about 40% in the average duration of contacts and of 30% in the daily time spent in social interactions, possibly driven by the onset of fever. However, differences in the number of daily contacts were found to be not statistically significant. In addition, we found that individuals who experienced clinical influenza during the study period were characterized by a significantly higher social activity. In particular, both the number of person-to-person contacts and the time spent in social interactions emerged as significant risk factors for influenza infection. Our findings highlight that Influenza-like illness can remarkably reduce the social activity of individuals and strengthen the idea that the heterogeneity in social habits among individuals can significantly contribute in shaping differences among the individuals' risk of infection.

The SANT2 domain of the murine tumor cell DnaJ-like protein 1 human homologue interacts with alpha1-antichymotrypsin and kinetically interferes with its serpin inhibitory activity.

PubMed

Kroczynska, Barbara; Evangelista, Christina M; Samant, Shalaka S; Elguindi, Ebrahim C; Blond, Sylvie Y

2004-03-19

The murine tumor cell DnaJ-like protein 1 or MTJ1/ERdj1 is a membrane J-domain protein enriched in microsomal and nuclear fractions. We previously showed that its lumenal J-domain stimulates the ATPase activity of the molecular chaperone BiP/GRP78 (Chevalier, M., Rhee, H., Elguindi, E. C., and Blond, S. Y. (2000) J. Biol. Chem. 275, 19620-19627). MTJ1/ERdj1 also contains a large carboxyl-terminal cytosolic extension composed of two tryptophan-mediated repeats or SANT domains for which the function(s) is unknown. Here we describe the cloning of the human homologue HTJ1 and its interaction with alpha(1)-antichymotrypsin (ACT), a member of the serine proteinase inhibitor (serpin) family. The interaction was initially identified in a two-hybrid screening and further confirmed in vitro by dot blots, native electrophoresis, and fluorescence studies. The second SANT domain of HTJ1 (SANT2) was found to be sufficient for binding to ACT, both in yeast and in vitro. Single tryptophan-alanine substitutions at two strictly conserved residues significantly (Trp-497) or totally (Trp-520) abolished the interaction with ACT. SANT2 binds to human ACT with an intrinsic affinity equal to 0.5 nm. Preincubation of ACT with nearly stoichiometric concentrations of SANT2 wild-type but not SANT2: W520A results in an apparent loss of ACT inhibitory activity toward chymotrypsin. Kinetic analysis indicates that the formation of the covalent inhibitory complex ACT-chymotrypsin is significantly delayed in the presence of SANT2 with no change on the catalytic efficiency of the enzyme. This work demonstrates for the first time that the SANT2 domain of MTJ1/HTJ1/ERdj1 mediates stable and high affinity protein-protein interactions.

Interaction of phenolic acids and their derivatives with human serum albumin: Structure-affinity relationships and effects on antioxidant activity.

PubMed

Zhang, Yunyue; Wu, Simin; Qin, Yinghui; Liu, Jiaxin; Liu, Jingwen; Wang, Qingyu; Ren, Fazheng; Zhang, Hao

2018-02-01

In this study, 111 phenolic acids and their derivatives were chosen to investigate their structure-affinity relationships when binding to human serum albumin (HSA), and effects on their antioxidant activity. A comprehensive mathematical model was employed to calculate the binding constants, using a fluorescence quenching method, and this was corrected for the inner-filter effect to improve accuracy. We found that a hydroxy group at the 2-position of the benzene ring exerted a positive effect on the affinities, while a 4-hydroxy substituent had a negative influence. Both methylation of the hydroxy groups and replacing the hydroxy groups with methyl groups at the 3- and 4-positions of the benzene ring enhanced the binding affinities. Hydrophobic force and hydrogen bonding were binding forces for the phenolic acids, and their methyl esters, respectively. The antioxidant activity of the HSA-phenolic acid interaction compounds was higher than that of the phenolic acids alone. Copyright © 2017. Published by Elsevier Ltd.

Heteronyms and avatars: a self-reflective system for artistic activity

NASA Astrophysics Data System (ADS)

Ayiter, Elif

2012-03-01

This text will examine how avatars and the socially interactive, online virtual worlds in which they become embodied may lead to an understanding of identity and of self-perception, how such shifts in awareness may relate to the notion of the undividedly holistic 'self' and whether such perceptual shifts may be instrumental in bringing forth virtual states of experiential creative activity which may also have their precursors in the literary pseudonym, particularly as evidenced in Fernando Pessoa's conception of 'heteronyms.' The output of my study is a self-observational social system of my own creation, of which the agents are a coterie of avatars of both sexes, endowed with distinct physical attributes, both human and non-human; with uniquely emergent personalities which have progressed towards further idiosyncrasy over a period of three years. I, their creator am also the observer of their undertakings, their interactions, and their creative output, all of which manifest as disparate facets of my own persona and my artistic activity.

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

Schormann, Norbert; Velu, Sadanandan E.; Murugesan, Srinivasan

Dihydrofolate reductase (DHFR) of the parasite Trypanosoma cruzi (T. cruzi) is a potential target for developing drugs to treat Chagas disease. We have undertaken a detailed structure-activity study of this enzyme. We report here synthesis and characterization of six potent inhibitors of the parasitic enzyme. Inhibitory activity of each compound was determined against T. cruzi and human DHFR. One of these compounds, ethyl 4-(5-[(2,4-diamino-6-quinazolinyl)methyl]amino-2-methoxyphenoxy)butanoate (6b) was co-crystallized with the bifunctional dihydrofolate reductase-thymidylate synthase enzyme of T. cruzi and the crystal structure of the ternary enzyme:cofactor:inhibitor complex was determined. Molecular docking was used to analyze the potential interactions of all inhibitorsmore » with T. cruzi DHFR and human DHFR. Inhibitory activities of these compounds are discussed in the light of enzyme-ligand interactions. Binding affinities of each inhibitor for the respective enzymes were calculated based on the experimental or docked binding mode. An estimated 60-70% of the total binding energy is contributed by the 2,4-diaminoquinazoline scaffold.« less

Data with a Mission: Building a Community for Interactive Data Visualization at the U.S. Environmental Protection Agency

EPA Science Inventory

The U.S Environmental Protection Agency’s (EPA) stated mission is to protect human health and the environment. A big part of our activities directed at fulfilling our mission directly involve using data. Environmental analysis, activity planning and communication are just a few o...

76 FR 28052 - Submission for OMB Review; Comment Request; Interactive Diet and Activity Tracking in AARP (iDATA...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Submission for OMB Review... Office of Management and Budget (OMB) a request to review and approve the information collection listed... measurement error structure of the diet and physical activity assessment instruments and the heterogeneity of...

Molecular Basis of Cardiac Delayed Rectifier Potassium Channel Function and Pharmacology.

PubMed

Wu, Wei; Sanguinetti, Michael C

2016-06-01

Human cardiomyocytes express 3 distinct types of delayed rectifier potassium channels. Human ether-a-go-go-related gene (hERG) channels conduct the rapidly activating current IKr; KCNQ1/KCNE1 channels conduct the slowly activating current IKs; and Kv1.5 channels conduct an ultrarapid activating current IKur. Here the authors provide a general overview of the mechanistic and structural basis of ion selectivity, gating, and pharmacology of the 3 types of cardiac delayed rectifier potassium ion channels. Most blockers bind to S6 residues that line the central cavity of the channel, whereas activators interact with the channel at 4 symmetric binding sites outside the cavity. Copyright © 2016 Elsevier Inc. All rights reserved.

Concerted functions of Streptococcus gordonii surface proteins PadA and Hsa mediate activation of human platelets and interactions with extracellular matrix.

PubMed

Haworth, Jennifer A; Jenkinson, Howard F; Petersen, Helen J; Back, Catherine R; Brittan, Jane L; Kerrigan, Steve W; Nobbs, Angela H

2017-01-01

A range of Streptococcus bacteria are able to interact with blood platelets to form a thrombus (clot). Streptococcus gordonii is ubiquitous within the human oral cavity and amongst the common pathogens isolated from subjects with infective endocarditis. Two cell surface proteins, Hsa and Platelet adherence protein A (PadA), in S. gordonii mediate adherence and activation of platelets. In this study, we demonstrate that PadA binds activated platelets and that an NGR (Asparagine-Glycine-Arginine) motif within a 657 amino acid residue N-terminal fragment of PadA is responsible for this, together with two other integrin-like recognition motifs RGT and AGD. PadA also acts in concert with Hsa to mediate binding of S. gordonii to cellular fibronectin and vitronectin, and to promote formation of biofilms. Evidence is presented that PadA and Hsa are each reliant on the other's active presentation on the bacterial cell surface, suggesting cooperativity in functions impacting both colonization and pathogenesis. © 2016 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd.

Synthesis, antimalarial activity in vitro, and docking studies of novel neolignan derivatives.

PubMed

Pereira, Glaécia A N; Souza, Gisele C; Santos, Lourivaldo S; Barata, Lauro E S; Meneses, Carla C F; Krettli, Antoniana U; Daniel-Ribeiro, Cláudio Tadeu; Alves, Cláudio Nahum

2017-09-01

The absence of effective vaccines against malaria and the difficulties associated with controlling mosquito vectors have left chemotherapy as the primary control measure against malaria. However, the emergence and spread of parasite resistance to conventional antimalarial drugs result in a worrisome scenario making the search for new drugs a priority. In the present study, the activities of nine neolignan derivatives were evaluated as follows: (i) against blood forms of chloroquine-resistant Plasmodium falciparum (clone W2), using the tritiated hypoxanthine incorporation and anti-HRPII assays; (ii) for cytotoxic activity against cultured human hepatoma cells (HepG2); and (iii) for intermolecular interaction with the P. falciparum cysteine protease of falcipain-2 (F2) by molecular docking. The neolignan derivatives 9 and 10 showed activity against the blood form of the chloroquine-resistant P. falciparum clone W2 and were not cytotoxic against cultured human hepatoma cells. A molecular docking study of these two neolignans with FP2 revealed several intermolecular interactions that should guide the design of future analogs. © 2017 John Wiley & Sons A/S.

Hair cortisol varies with season and lifestyle and relates to human interactions in German shepherd dogs.

PubMed

Roth, Lina S V; Faresjö, Åshild; Theodorsson, Elvar; Jensen, Per

2016-01-21

It is challenging to measure long-term endocrine stress responses in animals. We investigated whether cortisol extracted from dog hair reflected the levels of activity and stress long-term, during weeks and months. Hair samples from in total 59 German shepherds were analysed. Samples for measuring cortisol concentrations were collected at three occasions and we complemented the data with individual scores from the Canine Behavioural Assessment and Research Questionnaire (C-BARQ). Generalised linear mixed model (GLMM) results showed that hair cortisol varied with season and lifestyle: competition dogs had higher levels than companion, and professional working dogs, and levels were higher in January than in May and September. In addition, a positive correlation was found between the cortisol levels and the C-BARQ score for stranger-directed aggression (r = 0.31, P = 0.036). Interestingly, the factor "playing often with the dog" (r = -0.34, P = 0.019) and "reward with a treat/toy when the dog behaves correctly" (r = -0.37, P = 0.010) correlated negatively with cortisol levels, suggesting that positive human interactions reduce stress. In conclusion, hair cortisol is a promising method for revealing the activity of the HPA-axis over a longer period of time, and human interactions influence the cortisol level in dogs.

The interplay of cannabinoid and NMDA glutamate receptor systems in humans: preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects.

PubMed

Hallak, Jaime E C; Dursun, Serdar M; Bosi, Daniel C; de Macedo, Ligia Ribeiro Horta; Machado-de-Sousa, João Paulo; Abrão, João; Crippa, José A S; McGuire, Phillip; Krystal, John H; Baker, Glen B; Zuardi, Antonio W

2011-01-15

Interactions between glutamatergic and endocannabinoid systems may contribute to schizophrenia, dissociative states, and other psychiatric conditions. Cannabidiol (CBD), a cannabinoid-1/2 (CB1/2) receptor weak partial agonist or antagonist, may play a role in the treatment of schizophrenia. This study tested the hypothesis that CBD would attenuate the behavioral effects of the NMDA receptor antagonist, ketamine, in healthy human subjects. Ten male healthy volunteers were evaluated twice in a randomized order. In both sessions they received ketamine (bolus of 0.26 mg/kg/1 min followed by IV infusion of 0.25mg/kg over 30 min) preceded by either CBD (600 mg) or placebo. Psychopathology was assessed using the Brief Psychiatric Rating Scale (BPRS) and the CADSS (Clinician Administered Dissociative States Scale) at regular intervals from 30 min before to 90 min after ketamine administration. CBD significantly augmented the activating effects of ketamine, as measured by the activation subscales of the BPRS. However, CBD also showed a non-significant trend to reduce ketamine-induced depersonalization, as measured by the CADSS. These data describe a complex pattern of psychopharmacologic interactions between CBD and ketamine at the doses of each agent studied in this experiment. Copyright © 2010 Elsevier B.V. All rights reserved.

Transactivation Assays that Identify Indirect and Direct Activators of Human Pregnane X Receptor (PXR, NR1I2) and Constitutive Androstane Receptor (CAR, NR1I3).

PubMed

Pinne, Marija; Ponce, Elsa; Raucy, Judy L

2017-01-01

Nuclear Receptors (NRs), including PXR and CAR, are presumed to be ligand-dependent transcription factors, but ligand binding is not an absolute requirement for activation. Indeed, many compounds activate PXR and CAR by indirect mechanisms. Detecting these indirect activators of specific nuclear receptors in vitro has been difficult. As NR activation of either or both PXR and CAR can lead to drug-drug interactions and adverse drug effects, false negatives obtained with screening tools incapable of detecting indirect activators could present liabilities. The aim of this study was to establish assays that identify indirect activators of human PXR and CAR. Commercially available human PXR and CAR transactivation assays were used for analyses. We show that transactivation assays containing full-length nuclear receptors with native promoters can identify indirect activators of human CAR and PXRwhen compared to those of commercially available assays containing only the LBD of PXR and CAR. Of these two assay systems, only human PXR and CAR1 assays with full-length receptors and native promoters are capable of detecting indirect and ligand activators. With this capability, several kinase inhibitors were identified that activate PXR and CAR by indirect mechanisms. Furthermore by using both the LBD and full-length receptors, phenobarbital and midostaurin were found to be direct and indirect activators of PXR while human CAR activation by phenobarbital occurs by indirect mechanisms only. Cell based transactivation assays employing the full-length receptors and native promoters identify both direct and indirect activators of either or both human PXR and CAR. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Family Dog-Assisted Adapted Physical Activity: A Case Study

PubMed Central

Tepfer, Amanda; Ross, Samantha; MacDonald, Megan; Udell, Monique A. R.; Ruaux, Craig; Baltzer, Wendy

2017-01-01

Simple Summary Understanding how family dogs aid in aspects of daily living such as quality of life, physical activity and human animal interaction is critical towards better understanding child health. Using questionnaires and direct assessment we aimed to better understand the role of the family dog in an animal assisted adapted physical activity intervention. Findings were positive in respect to all primary outcomes in this case study. Generally, the role of the family dog in an adapted physical activity animal assisted intervention had positive results for child health, when the family dog assisted a child with cerebral palsy in this type of intervention. Abstract Purpose: The aim of this case study was to examine the individual effects of an adapted physical activity, animal-assisted intervention (APA-AAI) with the family dog on motor skills, physical activity, and quality of life of a child with cerebral palsy (CP). Method: This study used an A-B-A single-subject design. The assessment phase (phase A) occurred pre- and post-intervention. This consisted of standardized assessments of motor skills, quality of life questionnaires, physical activity (measured using the GT3X+ accelerometer) and the human-animal bond. The intervention (phase B) lasted 8 weeks and consisted of adapted physical activities performed with the family dog once a week for 60 min in a lab setting. In addition, the participant had at-home daily activities to complete with the family dog. Results: Visual analysis was used to analyze the data. Motor skill performance, physical activity, quality of life and human animal interaction gains were observed in each case. Conclusions: These preliminary results provided initial evidence that the family-dog can play a role in healthy lifestyles through APA-AAI in children with CP. PMID:28448430

Modulation of DNA Damage and Repair Pathways by Human Tumour Viruses

PubMed Central

Hollingworth, Robert; Grand, Roger J

2015-01-01

With between 10% and 15% of human cancers attributable to viral infection, there is great interest, from both a scientific and clinical viewpoint, as to how these pathogens modulate host cell functions. Seven human tumour viruses have been identified as being involved in the development of specific malignancies. It has long been known that the introduction of chromosomal aberrations is a common feature of viral infections. Intensive research over the past two decades has subsequently revealed that viruses specifically interact with cellular mechanisms responsible for the recognition and repair of DNA lesions, collectively known as the DNA damage response (DDR). These interactions can involve activation and deactivation of individual DDR pathways as well as the recruitment of specific proteins to sites of viral replication. Since the DDR has evolved to protect the genome from the accumulation of deleterious mutations, deregulation is inevitably associated with an increased risk of tumour formation. This review summarises the current literature regarding the complex relationship between known human tumour viruses and the DDR and aims to shed light on how these interactions can contribute to genomic instability and ultimately the development of human cancers. PMID:26008701

Accelerometry-based classification of human activities using Markov modeling.

PubMed

Mannini, Andrea; Sabatini, Angelo Maria

2011-01-01

Accelerometers are a popular choice as body-motion sensors: the reason is partly in their capability of extracting information that is useful for automatically inferring the physical activity in which the human subject is involved, beside their role in feeding biomechanical parameters estimators. Automatic classification of human physical activities is highly attractive for pervasive computing systems, whereas contextual awareness may ease the human-machine interaction, and in biomedicine, whereas wearable sensor systems are proposed for long-term monitoring. This paper is concerned with the machine learning algorithms needed to perform the classification task. Hidden Markov Model (HMM) classifiers are studied by contrasting them with Gaussian Mixture Model (GMM) classifiers. HMMs incorporate the statistical information available on movement dynamics into the classification process, without discarding the time history of previous outcomes as GMMs do. An example of the benefits of the obtained statistical leverage is illustrated and discussed by analyzing two datasets of accelerometer time series.

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.

Viruses and the nucleolus: the fatal attraction.

PubMed

Salvetti, Anna; Greco, Anna

2014-06-01

Viruses are small obligatory parasites and as a consequence, they have developed sophisticated strategies to exploit the host cell's functions to create an environment that favors their own replication. A common feature of most - if not all - families of human and non-human viruses concerns their interaction with the nucleolus. The nucleolus is a multifunctional nuclear domain, which, in addition to its well-known role in ribosome biogenesis, plays several crucial other functions. Viral infection induces important nucleolar alterations. Indeed, during viral infection numerous viral components localize in nucleoli, while various host nucleolar proteins are redistributed in other cell compartments or are modified, and non-nucleolar cellular proteins reach the nucleolus. This review highlights the interactions reported between the nucleolus and some human or animal viral families able to establish a latent or productive infection, selected on the basis of their known interactions with the nucleolus and the nucleolar activities, and their links with virus replication and/or pathogenesis. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease. Copyright © 2014 Elsevier B.V. All rights reserved.

What should I do next? Using shared representations to solve interaction problems.

PubMed

Pezzulo, Giovanni; Dindo, Haris

2011-06-01

Studies on how "the social mind" works reveal that cognitive agents engaged in joint actions actively estimate and influence another's cognitive variables and form shared representations with them. (How) do shared representations enhance coordination? In this paper, we provide a probabilistic model of joint action that emphasizes how shared representations help solving interaction problems. We focus on two aspects of the model. First, we discuss how shared representations permit to coordinate at the level of cognitive variables (beliefs, intentions, and actions) and determine a coherent unfolding of action execution and predictive processes in the brains of two agents. Second, we discuss the importance of signaling actions as part of a strategy for sharing representations and the active guidance of another's actions toward the achievement of a joint goal. Furthermore, we present data from a human-computer experiment (the Tower Game) in which two agents (human and computer) have to build together a tower made of colored blocks, but only the human knows the constellation of the tower to be built (e.g., red-blue-red-blue-…). We report evidence that humans use signaling strategies that take another's uncertainty into consideration, and that in turn our model is able to use humans' actions as cues to "align" its representations and to select complementary actions.

Antibacterial function of the human cathelicidin-18 peptide (LL-37) between theory and practice.

PubMed

Iacob, Simona A; Iacob, Diana G

2014-01-01

The human cathelicidin-18 is an antimicrobial, immunomodulatory and tissue repair peptide. The LL-37 fragment of this peptide which is in fact the active domain of the cathelicidin-18 is critical for the human antibacterial defense and epithelial integrity. It's activity against resistant pathogens, the potential of epithelial healing after microbial injury and the neutralization of bacterial endotoxin underlie the most important benefits of this peptide. However, there are still a number of questions that remain to be answered regarding the precise interactions of cathelicidin-18 within the immune system, the exact tissue concentrations or its possible pro-tumoral activity. In this respect, the therapeutic potential of cathelicidin-18 in various infections has been proved by in vitro experiments, but additional detailed clinical studies are still required to ascertain its antimicrobial role in vivo. We present a short review on the antibacterial activity of human cathelicidin-18 (LL-37) according to in vitro experiments while discussing its potential use in the clinical practice.

Lifting the veil on the dynamics of neuronal activities evoked by transcranial magnetic stimulation

PubMed Central

Li, Bingshuo; Virtanen, Juha P; Oeltermann, Axel; Schwarz, Cornelius; Giese, Martin A; Ziemann, Ulf

2017-01-01

Transcranial magnetic stimulation (TMS) is a widely used non-invasive tool to study and modulate human brain functions. However, TMS-evoked activity of individual neurons has remained largely inaccessible due to the large TMS-induced electromagnetic fields. Here, we present a general method providing direct in vivo electrophysiological access to TMS-evoked neuronal activity 0.8–1 ms after TMS onset. We translated human single-pulse TMS to rodents and unveiled time-grained evoked activities of motor cortex layer V neurons that show high-frequency spiking within the first 6 ms depending on TMS-induced current orientation and a multiphasic spike-rhythm alternating between excitation and inhibition in the 6–300 ms epoch, all of which can be linked to various human TMS responses recorded at the level of spinal cord and muscles. The advance here facilitates a new level of insight into the TMS-brain interaction that is vital for developing this non-invasive tool to purposefully explore and effectively treat the human brain. PMID:29165241

Prevalence of External Injuries in Small Cetaceans in Aruban Waters, Southern Caribbean

PubMed Central

Luksenburg, Jolanda A.

2014-01-01

Aruba, located close to the coasts of Colombia and Venezuela, is one of the most densely populated islands in the Caribbean and supports a wide range of marine-related socio-economic activities. However, little is known about the impacts of human activities on the marine environment. Injuries in marine mammals can be used to examine interactions with human activities and identify potential threats to the survival of populations. The prevalence of external injuries and tooth rake marks were examined in Atlantic spotted dolphin (Stenella frontalis) (n = 179), bottlenose dolphin (Tursiops truncatus) (n = 76) and false killer whale (Pseudorca crassidens) (n = 71) in Aruban waters using photo identification techniques. Eleven injury categories were defined and linked to either human-related activities or natural causes. All injury categories were observed. In total, 18.7% of all individuals had at least one injury. Almost half (41.7%) of the injuries could be attributed to human interactions, of which fishing gear was the most common cause (53.3%) followed by propeller hits (13.3%). Major disfigurements were observed in all three species and could be attributed to interactions with fishing gear. The results of this study indicate that fishing gear and propeller hits may pose threats to small and medium-sized cetaceans in Aruban waters. Thus, long-term monitoring of population trends is warranted. Shark-inflicted bite wounds were observed in Atlantic spotted dolphin and bottlenose dolphin. Bite wounds of cookie cutter sharks (Isistius sp.) were recorded in all three species, and include the first documented record of a cookie cutter shark bite in Atlantic spotted dolphin. This is one of the few studies which investigates the prevalence of injuries in cetaceans in the Caribbean. Further study is necessary to determine to which extent the injuries observed in Aruba affect the health and survival of local populations. PMID:24586473