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Sample records for gef-h1 mediated control

  1. Processes mediating expertise in air traffic control

    Van Meeuwen, Ludo; Jarodzka, Halszka; Brand-Gruwel, Saskia; Van Merriënboer, Jeroen; De Bock, Jeano; Kirschner, Paul A.

    2010-01-01

    Van Meeuwen, L., Jarodzka, H., Brand-Gruwel, S., Van Merriënboer, J. J. G., De Bock, J. J. P. R., & Kirschner, P. A. (2010, August). Processes mediating expertise in air traffic control. Meeting of the EARLI SIG6/7 Instructional Design and Learning and Instruction with Computers, Ulm, Germany.

  2. Processes mediating expertise in air traffic control

    Van Meeuwen, Ludo; Jarodzka, Halszka; Brand-Gruwel, Saskia; Van Merriënboer, Jeroen; De Bock, Jeano; Kirschner, Paul A.

    2011-01-01

    Van Meeuwen, L. W., Jarodzka, H., Brand-Gruwel, S., Van Merriënboer, J. J. G., De Bock, J. J. P. R., & Kirschner, P. A. (2010, September). Processes mediating expertise in air traffic control. Poster presented at the European Association for Aviation Psychology Conference, Budapest.

  3. Real-time Control Mediation in Agile Distributed Software Development

    Persson, John Stouby; Aaen, Ivan; Mathiassen, Lars

    2008-01-01

    Agile distributed environments pose particular challenges related to control of quality and collaboration in software development. Moreover, while face-to-face interaction is fundamental in agile development, distributed environments must rely extensively on mediated interactions. On this backdrop...... control was mediated over distance by technology through real-time exchanges. Contrary to previous research, the analysis suggests that both formal and informal elements of real-time mediated control were used; that evolving goals and adjustment of expectations were two of the main issues in real......-time mediated control exchanges; and, that the actors, despite distances in space and culture, developed a clan-like pattern mediated by technology to help control quality and collaboration in software development....

  4. The Dark Side of Computer-Mediated Control

    Cunha, J. V.; Carugati, Andrea; Leclercq, A.

    2015-01-01

    of computer-mediated control when work and its electronic representation are loosely coupled, because it is employees who report their work in IT systems. Data from a 15-month ethnographic study of the appropriation of a customer relationship management system in the sales department of a large organization......Research on the dark side of computer-mediated control has explained the consequences of computer-mediated control when work is tightly coupled with its electronic representation because information systems record work automatically. Our study complements prior research by addressing the dark side...

  5. Cdc42-mediated tubulogenesis controls cell specification

    Kesavan, Gokul; Sand, Fredrik Wolfhagen; Greiner, Thomas Uwe

    2009-01-01

    Understanding how cells polarize and coordinate tubulogenesis during organ formation is a central question in biology. Tubulogenesis often coincides with cell-lineage specification during organ development. Hence, an elementary question is whether these two processes are independently controlled......, or whether proper cell specification depends on formation of tubes. To address these fundamental questions, we have studied the functional role of Cdc42 in pancreatic tubulogenesis. We present evidence that Cdc42 is essential for tube formation, specifically for initiating microlumen formation and later...... for maintaining apical cell polarity. Finally, we show that Cdc42 controls cell specification non-cell-autonomously by providing the correct microenvironment for proper control of cell-fate choices of multipotent progenitors. For a video summary of this article, see the PaperFlick file with the Supplemental Data...

  6. Boundary mediated position control of traveling waves

    Martens, Steffen; Ziepke, Alexander; Engel, Harald

    Reaction control is an essential task in biological systems and chemical process industry. Often, the excitable medium supporting wave propagation exhibits an irregular shape and/or is limited in size. In particular, the analytic treatment of wave phenomena is notoriously difficult due to the spatial modulation of the domain's. Recently, we have provided a first systematic treatment by applying asymptotic perturbation analysis leading to an approximate description that involves a reduction of dimensionality; the 3D RD equation with spatially dependent NFBCs on the reactants reduces to a 1D reaction-diffusion-advection equation. Here, we present a novel method to control the position ϕ (t) of traveling waves in modulated domains according to a prespecified protocol of motion. Given this protocol, the ``optimal'' geometry of reactive domains Q (x) is found as the solution of the perturbatively derived equation of motion. Noteworthy, such a boundary control can be expressed in terms of the uncontrolled wave profile and its propagation velocity, rendering detailed knowledge of the reaction kinetics unnecessary. German Science Foundation DFG through the SFB 910 ''Control of Self-Organizing Nonlinear Systems''.

  7. Nitroxide-mediated controlled radical polymerisation: towards control of molar mass Controlled Radical Polymerisation

    Bon, S.A.F.; Bergman, F.A.C.; Es, van J.J.G.S.; Klumperman, B.; German, A.L.; Matyjaszewski, K.

    1998-01-01

    The mechanism of the TEMPO-mediated controlled radical polymerization of styrene in bulk is discussed. It is shown that the isotropic correlation time (tc) of a nitroxide can be used as a measure of the diffusive rate coefficient of trapping (ketD). A general empirical relationship for the density

  8. The mediating effect of sustainability control system on reverse ...

    This paper analyses part of the viability of green supply chain management practices created for fisheries industry to implement sustainability control system adoption as mediating on reverse logistics innovation and customer environmental collaboration towards sustainability performance. It examines reverse logistics ...

  9. T1R3 homomeric sweet taste receptor regulates adipogenesis through Gαs-mediated microtubules disassembly and Rho activation in 3T3-L1 cells.

    Yosuke Masubuchi

    Full Text Available We previously reported that 3T3-L1 cells express a functional sweet taste receptor possibly as a T1R3 homomer that is coupled to Gs and negatively regulates adipogenesis by a Gαs-mediated but cAMP-independent mechanism. Here, we show that stimulation of this receptor with sucralose or saccharin induced disassembly of the microtubules in 3T3-L1 preadipocytes, which was attenuated by overexpression of the dominant-negative mutant of Gαs (Gαs-G226A. In contrast, overexpression of the constitutively active mutant of Gαs (Gαs-Q227L as well as treatment with cholera toxin or isoproterenol but not with forskolin caused disassembly of the microtubules. Sweetener-induced microtubule disassembly was accompanied by activation of RhoA and Rho-associated kinase (ROCK. This was attenuated with by knockdown of GEF-H1, a microtubule-localized guanine nucleotide exchange factor for Rho GTPase. Furthermore, overexpression of the dominant-negative mutant of RhoA (RhoA-T19N blocked sweetener-induced dephosphorylation of Akt and repression of PPARγ and C/EBPα in the early phase of adipogenic differentiation. These results suggest that the T1R3 homomeric sweet taste receptor negatively regulates adipogenesis through Gαs-mediated microtubule disassembly and consequent activation of the Rho/ROCK pathway.

  10. Chloride (Cl−) ion-mediated shape control of palladium nanoparticles

    Nalajala, Naresh; Chakraborty, Arup; Bera, Bapi; Neergat, Manoj

    2016-01-01

    The shape control of Pd nanoparticles is investigated using chloride (Cl − ) ions as capping agents in an aqueous medium in the temperature range of 60–100 °C. With weakly adsorbing and strongly etching Cl − ions, oxygen plays a crucial role in shape control. The experimental factors considered are the concentration of the capping agents, reaction time and reaction atmosphere. Thus, Pd nanoparticles of various shapes with high selectivity can be synthesized. Moreover, the removal of Cl − ions from the nanoparticle surface is easier than that of Br − ions (moderately adsorbing and etching) and I − ions (strongly adsorbing and weakly etching). The cleaned Cl − ion-mediated shape-controlled Pd nanoparticles are electrochemically characterized and the order of the half-wave potential of the oxygen reduction reaction in oxygen-saturated 0.1 M HClO 4 solution is of the same order as that observed with single-crystal Pd surfaces. (paper)

  11. Mediatization

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction...

  12. PRMT1-mediated arginine methylation controls ATXN2L localization

    Kaehler, Christian; Guenther, Anika; Uhlich, Anja; Krobitsch, Sylvia, E-mail: krobitsc@molgen.mpg.de

    2015-05-15

    Arginine methylation is a posttranslational modification that is of importance in diverse cellular processes. Recent proteomic mass spectrometry studies reported arginine methylation of ataxin-2-like (ATXN2L), the paralog of ataxin-2, a protein that is implicated in the neurodegenerative disorder spinocerebellar ataxia type 2. Here, we investigated the methylation state of ATXN2L and its significance for ATXN2L localization. We first confirmed that ATXN2L is asymmetrically dimethylated in vivo, and observed that the nuclear localization of ATXN2L is altered under methylation inhibition. We further discovered that ATXN2L associates with the protein arginine-N-methyltransferase 1 (PRMT1). Finally, we showed that neither mutation of the arginine–glycine-rich motifs of ATXN2L nor methylation inhibition alters ATXN2L localization to stress granules, suggesting that methylation of ATXN2L is probably not mandatory. - Highlights: • ATXN2L is asymmetrically dimethylated in vivo. • ATXN2L interacts with PRMT1 under normal and stress conditions. • PRMT1-mediated dimethylation of ATXN2L controls its nuclear localization. • ATXN2L localization to stress granules appears independent of its methylation state.

  13. Governance and control as mediating instruments in an inter-firm relationship : Towards collaboration or transactions?

    Zahir-Ul-Hassan, Muhammad Kaleem; Minnaar, Reinald A.; Vosselman, E.G.J.

    2016-01-01

    This paper explores the mediation of governance and control structures in an inter-firm relationship between a semiconductor producer and its contractor. As mediating instruments the contract and the control structures are not just pre-given results of distanced managerial decision-making, but are

  14. Governance and control as mediating instruments in an inter-firm relationship: towards collaboration or transactions?

    Zahir-ul-Hassan, M.K.; Minnaar, R.A.; Vosselman, E.G.J.

    2016-01-01

    This paper explores the mediation of governance and control structures in an inter-firm relationship between a semiconductor producer and its contractor. As mediating instruments the contract and the control structures are not just pre-given results of distanced managerial decision-making, but are

  15. p53-Mediated Molecular Control of Autophagy in Tumor Cells

    Maria Mrakovcic

    2018-03-01

    Full Text Available Autophagy is an indispensable mechanism of the eukaryotic cell, facilitating the removal and renewal of cellular components and thereby balancing the cell’s energy consumption and homeostasis. Deregulation of autophagy is now regarded as one of the characteristic key features contributing to the development of tumors. In recent years, the suppression of autophagy in combination with chemotherapeutic treatment has been approached as a novel therapy in cancer treatment. However, depending on the type of cancer and context, interference with the autophagic machinery can either promote or disrupt tumorigenesis. Therefore, disclosure of the major signaling pathways that regulate autophagy and control tumorigenesis is crucial. To date, several tumor suppressor proteins and oncogenes have emerged as eminent regulators of autophagy whose depletion or mutation favor tumor formation. The mammalian cell “janitor” p53 belongs to one of these tumor suppressors that are most commonly mutated in human tumors. Experimental evidence over the last decade convincingly reports that p53 can act as either an activator or an inhibitor of autophagy depending on its subcellular localization and its mode of action. This finding gains particular significance as p53 deficiency or mutant variants of p53 that accumulate in the cytoplasm of tumor cells enable activation of autophagy. Accordingly, we recently identified p53 as a molecular hub that regulates autophagy and apoptosis in histone deacetylase inhibitor-treated uterine sarcoma cells. In light of this novel experimental evidence, in this review, we focus on p53 signaling as a mediator of the autophagic pathway in tumor cells.

  16. Mediator subunit18 controls flowering time and floral organ identity in Arabidopsis.

    Zhengui Zheng

    Full Text Available Mediator is a conserved multi-protein complex that plays an important role in regulating transcription by mediating interactions between transcriptional activator proteins and RNA polymerase II. Much evidence exists that Mediator plays a constitutive role in the transcription of all genes transcribed by RNA polymerase II. However, evidence is mounting that specific Mediator subunits may control the developmental regulation of specific subsets of RNA polymerase II-dependent genes. Although the Mediator complex has been extensively studied in yeast and mammals, only a few reports on Mediator function in flowering time control of plants, little is known about Mediator function in floral organ identity. Here we show that in Arabidopsis thaliana, MEDIATOR SUBUNIT 18 (MED18 affects flowering time and floral organ formation through FLOWERING LOCUS C (FLC and AGAMOUS (AG. A MED18 loss-of-function mutant showed a remarkable syndrome of later flowering and altered floral organ number. We show that FLC and AG mRNA levels and AG expression patterns are altered in the mutant. Our results support parallels between the regulation of FLC and AG and demonstrate a developmental role for Mediator in plants.

  17. Trajectories of late-life change in God-mediated control.

    Hayward, R David; Krause, Neal

    2013-01-01

    To track within-individual change during late life in the sense of personal control and God-mediated control (the belief that one can work collaboratively with God to achieve one's goals and exercise control over life events) and to evaluate the hypothesis that this element of religion is related to declining personal control. A longitudinal survey representative of older White and Black adults in the United States tracked changes in personal and God-mediated control in four waves over the course of 7 years. Growth curve analysis found that the pattern of change differed by race. White adults had less sense of God-mediated control at younger ages, which increased among those who were highly religious but decreased among those who were less religious. Black adults had higher God-mediated control, which increased over time among those with low personal control. These results indicate that God-mediated control generally increases during older adulthood, but that its relationships with personal control and religious commitment are complex and differ between Black and White adults.

  18. Attentional control mediates the effect of social anxiety on positive affect☆

    Morrison, Amanda S.; Heimberg, Richard G.

    2015-01-01

    The goal of the present studies was to examine whether attentional control, a self-regulatory attentional mechanism, mediates the effect of social anxiety on positive affect. We tested this mediation in two studies using undergraduate students selected to represent a broad range of severity of social anxiety. Self-report assessments of social anxiety, attentional control, and positive affect were collected in a cross-sectional design (Study 1) and in a longitudinal design with three assessment points (Study 2). Results of both studies supported the hypothesized mediational model. Specifically, social anxiety was inversely related to attentional control, which itself positively predicted positive affect. This mediation remained significant even when statistically controlling for the effects of depression. Additionally, the hypothesized model provided superior model fit to theoretically-grounded equivalent models in both studies. Implications of these findings for understanding diminished positive affect in social anxiety are discussed. PMID:23254261

  19. The Mediator subunit SFR6/MED16 controls defence gene expression mediated by salicylic acid and jasmonate responsive pathways.

    Wathugala, Deepthi L; Hemsley, Piers A; Moffat, Caroline S; Cremelie, Pieter; Knight, Marc R; Knight, Heather

    2012-07-01

    • Arabidopsis SENSITIVE TO FREEZING6 (SFR6) controls cold- and drought-inducible gene expression and freezing- and osmotic-stress tolerance. Its identification as a component of the MEDIATOR transcriptional co-activator complex led us to address its involvement in other transcriptional responses. • Gene expression responses to Pseudomonas syringae, ultraviolet-C (UV-C) irradiation, salicylic acid (SA) and jasmonic acid (JA) were investigated in three sfr6 mutant alleles by quantitative real-time PCR and susceptibility to UV-C irradiation and Pseudomonas infection were assessed. • sfr6 mutants were more susceptible to both Pseudomonas syringae infection and UV-C irradiation. They exhibited correspondingly weaker PR (pathogenesis-related) gene expression than wild-type Arabidopsis following these treatments or after direct application of SA, involved in response to both UV-C and Pseudomonas infection. Other genes, however, were induced normally in the mutants by these treatments. sfr6 mutants were severely defective in expression of plant defensin genes in response to JA; ectopic expression of defensin genes was provoked in wild-type but not sfr6 by overexpression of ERF5. • SFR6/MED16 controls both SA- and JA-mediated defence gene expression and is necessary for tolerance of Pseudomonas syringae infection and UV-C irradiation. It is not, however, a universal regulator of stress gene transcription and is likely to mediate transcriptional activation of specific regulons only. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  20. God-Mediated Control and Change in Self-Rated Health.

    Krause, Neal

    2010-10-01

    The purpose of this study was to see if feelings of God-mediated control are associated with change in self-rated health over time. In the process, an effort was made to see if a sense of meaning in life and optimism mediated the relationship between God-mediated control and change in health. The following hypothesized relationships were contained in the conceptual model that was developed to evaluate these issues: (1) people who go to church more often tend to have stronger God-mediated control beliefs than individuals who do not attend worship services as often; (2) people with a strong sense of God-mediated control are more likely to find a sense of meaning in life and be more optimistic than individuals who do not have a strong sense of God-mediated control; (3) people who are optimistic and who have a strong sense of meaning in life will rate their health more favorably over time than individuals who are not optimistic, as well as individuals who have not found a sense of meaning in life. Data from a longitudinal nationwide survey of older adults provided support for each of these hypotheses.

  1. Lateral presynaptic inhibition mediates gain control in an olfactory circuit.

    Olsen, Shawn R; Wilson, Rachel I

    2008-04-24

    Olfactory signals are transduced by a large family of odorant receptor proteins, each of which corresponds to a unique glomerulus in the first olfactory relay of the brain. Crosstalk between glomeruli has been proposed to be important in olfactory processing, but it is not clear how these interactions shape the odour responses of second-order neurons. In the Drosophila antennal lobe (a region analogous to the vertebrate olfactory bulb), we selectively removed most interglomerular input to genetically identified second-order olfactory neurons. Here we show that this broadens the odour tuning of these neurons, implying that interglomerular inhibition dominates over interglomerular excitation. The strength of this inhibitory signal scales with total feedforward input to the entire antennal lobe, and has similar tuning in different glomeruli. A substantial portion of this interglomerular inhibition acts at a presynaptic locus, and our results imply that this is mediated by both ionotropic and metabotropic receptors on the same nerve terminal.

  2. Social Control of Hypothalamus-Mediated Male Aggression.

    Yang, Taehong; Yang, Cindy F; Chizari, M Delara; Maheswaranathan, Niru; Burke, Kenneth J; Borius, Maxim; Inoue, Sayaka; Chiang, Michael C; Bender, Kevin J; Ganguli, Surya; Shah, Nirao M

    2017-08-16

    How environmental and physiological signals interact to influence neural circuits underlying developmentally programmed social interactions such as male territorial aggression is poorly understood. We have tested the influence of sensory cues, social context, and sex hormones on progesterone receptor (PR)-expressing neurons in the ventromedial hypothalamus (VMH) that are critical for male territorial aggression. We find that these neurons can drive aggressive displays in solitary males independent of pheromonal input, gonadal hormones, opponents, or social context. By contrast, these neurons cannot elicit aggression in socially housed males that intrude in another male's territory unless their pheromone-sensing is disabled. This modulation of aggression cannot be accounted for by linear integration of environmental and physiological signals. Together, our studies suggest that fundamentally non-linear computations enable social context to exert a dominant influence on developmentally hard-wired hypothalamus-mediated male territorial aggression. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. RACK1-mediated translation control promotes liver fibrogenesis

    Liu, Min; Peng, Peike; Wang, Jiajun [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Wang, Lan; Duan, Fangfang [Institute of Biomedical Science, Fudan University, Shanghai 200032 (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Ruan, Yuanyuan, E-mail: yuanyuanruan@fudan.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Institute of Biomedical Science, Fudan University, Shanghai 200032 (China)

    2015-07-31

    Activation of quiescent hepatic stellate cells (HSCs) is the central event of liver fibrosis. The translational machinery is an optimized molecular network that affects cellular homoeostasis and diseases, whereas the role of protein translation in HSCs activation and liver fibrosis is little defined. Our previous report suggests that up-regulation of receptor for activated C-kinase 1(RACK1) in HSCs is critical for liver fibrogenesis. In this study, we found that RACK1 promoted macrophage conditioned medium (MCM)-induced assembly of eIF4F and phosphorylation of eIF4E in primary HSCs. RACK1 enhanced the translation and expression of pro-fibrogenic factors collagen 1α1, snail and cyclin E1 induced by MCM. Administration of PP242 or knock-down of eIF4E suppressed RACK1-stimulated collagen 1α1 production, proliferation and migration in primary HSCs. In addition, depletion of eIF4E attenuated thioacetamide (TAA)-induced liver fibrosis in vivo. Our data suggest that RACK1-mediated stimulation of cap-dependent translation plays crucial roles in HSCs activation and liver fibrogenesis, and targeting translation initiation could be a promising strategy for the treatment of liver fibrosis. - Highlights: • RACK1 induces the assembly of eIF4F and phosphorylation of eIF4E in primary HSCs. • RACK1 stimulates the translation of collagen 1α1, snail and cyclin E1 in HSCs. • RACK1 promotes HSCs activation via cap-mediated translation. • Depletion of eIF4E suppresses liver fibrogenesis in vivo.

  4. RACK1-mediated translation control promotes liver fibrogenesis

    Liu, Min; Peng, Peike; Wang, Jiajun; Wang, Lan; Duan, Fangfang; Jia, Dongwei; Ruan, Yuanyuan; Gu, Jianxin

    2015-01-01

    Activation of quiescent hepatic stellate cells (HSCs) is the central event of liver fibrosis. The translational machinery is an optimized molecular network that affects cellular homoeostasis and diseases, whereas the role of protein translation in HSCs activation and liver fibrosis is little defined. Our previous report suggests that up-regulation of receptor for activated C-kinase 1(RACK1) in HSCs is critical for liver fibrogenesis. In this study, we found that RACK1 promoted macrophage conditioned medium (MCM)-induced assembly of eIF4F and phosphorylation of eIF4E in primary HSCs. RACK1 enhanced the translation and expression of pro-fibrogenic factors collagen 1α1, snail and cyclin E1 induced by MCM. Administration of PP242 or knock-down of eIF4E suppressed RACK1-stimulated collagen 1α1 production, proliferation and migration in primary HSCs. In addition, depletion of eIF4E attenuated thioacetamide (TAA)-induced liver fibrosis in vivo. Our data suggest that RACK1-mediated stimulation of cap-dependent translation plays crucial roles in HSCs activation and liver fibrogenesis, and targeting translation initiation could be a promising strategy for the treatment of liver fibrosis. - Highlights: • RACK1 induces the assembly of eIF4F and phosphorylation of eIF4E in primary HSCs. • RACK1 stimulates the translation of collagen 1α1, snail and cyclin E1 in HSCs. • RACK1 promotes HSCs activation via cap-mediated translation. • Depletion of eIF4E suppresses liver fibrogenesis in vivo

  5. Passion, Trait Self-Control, and Wellbeing: Comparing Two Mediation Models Predicting Wellbeing.

    Briki, Walid

    2017-01-01

    Research has found that passion and trait self-control represented key determinants of wellbeing. Yet, no study to date has attempted to investigate the mediating influences of trait self-control and passion for accounting for the relationships between passion, trait self-control, and wellbeing (dependent variable). Using different frameworks, such as the dualistic model of passion and the neo-socioanalytic theory, the present study proposed two mediation models, considering either trait self-control (model 1) or passion (model 2) as the mediating variable. Five hundred nine volunteers from the United States (326 females and 183 males; M age = 31.74, SD age = 11.05, from 18 to 70 years old), who reported being passionate about a specific activity (e.g., fishing, swimming, blogging; M passion = 5.94, SD passion = 0.89), answered questionnaires assessing harmonious and obsessive passion, trait self-control, and wellbeing (measured through hedonic and eudaimonic wellbeing scales). Preliminary analyses revealed that both models were significant ( model 1: absolute GoF = 0.366, relative GoF = 0.971, outer model GoF = 0.997, inner model GoF = 0.973, R 2 = 18.300%, p passion, trait self-control, and wellbeing, and no relationships of obsessive passion with trait self-control and wellbeing. Mediation analyses revealed that trait self-control significantly mediated the relationship between harmonious passion and wellbeing (i.e., partial mediation, VAF = 33.136%). Harmonious passion appeared to significantly mediate the positive effect of trait self-control on wellbeing; however, the size of the mediating effect indicated that (almost) no mediation would take place (i.e., VAF = 11.144%). The present study is the first to examine the relationships between passion, trait self-control, and wellbeing, and supports the view that trait self-control and harmonious passion represent not only adaptive and powerful constructs, but also key determinants of wellbeing. Implications for

  6. Proactive sustainability strategy and corporate sustainability performance: The mediating effect of sustainability control systems.

    Wijethilake, Chaminda

    2017-07-01

    This study examines to what extent corporations use sustainability control systems (SCS) to translate proactive sustainability strategy into corporate sustainability performance. The study investigates the mediating effect of SCS on the relationship between proactive sustainability strategy and corporate sustainability performance. Survey data were collected from top managers in 175 multinational and local corporations operating in Sri Lanka and analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). SCS were observed to only partially mediate the relationship between proactive sustainability strategy and corporate sustainability performance. The mediating effect of SCS is further examined under three sustainability strategies; environmental and social strategies reveal a partial mediation, while the economic strategy exhibits no mediation. The study also finds that (i) a proactive sustainability strategy is positively associated with SCS and corporate sustainability performance and (ii) SCS are positively associated with corporate sustainability performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. CRISPR-mediated control of the bacterial initiation of replication

    Wiktor, J.M.; Lesterlin, Christian; Sherratt, David J.; Dekker, C.

    2016-01-01

    Programmable control of the cell cycle has been shown to be a powerful tool in cell-biology studies. Here, we develop a novel system for controlling the bacterial cell cycle, based on binding of CRISPR/dCas9 to the origin-of-replication locus. Initiation of replication of bacterial chromosomes is

  8. Achievement goals and emotions: The mediational roles of perceived progress, control, and value.

    Hall, Nathan C; Sampasivam, Lavanya; Muis, Krista R; Ranellucci, John

    2016-06-01

    The link between achievement goals and achievement emotions is well established; however, research exploring potential mediators of this relationship is lacking. The control-value theory of achievement emotions (Pekrun, 2006, Educational Psychology Review, 18, 315) posits that perceptions of control and value mediate the relationship between achievement goals and achievement emotions, whereas the bidirectional theory of affect (Linnenbrink & Pintrich, 2002, Educational Psychologist, 37, 69) proposes that perceived progress mediates this relationship. The present study empirically evaluated three hypothesized mediators of the effects of achievement goals on learning-related emotions as proposed in the control-value theory and the bidirectional theory of affect. Undergraduate students (N = 273) from humanities, social science, and STEM disciplines participated. Participants completed web-based questionnaires evaluating academic achievement goals, perceptions of control, perceived task value, and achievement emotions. Results provided empirical support primarily for perceived progress as a mediator of mastery-approach goal effects on positive emotions (enjoyment, hope), showing indirect effects of mastery- and performance-approach goals on outcome-related emotions (hope, anxiety) via perceived control. Indirect effects of mastery- and performance-approach goals were further observed on anxiety via perceived value, with higher value levels predicting greater anxiety. Study findings partially support Linnenbrink and Pintrich's (2002, Educational Psychologist, 37, 69) bidirectional theory of affect while underscoring the potential for indirect effects of goals on emotions through perceived control as proposed by Pekrun (2006, Educational Psychology Review, 18, 315). © 2016 The British Psychological Society.

  9. Imidazoline and imidazolidine nitroxides as controlling agents in nitroxide-mediated pseudoliving radical polymerization

    Edeleva, M. V.; Marque, S. R. A.; Bagryanskaya, E. G.

    2018-04-01

    Controlled, or pseudoliving, radical polymerization provides unique opportunities for the synthesis of structurally diverse polymers with a narrow molecular-weight distribution. These reactions occur under relatively mild conditions with broad tolerance to functional groups in the monomers. The nitroxide-mediated pseudoliving radical polymerization is of particular interest for the synthesis of polymers for biomedical applications. This review briefly describes one of the mechanisms of controlled radical polymerization. The studies dealing with the use of imidazoline and imidazolidine nitroxides as controlling agents for nitroxide-mediated pseudoliving radical polymerization of various monomers are summarized and analyzed. The publications addressing the key steps of the controlled radical polymerization in the presence of imidazoline and imidazolidine nitroxides and new approaches to nitroxide-mediated polymerization based on protonation of both nitroxides and monomers are considered. The bibliography includes 154 references.

  10. Stress and adult smartphone addiction: Mediation by self-control, neuroticism, and extraversion.

    Cho, Hea-Young; Kim, Dai Jin; Park, Jae Woo

    2017-12-01

    This study employed descriptive statistics and correlation analysis to examine the influence of stress on smartphone addiction as well as the mediating effects of self-control, neuroticism, and extraversion using 400 men and women in their 20s to 40s followed by structural equation analysis. Our findings indicate that stress had a significant influence on smartphone addiction, and self-control mediates the influence of stress on smartphone addiction. As stress increases, self-control decreases, which subsequently leads to increased smartphone addiction. Self-control was confirmed as an important factor in the prevention of smartphone addiction. Finally, among personality factors, neuroticism, and extraversion mediate the influence of stress on smartphone addiction. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Effortless inhibition: habit mediates the relation between self-control and unhealthy snack consumption

    Adriaanse, Marieke A.; Kroese, Floor M.; Gillebaart, Marleen; De Ridder, Denise T. D.

    2014-01-01

    In contrast to prevailing beliefs, recent research suggests that trait self-control promotes health behavior not because those high in self-control are more successful at resisting single temptations, but rather because they develop adaptive habits. The present paper presents a first empirical test of this novel suggestion by investigating the mediating role of habit in explaining the relation between self-control and unhealthy snacking behavior. Results showed that self-control was negativel...

  12. Maladaptive perfectionism as mediator among psychological control, eating disorders, and exercise dependence symptoms in habitual exerciser.

    Costa, Sebastiano; Hausenblas, Heather A; Oliva, Patrizia; Cuzzocrea, Francesca; Larcan, Rosalba

    2016-03-01

    Background and aims The current study examined the mediating role of maladaptive perfectionism among parental psychological control, eating disorder symptoms, and exercise dependence symptoms by gender in habitual exercisers. Methods Participants were 348 Italian exercisers (n = 178 men and n = 170 women; M age = 20.57, SD = 1.13) who completed self-report questionnaires assessing their parental psychological control, maladaptive perfectionism, eating disorder symptoms, and exercise dependence symptoms. Results Results of the present study confirmed the mediating role of maladaptive perfectionism for eating disorder and exercise dependence symptoms for the male and female exercisers in the maternal data. In the paternal data, maladaptive perfectionism mediated the relationships between paternal psychological control and eating disorder and exercise dependence symptoms as full mediator for female participants and as partial mediator for male participants. Discussion Findings of the present study suggest that it may be beneficial to consider dimensions of maladaptive perfectionism and parental psychological control when studying eating disorder and exercise dependence symptoms in habitual exerciser.

  13. CRISPR-mediated control of the bacterial initiation of replication.

    Wiktor, Jakub; Lesterlin, Christian; Sherratt, David J; Dekker, Cees

    2016-05-05

    Programmable control of the cell cycle has been shown to be a powerful tool in cell-biology studies. Here, we develop a novel system for controlling the bacterial cell cycle, based on binding of CRISPR/dCas9 to the origin-of-replication locus. Initiation of replication of bacterial chromosomes is accurately regulated by the DnaA protein, which promotes the unwinding of DNA at oriC We demonstrate that the binding of CRISPR/dCas9 to any position within origin or replication blocks the initiation of replication. Serial-dilution plating, single-cell fluorescence microscopy, and flow-cytometry experiments show that ongoing rounds of chromosome replication are finished upon CRISPR/dCas9 binding, but no new rounds are initiated. Upon arrest, cells stay metabolically active and accumulate cell mass. We find that elevating the temperature from 37 to 42°C releases the CRISR/dCas9 replication inhibition, and we use this feature to recover cells from the arrest. Our simple and robust method of controlling the bacterial cell cycle is a useful asset for synthetic biology and DNA-replication studies in particular. The inactivation of CRISPR/dCas9 binding at elevated temperatures may furthermore be of wide interest for CRISPR/Cas9 applications in genomic engineering. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. College drinking behaviors: mediational links between parenting styles, impulse control, and alcohol-related outcomes.

    Patock-Peckham, Julie A; Morgan-Lopez, Antonio A

    2006-06-01

    Mediational links between parenting styles (authoritative, authoritarian, permissive), impulsiveness (general control), drinking control (specific control), and alcohol use and abuse were tested. A pattern-mixture approach (for modeling non-ignorable missing data) with multiple-group structural equation models with 421 (206 female, 215 male) college students was used. Gender was examined as a potential moderator of parenting styles on control processes related to drinking. Specifically, the parent-child gender match was found to have implications for increased levels of impulsiveness (a significant mediator of parenting effects on drinking control). These findings suggest that a parent with a permissive parenting style who is the same gender as the respondent can directly influence control processes and indirectly influence alcohol use and abuse.

  15. Estrogen-mediated Height Control in Girls with Marfan Syndrome.

    Lee, Dong-Yun; Hyun, Hye Sun; Huh, Rimm; Jin, Dong-Kyu; Kim, Duk-Kyung; Yoon, Byung-Koo; Choi, DooSeok

    2016-02-01

    This study evaluated the efficacy of a stepwise regimen of estradiol valerate for height control in girls with Marfan syndrome. Eight girls with Marfan syndrome who had completed estrogen treatment for height control were included. Estradiol valerate was started at a dose of 2 mg/day, and then was increased. The projected final height was estimated using the initial height percentile (on a disease-specific growth curve for Korean Marfan syndrome [gcPFHt]), and the initial bone age (baPFHt). After the estrogen treatment, the projected final height was compared to the actual final height (FHt). The median baseline chronological and bone age were 10.0 and 10.5 years, respectively. After a median of 36.5 months of treatment, the median FHt (172.6 cm) was shorter than the median gcPFHt (181.0 cm) and baPFHt (175.9 cm). In the six patients who started treatment before the age of 11 years, the median FHt (171.8 cm) was shorter than the median gcPFHt (181.5 cm) and baPFHt (177.4 cm) after treatment. The median differences between the FHt and gcPFHt and baPFHt were 9.2 and 8.3 cm, respectively. In two patients started treatment after the age of 11, the differences between FHt and gcPFHt, and baPFHt after treatment were -4 and 1.4 cm, and -1.2 and 0 cm for each case, respectively. A stepwise increasing regimen of estradiol valerate may be an effective treatment for height control in girls with Marfan syndrome, especially when started under 11 years old.

  16. Spin-orbit mediated control of spin qubits

    Flindt, Christian; Sørensen, A.S; Flensberg, Karsten

    2006-01-01

    We propose to use the spin-orbit interaction as a means to control electron spins in quantum dots, enabling both single-qubit and two-qubit operations. Very fast single-qubit operations may be achieved by temporarily displacing the electrons. For two-qubit operations the coupling mechanism is bas...... on a combination of the spin-orbit coupling and the mutual long-ranged Coulomb interaction. Compared to existing schemes using the exchange coupling, the spin-orbit induced coupling is less sensitive to random electrical fluctuations in the electrodes defining the quantum dots....

  17. Safety aid use and social anxiety symptoms: The mediating role of perceived control.

    Korte, Kristina J; Unruh, Amanda S; Oglesby, Mary E; Schmidt, Norman B

    2015-08-30

    The use of safety aids, cognitive or behavioral strategies used to reduce or cope with anxiety, has emerged as a key construct of interest in anxiety disorders due to their role in the development and maintenance of anxiety symptoms. It has been suggested that individuals with anxiety engage in safety aid use to reduce their anxiety and feel more in control of a situation; however, no studies to date have examined the association between perceived control, that is, perceived level of control over internal events in anxiety provoking situations, and the use of safety aids. The purpose of the present study was to examine the association of perceived control, the use of safety aids, and symptoms of social anxiety. It was predicted that the association between safety aid use and social anxiety symptoms would be mediated by perceived control. This prediction was examined in a large sample of 281 participants. As predicted, perceived control was a significant mediator of the association between the use of safety aids and social anxiety symptoms. This effect remained significant after running a multiple mediation model with distress tolerance added as a competing mediator. Implications for future research are discussed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Parental behavioral and psychological control and problematic internet use among Chinese adolescents: the mediating role of self-control.

    Li, Xian; Li, Dongping; Newman, Joan

    2013-06-01

    Previous research has reported contradictory effects of parental control on adolescents' problematic Internet use (PIU). To reconcile the discrepant findings, the current study examined the differential effects of parental behavioral control (solicitation and restriction) and psychological control (guilt induction, love withdrawal, and authority assertion) on adolescents' PIU. The mediating effect of self-control on the relationships between parental control and PIU was also examined. A total of 694 Chinese adolescents (M=13.67 years) completed questionnaire measures of parental behavioral control, psychological control, self-control, and PIU. After adjusting for age, gender, and family financial status, it was found that parental restriction (a form of behavioral control) was negatively associated with PIU, whereas love withdrawal (a form of psychological control) was positively associated with PIU. Increased self-control was associated with decreased PIU, and changes in self-control at least partially mediated the differential effects of parental behavioral and psychological control on PIU. Theoretical and practical implications of these findings are discussed.

  19. Improved Metabolic Control in Diabetes, HSP60, and Proinflammatory Mediators

    Claudio Blasi

    2012-01-01

    Full Text Available The diabetes-atherosclerosis relationship remains to be fully defined. Repeated prolonged hyperglycemia, increased ROS production and endothelial dysfunction are important factors. One theory is that increased blood levels of heat shock protein (HSP60 are proinflammatory, through activation of innate immunity, and contribute to the progression of vascular disease. It was hypothesized that improvement of diabetes control in patients presenting with metabolic syndrome would lower HSP60, and anti-HSP60 antibody levels and decrease inflammatory markers. Paired sera of 17 Italian patients, before and after intensive treatment, were assayed for cytokines, HSP60 and anti-HSP60 antibodies. As expected, intensive treatment was associated with a decrease in HgbA1C (P<0.001 and BMI (P<0.001. After treatment, there was a significant decrease in IL-6 (P<0.05. HSP60 levels were before treatment −6.9+1.9, after treatment −7.1+2.0 ng/mL (P=ns. Overall HSP60 concentrations were lower than published reports. Anti-HSP60 antibody titers were high and did not decrease with treatment. In conclusion, improvement of diabetic control did not alter HSP60 concentrations or antiHSP60 antibody titers, but led to a reduction of IL-6 levels.

  20. Laser pulse control of bridge mediated heterogeneous electron transfer

    Wang Luxia; May, Volkhard

    2009-01-01

    Ultrafast heterogeneous electron transfer from surface attached dye molecules into semiconductor band states is analyzed. The focus is on systems where the dye is separated from the surface by different bridge anchor groups. To simulate the full quantum dynamics of the transfer process a model of reduced dimensionality is used. It comprises the electronic levels of the dye, the bridge anchor group electronic levels and the continuum of semiconductor band states, all defined versus a single intramolecular vibrational coordinate. The effect of the bridge states is demonstrated, firstly, in studying the injection dynamics following an impulsive excitation of the dye. Then, by discussing different control tasks it is demonstrate in which way the charge injection process can be influenced by tailored laser pulses. To highlight the importance of electron wave function interference emphasis is put on asymmetric two-bridge molecule systems which are also characterized by different and complex valued electronic transfer matrix elements.

  1. Radiation-pressure-mediated control of an optomechanical cavity

    Cripe, Jonathan; Aggarwal, Nancy; Singh, Robinjeet; Lanza, Robert; Libson, Adam; Yap, Min Jet; Cole, Garrett D.; McClelland, David E.; Mavalvala, Nergis; Corbitt, Thomas

    2018-01-01

    We describe and demonstrate a method to control a detuned movable-mirror Fabry-Pérot cavity using radiation pressure in the presence of a strong optical spring. At frequencies below the optical spring resonance, self-locking of the cavity is achieved intrinsically by the optomechanical (OM) interaction between the cavity field and the movable end mirror. The OM interaction results in a high rigidity and reduced susceptibility of the mirror to external forces. However, due to a finite delay time in the cavity, this enhanced rigidity is accompanied by an antidamping force, which destabilizes the cavity. The cavity is stabilized by applying external feedback in a frequency band around the optical spring resonance. The error signal is sensed in the amplitude quadrature of the transmitted beam with a photodetector. An amplitude modulator in the input path to the cavity modulates the light intensity to provide the stabilizing radiation pressure force.

  2. Phytochrome-mediated responses: Implications for controlled environment research facilities

    Smith, Harry

    1994-01-01

    Light is undoubtedly the most important environmental variable for plant growth and development; plants not only use radiant energy in photosynthesis, they also respond to the quantity, quality, direction and timing of incident radiation through photomorphogenic response that can have huge effects on the rate of growth and the pattern of development. It is surprising, therefore, that the manufacturers and suppliers of controlled environment facilities have been singularly uninventive in the design of the lighting assemblies they provide. The consumer has one choice only - a lighting assembly that provides irradiance levels usually only a fraction of sunlight, and a control system that is limited to regulating the timing of the on-off switch. The reasons for these limitations are partly technological, but in the main they result from ignorance on the part of both the consumer and the manufacturer. A specific and powerful example of this ignorance relates to the importance of the so-called far-red wavelengths (FR = 700-800 nm). Because the human eye can hardly detect wavelengths above 700 nm, and photosynthesis also cuts off at about 700 nm, the majority of plant and crop physiologists are still almost completely unaware that FR radiation can have massive effects on growth rate and development. In consequence, most growth cabinets have light sources based on fluorescent tubes, and provide very little FR apart from that emitted by a token number of small incandescent bulbs. Larger growth facilities often use broader spectrum light sources, but growth facilities that provide the capability to vary the FR incident upon the plants are about as abundant as seals in the Sahara. This article sets the background of the significance of FR radiation in the natural environment and its importance for plant growth and development in the hope that it might inform intelligently those concerned with improving the design of plant growth facilities.

  3. Phytochrome-mediated responses implications for controlled environment research facilities

    Smith, H. [Univ. of Leicester (United Kingdom)

    1994-12-31

    Light is undoubtedly the most important environmental variable for plant growth and development; plants not only use radiant energy in photosynthesis, they also respond to the quantity, quality, direction and timing of incident radiation through photomorphogenic responses that can have huge effects on the rate of growth and the pattern of development. It is surprising, therefore, that the manufacturers and suppliers of controlled environment facilities have been singularly uninventive in the design of the lighting assemblies they provide. The consumer has one choice only - a lighting assembly that provides irradiance levels usually only a fraction of sunlight, and a control system that is limited to regulating the timing of the on-off switch. The reasons for these limitations are partly technological, but in the main they result from ignorance on the part of both the consumer and the manufacturer. A specific and powerful example of this ignorance relates to the importance of the so-called far-red wavelengths (FR = 700-800 nm). Because the human eye can hardly detect wavelengths above 700 nm, and photosynthesis also cuts off at ca. 700 mn, the majority of plant and crop physiologists are still almost completely unaware that FR radiation can have massive effects on growth rate and development. In consequence, most growth cabinets have light sources based on fluorescent tubes, and provide very little FR apart from that emitted by a token number of small incandescent bulbs. Larger growth facilities often use broader spectrum light sources, but growth facilities that provide the capability to vary the FR incident upon the plants are about as abundant as seals in the Sahara. This article sets the background of the significance of FR radiation in the natural environment and its importance for plant growth and development in the hope that it might inform intelligently those concerned with improving the design of plant growth facilities.

  4. Motivation toward Physical Exercise and Subjective Wellbeing: The Mediating Role of Trait Self-Control

    Walid Briki

    2016-10-01

    Full Text Available Motivation toward physical exercise (MPE and trait self-control (TSC were identified as key predictors of subjective wellbeing (SWB. However, there has not been any research designed to examine the mediating role of TSC in the relationship between MPE and SWB. The present study utilizes self-determination theory, control-process theory of self-regulation, and theory of multiple pathways of TSC in order to examine whether TSC mediates the relationships of autonomous MPE (A-MPE, controlled MPE (C-MPE, and impersonal MPE (NO-MPE with SWB using structural equation modeling (XLSTAT PLS. Three hundred seventeen adult American individuals (Mage = 32.97, SDage = 11.30, who reported to be regular exercisers, voluntarily answered questionnaires assessing MPE, TSC, and SWB. Correlational analyses revealed positive relationships between A-MPE, TSC, and SWB, and negative relationships of C-MPE and NO-MPE with TSC and SWB. Mediation analyses revealed that TSC mediated the relationships of A-MPE (partial mediation and C-MPE (full mediation with SWB, but did not mediate the relationship between NO-MPE and SWB. The estimates of the quality of the hypothesized model were acceptable (outer model GoF = .935; absolute GoF = .330; relative GoF = .942; inner model GoF = 1.008; R2 = 36.947%. Finally, this study supports the view that MPE can influence SWB through TSC, and incites to pursue the examination of the relationships between self-determined motivation, self-regulation mechanisms, and health-related outcomes.

  5. Global efficiency of structural networks mediates cognitive control in Mild Cognitive Impairment

    Rok Berlot

    2016-12-01

    Full Text Available Background: Cognitive control has been linked to both the microstructure of individual tracts and the structure of whole-brain networks, but their relative contributions in health and disease remain unclear. Objective: To determine the contribution of both localised white matter tract damage and disruption of global network architecture to cognitive control, in older age and Mild Cognitive Impairment (MCI.Methods: 25 patients with MCI and 20 age, sex and intelligence-matched healthy volunteers were investigated with 3 Tesla structural magnetic resonance imaging (MRI. Cognitive control and episodic memory were evaluated with established tests. Structural network graphs were constructed from diffusion MRI-based whole-brain tractography. Their global measures were calculated using graph theory. Regression models utilized both global network metrics and microstructure of specific connections, known to be critical for each domain, to predict cognitive scores. Results: Global efficiency and the mean clustering coefficient of networks were reduced in MCI. Cognitive control was associated with global network topology. Episodic memory, in contrast, correlated with individual temporal tracts only. Relationships between cognitive control and network topology were attenuated by addition of single tract measures to regression models, consistent with a partial mediation effect. The mediation effect was stronger in MCI than healthy volunteers, explaining 23-36% of the effect of cingulum microstructure on cognitive control performance. Network clustering was a significant mediator in the relationship between tract microstructure and cognitive control in both groups. Conclusions: The status of critical connections and large-scale network topology are both important for maintenance of cognitive control in MCI. Mediation via large-scale networks is more important in patients with MCI than healthy volunteers. This effect is domain-specific, and true for cognitive

  6. Thermodynamic control of small RNA-mediated gene silencing

    Kumiko eUi-Tei

    2012-06-01

    Full Text Available Small interfering RNAs (siRNAs and microRNAs (miRNAs are crucial regulators of posttranscriptional gene silencing, which is referred to as RNA interference (RNAi or RNA silencing. In RNAi, siRNA loaded onto the RNA-induced silencing complex (RISC downregulates target gene expression by cleaving mRNA whose sequence is perfectly complementary to the siRNA guide strand. We previously showed that highly functional siRNAs possessed the following characteristics: A or U residues at nucleotide position 1 measured from the 5’ terminal, four to seven A/Us in positions 1–7, and G or C residues at position 19. This finding indicated that an RNA strand with a thermodynamically unstable 5’ terminal is easily retained in the RISC and functions as a guide strand. In addition, it is clear that unintended genes with complementarities only in the seed region (positions 2–8 are also downregulated by off-target effects. siRNA efficiency is mainly determined by the Watson-Crick base-pairing stability formed between the siRNA seed region and target mRNA. siRNAs with a low seed-target duplex melting temperature (Tm have little or no seed-dependent off-target activity. Thus, important parts of the RNA silencing machinery may be regulated by nucleotide base-pairing thermodynamic stability. A mechanistic understanding of thermodynamic control may enable an efficient target gene-specific RNAi for functional genomics and safe therapeutic applications.

  7. Parenting Styles and Bullying at School: The Mediating Role of Locus of Control

    Georgiou, Stelios N.; Ioannou, Myria; Stavrinides, Panayiotis

    2017-01-01

    The current study examined the mediating role of children's locus of control in the relation between parenting styles and bully-victim experiences at school. Participants were 447 students aged 10 and 11 years old from 13 different elementary, urban, and rural schools in Cyprus. Analyses using structural equation modeling showed that parenting…

  8. Inhibitory Control Mediates the Relationship between Depressed Mood and Overgeneral Memory Recall in Children

    Raes, Filip; Verstraeten, Katrien; Bijttebier, Patricia; Vasey, Michael W.; Dalgleish, Tim

    2010-01-01

    It has been well established that depressed mood is related to overgeneral memory recall (OGM), which refers to a relative difficulty in retrieving specific information from one's autobiographical memory (AM). The present study examined whether OGM is also related to depressed mood in children and whether lack of inhibitory control mediates this…

  9. Perceived Academic Control: Mediating the Effects of Optimism and Social Support on College Students' Psychological Health

    Ruthig, Joelle C.; Haynes, Tara L.; Stupnisky, Robert H.; Perry, Raymond P.

    2009-01-01

    The first year of college presents numerous challenges experienced as overwhelming by some freshmen who may become overly stressed and depressed. This longitudinal study examined perceived academic control (PAC) as a mediator of optimism and social support's buffering effects on freshman students' psychological health. Multiple regressions…

  10. Mother-adolescent conflict as a mediator between adolescent problem behaviors and maternal psychological control.

    Steeger, Christine M; Gondoli, Dawn M

    2013-04-01

    This study examined mother-adolescent conflict as a mediator of longitudinal reciprocal relations between adolescent aggression and depressive symptoms and maternal psychological control. Motivated by family systems theory and the transactions that occur between individual and dyadic levels of the family system, we examined the connections among these variables during a developmental period when children and parents experience significant psychosocial changes. Three years of self-report data were collected from 168 mother-adolescent dyads, beginning when the adolescents (55.4% girls) were in 6th grade. Models were tested using longitudinal path analysis. Results indicated that the connection between adolescent aggression (and depressive symptoms) and maternal psychological control was best characterized as adolescent-driven, indirect, and mediated by mother-adolescent conflict; there were no indications of parent-driven indirect effects. That is, prior adolescent aggression and depressive symptoms were associated with increased conflict. In turn, conflict was associated with increased psychological control. Within our mediation models, reciprocal direct effects between both problem behaviors and conflict and between conflict and psychological control were also found. Additionally, exploratory analyses regarding the role of adolescent gender as a moderator of variable relations were conducted. These analyses revealed no gender-related patterns of moderation, whether moderated mediation or specific path tests for moderation were considered. This study corroborates prior research finding support for child effects on parenting behaviors during early adolescence. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  11. Computer-mediated communication in adults with high-functioning autism spectrum disorders and controls

    van der Aa, Christine; Pollmann, Monique; Plaat, Aske; van der Gaag, Rutger Jan

    2016-01-01

    It has been suggested that people with Autism Spectrum Disorders (ASD) are attracted to computer-mediated communication (CMC). In this study, we compare CMC use in adults with high-functioning ASD (N = 113) and a control group (N = 72). We find that people with ASD spend more time on CMC than

  12. Polarization control of intermediate state absorption in resonance-mediated multi-photon absorption process

    Xu, Shuwu; Yao, Yunhua; Jia, Tianqing; Ding, Jingxin; Zhang, Shian; Sun, Zhenrong; Huang, Yunxia

    2015-01-01

    We theoretically and experimentally demonstrate the control of the intermediate state absorption in an (n + m) resonance-mediated multi-photon absorption process by the polarization-modulated femtosecond laser pulse. An analytical solution of the intermediate state absorption in a resonance-mediated multi-photon absorption process is obtained based on the time-dependent perturbation theory. Our theoretical results show that the control efficiency of the intermediate state absorption by the polarization modulation is independent of the laser intensity when the transition from the intermediate state to the final state is coupled by the single-photon absorption, but will be affected by the laser intensity when this transition is coupled by the non-resonant multi-photon absorption. These theoretical results are experimentally confirmed via a two-photon fluorescence control in (2 + 1) resonance-mediated three-photon absorption of Coumarin 480 dye and a single-photon fluorescence control in (1 + 2) resonance-mediated three-photon absorption of IR 125 dye. (paper)

  13. The LEGO toolbox: Supramolecular building blocks by nitroxide-mediated controlled radical polymerization

    Lohmeijer, B.G.G.; Schubert, U.S.

    2005-01-01

    A terpyridine-functionalized alkoxyamine unimolecular initiator was used for the nitroxide-mediated controlled living radical polymerization of n-butylacrylate, N,N-dimethylacrylamide, 4-vinylpyridine, 2-vinylpyridine, and isoprene. For the former three monomers, the kinetics were studied. All

  14. Job autonomy in relation to work engagement and workaholism: Mediation of autonomous and controlled work motivation.

    Malinowska, Diana; Tokarz, Aleksandra; Wardzichowska, Anna

    2018-02-07

    This study integrates the Self Determination Theory and the Job Demands-Resource model in explaining motivational antecedents of 2 forms of excessive work: work engagement and workaholism. It specifically examines the relationship between job autonomy, situational work motivation, work engagement, and workaholism. The sample comprised 318 full-time employees of an international outsourcing company located in Poland. The mediation analysis was used for testing hypotheses about the mediation of autonomous and controlled motivation in the relationship between job autonomy, work engagement, and workaholism. The results have confirmed that autonomous motivation mediates the relationship between job autonomy and work engagement. The assumption about the mediation role of controlled motivation in the relationship between job autonomy and workaholism has not been confirmed; however, external regulation (i.e., controlled motivation) is a significant predictor of workaholism. Giving employees more job autonomy might increase their intrinsic and identified regulation and may therefore lead to more energetic, enthusiastic, and dedicated engagement with their jobs. Workaholism may be predicted by external regulation, and work characteristics other than job autonomy may play an important role in enhancing this controlled type of motivation. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  15. Inhibitory Control Mediates the Association between Perceived Stress and Secure Relationship Quality.

    Herd, Toria; Li, Mengjiao; Maciejewski, Dominique; Lee, Jacob; Deater-Deckard, Kirby; King-Casas, Brooks; Kim-Spoon, Jungmeen

    2018-01-01

    Past research has demonstrated negative associations between exposure to stressors and quality of interpersonal relationships among children and adolescents. Nevertheless, underlying mechanisms of this association remain unclear. Chronic stress has been shown to disrupt prefrontal functioning in the brain, including inhibitory control abilities, and evidence is accumulating that inhibitory control may play an important role in secure interpersonal relationship quality, including peer problems and social competence. In this prospective longitudinal study, we examine whether changes in inhibitory control, measured at both behavioral and neural levels, mediate the association between stress and changes in secure relationship quality with parents and peers. The sample included 167 adolescents (53% males) who were first recruited at age 13 or 14 years and assessed annually three times. Adolescents' inhibitory control was measured by their behavioral performance and brain activities, and adolescents self-reported perceived stress levels and relationship quality with mothers, fathers, and peers. Results suggest that behavioral inhibitory control mediates the association between perceived stress and adolescent's secure relationship quality with their mothers and fathers, but not their peers. In contrast, given that stress was not significantly correlated with neural inhibitory control, we did not further test the mediation path. Our results highlight the role of inhibitory control as a process through which stressful life experiences are related to impaired secure relationship quality between adolescents and their mothers and fathers.

  16. Work stress and emotional exhaustion in nurses: the mediating role of internal locus of control.

    Partlak Günüşen, Neslihan; Ustün, Besti; Erdem, Sabri

    2014-01-01

    Burnout is a major problem for nursing. There is a strong relationship between work stress and emotional exhaustion. Although studies report a negative correlation between the internal locus of control and emotional exhaustion and work stress, the number of studies available on the subject is limited. This study intends to examine the extent to which the relationship between work stress and emotional exhaustion is mediated by nurses' internal locus of control. The study adopted a cross-sectional survey design. The data were analyzed using structural equation modeling techniques. The study sample consisted of 347 nurses who worked in a university hospital in Izmir, Turkey and who agreed to participate in the study. The Work-Related Strain Inventory was used to evaluate the nurses' work stress level, Maslach Burnout Inventory was used to evaluate their emotional exhaustion levels, and the Locus of Control Scale was used to evaluate the internal locus of control. The variables of the study were based on the Neuman Systems Model. Work stress was positively related to internal locus of control (β3 = .21, p 0.1). Internal locus of control was negatively related to emotional exhaustion (β = -.14, p Work stress is directly (β = .87, p Work stress is directly (β = .87, p work stress was mediated, the impact of internal locus of control was limited. It is recommended that different variables be included in future studies so that they can mediate the relationship between work stress and emotional exhaustion.

  17. Inhibitory Control Mediates the Association between Perceived Stress and Secure Relationship Quality

    Toria Herd

    2018-02-01

    Full Text Available Past research has demonstrated negative associations between exposure to stressors and quality of interpersonal relationships among children and adolescents. Nevertheless, underlying mechanisms of this association remain unclear. Chronic stress has been shown to disrupt prefrontal functioning in the brain, including inhibitory control abilities, and evidence is accumulating that inhibitory control may play an important role in secure interpersonal relationship quality, including peer problems and social competence. In this prospective longitudinal study, we examine whether changes in inhibitory control, measured at both behavioral and neural levels, mediate the association between stress and changes in secure relationship quality with parents and peers. The sample included 167 adolescents (53% males who were first recruited at age 13 or 14 years and assessed annually three times. Adolescents’ inhibitory control was measured by their behavioral performance and brain activities, and adolescents self-reported perceived stress levels and relationship quality with mothers, fathers, and peers. Results suggest that behavioral inhibitory control mediates the association between perceived stress and adolescent’s secure relationship quality with their mothers and fathers, but not their peers. In contrast, given that stress was not significantly correlated with neural inhibitory control, we did not further test the mediation path. Our results highlight the role of inhibitory control as a process through which stressful life experiences are related to impaired secure relationship quality between adolescents and their mothers and fathers.

  18. Human GW182 Paralogs Are the Central Organizers for RNA-Mediated Control of Transcription.

    Hicks, Jessica A; Li, Liande; Matsui, Masayuki; Chu, Yongjun; Volkov, Oleg; Johnson, Krystal C; Corey, David R

    2017-08-15

    In the cytoplasm, small RNAs can control mammalian translation by regulating the stability of mRNA. In the nucleus, small RNAs can also control transcription and splicing. The mechanisms for RNA-mediated nuclear regulation are not understood and remain controversial, hindering the effective application of nuclear RNAi and investigation of its natural regulatory roles. Here, we reveal that the human GW182 paralogs TNRC6A/B/C are central organizing factors critical to RNA-mediated transcriptional activation. Mass spectrometry of purified nuclear lysates followed by experimental validation demonstrates that TNRC6A interacts with proteins involved in protein degradation, RNAi, the CCR4-NOT complex, the mediator complex, and histone-modifying complexes. Functional analysis implicates TNRC6A, NAT10, MED14, and WDR5 in RNA-mediated transcriptional activation. These findings describe protein complexes capable of bridging RNA-mediated sequence-specific recognition of noncoding RNA transcripts with the regulation of gene transcription. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Maternal Parenting as a Mediator of the Relationship between Intimate Partner Violence and Effortful Control

    Gustafsson, Hanna C.; Cox, Martha J.; Blair, Clancy

    2011-01-01

    The current study examined the relationship between intimate partner violence (IPV), maternal parenting behaviors, and child effortful control in a diverse sample of 705 families living in predominantly low-income, rural communities. Using structural equation modeling, the authors simultaneously tested whether observed sensitive parenting and/or harsh-intrusive parenting over the toddler years mediated the relationship between early IPV and later effortful control. Results suggest that parent...

  20. Self-control mediates the relationship between time perspective and BMI.

    Price, Menna; Higgs, Suzanne; Lee, Michelle

    2017-01-01

    Trait future time perspective measures the extent to which behaviour is dominated by a striving for future goals and rewards. Trait present time perspective measures orientation towards immediate pleasure. Previous research has explored the relationship between future and present time perspective and BMI with mixed findings. In addition, the psychological mechanism underlying this relationship is unclear. Self-control is a likely candidate, as it has been related to both BMI and time perspective, but the relationship between all of these concepts has not been examined in a single study. Therefore, the aim of this study was to examine if trait self-control mediates the relationship between time perspective (future and present) and BMI. Self-report time perspective (ZTPI), self-control (SCS) and height/weight data were collected using an online survey from a mixed student and community sample (N = 218) with wide ranging age (mean 29, SD 11, range 18-73 years) and BMI (mean 24, SD 4, range 15-43). The results of a structural equation model including both facets of time perspective suggested that the traits are related yet distinct measures that independently predict BMI through changes in self-control. Bootstrap mediation analysis showed that self-control mediated the relationship between both future time perspective (95% CI, -0.10 to -0.02) and present time perspective (95% CI, 0.03 to 0.17), and BMI in opposite directions. Participants with higher future time perspective scores (higher present time perspective scores) had higher (lower) self-control, which predicted lower (higher) BMI. These results are consistent with previous research suggesting an important role for time perspective in health outcomes. Self-control likely mediates the relationship between temporal perspectives and BMI, suggesting that time perspective may be a target for individualised interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Religiousness and aggression in adolescents: The mediating roles of self-control and compassion.

    Shepperd, James A; Miller, Wendi A; Smith, Colin Tucker

    2015-01-01

    Although people have used religion to justify aggression, evidence suggests that greater religiousness corresponds with less aggression. We explored two explanations for the religion-aggression link. First, most major religions teach self-control (e.g., delaying gratification, resisting temptation), which diminishes aggression. Second, most major religions emphasize compassionate beliefs and behavior (i.e., perspective taking, forgiveness, a broader love of humanity) that are incompatible with aggression. We tested whether self-control and compassion mediated the relationship between religion and aggression (direct and indirect) in a longitudinal study of 1,040 adolescents in the United States. Structural equation analyses revealed that self-control and compassion together completely mediated the religion-aggression relationship for both types of aggression. © 2015 Wiley Periodicals, Inc.

  2. Callous-Unemotional Traits and Effortful Control Mediate the Effect of Parenting Intervention on Preschool Conduct Problems.

    Elizur, Yoel; Somech, Lior Y

    2018-02-24

    Parenting intervention (PI) is an effective treatment for children's conduct problems (CP) that has been shown to be mediated by improved parenting practices and parenting self-efficacy. Recently, Hitkashrut's randomized controlled trial demonstrated that ineffective parenting (IP) mediated effects on callous-unemotional (CU) traits and effortful control (EC), while controlling for more general treatment effects on CP. These temperament and personality-based features predict the formation of early-onset antisocial trajectories with poor long-term prognosis. The objective of this study was to use Hitkashrut's 3-wave dataset to test posttreatment EC and CU mediation of treatment effect on 1-year follow-up CP, and to determine whether mediation by each child-level potential mediator remains significant when tested concurrently with the parenting mediator. Parents of 209 3-5 year-old preschoolers (163 boys; 46 girls), with subclinical-clinical range CP were assigned to 14-session co-parent training groups (n = 140 couples), or to minimal intervention control groups (n = 69 couples). Assessments were based on both parents' questionnaires. An intent-to-treat analysis showed that EC and CU traits simultaneously mediated treatment effects on CP in one EC/CU mediational model. The concurrent testing of child- and parent-level mediators showed mediation by IP and CU traits in the CU/IP model, and IP mediation in the EC/IP model. Similar results were obtained in mediational analyses that controlled for the shared variance between the mediators and CP at T2. Overall, the findings support an intervention model of coaching parents of high-CP children to promote moral self-regulatory competencies while concurrently applying behavioral methods that directly target CP.

  3. Effortless Inhibition: Habit Mediates the Relation Between Self-Control and Unhealthy Snack Consumption

    Marieke eAdriaanse

    2014-05-01

    Full Text Available In contrast to prevailing beliefs, recent research suggests that trait self-control promotes health behavior not because those high in self-control are more successful at resisting single temptations, but rather because they develop adaptive habits. The present paper presents a first empirical test of this novel suggestion by investigating the mediating role of habit in explaining the relation between self-control and unhealthy snacking behavior. Results showed that self-control was negatively associated with unhealthy snack consumption and unhealthy snacking habits. As hypothesized, the relation between self-control and unhealthy snack intake was mediated by habit strength. Self-control was not associated with fruit consumption or fruit consumption habits. These results provide the first evidence for the notion that high self-control may influence the formation of habits and in turn affect behavior. Moreover, results imply that self-control may be particularly influential in case of inhibiting unhealthy food intake rather than promoting healthy food intake.

  4. Exploring the relationship between socioeconomic status, control beliefs and exercise behavior: a multiple mediator model.

    Murray, Terra C; Rodgers, Wendy M; Fraser, Shawn N

    2012-02-01

    The purpose of this study was to examine the relationship between control beliefs, socioeconomic status and exercise intentions and behavior. Specifically, we examined whether distal and proximal control beliefs mediated the association between socioeconomic status and exercise intentions and behavior. A one time, cross sectional mail out survey (N = 350) was conducted in a large urban Canadian city. Distal (i.e., personal constraints) and proximal (i.e., scheduling self-efficacy) control beliefs mediated the association between socioeconomic status and exercise, explaining approximately 30% of the variance. Proximal control beliefs (i.e., scheduling self-efficacy) partially mediated the association between socioeconomic status and intentions, with the models explaining approximately 50% of the variance. Compared to individuals with lower socioeconomic status, individuals with higher socioeconomic status reported more exercise and stronger intentions to exercise. This was at least partly because higher socioeconomic status respondents reported fewer barriers in their lives, and were more confident to cope with the scheduling demands of exercise.

  5. Mother–Adolescent Conflict as a Mediator Between Adolescent Problem Behaviors and Maternal Psychological Control

    Steeger, Christine M.; Gondoli, Dawn M.

    2012-01-01

    This study examined mother–adolescent conflict as a mediator of longitudinal reciprocal relations between adolescent aggression and depressive symptoms and maternal psychological control. Motivated by family systems theory and the transactions that occur between individual and dyadic levels of the family system, we examined the connections among these variables during a developmental period when children and parents experience significant psychosocial changes. Three years of self-report data ...

  6. Control of Dog Mediated Human Rabies in Haiti: No Time to Spare.

    Max F Millien

    Full Text Available The American region has pledged to eliminate dog-mediated human rabies by 2015. As part of these efforts, we describe the findings of a desk and field mission review of Haiti's rabies situation by the end of 2013. While government officials recognize the importance of dog-mediated rabies control, and the national rabies plan adequately contemplates the basic capacities to that effect, regular and sufficient implementation, for example, of dog vaccination, is hampered by limited funding. Compounding insufficient funding and human resources, official surveillance figures do not accurately reflect the risk to the population, as evidenced by the large number of rabid dogs detected by focalized and enhanced surveillance activities conducted by the Ministry of Agriculture, Natural Resources and Rural Development (MARNDR and the Health and Population Ministry (MSPP with the technical assistance of the United States Centers for Disease Control and Prevention. Although international support is common, either in the form of on-the-ground technical support or donations of immunobiologicals, it is not comprehensive. In addition, there is limited coordination with MARNDR/MSPP and with other actors at the strategic or operational level due to human resources limitations. Given these findings, the 2015 elimination goal in the region is compromised by the situation in Haiti where control of the disease is not yet in sight despite the best efforts of the resolute national officials. More importantly, dog-mediated rabies is still a threat to the Haitian population.

  7. Perceived discrimination and psychological well-being: the mediating and moderating role of sense of control.

    Jang, Yuri; Chiriboga, David A; Small, Brent J

    2008-01-01

    Being discriminated against is an unpleasant and stressful experience, and its connection to reduced psychological well-being is well-documented. The present study hypothesized that a sense of control would serve as both mediator and moderator in the dynamics of perceived discrimination and psychological well-being. In addition, variations by age, gender, and race in the effects of perceived discrimination were explored. Data from the Midlife Development in the United States (MIDUS) survey (N=1554; age range = 45 to 74) provided supportive evidence for the hypotheses. The relationships between perceived discrimination and positive and negative affect were reduced when sense of control was controlled, demonstrating the role of sense of control as a mediator. The moderating role of sense of control was also supported, but only in the analysis for negative affect: the combination of a discriminatory experience and low sense of control markedly increased negative affect. In addition, age and gender variations were observed: the negative impact of perceived discrimination on psychological well-being was more pronounced among younger adults and females compared to their counterparts. The findings elucidated the mechanisms by which perceived discrimination manifested its psychological outcomes, and suggest ways to reduce adverse consequences associated with discriminatory experiences.

  8. Alcohol-specific parenting, adolescents' self-control, and alcohol use: a moderated mediation model.

    Koning, Ina M; van den Eijnden, Regina J J M; Vollebergh, Wilma A M

    2014-01-01

    There is convincing evidence that parental rules about alcohol are important in curbing adolescents' alcohol use. However, little is known about the mechanisms through which the direct link between alcohol-specific parenting and alcohol use is obtained. In this study, we investigated the mediating effect of adolescent self-control on the relationship between alcohol-specific rules and adolescents' drinking behavior and whether this mediation effect depends on the level of quality of communication. A total of 883 adolescents participated in this longitudinal study at ages 13, 14, and 15 years. Strict rules predicted lower rates of drinking, but no direct effect of the quality of communication on adolescents' alcohol use was found. A higher level of self-control was related to lower rates of drinking in adolescents. The indirect effect of rules about alcohol through adolescents' self-control was statistically significant, yet only in adolescents with high qualitative parent-child communication about alcohol. In adolescents with low quality of parent-child communication, self-control was not related to drinking. These findings imply that strict rule setting in combination with qualitative parent-child communication is an important target for prevention. In addition, findings point at the importance of high qualitative parent-child communication for adolescents' motivation to engage in self-control to avoid drinking.

  9. Mediating effects of emotional exhaustion on the relationship between job demand–control model and mental health.

    Huang, Yu-Hwa; Du, Pey-Ian; Chen, Chin-Hui; Yang, Chin-Ann; Huang, Ing-Chung

    2011-04-01

    This study attempted to investigate the role of emotional exhaustion as a mediator on the relationship between job demands-control (JDC) model and mental health. Three-wave data from 297 employees were collected. The results showed that job demands were positively related to emotional exhaustion, and increasing job demands will increase the level of emotional exhaustion. Job control was negatively associated with emotional exhaustion; therefore, increasing job control will decrease the level of emotional exhaustion. Emotional exhaustion was negatively related to mental health. Emotional exhaustion fully mediated the relationship between job demands and mental health, and partially mediated the positive relationship between job control and mental health. In addition, job control was positively associated with mental health directly. The remarkable finding of the present study was that emotional exhaustion served as the key mediator between the JDC model and mental health. Theoretical and managerial implications and limitations were discussed.

  10. Aggregation control of quantum dots through ion-mediated hydrogen bonding shielding.

    Liu, Jianbo; Yang, Xiaohai; Wang, Kemin; He, Xiaoxiao; Wang, Qing; Huang, Jin; Liu, Yan

    2012-06-26

    Nanoparticle stabilization against detrimental aggregation is a critical parameter that needs to be well controlled. Herein, we present a facile and rapid ion-mediated dispersing technique that leads to hydrophilic aggregate-free quantum dots (QDs). Because of the shielding of the hydrogen bonds between cysteamine-capped QDs, the presence of F(-) ions disassembled the aggregates of QDs and afforded their high colloidal stability. The F(-) ions also greatly eliminated the nonspecific adsorption of the QDs on glass slides and cells. Unlike the conventional colloidal stabilized method that requires the use of any organic ligand and/or polymer for the passivation of the nanoparticle surface, the proposed approach adopts the small size and large diffusion coefficient of inorganic ions as dispersant, which offers the disaggregation a fast reaction dynamics and negligible influence on their intrinsic surface functional properties. Therefore, the ion-mediated dispersing strategy showed great potential in chemosensing and biomedical applications.

  11. Transcription factor YY1 can control AID-mediated mutagenesis in mice.

    Zaprazna, Kristina; Basu, Arindam; Tom, Nikola; Jha, Vibha; Hodawadekar, Suchita; Radova, Lenka; Malcikova, Jitka; Tichy, Boris; Pospisilova, Sarka; Atchison, Michael L

    2018-02-01

    Activation-induced cytidine deminase (AID) is crucial for controlling the immunoglobulin (Ig) diversification processes of somatic hypermutation (SHM) and class switch recombination (CSR). AID initiates these processes by deamination of cytosine, ultimately resulting in mutations or double strand DNA breaks needed for SHM and CSR. Levels of AID control mutation rates, and off-target non-Ig gene mutations can contribute to lymphomagenesis. Therefore, factors that control AID levels in the nucleus can regulate SHM and CSR, and may contribute to disease. We previously showed that transcription factor YY1 can regulate the level of AID in the nucleus and Ig CSR. Therefore, we hypothesized that conditional knock-out of YY1 would lead to reduction in AID localization at the Ig locus, and reduced AID-mediated mutations. Using mice that overexpress AID (IgκAID yy1 f/f ) or that express normal AID levels (yy1 f/f ), we found that conditional knock-out of YY1 results in reduced AID nuclear levels, reduced localization of AID to the Sμ switch region, and reduced AID-mediated mutations. We find that the mechanism of YY1 control of AID nuclear accumulation is likely due to YY1-AID physical interaction which blocks AID ubiquitination. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. The relationship between self-control and health: The mediating effect of avoidant coping.

    Boals, Adriel; Vandellen, Michelle R; Banks, Jonathan B

    2011-08-01

    Trait self-control is related to a number of positive outcomes, including mental health, interpersonal success, academic success and health-related behaviours. This study sought to explore the relationships between self-control, reports of mental and physical health symptoms and coping styles. The results revealed that higher self-control was related to fewer mental and physical health symptoms and less avoidance coping. There was not a significant relationship between self-control and problem-focused or emotion-focused coping styles. Further, the relationships between self-control and mental and physical health outcomes were partially mediated by avoidance coping style. Specifically, the data suggest lower self-control is associated with unhealthy coping strategies (avoidance coping), which in turn are associated with worse mental health outcomes and greater reports of physical health symptoms. Thus lower trait self-control can serve as an indicator, suggesting circumstances in which individuals' tendencies to engage in unhealthy coping strategies are increased. These findings add to a growing body of literature underscoring the importance of trait self-control.

  13. Mediators of the association between narcissism and compulsive buying: the roles of materialism and impulse control.

    Rose, Paul

    2007-12-01

    Building upon past research about the guiding values and self-regulation difficulties of people with narcissistic personalities, this study tested a model of the association between narcissism and compulsive consumption. In data obtained from a sample of undergraduate consumers (N=238) with varying degrees of spending problems, positive associations emerged between narcissism, materialism, and compulsive buying. Impulse control was negatively correlated with each of these variables. Mediation tests revealed that both impulse control and materialism accounted for significant portions of the shared variance between narcissism and compulsive consumption. These findings highlight the importance of both personal values and impulse control as correlates of addictive buying. They also add to growing evidence that people who are relatively narcissistic are poor self-regulators who may be at risk of developing a variety of addictive behaviors.

  14. Nutrient Control of Yeast Gametogenesis Is Mediated by TORC1, PKA and Energy Availability.

    Hilla Weidberg

    2016-06-01

    Full Text Available Cell fate choices are tightly controlled by the interplay between intrinsic and extrinsic signals, and gene regulatory networks. In Saccharomyces cerevisiae, the decision to enter into gametogenesis or sporulation is dictated by mating type and nutrient availability. These signals regulate the expression of the master regulator of gametogenesis, IME1. Here we describe how nutrients control IME1 expression. We find that protein kinase A (PKA and target of rapamycin complex I (TORC1 signalling mediate nutrient regulation of IME1 expression. Inhibiting both pathways is sufficient to induce IME1 expression and complete sporulation in nutrient-rich conditions. Our ability to induce sporulation under nutrient rich conditions allowed us to show that respiration and fermentation are interchangeable energy sources for IME1 transcription. Furthermore, we find that TORC1 can both promote and inhibit gametogenesis. Down-regulation of TORC1 is required to activate IME1. However, complete inactivation of TORC1 inhibits IME1 induction, indicating that an intermediate level of TORC1 signalling is required for entry into sporulation. Finally, we show that the transcriptional repressor Tup1 binds and represses the IME1 promoter when nutrients are ample, but is released from the IME1 promoter when both PKA and TORC1 are inhibited. Collectively our data demonstrate that nutrient control of entry into sporulation is mediated by a combination of energy availability, TORC1 and PKA activities that converge on the IME1 promoter.

  15. Electrochemiluminescent DNA sensor based on controlled Zn-mediated grafting of diazonium precursors.

    Torréns, Mabel; Ortiz, Mayreli; Bejarano-Nosas, Diego; O'Sullivan, Ciara K

    2015-07-01

    Controlled Zn-mediated grafting of a thin layer of a diazonium salt was used to functionalise a carbon electrode with ruthenium(II)-tris-bipyridine (Ru)-labelled DNA for use as a capture probe in an electrochemiluminescent genosensor. A secondary reporter probe was labelled with a ferrocene (Fc) molecule, and in the presence of the single-stranded DNA target a genocomplex formed, where the Fc-label effectively quenched the electrochemiluminescence of the signal emitted from the Ru-label. The spacing of the labels for maximum sensitivity and minimum detection limit was optimised, and the signal reproducibility and stability of the method was established.

  16. A collapsin response mediator protein 2 isoform controls myosin II-mediated cell migration and matrix assembly by trapping ROCK II

    Yoneda, Atsuko; Morgan-Fisher, Marie; Wait, Robin

    2012-01-01

    Collapsin response mediator protein 2 (CRMP-2) is known as a regulator of neuronal polarity and differentiation through microtubule assembly and trafficking. Here, we show that CRMP-2 is ubiquitously expressed and a splice variant (CRMP-2L), which is expressed mainly in epithelial cells among...... nonneuronal cells, regulates myosin II-mediated cellular functions, including cell migration. While the CRMP-2 short form (CRMP-2S) is recognized as a substrate of the Rho-GTP downstream kinase ROCK in neuronal cells, a CRMP-2 complex containing 2L not only bound the catalytic domain of ROCK II through two......-2L but not -2S inhibited fibronectin matrix assembly in fibroblasts. Underlying these responses, CRMP-2L regulated the kinase activity of ROCK II but not ROCK I, independent of GTP-RhoA levels. This study provides a new insight into CRMP-2 as a controller of myosin II-mediated cellular functions...

  17. Right ventrolateral prefrontal cortex mediates individual differences in conflict-driven cognitive control

    Egner, Tobias

    2013-01-01

    Conflict adaptation – a conflict-triggered improvement in the resolution of conflicting stimulus or response representations – has become a widely used probe of cognitive control processes in both healthy and clinical populations. Previous functional magnetic resonance imaging (fMRI) studies have localized activation foci associated with conflict resolution to dorsolateral prefrontal cortex (dlPFC). The traditional group-analysis approach employed in these studies highlights regions that are, on average, activated during conflict resolution, but does not necessarily reveal areas mediating individual differences in conflict resolution, because between-subject variance is treated as noise. Here, we employed a complementary approach in order to elucidate the neural bases of variability in the proficiency of conflict-driven cognitive control. We analyzed two independent fMRI data sets of face-word Stroop tasks by using individual variability in the behavioral expression of conflict adaptation as the metric against which brain activation was regressed, while controlling for individual differences in mean reaction time and Stroop interference. Across the two experiments, a replicable neural substrate of individual variation in conflict adaptation was found in ventrolateral prefrontal cortex (vlPFC), specifically, in the right inferior frontal gyrus, pars orbitalis (BA 47). Unbiased regression estimates showed that variability in activity in this region accounted for ~40% of the variance in behavioral expression of conflict adaptation across subjects, thus documenting a heretofore unsuspected key role for vlPFC in mediating conflict-driven adjustments in cognitive control. We speculate that vlPFC plays a primary role in conflict control that is supplemented by dlPFC recruitment under conditions of suboptimal performance. PMID:21568631

  18. Photoperiod- and temperature-mediated control of growth cessation and dormancy in trees: a molecular perspective.

    Maurya, Jay P; Bhalerao, Rishikesh P

    2017-09-01

    How plants adapt their developmental patterns to regular seasonal changes is an important question in biology. The annual growth cycle in perennial long-lived trees is yet another example of how plants can adapt to seasonal changes. The two main signals that plants rely on to respond to seasonal changes are photoperiod and temperature, and these signals have critical roles in the temporal regulation of the annual growth cycle of trees. This review presents the latest findings to provide insight into the molecular mechanisms that underlie how photoperiodic and temperature signals regulate seasonal growth in trees. The results point to a high level of conservation in the signalling pathways that mediate photoperiodic control of seasonal growth in trees and flowering in annual plants such as arabidopsis. Furthermore, the data indicate that symplastic communication may mediate certain aspects of seasonal growth. Although considerable insight into the control of phenology in model plants such as poplar and spruce has been obtained, the future challenge is extending these studies to other, non-model trees. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  19. Safety climate and self-reported injury: assessing the mediating role of employee safety control.

    Huang, Yueng-Hsiang; Ho, Michael; Smith, Gordon S; Chen, Peter Y

    2006-05-01

    To further reduce injuries in the workplace, companies have begun focusing on organizational factors which may contribute to workplace safety. Safety climate is an organizational factor commonly cited as a predictor of injury occurrence. Characterized by the shared perceptions of employees, safety climate can be viewed as a snapshot of the prevailing state of safety in the organization at a discrete point in time. However, few studies have elaborated plausible mechanisms through which safety climate likely influences injury occurrence. A mediating model is proposed to link safety climate (i.e., management commitment to safety, return-to-work policies, post-injury administration, and safety training) with self-reported injury through employees' perceived control on safety. Factorial evidence substantiated that management commitment to safety, return-to-work policies, post-injury administration, and safety training are important dimensions of safety climate. In addition, the data support that safety climate is a critical factor predicting the history of a self-reported occupational injury, and that employee safety control mediates the relationship between safety climate and occupational injury. These findings highlight the importance of incorporating organizational factors and workers' characteristics in efforts to improve organizational safety performance.

  20. The Arabidopsis SWI/SNF protein BAF60 mediates seedling growth control by modulating DNA accessibility

    Jégu, Teddy

    2017-06-15

    Plant adaptive responses to changing environments involve complex molecular interplays between intrinsic and external signals. Whilst much is known on the signaling components mediating diurnal, light, and temperature controls on plant development, their influence on chromatin-based transcriptional controls remains poorly explored.In this study we show that a SWI/SNF chromatin remodeler subunit, BAF60, represses seedling growth by modulating DNA accessibility of hypocotyl cell size regulatory genes. BAF60 binds nucleosome-free regions of multiple G box-containing genes, opposing in cis the promoting effect of the photomorphogenic and thermomorphogenic regulator Phytochrome Interacting Factor 4 (PIF4) on hypocotyl elongation. Furthermore, BAF60 expression level is regulated in response to light and daily rhythms.These results unveil a short path between a chromatin remodeler and a signaling component to fine-tune plant morphogenesis in response to environmental conditions.

  1. The Arabidopsis SWI/SNF protein BAF60 mediates seedling growth control by modulating DNA accessibility

    Jé gu, Teddy; Veluchamy, Alaguraj; Ramirez Prado, Juan Sebastian; Rizzi-Paillet, Charley; Perez, Magalie; Lhomme, Anaï s; Latrasse, David; Coleno, Emeline; Vicaire, Serge; Legras, Sté phanie; Jost, Bernard; Rougé e, Martin; Barneche, Fredy; Bergounioux, Catherine; Crespi, Martin; Mahfouz, Magdy M.; Hirt, Heribert; Raynaud, Cé cile; Benhamed, Moussa

    2017-01-01

    Plant adaptive responses to changing environments involve complex molecular interplays between intrinsic and external signals. Whilst much is known on the signaling components mediating diurnal, light, and temperature controls on plant development, their influence on chromatin-based transcriptional controls remains poorly explored.In this study we show that a SWI/SNF chromatin remodeler subunit, BAF60, represses seedling growth by modulating DNA accessibility of hypocotyl cell size regulatory genes. BAF60 binds nucleosome-free regions of multiple G box-containing genes, opposing in cis the promoting effect of the photomorphogenic and thermomorphogenic regulator Phytochrome Interacting Factor 4 (PIF4) on hypocotyl elongation. Furthermore, BAF60 expression level is regulated in response to light and daily rhythms.These results unveil a short path between a chromatin remodeler and a signaling component to fine-tune plant morphogenesis in response to environmental conditions.

  2. Controlled/living photopolymerization of methyl methacrylate in miniemulsion mediated by HTEMPO

    Xiaoxuan LIU; Yanni JING; Yingkun BAI

    2008-01-01

    Controlled/living photopolymerization of methyl methacrylate (MMA) in miniemulsion mediated by 4-hydroxy-2,2,6,6-tetramethyl-piperidinyloxy (HTEMPO) was carried out at ambient temperatures. MMA miniemulsion was prepared by using an anionic surfactant with cetylalcohol as a co-stabilizer. The photopolymerization led to stable lattices and they were obtained with no coagulation during synthesis and no destabilization over time. It was found that the obtained MMA homopolymers exhibited relatively narrow mole-cular weight distribution (PDI = 1.27- 1.36) which was characterized by GPC. The plots of number-average molecular weight in (Mn) vs. Conversion and ln([MO]/[M]) vs. Time both were linear indicating that the reaction was a controlled/living free radical polymerization.

  3. A randomised controlled trial evaluating family mediated exercise (FAME therapy following stroke

    Stokes Emma

    2008-06-01

    Full Text Available Abstract Background Stroke is a leading cause of disability among adults worldwide. Evidence suggests that increased duration of exercise therapy following stroke has a positive impact on functional outcome following stroke. The main objective of this randomised controlled trial is to evaluate the impact of additional family assisted exercise therapy in people with acute stroke. Methods/Design A prospective multi-centre single blind randomised controlled trial will be conducted. Forty patients with acute stroke will be randomised into either an experimental or control group. The experimental group will receive routine therapy and additional lower limb exercise therapy in the form of family assisted exercises. The control group will receive routine therapy with no additional formal input from their family members. Participants will be assessed at baseline, post intervention and followed up at three months using a series of standardised outcome measures. A secondary aim of the project is to evaluate the impact of the family mediated exercise programme on the person with stroke and the individual(s assisting in the delivery of exercises using a qualitative methodology. The study has gained ethical approval from the Research Ethics Committees of each of the clinical sites involved in the study. Discussion This study will evaluate a structured programme of exercises that can be delivered to people with stroke by their 'family members/friends'. Given that the progressive increase in the population of older people is likely to lead to an increased prevalence of stroke in the future, it is important to reduce the burden of this illness on the individual, the family and society. Family mediated exercises can maximise the carry over outside formal physiotherapy sessions, giving patients the opportunity for informal practice. Trial Registration The protocol for this study is registered with the US NIH Clinical trials registry (NCT00666744

  4. Gratitude mediates quality of life differences between fibromyalgia patients and healthy controls.

    Toussaint, Loren; Sirois, Fuschia; Hirsch, Jameson; Weber, Annemarie; Vajda, Christian; Schelling, Jorg; Kohls, Niko; Offenbacher, Martin

    2017-09-01

    Despite a growing literature on the benefits of gratitude for adjustment to chronic illness, little is known about gratitude in medical populations compared to healthy populations, or the degree to which potential deficits in gratitude might impact quality of life. The purpose of the present study was to (1) examine levels of gratitude and quality of life in fibromyalgia patients and healthy controls and (2) consider the role of gratitude in explaining quality of life differences between fibromyalgia patients and healthy controls. Participants were 173 fibromyalgia patients and 81 healthy controls. All participants completed measures of gratitude, quality of life, and socio-demographics. Although gratitude was positively associated with quality of life, levels of gratitude and quality of life were lower in the fibromyalgia sample relative to the healthy controls. This difference in gratitude partially mediated differences in quality of life between the two groups after controlling for socio-demographic variables. Our findings suggest that gratitude is a valuable positive psychological trait for quality of life in people with fibromyalgia. Interventions to improve gratitude in this patient population may also bring enhancement in quality of life.

  5. Characteristics of the home food environment that mediate immediate and sustained increases in child fruit and vegetable consumption: mediation analysis from the Healthy Habits cluster randomised controlled trial.

    Wyse, Rebecca; Wolfenden, Luke; Bisquera, Alessandra

    2015-09-17

    The home food environment can influence the development of dietary behaviours in children, and interventions that modify characteristics of the home food environment have been shown to increase children's fruit and vegetable consumption. However to date, interventions to increase children's fruit and vegetable consumption have generally produced only modest effects. Mediation analysis can help in the design of more efficient and effective interventions by identifying the mechanisms through which interventions have an effect. This study aimed to identify characteristics of the home food environment that mediated immediate and sustained increases in children's fruit and vegetable consumption following the 4-week Healthy Habits telephone-based parent intervention. Analysis was conducted using 2-month (immediate) and 12-month (sustained) follow-up data from a cluster randomised control trial of a home food environment intervention to increase the fruit and vegetable consumption of preschool children. Using recursive path analysis, a series of mediation models were created to investigate the direct and indirect effects of immediate and sustained changes to characteristics of the home food environment (fruit and vegetable availability, accessibility, parent intake, parent providing behaviour, role-modelling, mealtime eating practices, child feeding strategies, and pressure to eat), on the change in children's fruit and vegetable consumption. Of the 394 participants in the randomised trial, 357 and 329 completed the 2- and 12-month follow-up respectively. The final mediation model suggests that the effect of the intervention on the children's fruit and vegetable consumption was mediated by parent fruit and vegetable intake and parent provision of these foods at both 2- and 12-month follow-up. Analysis of data from the Healthy Habits trial suggests that two environmental variables (parental intake and parent providing) mediate the immediate and sustained effect of the

  6. Can Job Control Ameliorate Work-family Conflict and Enhance Job Satisfaction among Chinese Registered Nurses? A Mediation Model

    Xiaotong Ding

    2018-04-01

    Full Text Available Background: Low job satisfaction is the most common cause of nurses' turnover and influences the quality of nursing service. Moreover, we have no idea regarding whether job control, as an individual factor, can play a role in the relationship. Objective: To explore the relationship between work-family conflict and job satisfaction among Chinese registered nurses and the mediating role of job control in this relationship. Methods: From August 2015 to November 2016, 487 Chinese registered nurses completed a survey. The study used work-family conflict scale, job control scale, job satisfaction scale, as well as general information. Multiple regression analysis was used to explore the independent factors of job satisfaction. Structural equation model was used to explore the mediating role of job control. Results: Work-family conflict was negatively correlated with job satisfaction (r ‑0.432, p<0.01. In addition, job control was positively related to job satisfaction (r 0.567, p<0.01. Work-family conflict and job control had significant predictive effects on job satisfaction. Job control partially mediated the relationship between work-family conflict and job satisfaction. Conclusion: Work-family conflict affected job satisfaction and job control was a mediator in this relationship among Chinese registered nurses. Job control could potentially improve nurses' job satisfaction.

  7. Can Job Control Ameliorate Work-family Conflict and Enhance Job Satisfaction among Chinese Registered Nurses? A Mediation Model.

    Ding, Xiaotong; Yang, Yajuan; Su, Dan; Zhang, Ting; Li, Lunlan; Li, Huiping

    2018-04-01

    Low job satisfaction is the most common cause of nurses' turnover and influences the quality of nursing service. Moreover, we have no idea regarding whether job control, as an individual factor, can play a role in the relationship. To explore the relationship between work-family conflict and job satisfaction among Chinese registered nurses and the mediating role of job control in this relationship. From August 2015 to November 2016, 487 Chinese registered nurses completed a survey. The study used work-family conflict scale, job control scale, job satisfaction scale, as well as general information. Multiple regression analysis was used to explore the independent factors of job satisfaction. Structural equation model was used to explore the mediating role of job control. Work-family conflict was negatively correlated with job satisfaction (r ‑0.432, pjob control was positively related to job satisfaction (r 0.567, pjob control had significant predictive effects on job satisfaction. Job control partially mediated the relationship between work-family conflict and job satisfaction. Work-family conflict affected job satisfaction and job control was a mediator in this relationship among Chinese registered nurses. Job control could potentially improve nurses' job satisfaction.

  8. DNA methylation mediated control of gene expression is critical for development of crown gall tumors.

    Jochen Gohlke

    Full Text Available Crown gall tumors develop after integration of the T-DNA of virulent Agrobacterium tumefaciens strains into the plant genome. Expression of the T-DNA-encoded oncogenes triggers proliferation and differentiation of transformed plant cells. Crown gall development is known to be accompanied by global changes in transcription, metabolite levels, and physiological processes. High levels of abscisic acid (ABA in crown galls regulate expression of drought stress responsive genes and mediate drought stress acclimation, which is essential for wild-type-like tumor growth. An impact of epigenetic processes such as DNA methylation on crown gall development has been suggested; however, it has not yet been investigated comprehensively. In this study, the methylation pattern of Arabidopsis thaliana crown galls was analyzed on a genome-wide scale as well as at the single gene level. Bisulfite sequencing analysis revealed that the oncogenes Ipt, IaaH, and IaaM were unmethylated in crown galls. Nevertheless, the oncogenes were susceptible to siRNA-mediated methylation, which inhibited their expression and subsequently crown gall growth. Genome arrays, hybridized with methylated DNA obtained by immunoprecipitation, revealed a globally hypermethylated crown gall genome, while promoters were rather hypomethylated. Mutants with reduced non-CG methylation developed larger tumors than the wild-type controls, indicating that hypermethylation inhibits plant tumor growth. The differential methylation pattern of crown galls and the stem tissue from which they originate correlated with transcriptional changes. Genes known to be transcriptionally inhibited by ABA and methylated in crown galls became promoter methylated upon treatment of A. thaliana with ABA. This suggests that the high ABA levels in crown galls may mediate DNA methylation and regulate expression of genes involved in drought stress protection. In summary, our studies provide evidence that epigenetic processes

  9. The effects of redox controls mediated by glutathione peroxidases on root architecture in Arabidopsis thaliana.

    Passaia, Gisele; Queval, Guillaume; Bai, Juan; Margis-Pinheiro, Marcia; Foyer, Christine H

    2014-03-01

    Glutathione peroxidases (GPXs) fulfil important functions in oxidative signalling and protect against the adverse effects of excessive oxidation. However, there has been no systematic characterization of the functions of the different GPX isoforms in plants. The roles of the different members of the Arabidopsis thaliana GPX gene (AtGPX) family were therefore investigated using gpx1, gpx2, gpx3, gpx4, gpx6, gpx7, and gpx8 T-DNA insertion mutant lines. The shoot phenotypes were largely similar in all genotypes, with small differences from the wild type observed only in the gpx2, gpx3, gpx7, and gpx8 mutants. In contrast, all the mutants showed altered root phenotypes compared with the wild type. The gpx1, gpx4, gpx6, gpx7, and gpx8 mutants had a significantly greater lateral root density (LRD) than the wild type. Conversely, the gpx2 and gpx3 mutants had significantly lower LRD values than the wild type. Auxin increased the LRD in all genotypes, but the effect of auxin was significantly greater in the gpx1, gpx4, and gpx7 mutants than in the wild type. The application of auxin increased GPX4 and GPX7 transcripts, but not GPX1 mRNAs in the roots of wild-type plants. The synthetic strigolactone GR24 and abscisic acid (ABA) decreased LRD to a similar extent in all genotypes, except gpx6, which showed increased sensitivity to ABA. These data not only demonstrate the importance of redox controls mediated by AtGPXs in the control of root architecture but they also show that the plastid-localized GPX1 and GPX7 isoforms are required for the hormone-mediated control of lateral root development.

  10. A Mediation Analysis of Mothers' Dietary Intake: The Entre Familia: Reflejos de Salud Randomized Controlled Trial.

    Horton, Lucy A; Ayala, Guadalupe X; Slymen, Donald J; Ibarra, Leticia; Hernandez, Erika; Parada, Humberto; Rock, Cheryl L; Arredondo, Elva M; Elder, John P

    2017-12-01

    Examine intervention effects among mothers involved in a healthy eating randomized controlled trial. Furthermore, examine the mediating roles of individual and familial influences on observed outcomes. Between 2009 and 2011, 361 families were recruited; half were assigned to an 11-session community health worker-delivered family-based intervention targeting Spanish-speaking Latino families in Imperial County, California. The intervention was delivered over a 4-month period. Home visits and telephone calls were delivered approximately weekly, with tapering near the end of the intervention to promote independence from the promotora. In this article, mothers' self-reported dietary intake was the primary outcome. Evaluation measures were taken at baseline, 4 months, and 10 months. Daily servings of fruits were higher among intervention versus control mothers (mean = 1.86 vs. mean = 1.47; effect size [ES] = 0.22) at 10 months post-baseline. Mothers in the intervention versus control condition also reported consuming a lower percent energy from fat (mean = 30.0% vs. 31.0%; ES = 0.30) and a higher diet quality (mean = 2.93 vs. mean = 2.67; ES = 0.29). Mediators of improvements were behavioral strategies to increase fiber and lower fat intake, family support for vegetable purchasing, and decreased unhealthy eating behaviors and perceived family barriers to healthy eating. Family-based behavioral interventions are effective for changing the skills and family system needed to improve diet among Latina mothers. Health care providers and other practitioners are encouraged to target skill development and fostering a socially supportive environment.

  11. Phosphorylation of carbonic anhydrase IX controls its ability to mediate extracellular acidification in hypoxic tumors.

    Ditte, Peter; Dequiedt, Franck; Svastova, Eliska; Hulikova, Alzbeta; Ohradanova-Repic, Anna; Zatovicova, Miriam; Csaderova, Lucia; Kopacek, Juraj; Supuran, Claudiu T; Pastorekova, Silvia; Pastorek, Jaromir

    2011-12-15

    In the hypoxic regions of a tumor, carbonic anhydrase IX (CA IX) is an important transmembrane component of the pH regulatory machinery that participates in bicarbonate transport. Because tumor pH has implications for growth, invasion, and therapy, determining the basis for the contributions of CA IX to the hypoxic tumor microenvironment could lead to new fundamental and practical insights. Here, we report that Thr443 phosphorylation at the intracellular domain of CA IX by protein kinase A (PKA) is critical for its activation in hypoxic cells, with the fullest activity of CA IX also requiring dephosphorylation of Ser448. PKA is activated by cAMP, which is elevated by hypoxia, and we found that attenuating PKA in cells disrupted CA IX-mediated extracellular acidification. Moreover, following hypoxia induction, CA IX colocalized with the sodium-bicarbonate cotransporter and other PKA substrates in the leading edge membranes of migrating tumor cells, in support of the concept that bicarbonate metabolism is spatially regulated at cell surface sites with high local ion transport and pH control. Using chimeric CA IX proteins containing heterologous catalytic domains derived from related CA enzymes, we showed that CA IX activity was modulated chiefly by the intracellular domain where Thr443 is located. Our findings indicate that CA IX is a pivotal mediator of the hypoxia-cAMP-PKA axis, which regulates pH in the hypoxic tumor microenvironment.

  12. GSK3 controls axon growth via CLASP-mediated regulation of growth cone microtubules

    Hur, Eun-Mi; Saijilafu; Lee, Byoung Dae; Kim, Seong-Jin; Xu, Wen-Lin; Zhou, Feng-Quan

    2011-01-01

    Suppression of glycogen synthase kinase 3 (GSK3) activity in neurons yields pleiotropic outcomes, causing both axon growth promotion and inhibition. Previous studies have suggested that specific GSK3 substrates, such as adenomatous polyposis coli (APC) and collapsin response mediator protein 2 (CRMP2), support axon growth by regulating the stability of axonal microtubules (MTs), but the substrate(s) and mechanisms conveying axon growth inhibition remain elusive. Here we show that CLIP (cytoplasmic linker protein)-associated protein (CLASP), originally identified as a MT plus end-binding protein, displays both plus end-binding and lattice-binding activities in nerve growth cones, and reveal that the two MT-binding activities regulate axon growth in an opposing manner: The lattice-binding activity mediates axon growth inhibition induced by suppression of GSK3 activity via preventing MT protrusion into the growth cone periphery, whereas the plus end-binding property supports axon extension via stabilizing the growing ends of axonal MTs. We propose a model in which CLASP transduces GSK3 activity levels to differentially control axon growth by coordinating the stability and configuration of growth cone MTs. PMID:21937714

  13. Epimorphin mediates mammary luminal morphogenesis through control of C/EBPbeta

    Hirai, Yohei; Radisky, Derek; Boudreau, Rosanne; Simian, Marina; Stevens, Mary E.; Oka, Yumiko; Takebe, Kyoko; Niwa, Shinichiro; Bissell, Mina J.

    2002-01-01

    We have previously shown that epimorphin, a protein expressed on the surface of myoepithelial and fibroblast cells of the mammary gland, acts as a multifunctional morphogen of mammary epithelial cells. Here, we present the molecular mechanism by which epimorphin mediates luminal morphogenesis. Treatment of cells with epimorphin to induce lumen formation greatly increases the overall expression of transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) and alters the relative expression of its two principal isoforms, LIP and LAP. These alterations were shown to be essential for the morphogenetic activities, as constitutive expression of LIP was sufficient to produce lumen formation, while constitutive expression of LAP blocked epimorphin-mediated luminal morphogenesis. Furthermore, in a transgenic mouse model in which epimorphin expression was expressed in an apolar fashion on the surface of mammary epithelial cells, we found increased expression of C/EBPbeta, increased relative expression of LIP to LAP, and enlarged ductal lumina. Together, our studies demonstrate a role for epimorphin in luminal morphogenesis through control of C/EBPbeta expression

  14. A genetically mediated bias in decision making driven by failure of amygdala control.

    Roiser, Jonathan P; de Martino, Benedetto; Tan, Geoffrey C Y; Kumaran, Dharshan; Seymour, Ben; Wood, Nicholas W; Dolan, Raymond J

    2009-05-06

    Genetic variation at the serotonin transporter-linked polymorphic region (5-HTTLPR) is associated with altered amygdala reactivity and lack of prefrontal regulatory control. Similar regions mediate decision-making biases driven by contextual cues and ambiguity, for example the "framing effect." We hypothesized that individuals hemozygous for the short (s) allele at the 5-HTTLPR would be more susceptible to framing. Participants, selected as homozygous for either the long (la) or s allele, performed a decision-making task where they made choices between receiving an amount of money for certain and taking a gamble. A strong bias was evident toward choosing the certain option when the option was phrased in terms of gains and toward gambling when the decision was phrased in terms of losses (the frame effect). Critically, this bias was significantly greater in the ss group compared with the lala group. In simultaneously acquired functional magnetic resonance imaging data, the ss group showed greater amygdala during choices made in accord, compared with those made counter to the frame, an effect not seen in the lala group. These differences were also mirrored by differences in anterior cingulate-amygdala coupling between the genotype groups during decision making. Specifically, lala participants showed increased coupling during choices made counter to, relative to those made in accord with, the frame, with no such effect evident in ss participants. These data suggest that genetically mediated differences in prefrontal-amygdala interactions underpin interindividual differences in economic decision making.

  15. Coordination of KSHV Latent and Lytic Gene Control by CTCF-Cohesin Mediated Chromosome Conformation

    Kang, Hyojeung; Wiedmer, Andreas; Yuan, Yan; Robertson, Erle; Lieberman, Paul M.

    2011-01-01

    Herpesvirus persistence requires a dynamic balance between latent and lytic cycle gene expression, but how this balance is maintained remains enigmatic. We have previously shown that the Kaposi's Sarcoma-Associated Herpesvirus (KSHV) major latency transcripts encoding LANA, vCyclin, vFLIP, v-miRNAs, and Kaposin are regulated, in part, by a chromatin organizing element that binds CTCF and cohesins. Using viral genome-wide chromatin conformation capture (3C) methods, we now show that KSHV latency control region is physically linked to the promoter regulatory region for ORF50, which encodes the KSHV immediate early protein RTA. Other linkages were also observed, including an interaction between the 5′ and 3′ end of the latency transcription cluster. Mutation of the CTCF-cohesin binding site reduced or eliminated the chromatin conformation linkages, and deregulated viral transcription and genome copy number control. siRNA depletion of CTCF or cohesin subunits also disrupted chromosomal linkages and deregulated viral latent and lytic gene transcription. Furthermore, the linkage between the latent and lytic control region was subject to cell cycle fluctuation and disrupted during lytic cycle reactivation, suggesting that these interactions are dynamic and regulatory. Our findings indicate that KSHV genomes are organized into chromatin loops mediated by CTCF and cohesin interactions, and that these inter-chromosomal linkages coordinate latent and lytic gene control. PMID:21876668

  16. Mediating Parent Learning to Promote Social Communication for Toddlers with Autism: Effects from a Randomized Controlled Trial

    Schertz, Hannah H.; Odom, Samuel L.; Baggett, Kathleen M.; Sideris, John H.

    2018-01-01

    A randomized controlled trial was conducted to evaluate effects of the Joint Attention Mediated Learning (JAML) intervention. Toddlers with autism spectrum disorders (ASD) aged 16-30 months (n = 144) were randomized to intervention and community control conditions. Parents, who participated in 32 weekly home-based sessions, followed a mediated…

  17. DMPD: Protein kinase C epsilon: a new target to control inflammation andimmune-mediated disorders. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 14643884 Protein kinase C epsilon: a new target to control inflammation andimmune-m...g) (.html) (.csml) Show Protein kinase C epsilon: a new target to control inflammation andimmune-mediated di...sorders. PubmedID 14643884 Title Protein kinase C epsilon: a new target to contro

  18. Self-reported impulsivity, but not behavioral approach or inhibition, mediates the relationship between stress and self-control.

    Hamilton, Kristen R; Sinha, Rajita; Potenza, Marc N

    2014-11-01

    Stress has been associated with poor self-control. Individual differences in impulsivity and other behavioral tendencies may influence the relationship of stress with self-control, although this possibility has not been examined to date. The present research investigated whether cumulative stress is associated with poor self-control, and whether this relationship is mediated by impulsivity, behavioral approach, and behavioral inhibition in men and women. A community sample of 566 adults (319 women and 247 men) was assessed on the Cumulative Adversity Interview, Brief Self-control Scale, Barratt Impulsivity Scale, and Behavioral Activation System and Behavioral Inhibition System Scale (BIS/BAS). Data were analyzed using regression and bootstrapping techniques. In the total sample, the effects of cumulative stress on self-control were mediated by impulsivity. Neither behavioral inhibition nor behavioral approach mediated the association between cumulative stress and self-control in the total sample. Results were similar when men and women were considered separately, with impulsivity, but not behavioral inhibition or approach, mediating the association between cumulative stress and self-control. Impulsive individuals might benefit preferentially from interventions focusing on stress management and strategies for improving self-control. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. More than Resisting Temptation: Beneficial Habits Mediate the Relationship between Self-Control and Positive Life Outcomes

    Galla, Brian M.; Duckworth, Angela L.

    2015-01-01

    Why does self-control predict such a wide array of positive life outcomes? Conventional wisdom holds that self-control is used to effortfully inhibit maladaptive impulses, yet this view conflicts with emerging evidence that self-control is associated with less inhibition in daily life. We propose that one of the reasons individuals with better self-control use less effortful inhibition, yet make better progress on their goals is that they rely on beneficial habits. Across six studies (total N = 2,274), we found support for this hypothesis. In Study 1, habits for eating healthy snacks, exercising, and getting consistent sleep mediated the effect of self-control on both increased automaticity and lower reported effortful inhibition in enacting those behaviors. In Studies 2 and 3, study habits mediated the effect of self-control on reduced motivational interference during a work-leisure conflict and on greater ability to study even under difficult circumstances. In Study 4, homework habits mediated the effect of self-control on classroom engagement and homework completion. Study 5 was a prospective longitudinal study of teenage youth who participated in a five-day meditation retreat. Better self-control before the retreat predicted stronger meditation habits three months after the retreat, and habits mediated the effect of self-control on successfully accomplishing meditation practice goals. Finally, in Study 6, study habits mediated the effect of self-control on homework completion and two objectively measured long-term academic outcomes: grade point average and first-year college persistence. Collectively, these results suggest that beneficial habits--perhaps more so than effortful inhibition--are an important factor linking self-control with positive life outcomes. PMID:25643222

  20. More than resisting temptation: Beneficial habits mediate the relationship between self-control and positive life outcomes.

    Galla, Brian M; Duckworth, Angela L

    2015-09-01

    Why does self-control predict such a wide array of positive life outcomes? Conventional wisdom holds that self-control is used to effortfully inhibit maladaptive impulses, yet this view conflicts with emerging evidence that self-control is associated with less inhibition in daily life. We propose that one of the reasons individuals with better self-control use less effortful inhibition, yet make better progress on their goals is that they rely on beneficial habits. Across 6 studies (total N = 2,274), we found support for this hypothesis. In Study 1, habits for eating healthy snacks, exercising, and getting consistent sleep mediated the effect of self-control on both increased automaticity and lower reported effortful inhibition in enacting those behaviors. In Studies 2 and 3, study habits mediated the effect of self-control on reduced motivational interference during a work-leisure conflict and on greater ability to study even under difficult circumstances. In Study 4, homework habits mediated the effect of self-control on classroom engagement and homework completion. Study 5 was a prospective longitudinal study of teenage youth who participated in a 5-day meditation retreat. Better self-control before the retreat predicted stronger meditation habits 3 months after the retreat, and habits mediated the effect of self-control on successfully accomplishing meditation practice goals. Finally, in Study 6, study habits mediated the effect of self-control on homework completion and 2 objectively measured long-term academic outcomes: grade point average and first-year college persistence. Collectively, these results suggest that beneficial habits-perhaps more so than effortful inhibition-are an important factor linking self-control with positive life outcomes. (c) 2015 APA, all rights reserved).

  1. RNA- and protein-mediated control of Listeria monocytogenes virulence gene expression

    Lebreton, Alice; Cossart, Pascale

    2017-01-01

    ABSTRACT The model opportunistic pathogen Listeria monocytogenes has been the object of extensive research, aiming at understanding its ability to colonize diverse environmental niches and animal hosts. Bacterial transcriptomes in various conditions reflect this efficient adaptability. We review here our current knowledge of the mechanisms allowing L. monocytogenes to respond to environmental changes and trigger pathogenicity, with a special focus on RNA-mediated control of gene expression. We highlight how these studies have brought novel concepts in prokaryotic gene regulation, such as the ‘excludon’ where the 5′-UTR of a messenger also acts as an antisense regulator of an operon transcribed in opposite orientation, or the notion that riboswitches can regulate non-coding RNAs to integrate complex metabolic stimuli into regulatory networks. Overall, the Listeria model exemplifies that fine RNA tuners act together with master regulatory proteins to orchestrate appropriate transcriptional programmes. PMID:27217337

  2. Streptophage-mediated control of off-flavour taint producing streptomycetes isolated from barramundi ponds

    Jodi Anne Jonns

    2017-06-01

    Following the determination of the streptophage susceptibility of the isolates one of the most odourous streptomycete species (USC-14510 was selected to be tested further using different pond simulations resembling real-life applications. Geosmin was tested as the indicator of off-flavour taint production and as it has been previously reported that the cyanobacteria-actinomycete interactions occurring in ponds result in even greater levels of geosmin and 2-methylisoborneol, the geosmin levels for the isolate in the presence of cyanobacteria and streptophages were also tested. Findings indicated that the highly odourous Streptomyces species (USC-14510 once infected with streptophages, can lose its capacity to produce off-flavour taints. Pond simulation studies also revealed geosmin production was significantly reduced when streptophages were introduced into the pond water where streptomycete species were grown. The bacteriophage control method developed in the presented study might again confirm significant potential for the bacteriophage-mediated remediation strategy to be adapted by the aquaculture industry.

  3. Hyperglycemic conditions inhibit C3-mediated immunologic control of Staphylococcus aureus

    Hair Pamela S

    2012-03-01

    Full Text Available Abstract Background Diabetic patients are at increased risk for bacterial infections; these studies provide new insight into the role of the host defense complement system in controlling bacterial pathogens in hyperglycemic environments. Methods The interactions of complement C3 with bacteria in elevated glucose were assayed for complement activation to opsonic forms, phagocytosis and bacterial killing. C3 was analyzed in euglycemic and hyperglycemic conditions by mass spectrometry to measure glycation and structural differences. Results Elevated glucose inhibited S. aureus activation of C3 and deposition of C3b and iC3b on the bacterial surface. S. aureus-generated C5a and serum-mediated phagocytosis by neutrophils were both decreased in elevated glucose conditions. Interestingly, elevated glucose increased the binding of unactivated C3 to S. aureus, which was reversible on return to normal glucose concentrations. In a model of polymicrobial infection, S. aureus in elevated glucose conditions depleted C3 from serum resulting in decreased complement-mediated killing of E. coli. To investigate the effect of differing glucose concentration on C3 structure and glycation, purified C3 incubated with varying glucose concentrations was analyzed by mass spectrometry. Glycation was limited to the same three lysine residues in both euglycemic and hyperglycemic conditions over one hour, thus glycation could not account for observed changes between glucose conditions. However, surface labeling of C3 with sulfo-NHS-biotin showed significant changes in the surface availability of seven lysine residues in response to increasing glucose concentrations. These results suggest that the tertiary structure of C3 changes in response to hyperglycemic conditions leading to an altered interaction of C3 with bacterial pathogens. Conclusions These results demonstrate that hyperglycemic conditions inhibit C3-mediated complement effectors important in the immunological

  4. ERECTA signaling controls Arabidopsis inflorescence architecture through chromatin-mediated activation of PRE1 expression.

    Cai, Hanyang; Zhao, Lihua; Wang, Lulu; Zhang, Man; Su, Zhenxia; Cheng, Yan; Zhao, Heming; Qin, Yuan

    2017-06-01

    Flowering plants display a remarkable diversity in inflorescence architecture, and pedicel length is one of the key contributors to this diversity. In Arabidopsis thaliana, the receptor-like kinase ERECTA (ER) mediated signaling pathway plays important roles in regulating inflorescence architecture by promoting cell proliferation. However, the regulating mechanism remains elusive in the pedicel. Genetic interactions between ERECTA signaling and the chromatin remodeling complex SWR1 in the control of inflorescence architecture were studied. Comparative transcriptome analysis was applied to identify downstream components. Chromatin immunoprecipitation and nucleosome occupancy was further investigated. The results indicated that the chromatin remodeler SWR1 coordinates with ERECTA signaling in regulating inflorescence architecture by activating the expression of PRE1 family genes and promoting pedicel elongation. It was found that SWR1 is required for the incorporation of the H2A.Z histone variant into nucleosomes of the whole PRE1 gene family and the ERECTA controlled expression of PRE1 gene family through regulating nucleosome dynamics. We propose that utilization of a chromatin remodeling complex to regulate gene expression is a common theme in developmental control across kingdoms. These findings shed light on the mechanisms through which chromatin remodelers orchestrate complex transcriptional regulation of gene expression in coordination with a developmental cue. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  5. Fluid Intelligence as a Mediator of the Relationship between Executive Control and Balanced Time Perspective.

    Zajenkowski, Marcin; Stolarski, Maciej; Witowska, Joanna; Maciantowicz, Oliwia; Łowicki, Paweł

    2016-01-01

    This study examined the cognitive foundations of the balanced time perspective (BTP) proposed by Zimbardo and Boyd (1999). Although BTP is defined as the mental ability to switch effectively between different temporal perspectives, its connection with cognitive functioning has not yet been established. We addressed this by exploring the relationships between time perspectives and both fluid intelligence (measured with Raven's and Cattell's tests) and executive control (Go/No-go and anti-saccade tasks). An investigation conducted among Polish adults ( N = 233) revealed that more balanced TP profile was associated with higher fluid intelligence, and higher executive control. Moreover, we found that the relationship between executive control and BTP was completely mediated by fluid intelligence with the effect size (the ratio of the indirect effect to the total effect) of 0.75, which suggests that cognitive abilities play an important role in adoption of temporal balance. The findings have relevance to time perspective theory as they provide valuable insight into the mechanisms involved in assigning human experience to certain time frames.

  6. Electroacupuncture Potentiates Cannabinoid Receptor-Mediated Descending Inhibitory Control in a Mouse Model of Knee Osteoarthritis

    Xiao-Cui Yuan

    2018-04-01

    Full Text Available Knee osteoarthritis (KOA is a highly prevalent, chronic joint disorder, which can lead to chronic pain. Although electroacupuncture (EA is effective in relieving chronic pain in the clinic, the involved mechanisms remain unclear. Reduced diffuse noxius inhibitory controls (DNIC function is associated with chronic pain and may be related to the action of endocannabinoids. In the present study, we determined whether EA may potentiate cannabinoid receptor-mediated descending inhibitory control and inhibit chronic pain in a mouse model of KOA. We found that the optimized parameters of EA inhibiting chronic pain were the low frequency and high intensity (2 Hz + 1 mA. EA reversed the reduced expression of CB1 receptors and the 2-arachidonoylglycerol (2-AG level in the midbrain in chronic pain. Microinjection of the CB1 receptor antagonist AM251 into the ventrolateral periaqueductal gray (vlPAG can reversed the EA effect on pain hypersensitivity and DNIC function. In addition, CB1 receptors on GABAergic but not glutamatergic neurons are involved in the EA effect on DNIC function and descending inhibitory control of 5-HT in the medulla, thus inhibiting chronic pain. Our data suggest that endocannabinoid (2-AG-CB1R-GABA-5-HT may be a novel signaling pathway involved in the effect of EA improving DNIC function and inhibiting chronic pain.

  7. Hydrogen Peroxide- and Nitric Oxide-mediated Disease Control of Bacterial Wilt in Tomato Plants

    Jeum Kyu Hong

    2013-12-01

    Full Text Available Reactive oxygen species (ROS generation in tomato plants by Ralstonia solanacearum infection and the role of hydrogen peroxide (H₂O₂ and nitric oxide in tomato bacterial wilt control were demonstrated. During disease development of tomato bacterial wilt, accumulation of superoxide anion (O₂− and H₂O₂ was observed and lipid peroxidation also occurred in the tomato leaf tissues. High doses of H₂O₂and sodium nitroprusside (SNP nitric oxide donor showed phytotoxicity to detached tomato leaves 1 day after petiole feeding showing reduced fresh weight. Both H₂O₂and SNP have in vitro antibacterial activities against R. solanacearum in a dose-dependent manner, as well as plant protection in detached tomato leaves against bacterial wilt by 10⁶ and 10⁷ cfu/ml of R. solanacearum. H₂O₂- and SNP-mediated protection was also evaluated in pots using soil-drench treatment with the bacterial inoculation, and relative ‘area under the disease progressive curve (AUDPC’ was calculated to compare disease protection by H₂O₂ and/or SNP with untreated control. Neither H₂O₂ nor SNP protect the tomato seedlings from the bacterial wilt, but H₂O₂+ SNP mixture significantly decreased disease severity with reduced relative AUDPC. These results suggest that H₂O₂ and SNP could be used together to control bacterial wilt in tomato plants as bactericidal agents.

  8. Fate control and well-being in Chinese rural people living with HIV: mediation effect of resilience.

    Yu, Nancy Xiaonan; Zhang, Jianxin; Chow, Amy Y M; Chan, Celia H Y; Chan, Cecilia L W

    2017-01-01

    Fate control has been often misconceptualized as a superstitious belief and overlooked in health psychology. It is not known how this cultural belief might impact the well-being of Chinese people living with HIV. This study examined the protective role of fate control for well-being and the potential mediation effect of resilience. Participants in this study were rural patients who contracted HIV via commercial blood donation. In this cross-sectional survey, 250 participants completed measures of fate control, well-being, and resilience. The results showed that fate control and resilience were positively associated with well-being. Resilience mediated the association between fate control and well-being. Our findings provide insight into the adaptive function of fate control as a cognitive defensive mechanism and highlight the need to incorporate this cultural belief in developing culturally sensitive intervention programs for resilience enhancement tailored for this understudied population infected with HIV living in rural China.

  9. Reduced Inhibitory Control Mediates the Relationship Between Cortical Thickness in the Right Superior Frontal Gyrus and Body Mass Index.

    Lavagnino, Luca; Mwangi, Benson; Bauer, Isabelle E; Cao, Bo; Selvaraj, Sudhakar; Prossin, Alan; Soares, Jair C

    2016-08-01

    Unhealthy eating behaviors often develop in the setting of inadequate inhibitory control, a function broadly ascribed to the prefrontal cortex (PFC). Regulation of inhibitory control by the PFC and its anatomical components and their contribution to increasing body mass index (BMI) are poorly understood. To study the role of PFC in the regulation of inhibitory control and body weight, we examined measures of cortical thickness in PFC sub-regions, inhibitory control (color-word interference task (CWIT)), and BMI in 91 healthy volunteers. We tested the predictive effect of PFC sub-regional cortical thickness on BMI and mediation by inhibitory control measured with CWIT. Measures of depression (BDI-II), anxiety (STAI-T) and trauma-related symptoms (TSC-40) were collected; the disinhibition scale of the three-factor eating questionnaire (TFEQ) was used to assess disinhibited eating. We then tested the relationship between BD-II, STAI-T, TSC-40, TFEQ, CWIT, and BMI with correlation analyses. Right superior frontal gyrus cortical thickness significantly predicted BMI (β=-0.91; t=-3.2; p=0.002). Mediation analysis showed a significant indirect effect of cortical thickness on BMI mediated by inhibitory control (95% CI=-6.1, -0.67). BMI was unrelated to BDI-II, STAI-T, TSC-40, or TFEQ scores. We found an inverse relationship between cortical thickness in the right-superior frontal gyrus and BMI, which was fully mediated by inhibitory control neurocognitive performance. Our results suggest possible targets for neuromodulation in obesity (ie superior frontal gyrus) and a quantifiable mediator of their effects (ie inhibitory control).

  10. Crop domestication, global human-mediated migration, and the unresolved role of geography in pest control

    Yolanda H. Chen

    2016-05-01

    Full Text Available Abstract Ecological pest management seeks to improve pest control through the manipulation of ecological processes that promote natural enemies and suppress pests. These approaches can involve cultural practices such as reduced tillage, increased use of non-crop plants that provide food and shelter for natural enemies, and intercropping to enhance the abundance and diversity of natural enemies. A major assumption of ecological pest management is that these activities can be equally effective for all insect herbivores. Here, I propose that these strategies may only be effective for a subset of pests and geographic regions because most insect pests have complex evolutionary histories that make them difficult to manage. I discuss how crop domestication and human-mediated migration are major evolutionary events that shape the geography of interactions between plants, herbivores, and natural enemies. Insect herbivores can evolve to be pests through three major modes: 1 herbivores associated with the crop wild ancestor may shift onto the domesticated crop, 2 herbivores may host-shift from native host plants onto an introduced crop, or 3 human-mediated migration can introduce insect pests into new cropping regions. The resulting geographic structure can influence the success of pest management by altering ecological factors such as: species distributions, patterns of biodiversity, community structure, and natural enemy attack rates. I discuss how the different modes of insect pest evolution structure a set of relevant questions and approaches for ecological pest management. By acknowledging how agricultural history and geography shape the ecology and evolution of insect pests, we may collectively develop a better capacity to identify where and how ecological pest management approaches can be most broadly effective.

  11. Phosphorylation-mediated control of histone chaperone ASF1 levels by Tousled-like kinases.

    Maxim Pilyugin

    Full Text Available Histone chaperones are at the hub of a diverse interaction networks integrating a plethora of chromatin modifying activities. Histone H3/H4 chaperone ASF1 is a target for cell-cycle regulated Tousled-like kinases (TLKs and both proteins cooperate during chromatin replication. However, the precise role of post-translational modification of ASF1 remained unclear. Here, we identify the TLK phosphorylation sites for both Drosophila and human ASF1 proteins. Loss of TLK-mediated phosphorylation triggers hASF1a and dASF1 degradation by proteasome-dependent and independent mechanisms respectively. Consistent with this notion, introduction of phosphorylation-mimicking mutants inhibits hASF1a and dASF1 degradation. Human hASF1b is also targeted for proteasome-dependent degradation, but its stability is not affected by phosphorylation indicating that other mechanisms are likely to be involved in control of hASF1b levels. Together, these results suggest that ASF1 cellular levels are tightly controlled by distinct pathways and provide a molecular mechanism for post-translational regulation of dASF1 and hASF1a by TLK kinases.

  12. Surface receptor Toso controls B cell-mediated regulation of T cell immunity.

    Yu, Jinbo; Duong, Vu Huy Hoang; Westphal, Katrin; Westphal, Andreas; Suwandi, Abdulhadi; Grassl, Guntram A; Brand, Korbinian; Chan, Andrew C; Föger, Niko; Lee, Kyeong-Hee

    2018-05-01

    The immune system is tightly controlled by regulatory processes that allow for the elimination of invading pathogens, while limiting immunopathological damage to the host. In the present study, we found that conditional deletion of the cell surface receptor Toso on B cells unexpectedly resulted in impaired proinflammatory T cell responses, which led to impaired immune protection in an acute viral infection model and was associated with reduced immunopathological tissue damage in a chronic inflammatory context. Toso exhibited its B cell-inherent immunoregulatory function by negatively controlling the pool of IL-10-competent B1 and B2 B cells, which were characterized by a high degree of self-reactivity and were shown to mediate immunosuppressive activity on inflammatory T cell responses in vivo. Our results indicate that Toso is involved in the differentiation/maintenance of regulatory B cells by fine-tuning B cell receptor activation thresholds. Furthermore, we showed that during influenza A-induced pulmonary inflammation, the application of Toso-specific antibodies selectively induced IL-10-competent B cells at the site of inflammation and resulted in decreased proinflammatory cytokine production by lung T cells. These findings suggest that Toso may serve as a novel therapeutic target to dampen pathogenic T cell responses via the modulation of IL-10-competent regulatory B cells.

  13. Differentiating neural systems mediating the acquisition versus expression of goal-directed and habitual behavioral control

    Liljeholm, Mimi; Dunne, Simon; O'Doherty, John P.

    2015-01-01

    Considerable behavioral data indicates that operant actions can become habitual, as evidenced by insensitivity to changes in the action-outcome contingency and in subjective outcome values. Notably, although several studies have investigated the neural substrates of habits, none has clearly differentiated the areas of the human brain that support habit formation from those that implement habitual control. We scanned participants with fMRI as they learned and performed an operant task in which the conditional structure of the environment encouraged either goal-directed encoding of the consequences of actions, or a habit-like mapping of actions to antecedent cues. Participants were also scanned during a subsequent assessment of insensitivity to outcome devaluation. We identified dissociable roles of the cerebellum and ventral striatum, across learning and test performance, in behavioral insensitivity to outcome devaluation. We also show that the inferior parietal lobule – an area previously implicated in several aspects of goal-directed action selection, including the attribution of intent and awareness of agency – predicts sensitivity to outcome devaluation. Finally, we reveal a potential functional homology between the human subgenual cortex and rodent infralimbic cortex in the implementation of habitual control. In summary, our findings suggest a broad systems division, at the cortical and subcortical levels, between brain areas mediating the encoding and expression of action-outcome and stimulus-response associations. PMID:25892332

  14. CD4+ lymphocytes control gut epithelial apoptosis and mediate survival in sepsis.

    Stromberg, Paul E; Woolsey, Cheryl A; Clark, Andrew T; Clark, Jessica A; Turnbull, Isaiah R; McConnell, Kevin W; Chang, Katherine C; Chung, Chun-Shiang; Ayala, Alfred; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2009-06-01

    Lymphocytes help determine whether gut epithelial cells proliferate or differentiate but are not known to affect whether they live or die. Here, we report that lymphocytes play a controlling role in mediating gut epithelial apoptosis in sepsis but not under basal conditions. Gut epithelial apoptosis is similar in unmanipulated Rag-1(-/-) and wild-type (WT) mice. However, Rag-1(-/-) animals have a 5-fold augmentation in gut epithelial apoptosis following cecal ligation and puncture (CLP) compared to septic WT mice. Reconstitution of lymphocytes in Rag-1(-/-) mice via adoptive transfer decreases intestinal apoptosis to levels seen in WT animals. Subset analysis indicates that CD4(+) but not CD8(+), gammadelta, or B cells are responsible for the antiapoptotic effect of lymphocytes on the gut epithelium. Gut-specific overexpression of Bcl-2 in transgenic mice decreases mortality following CLP. This survival benefit is lymphocyte dependent since gut-specific overexpression of Bcl-2 fails to alter survival when the transgene is overexpressed in Rag-1(-/-) mice. Further, adoptively transferring lymphocytes to Rag-1(-/-) mice that simultaneously overexpress gut-specific Bcl-2 results in improved mortality following sepsis. Thus, sepsis unmasks CD4(+) lymphocyte control of gut apoptosis that is not present under homeostatic conditions, which acts as a key determinant of both cellular survival and host mortality.

  15. Litter Controls Earthworm-Mediated Carbon and Nitrogen Transformations in Soil from Temperate Riparian Buffers

    Maria Kernecker

    2014-01-01

    Full Text Available Nutrient cycling in riparian buffers is partly influenced by decomposition of crop, grass, and native tree species litter. Nonnative earthworms in riparian soils in southern Quebec are expected to speed the processes of litter decomposition and nitrogen (N mineralization, increasing carbon (C and N losses in gaseous forms or via leachate. A 5-month microcosm experiment evaluated the effect of Aporrectodea turgida on the decomposition of 3 litter types (deciduous leaves, reed canarygrass, and soybean stem residue. Earthworms increased CO2 and N2O losses from microcosms with soybean residue, by 112% and 670%, respectively, but reduced CO2 and N2O fluxes from microcosms with reed canarygrass by 120% and 220%, respectively. Litter type controlled the CO2 flux (soybean ≥ deciduous-mix litter = reed canarygrass > no litter and the N2O flux (soybean ≥ no litter ≥ reed canarygrass > deciduous-mix litter. However, in the presence of earthworms, there was a slight increase in C and N gaseous losses of C and N relative to their losses via leachate, across litter treatments. We conclude that litter type determines the earthworm-mediated decomposition effect, highlighting the importance of vegetation management in controlling C and N losses from riparian buffers to the environment.

  16. A Collapsin Response Mediator Protein 2 Isoform Controls Myosin II-Mediated Cell Migration and Matrix Assembly by Trapping ROCK II

    Morgan-Fisher, Marie; Wait, Robin; Couchman, John R.; Wewer, Ulla M.

    2012-01-01

    Collapsin response mediator protein 2 (CRMP-2) is known as a regulator of neuronal polarity and differentiation through microtubule assembly and trafficking. Here, we show that CRMP-2 is ubiquitously expressed and a splice variant (CRMP-2L), which is expressed mainly in epithelial cells among nonneuronal cells, regulates myosin II-mediated cellular functions, including cell migration. While the CRMP-2 short form (CRMP-2S) is recognized as a substrate of the Rho-GTP downstream kinase ROCK in neuronal cells, a CRMP-2 complex containing 2L not only bound the catalytic domain of ROCK II through two binding domains but also trapped and inhibited the kinase. CRMP-2L protein levels profoundly affected haptotactic migration and the actin-myosin cytoskeleton of carcinoma cells as well as nontransformed epithelial cell migration in a ROCK activity-dependent manner. Moreover, the ectopic expression of CRMP-2L but not -2S inhibited fibronectin matrix assembly in fibroblasts. Underlying these responses, CRMP-2L regulated the kinase activity of ROCK II but not ROCK I, independent of GTP-RhoA levels. This study provides a new insight into CRMP-2 as a controller of myosin II-mediated cellular functions through the inhibition of ROCK II in nonneuronal cells. PMID:22431514

  17. Parental supervision for their children's toothbrushing: Mediating effects of planning, self-efficacy, and action control.

    Hamilton, Kyra; Cornish, Stephen; Kirkpatrick, Aaron; Kroon, Jeroen; Schwarzer, Ralf

    2018-05-01

    With 60-90% of children worldwide reportedly experiencing dental caries, poor oral health in the younger years is a major public health issue. As parents are important to children's oral hygiene practices, we examined the key self-regulatory behaviours of parents for supervising their children's toothbrushing using the health action process approach. Participants (N = 281, 197 mothers) comprised Australian parents of 2- to 5-year-olds. A longitudinal design was used to investigate the sequential mediation chain for the effect of intention (Time 1) on parental supervision for their youngest child's toothbrushing (Time 3), via self-efficacy and planning (Time 2), and action control (Time 3). A latent-variable structural equation model, controlling for baseline behaviour and habit, revealed significant indirect effects from intention via self-efficacy and action control and intention via planning and action control, on parental supervision behaviour. The model was a good fit to the data, explaining 74% of the variance in parents' supervising behaviour for their children's toothbrushing. While national recommendations are provided to guide parents in promoting good oral hygiene practices with their children, current results show the importance of going beyond simple knowledge transmission to support parents' intentions to supervise their children's toothbrushing actually materialize. Current findings make a significant contribution to the cumulative empirical evidence regarding self-regulatory components in health behaviour change and can inform intervention development to increase parents' participation in childhood oral hygiene practices, thus helping to curb rising oral health conditions and diseases. Statement of contribution What is already known on this subject? Self-regulatory skills are important to translate intentions into behaviour. Self-efficacy, planning, and action control are key self-regulatory skills for behaviour change. What does this study add

  18. Mediators of cognitive behavioral therapy for anxiety-disordered children and adolescents : cognition, perceived control, and coping

    Hogendoorn, Sanne M; Prins, Pier J M; Boer, Frits; Vervoort, Leentje; Wolters, Lidewij H; Moorlag, Harma; Nauta, Maaike H; Garst, Harry; Hartman, Catharina A; de Haan, Else

    2014-01-01

    The purpose is to investigate whether a change in putative mediators (negative and positive thoughts, coping strategies, and perceived control over anxious situations) precedes a change in anxiety symptoms in anxiety-disordered children and adolescents receiving cognitive behavioral therapy (CBT).

  19. Therapist-Aided Exposure for Women with Lifelong Vaginismus: Mediators of Treatment Outcome: A Randomized Waiting List Control Trial.

    Ter Kuile, Moniek M; Melles, Reinhilde J; Tuijnman-Raasveld, Charlotte C; de Groot, Helen E; van Lankveld, Jacques J D M

    2015-08-01

    Therapist-aided exposure seems an effective treatment for lifelong vaginismus, but mechanisms of action have not yet been established. The purpose of the present study was to investigate whether treatment outcome of a therapist-aided exposure treatment was mediated by changes in positive and negative penetration beliefs or feelings of sexual disgust. Participants with lifelong vaginismus were allocated at random to a 3-month exposure (n = 35) or a waiting list control condition (n = 35). Full intercourse was assessed daily during 12 weeks. Secondary outcome measures (complaints about vaginismus and coital pain) were assessed at baseline and after 12 weeks. Possible mediators: penetration beliefs (catastrophic pain beliefs, genital incompatibility beliefs, perceived control beliefs) and feelings of sexual disgust were assessed at baseline and 6 weeks. Treatment outcome (coital frequency, symptoms of vaginismus, and coital pain) at 12 weeks was mediated by changes in negative and positive penetration beliefs at 6 weeks, in particular by more pronounced reduction of catastrophic pain penetration beliefs. No evidence was found that changes in feelings of sexual disgust mediated treatment outcome. The results strongly suggest that therapist-aided exposure affects negative penetration beliefs and that these changes in negative penetration beliefs mediate treatment outcome in women with lifelong vaginismus. Implications for treatment are discussed. © 2015 International Society for Sexual Medicine.

  20. Locus of control fails to mediate between stress and anxiety and depression in parents of children with a developmental disorder.

    Hamlyn-Wright, Sarah; Draghi-Lorenz, Riccardo; Ellis, Jason

    2007-11-01

    Stress, anxiety and depression are raised amongst parents of children with a developmental disorder. However, the processes by which stress leads to depression and anxiety are poorly understood. In a cross-sectional survey, levels of parental stress, depression and anxiety were compared between parents of children with an autistic disorder, children with Down's syndrome and children with no disorder (N = 619) and the mediational role of locus of control was examined. Anxiety and depression were higher in parents of children with a disorder, and highest in parents of children with autism. Locus of control was more external in parents of children with autism. Locus of control failed to mediate the relationship between stress and both anxiety and depression in parents of children with a disorder. This suggests that help for parents of a child with a disorder may be effective if focused on the sources of stress rather than perceived control over events.

  1. Vagal afferents modulate cytokine-mediated respiratory control at the neonatal medulla oblongata.

    Balan, Kannan V; Kc, Prabha; Hoxha, Zana; Mayer, Catherine A; Wilson, Christopher G; Martin, Richard J

    2011-09-30

    Perinatal sepsis and inflammation trigger lung and brain injury in preterm infants, and associated apnea of prematurity. We hypothesized that endotoxin exposure in the immature lung would upregulate proinflammatory cytokine mRNA expression in the medulla oblongata and be associated with impaired respiratory control. Lipopolysaccharide (LPS, 0.1mg/kg) or saline was administered intratracheally to rat pups and medulla oblongatas were harvested for quantifying expression of mRNA for proinflammatory cytokines. LPS-exposure significantly increased medullary mRNA for IL-1β and IL-6, and vagotomy blunted this increase in IL-1β, but not IL-6. Whole-body flow plethysmography revealed that LPS-exposed pups had an attenuated ventilatory response to hypoxia both before and after carotid sinus nerve transection. Immunochemical expression of IL-1β within the nucleus of the solitary tract and area postrema was increased after LPS-exposure. In summary, intratracheal endotoxin-exposure in rat pups is associated with upregulation of proinflammatory cytokines in the medulla oblongata that is vagally mediated for IL-1β and associated with an impaired hypoxic ventilatory response. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Mycobacterium tuberculosis Controls Phagosomal Acidification by Targeting CISH-Mediated Signaling.

    Queval, Christophe J; Song, Ok-Ryul; Carralot, Jean-Philippe; Saliou, Jean-Michel; Bongiovanni, Antonino; Deloison, Gaspard; Deboosère, Nathalie; Jouny, Samuel; Iantomasi, Raffaella; Delorme, Vincent; Debrie, Anne-Sophie; Park, Sei-Jin; Gouveia, Joana Costa; Tomavo, Stanislas; Brosch, Roland; Yoshimura, Akihiko; Yeramian, Edouard; Brodin, Priscille

    2017-09-26

    Pathogens have evolved a range of mechanisms to counteract host defenses, notably to survive harsh acidic conditions in phagosomes. In the case of Mycobacterium tuberculosis, it has been shown that regulation of phagosome acidification could be achieved by interfering with the retention of the V-ATPase complexes at the vacuole. Here, we present evidence that M. tuberculosis resorts to yet another strategy to control phagosomal acidification, interfering with host suppressor of cytokine signaling (SOCS) protein functions. More precisely, we show that infection of macrophages with M. tuberculosis leads to granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion, inducing STAT5-mediated expression of cytokine-inducible SH2-containing protein (CISH), which selectively targets the V-ATPase catalytic subunit A for ubiquitination and degradation by the proteasome. Consistently, we show that inhibition of CISH expression leads to reduced replication of M. tuberculosis in macrophages. Our findings further broaden the molecular understanding of mechanisms deployed by bacteria to survive. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Mycobacterium tuberculosis Controls Phagosomal Acidification by Targeting CISH-Mediated Signaling

    Christophe J. Queval

    2017-09-01

    Full Text Available Pathogens have evolved a range of mechanisms to counteract host defenses, notably to survive harsh acidic conditions in phagosomes. In the case of Mycobacterium tuberculosis, it has been shown that regulation of phagosome acidification could be achieved by interfering with the retention of the V-ATPase complexes at the vacuole. Here, we present evidence that M. tuberculosis resorts to yet another strategy to control phagosomal acidification, interfering with host suppressor of cytokine signaling (SOCS protein functions. More precisely, we show that infection of macrophages with M. tuberculosis leads to granulocyte-macrophage colony-stimulating factor (GM-CSF secretion, inducing STAT5-mediated expression of cytokine-inducible SH2-containing protein (CISH, which selectively targets the V-ATPase catalytic subunit A for ubiquitination and degradation by the proteasome. Consistently, we show that inhibition of CISH expression leads to reduced replication of M. tuberculosis in macrophages. Our findings further broaden the molecular understanding of mechanisms deployed by bacteria to survive.

  4. Long-range spin wave mediated control of defect qubits in nanodiamonds

    Andrich, Paolo; de las Casas, Charles F.; Liu, Xiaoying; Bretscher, Hope L.; Berman, Jonson R.; Heremans, F. Joseph; Nealey, Paul F.; Awschalom, David D.

    2017-07-17

    Hybrid architectures that combine nitrogen-vacancy (NV) centers in diamond with other materials and physical systems have been proposed to enhance the NV center’s capabilities in many quantum sensing and information applications. In particular, spin waves (SWs) in ferromagnetic materials are a promising candidate to implement these platforms due to their strong magnetic fields, which could be used to efficiently interact with the NV centers. Here we develop an yttrium iron garnet-nanodiamond hybrid architecture constructed with the help of directed assembly and transfer printing techniques. Operating at ambient conditions, we demonstrate that surface confined SWs excited in the ferromagnet (FM) can strongly amplify the interactions between a microwave source and the NV centers by enhancing the local microwave magnetic field by several orders of magnitude. Crucially, we show the existence of a regime in which coherent interactions between SWs and NV centers dominate over incoherent mechanisms associated with the broadband magnetic field noise generated by the FM. These accomplishments enable the SW mediated coherent control of spin qubits over distances larger than 200 um, and allow low power operations for future spintronic technologies.

  5. How Structure-Directing Agents Control Nanocrystal Shape: Polyvinylpyrrolidone-Mediated Growth of Ag Nanocubes.

    Qi, Xin; Balankura, Tonnam; Zhou, Ya; Fichthorn, Kristen A

    2015-11-11

    The importance of structure-directing agents (SDAs) in the shape-selective synthesis of colloidal nanostructures has been well documented. However, the mechanisms by which SDAs actuate shape control are poorly understood. In the polyvinylpyrrolidone (PVP)-mediated growth of {100}-faceted Ag nanocrystals, this capability has been attributed to preferential binding of PVP to Ag(100). We use molecular dynamics simulations to probe the mechanisms by which Ag atoms add to Ag(100) and Ag(111) in ethylene glycol solution with PVP. We find that PVP induces kinetic Ag nanocrystal shapes by regulating the relative Ag fluxes to these facets. Stronger PVP binding to Ag(100) leads to a larger Ag flux to Ag(111) and cubic nanostructures through two mechanisms: enhanced Ag trapping by more extended PVP films on Ag(111) and a reduced free-energy barrier for Ag to cross lower-density films on Ag(111). These flux-regulating capabilities depend on PVP concentration and chain length, consistent with experiment.

  6. Hemi-fused structure mediates and controls fusion and fission in live cells.

    Zhao, Wei-Dong; Hamid, Edaeni; Shin, Wonchul; Wen, Peter J; Krystofiak, Evan S; Villarreal, Seth A; Chiang, Hsueh-Cheng; Kachar, Bechara; Wu, Ling-Gang

    2016-06-23

    Membrane fusion and fission are vital for eukaryotic life. For three decades, it has been proposed that fusion is mediated by fusion between the proximal leaflets of two bilayers (hemi-fusion) to produce a hemi-fused structure, followed by fusion between the distal leaflets, whereas fission is via hemi-fission, which also produces a hemi-fused structure, followed by full fission. This hypothesis remained unsupported owing to the lack of observation of hemi-fusion or hemi-fission in live cells. A competing fusion hypothesis involving protein-lined pore formation has also been proposed. Here we report the observation of a hemi-fused Ω-shaped structure in live neuroendocrine chromaffin cells and pancreatic β-cells, visualized using confocal and super-resolution stimulated emission depletion microscopy. This structure is generated from fusion pore opening or closure (fission) at the plasma membrane. Unexpectedly, the transition to full fusion or fission is determined by competition between fusion and calcium/dynamin-dependent fission mechanisms, and is notably slow (seconds to tens of seconds) in a substantial fraction of the events. These results provide key missing evidence in support of the hemi-fusion and hemi-fission hypothesis in live cells, and reveal the hemi-fused intermediate as a key structure controlling fusion and fission, as fusion and fission mechanisms compete to determine the transition to fusion or fission.

  7. RUNX2 Mediates Plasmacytoid Dendritic Cell Egress from the Bone Marrow and Controls Viral Immunity

    Michaël Chopin

    2016-04-01

    Full Text Available Plasmacytoid dendritic cells (pDCs represent a unique immune cell type that responds to viral nucleic acids through the rapid production of type I interferons. Within the hematopoietic system, the transcription factor RUNX2 is exclusively expressed in pDCs and is required for their peripheral homeostasis. Here, we show that RUNX2 plays an essential role in promoting pDC localization and function. RUNX2 is required for the appropriate expression of the integrin-mediated adhesion machinery, as well as for the down-modulation of the chemokine receptor CXCR4, which allows pDC egress into the circulation. RUNX2 also facilitates the robust response to viral infection through the control of IRF7, the major regulator of type I interferon production. Mice lacking one copy of Runx2 have reduced numbers of peripheral pDCs and IFN-α expression, which might contribute to the reported difficulties of individuals with cleidocranial dysplasia, who are haploinsufficient for RUNX2, to clear viral infections.

  8. Physical control of carrier-mediated ion-transporters by entrainment of their turnover rate

    Chen, Wei; Mathis, Clausell; Fang, Zhihui; Mast, Jason; Hamidi, Karim; Kelly, Patrick; Eve, Max

    2012-02-01

    In the past, tremendous efforts have been made to physically activate carrier-mediated ion-transporters, such as Na/K pumps. However, the outcome is not significant. Recently, we developed a new technique which can effectively and efficiently control the pumping rate by introducing a concept of an electronic synchrotron accelerator to the biological system. The approach consists of two steps. First, a specially designed oscillating electric field is used to force or synchronize individual pump molecules to run at the same turnover rate and phase as the field oscillation frequency. Then, by gradually changing the field frequency and carefully keeping the pump synchronization we can entrain the pump molecules so that their pumping rate can be progressively modulated, either decelerated or accelerated, following the field frequency to a defined value. Based on theoretical analysis of the underlying mechanisms involved in the technique, computer simulation of the entrainment process, and intensive experimental studies we have realized significant activation of the Na/K pumping rate up to ten-folds quickly in less than ten seconds.

  9. Glutaredoxin-2 is required to control oxidative phosphorylation in cardiac muscle by mediating deglutathionylation reactions.

    Mailloux, Ryan J; Xuan, Jian Ying; McBride, Skye; Maharsy, Wael; Thorn, Stephanie; Holterman, Chet E; Kennedy, Christopher R J; Rippstein, Peter; deKemp, Robert; da Silva, Jean; Nemer, Mona; Lou, Marjorie; Harper, Mary-Ellen

    2014-05-23

    Glutaredoxin-2 (Grx2) modulates the activity of several mitochondrial proteins in cardiac tissue by catalyzing deglutathionylation reactions. However, it remains uncertain whether Grx2 is required to control mitochondrial ATP output in heart. Here, we report that Grx2 plays a vital role modulating mitochondrial energetics and heart physiology by mediating the deglutathionylation of mitochondrial proteins. Deletion of Grx2 (Grx2(-/-)) decreased ATP production by complex I-linked substrates to half that in wild type (WT) mitochondria. Decreased respiration was associated with increased complex I glutathionylation diminishing its activity. Tissue glucose uptake was concomitantly increased. Mitochondrial ATP output and complex I activity could be recovered by restoring the redox environment to that favoring the deglutathionylated states of proteins. Grx2(-/-) hearts also developed left ventricular hypertrophy and fibrosis, and mice became hypertensive. Mitochondrial energetics from Grx2 heterozygotes (Grx2(+/-)) were also dysfunctional, and hearts were hypertrophic. Intriguingly, Grx2(+/-) mice were far less hypertensive than Grx2(-/-) mice. Thus, Grx2 plays a vital role in modulating mitochondrial metabolism in cardiac muscle, and Grx2 deficiency leads to pathology. As mitochondrial ATP production was restored by the addition of reductants, these findings may be relevant to novel redox-related therapies in cardiac disease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Singlet oxygen explicit dosimetry to predict local tumor control for HPPH-mediated photodynamic therapy

    Penjweini, Rozhin; Kim, Michele M.; Ong, Yi Hong; Zhu, Timothy C.

    2017-02-01

    This preclinical study examines four dosimetric quantities (light fluence, photosensitizer photobleaching ratio, PDT dose, and reacted singlet oxygen ([1O2]rx)) to predict local control rate (LCR) for 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH)-mediated photodynamic therapy (PDT). Mice bearing radiation-induced fibrosarcoma (RIF) tumors were treated with different in-air fluences (135, 250 and 350 J/cm2) and in-air fluence rates (50, 75 and 150 mW/cm2) at 0.25 mg/kg HPPH and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 665 nm wavelength. A macroscopic model was used to calculate ([1O2]rx)) based on in vivo explicit dosimetry of the initial tissue oxygenation, photosensitizer concentration, and tissue optical properties. PDT dose was defined as a temporal integral of drug concentration and fluence rate (φ) at a 3 mm tumor depth. Light fluence rate was calculated throughout the treatment volume based on Monte-Carlo simulation and measured tissue optical properties. The tumor volume of each mouse was tracked for 30 days after PDT and Kaplan-Meier analyses for LCR were performed based on a tumor volume <=100 mm3, for four dose metrics: fluence, HPPH photobleaching rate, PDT dose, and ([1O2]rx)). The results of this study showed that ([1O2]rx)) is the best dosimetric quantity that can predict tumor response and correlate with LCR.

  11. Long-range gap junctional signaling controls oncogene-mediated tumorigenesis in Xenopus laevis embryos

    Brook T Chernet

    2015-01-01

    Full Text Available In addition to the immediate microenvironment, long-range signaling may be an important component of cancer. Molecular-genetic analyses have implicated gap junctions – key mediators of cell-cell communication – in carcinogenesis. We recently showed that the resting voltage potential of distant cell groups is a key determinant of metastatic transformation and tumor induction. Here, we show in the Xenopus laevis model that gap junctional communication (GJC is a modulator of the long-range bioelectric signaling that regulates tumor formation. Genetic disruption of GJC taking place within tumors, within remote host tissues, or between the host and tumors – significantly lowers the incidence of tumors induced by KRAS mutations. The most pronounced suppression of tumor incidence was observed upon GJC disruption taking place farther away from oncogene-expressing cells, revealing a role for GJC in distant cells in the control of tumor growth. In contrast, enhanced GJC communication through the overexpression of wild-type connexin Cx26 increased tumor incidence. Our data confirm a role for GJC in tumorigenesis, and reveal that this effect is non-local. Based on these results and on published data on movement of ions through GJs, we present a quantitative model linking the GJC coupling and bioelectrical state of cells to the ability of oncogenes to initiate tumorigenesis. When integrated with data on endogenous bioelectric signaling during left-right patterning, the model predicts differential tumor incidence outcomes depending on the spatial configurations of gap junction paths relative to tumor location and major anatomical body axes. Testing these predictions, we found that the strongest influence of GJ modulation on tumor suppression by hyperpolarization occurred along the embryonic left-right axis. Together, these data reveal new, long-range aspects of cancer control by the host’s physiological parameters.

  12. COUP-TFII mediates progesterone regulation of uterine implantation by controlling ER activity.

    Isao Kurihara

    2007-06-01

    Full Text Available Progesterone and estrogen are critical regulators of uterine receptivity. To facilitate uterine remodeling for embryo attachment, estrogen activity in the uterine epithelia is attenuated by progesterone; however, the molecular mechanism by which this occurs is poorly defined. COUP-TFII (chicken ovalbumin upstream promoter transcription factor II; also known as NR2F2, a member of the nuclear receptor superfamily, is highly expressed in the uterine stroma and its expression is regulated by the progesterone-Indian hedgehog-Patched signaling axis that emanates from the epithelium. To further assess COUP-TFII uterine function, a conditional COUP-TFII knockout mouse was generated. This mutant mouse is infertile due to implantation failure, in which both embryo attachment and uterine decidualization are impaired. Using this animal model, we have identified a novel genetic pathway in which BMP2 lies downstream of COUP-TFII. Epithelial progesterone-induced Indian hedgehog regulates stromal COUP-TFII, which in turn controls BMP2 to allow decidualization to manifest in vivo. Interestingly, enhanced epithelial estrogen activity, which impedes maturation of the receptive uterus, was clearly observed in the absence of stromal-derived COUP-TFII. This finding is consistent with the notion that progesterone exerts its control of implantation through uterine epithelial-stromal cross-talk and reveals that stromal-derived COUP-TFII is an essential mediator of this complex cross-communication pathway. This finding also provides a new signaling paradigm for steroid hormone regulation in female reproductive biology, with attendant implications for furthering our understanding of the molecular mechanisms that underlie dysregulation of hormonal signaling in such human reproductive disorders as endometriosis and endometrial cancer.

  13. Job attitudes and well-being among public vs. private physicians: organizational justice and job control as mediators.

    Heponiemi, Tarja; Kuusio, Hannamaria; Sinervo, Timo; Elovainio, Marko

    2011-08-01

    The present study examined whether there are differences in job-related attitudes and well-being among physicians working in private sector and public sector. In addition, we examined whether psychosocial factors (organizational justice and job control) could mediate these possible differences in different sectors. Cross-sectional survey data from the Finnish Health Professional Study was used. A random sample of Finnish physicians included 1522 women and 1047 men aged 25-65 years. Outcome variables were job satisfaction, organizational commitment, psychological distress, work ability and sleeping problems. Job control and organizational justice were measured using established questionnaires. Series of regression analyses were performed and the mediational effects were tested following the procedures outlined by Baron and Kenny. Physicians working in private sector had higher levels of job satisfaction and organizational commitment and lower levels of psychological distress and sleeping problems when compared with physicians working in public sector. Private physicians also had higher levels of organizational justice, which acted as a mediator behind more positive attitudes and better well-being in private sector. Private physicians had higher levels of job control but it did not act as a mediator. Private physicians feel better than public physicians and this is partly due to higher organizational justice in private sector. Public health care organizations should invest effort to increase the fairness in their organizations and management and pay more attention in improving the well-being of their employees, which could possibly increase the attractiveness of public sector as a career option.

  14. Delay Discounting Mediates Parent-Adolescent Relationship Quality and Risky Sexual Behavior for Low Self-Control Adolescents

    Kahn, Rachel E.; Holmes, Christopher; Farley, Julee P.; Kim-Spoon, Jungmeen

    2015-01-01

    Parent-adolescent relationship quality and delay discounting may play important roles in adolescents’ sexual decision making processes, and levels of self-control during adolescence could act as a buffer within these factors. This longitudinal study included 219 adolescent (55% male; mean age = 12.66 years at Wave 1; mean age = 15.10 years at Wave 2) and primary caregiver dyads. Structural equation modeling was utilized to determine whether delay discounting mediated the association between parent-adolescent relationship quality and adolescents’ risky sexual behavior and how this mediated association may differ between those with high versus low self-control. The results revealed parent-adolescent relationship quality plays a role in the development of risky sexual behavior indirectly through levels of delay discounting, but only for adolescents with low self-control. These findings could inform sex education policies and health prevention programs that address adolescent risky sexual behavior. PMID:26202153

  15. HLA-A*7401-mediated control of HIV viremia is independent of its linkage disequilibrium with HLA-B*5703

    Matthews, Philippa C; Adland, Emily; Listgarten, Jennifer

    2011-01-01

    -clade-infected subjects. We present evidence that HLA-A*7401 operates an effect that is independent of HLA-B*5703, with which it is in linkage disequilibrium in some populations, to mediate lowered viremia. We describe a novel statistical approach to detecting additive effects between class I alleles in control of HIV-1...... epitopes appear immunodominant. We identify eight novel putative HLA-A*7401-restricted epitopes, of which three have been defined to the optimal epitope. In common with HLA-B alleles linked with slow progression, viremic control through an HLA-A*7401-restricted response appears to be associated...... with the selection of escape mutants within Gag epitopes that reduce viral replicative capacity. These studies highlight the potentially important contribution of an HLA-A allele to immune control of HIV infection, which may have been concealed by a stronger effect mediated by an HLA-B allele with which...

  16. Smartphone Addiction and School Life Adjustment Among High School Students: The Mediating Effect of Self-Control.

    Heo, YoungJin; Lee, Kyunghee

    2018-05-08

    Previous studies have reported associations among smartphone addiction, school adjustment, and self-control. However, the causal relationship between smartphone addiction and school adjustment has not been clearly demonstrated. The current study examined the association between smartphone addiction and school adjustment and investigated the mediating effect of self-control in this association. A total of 790 students from five high schools in Daegu City, South Korea, were asked to provide demographic information and complete a self-diagnostic smartphone addiction scale and validated Korean version of a self-control scale. Among at-risk students, self-control did not mediate the relation between smartphone addiction and school adjustment; among those not at risk, there was a partial mediating effect. To improve school adjustment among high school students, prevention of smartphone addiction seems important. Smartphone addiction could be managed by strengthening self-control to promote healthy use of smartphones. The current results can serve as groundwork for the development of programs to improve school adjustment among high school students. [Journal of Psychosocial Nursing and Mental Health Services, xx(x), xx-xx.]. Copyright 2018, SLACK Incorporated.

  17. Harsh parenting and academic achievement in Chinese adolescents: Potential mediating roles of effortful control and classroom engagement.

    Wang, Mingzhong; Deng, Xueli; Du, Xiuxiu

    2018-04-01

    This study examined (a) the potential mediating roles of effortful control and classroom engagement in the association between harsh parenting and adolescent academic achievement, and (b) the potential moderating role of gender. Sixth through eighth graders in rural China (n=815, mean age=12.55years) reported on harsh parenting, effortful control, and classroom engagement. Parents also reported on each other's harsh parenting. Academic achievement was assessed by students' test scores and teacher-rated academic performance. Results of structural equation modeling revealed gender differences in patterns of association among the model variables. Harsh parenting was negatively and directly associated with academic achievement for both boys and girls. It was also negatively and indirectly associated with academic achievement via effortful control and classroom engagement sequentially, forming a common indirect "path" for boys and girls. The indirect negative effect of harsh parenting on boys' academic achievement was mainly realized through the mediator of effortful control, whereas this same indirect effect for girls was mainly realized through the mediator of classroom engagement. Jointly, effortful control and classroom engagement precipitates more indirect effects for boys than for girls in the association between harsh parenting and academic achievement. The discussion analyzes the potential "paths" from harsh parenting to adolescent academic achievement, as well as gender differences in these "paths." The current study has implications for teachers and parents eager to improve students' classroom engagement and academic achievement. Copyright © 2017. Published by Elsevier Ltd.

  18. Mechanism of Integrim-Mediated Growth Control in Normal, Transformed, and Neoplastic Breast Cells

    Wayner, Elizabeth

    1999-01-01

    .... The primary cell adhesion receptors that mediate binding to extracellular matrix proteins are integrins Our data suggest that alpha 3 beta 1 and alpha 6 beta 4 are the primary integrins responsible...

  19. Assessing the relationships among stress, god-mediated control, and psychological distress/well-being: Does the level of education matter?

    Krause, Neal

    2018-01-24

    One of the primary functions of religion is to help people cope with stressful life events. The purpose of the current study is to see if God-mediated control beliefs perform this stress-buffering function. God-mediated control refers to the belief that people work together with God to reduce the effects of unwanted stressors in their lives. An effort is made to probe this relationship more deeply by seeing whether the stress moderating function of God-mediated control beliefs varies across levels of educational attainment. Findings from a recent nationwide survey suggest that strong God-mediated control beliefs reduce the magnitude of the relationship between stress and depressive symptoms, anxiety, happiness, and hope, but only among more highly educated study participants. In contrast, God-mediated control beliefs do not appear to influence the relationship between stress and distress/well-being among study participants with lower levels of educational attainment.

  20. Cytosolic chaperones mediate quality control of higher-order septin assembly in budding yeast.

    Johnson, Courtney R; Weems, Andrew D; Brewer, Jennifer M; Thorner, Jeremy; McMurray, Michael A

    2015-04-01

    Septin hetero-oligomers polymerize into cytoskeletal filaments with essential functions in many eukaryotic cell types. Mutations within the oligomerization interface that encompasses the GTP-binding pocket of a septin (its "G interface") cause thermoinstability of yeast septin hetero-oligomer assembly, and human disease. When coexpressed with its wild-type counterpart, a G interface mutant is excluded from septin filaments, even at moderate temperatures. We show that this quality control mechanism is specific to G interface mutants, operates during de novo septin hetero-oligomer assembly, and requires specific cytosolic chaperones. Chaperone overexpression lowers the temperature permissive for proliferation of cells expressing a G interface mutant as the sole source of a given septin. Mutations that perturb the septin G interface retard release from these chaperones, imposing a kinetic delay on the availability of nascent septin molecules for higher-order assembly. Un-expectedly, the disaggregase Hsp104 contributes to this delay in a manner that does not require its "unfoldase" activity, indicating a latent "holdase" activity toward mutant septins. These findings provide new roles for chaperone-mediated kinetic partitioning of non-native proteins and may help explain the etiology of septin-linked human diseases. © 2015 Johnson et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  1. Vitamin D receptor-mediated control of Soggy, Wise, and Hairless gene expression in keratinocytes.

    Hsieh, Jui-Cheng; Estess, Rudolf C; Kaneko, Ichiro; Whitfield, G Kerr; Jurutka, Peter W; Haussler, Mark R

    2014-02-01

    The vitamin D receptor (VDR), but not its hormonal ligand, 1,25-dihydroxyvitamin D3 (1,25D), is required for the progression of the mammalian hair cycle. We studied three genes relevant to hair cycle signaling, DKKL1 (Soggy), SOSTDC1 (Wise), and HR (Hairless), to determine whether their expression is regulated by VDR and/or its 1,25D ligand. DKKL1 mRNA was repressed 49-72% by 1,25D in primary human and CCD-1106 KERTr keratinocytes; a functional vitamin D responsive element (VDRE) was identified at -9590 bp in murine Soggy. Similarly, SOSTDC1 mRNA was repressed 41-59% by 1,25D in KERTr and primary human keratinocytes; a functional VDRE was located at -6215 bp in human Wise. In contrast, HR mRNA was upregulated 1.56- to 2.77-fold by 1,25D in primary human and KERTr keratinocytes; a VDRE (TGGTGAgtgAGGACA) consisting of an imperfect direct repeat separated by three nucleotides (DR3) was identified at -7269 bp in the human Hairless gene that mediated dramatic induction, even in the absence of 1,25D ligand. In parallel, a DR4 thyroid hormone responsive element, TGGTGAggccAGGACA, was identified at +1304 bp in the human HR gene that conferred tri-iodothyronine (T3)-independent transcriptional activation. Because the thyroid hormone receptor controls HR expression in the CNS, whereas VDR functions in concert with the HR corepressor specifically in skin, a model is proposed wherein unliganded VDR upregulates the expression of HR, the gene product of which acts as a downstream comodulator to feedback-repress DKKL1 and SOSTDC1, resulting in integration of bone morphogenic protein and Wnt signaling to drive the mammalian hair cycle and/or influencing epidermal function.

  2. How information about overdetection changes breast cancer screening decisions: a mediation analysis within a randomised controlled trial.

    Hersch, Jolyn; McGeechan, Kevin; Barratt, Alexandra; Jansen, Jesse; Irwig, Les; Jacklyn, Gemma; Houssami, Nehmat; Dhillon, Haryana; McCaffery, Kirsten

    2017-10-06

    In a randomised controlled trial, we found that informing women about overdetection changed their breast screening decisions. We now present a mediation analysis exploring the psychological pathways through which study participants who received the intervention processed information about overdetection and how this influenced their decision-making. We examined a series of potential mediators in the causal chain between exposure to overdetection information and women's subsequently reported breast screening intentions. Serial multiple mediation analysis within a randomised controlled trial. New South Wales, Australia. 811 women aged 48-50 years with no personal history of breast cancer. Two versions of a decision aid giving women information about breast cancer deaths averted and false positives from mammography screening, either with (intervention) or without (control) information on overdetection. Intentions to undergo breast cancer screening in the next 2-3 years. Knowledge about overdetection, worry about breast cancer, attitudes towards breast screening and anticipated regret. The effect of information about overdetection on women's breast screening intentions was mediated through multiple cognitive and affective processes. In particular, the information led to substantial improvements in women's understanding of overdetection, and it influenced-both directly and indirectly via its effect on knowledge-their attitudes towards having screening. Mediation analysis showed that the mechanisms involving knowledge and attitudes were particularly important in determining women's intentions about screening participation. Even in this emotive context, new information influenced women's decision-making by changing their understanding of possible consequences of screening and their attitudes towards undergoing it. These findings emphasise the need to provide good-quality information on screening outcomes and to communicate this information effectively, so that women can

  3. The dampening effect of employees' future orientation on cyberloafing behaviors: the mediating role of self-control.

    Zhang, Heyun; Zhao, Huanhuan; Liu, Jingxuan; Xu, Yan; Lu, Hui

    2015-01-01

    Previous studies on reducing employees' cyberloafing behaviors have primarily examined the external control factors but seldomly taken individual internal subjective factors into consideration. Future orientation, an important individual factor, is defined as the extent to which one plans for future time and considers future consequences of one's current behavior. To explore further whether and how employees' future orientation can dampen their cyberloafing behaviors, two studies were conducted to examine the relationship between employees' future orientation and cyberloafing behaviors. The mediation effect of employees' objective and subjective self-control between them was also examined. In Study 1, a set of questionnaires was completed, and the results revealed that the relationship between employees' future orientation and cyberloafing behaviors was negative, and objective self-control mediated the relationship. Next, we conducted a priming experiment (Study 2) to examine the causal relationship and psychological mechanism between employees' future orientation and cyberloafing behaviors. The results demonstrated that employees' future-orientation dampened their attitudes and intentions to engage in cyberloafing, and subjective self-control mediated this dampening effect. Theoretical and practical implications of these findings are also discussed.

  4. The dampening effect of employees’ future orientation on cyberloafing behaviors: the mediating role of self-control

    Zhang, Heyun; Zhao, Huanhuan; Liu, Jingxuan; Xu, Yan; Lu, Hui

    2015-01-01

    Previous studies on reducing employees’ cyberloafing behaviors have primarily examined the external control factors but seldomly taken individual internal subjective factors into consideration. Future orientation, an important individual factor, is defined as the extent to which one plans for future time and considers future consequences of one’s current behavior. To explore further whether and how employees’ future orientation can dampen their cyberloafing behaviors, two studies were conducted to examine the relationship between employees’ future orientation and cyberloafing behaviors. The mediation effect of employees’ objective and subjective self-control between them was also examined. In Study 1, a set of questionnaires was completed, and the results revealed that the relationship between employees’ future orientation and cyberloafing behaviors was negative, and objective self-control mediated the relationship. Next, we conducted a priming experiment (Study 2) to examine the causal relationship and psychological mechanism between employees’ future orientation and cyberloafing behaviors. The results demonstrated that employees’ future-orientation dampened their attitudes and intentions to engage in cyberloafing, and subjective self-control mediated this dampening effect. Theoretical and practical implications of these findings are also discussed. PMID:26483735

  5. The dampening effect of employees’ future orientation on cyberloafing behaviors: The mediating role of self-control

    Heyun eZhang

    2015-09-01

    Full Text Available Previous studies on reducing employees’ cyberloafing behaviors have primarily examined the external control factors but seldomly taken individual internal subjective factors into consideration. Future orientation, an important individual factor, is defined as the extent to which one plans for future time and considers future consequences of one’s current behavior. To explore further whether and how employees’ future orientation can dampen their cyberloafing behaviors, two studies were conducted to examine the relationship between employees’ future orientation and cyberloafing behaviors. The mediation effect of employees’ objective and subjective self-control between them was also examined. In Study 1, a set of questionnaires was completed, and the results revealed that the relationship between employees’ future orientation and cyberloafing behaviors was negative, and objective self-control mediated the relationship. Next, we conducted a priming experiment (Study 2 to examine the causal relationship and psychological mechanism between employees’ future orientation and cyberloafing behaviors. The results demonstrated that employees’ future-orientation dampened their attitudes and intentions to engage in cyberloafing, and subjective self-control mediated this dampening effect. Theoretical and practical implications of these findings are also discussed.

  6. Locus of control, self-efficacy, and the mediating effect of outcome control: predicting course-level and global outcomes in an academic context.

    Au, Evelyn W M

    2015-01-01

    The current study utilizes Skinner's framework to examine the unique contributions of internal locus of control, self-efficacy, and perceived outcome control over course performance on students' academic experiences. Undergraduate students (N = 225) took part in a longitudinal study and completed two surveys (Time 1: just before their mid-term exams; Time 2: just before their final exam in the same semester). Both locus of control and self-efficacy at Time 1 predicted course-level perceived control over course performance at Time 2. Student-level perceived control over course performance at Time 2 mediated the relationship between self-efficacy at Time 1 and course-level perseverance, course-specific stress, and course enjoyment at Time 2. For global perceived stress and life satisfaction measured at Time 2, both locus of control and self-efficacy at Time 1 had only a direct effect on global perceived stress at Time 2, but only self-efficacy at Time 1 predicted life satisfaction at Time 2. Both locus of control and self-efficacy uniquely contribute to students' academic experiences. Student-level perceived control plays an important mediating role between locus of control and self-efficacy at Time 1, and course-level perseverance, course-specific stress, and course enjoyment at Time 2.

  7. The Mediating Effect of Self-Control on Parenting and Delinquency: A Gendered Approach With a Multinational Sample.

    Muftić, Lisa R; Updegrove, Alexander H

    2017-08-01

    This study aims to clarify the relationships between parenting techniques, low self-control, and juvenile delinquency in Gottfredson and Hirschi's general theory of crime while controlling for alternative explanations of delinquency. We relied on a sample of 35,511 adolescent students from 31 countries from the International Self-Report Delinquency 2 Study. Results indicate that parenting exhibits a direct effect on adolescents' violence perpetration and property offending, and that while self-control weakens the strength of this relationship, it fails to fully mediate it. Males reported lower levels of self-control, exposure to poorer parenting techniques, and higher rates of violence perpetration and property offending. The relationship between parenting, self-control, and juvenile delinquency was similar for females and males. These results provide evidence that parenting has important implications for adolescents' involvement in delinquency above and beyond its influence on their level of self-control.

  8. Impaired cognitive control mediates the relationship between cortical thickness of the superior frontal gyrus and role functioning in schizophrenia.

    Tully, Laura M; Lincoln, Sarah Hope; Liyanage-Don, Nadia; Hooker, Christine I

    2014-02-01

    Structural abnormalities in the lateral prefrontal cortex (LPFC) are well-documented in schizophrenia and recent evidence suggests that these abnormalities relate to functional outcome. Cognitive control mechanisms, reliant on the LPFC, are impaired in schizophrenia and predict functional outcome, thus impaired cognitive control could mediate the relationship between neuroanatomical abnormalities in the LPFC and functional outcome. We used surface-based morphometry to investigate relationships between cortical surface characteristics, cognitive control, and measures of social and role functioning in 26 individuals with schizophrenia and 29 healthy controls. Results demonstrate that schizophrenia participants had thinner cortex in a region of the superior frontal gyrus (BA10). Across all participants, decreased cortical thickness in this region related to decreased cognitive control and decreased role functioning. Moreover, cognitive control fully mediated the relationship between cortical thickness in the superior frontal gyrus and role functioning, indicating that neuroanatomical abnormalities in the LPFC adversely impact role functioning via impaired cognitive control processes. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Compromised virus control and augmented perforin-mediated immunopathology in IFN-gamma-deficient mice infected with lymphocytic choriomeningitis virus

    Nansen, A; Jensen, Teis; Christensen, Jan Pravsgaard

    1999-01-01

    To define the role of IFN-gamma in the control of acute infection with a noncytopathogenic virus, mice with targeted defects of the genes encoding IFN-gamma, perforin, or both were infected i.v. with two strains of lymphocytic choriomeningitis virus differing markedly in their capacity to spread...... in wild-type mice. Our results reveal that IFN-gamma is pivotal to T cell-mediated control of a rapidly invasive stain, whereas it is less important in the acute elimination of a slowly invasive strain. Moreover, the majority of mice infected with the rapidly invasive strain succumb to a wasting syndrome...... mediated by CD8+ effector cells. The primary effector mechanism underlying this disease is perforin-dependent lysis, but other mechanisms are also involved. Wasting disease can be prevented if naive CD8+ cells from mice transgenic for an MHC class I-restricted lymphocytic choriomeningitis virus...

  10. Effect of sports participation on Internet addiction mediated by self-control: A case of Korean adolescents

    Jae-Ahm Park

    2016-09-01

    SEM indicated a significant effect of sports participation on Internet addiction mediated by self-control. The results suggest the effectiveness of and need for sport and physical activity in Internet addiction treatment programs and for other addictions as well. Moreover, sports participation has a wider variety of psychological and physical benefits unlike intervention strategies or pharmacological treatments. Thus, the adoption of sports needs to be broadened from physical development to treating diverse psychological problems among adolescents.

  11. Mediators of cognitive behavioral therapy for anxiety-disordered children and adolescents: cognition, perceived control, and coping.

    Hogendoorn, Sanne M; Prins, Pier J M; Boer, Frits; Vervoort, Leentje; Wolters, Lidewij H; Moorlag, Harma; Nauta, Maaike H; Garst, Harry; Hartman, Catharina A; de Haan, Else

    2014-01-01

    The purpose is to investigate whether a change in putative mediators (negative and positive thoughts, coping strategies, and perceived control over anxious situations) precedes a change in anxiety symptoms in anxiety-disordered children and adolescents receiving cognitive behavioral therapy (CBT). Participants were 145 Dutch children (8-18 years old, M = 12.5 years, 57% girls) with a primary anxiety disorder. Assessments were completed pretreatment, in-treatment, posttreatment, and at 3-month follow-up. Sequential temporal dependencies between putative mediators and parent- and child-reported anxiety symptoms were investigated in AMOS using longitudinal Latent Difference Score Modeling. During treatment an increase of positive thoughts preceded a decrease in child-reported anxiety symptoms. An increase in three coping strategies (direct problem solving, positive cognitive restructuring, and seeking distraction) preceded a decrease in parent-reported anxiety symptoms. A reciprocal effect was found for perceived control: A decrease in parent-reported anxiety symptoms both preceded and followed an increase in perceived control. Using a longitudinal design, a temporal relationship between several putative mediators and CBT-outcome for anxious children was explored. The results suggest that a change in positive thoughts, but not negative thoughts, and several coping strategies precedes a change in symptom reduction and, therefore, at least partly support theoretical models of anxiety upon which the anxiety intervention is based.

  12. Predictive Effects of Good Self-Control and Poor Regulation on Alcohol-Related Outcomes: Do Protective Behavioral Strategies Mediate?

    Pearson, Matthew R.; Kite, Benjamin A.; Henson, James M.

    2016-01-01

    In the present study, we examined whether use of protective behavioral strategies mediated the relationship between self-control constructs and alcohol-related outcomes. According to the two-mode model of self-control, good self-control (planfulness; measured with Future Time Perspective, Problem Solving, and Self-Reinforcement) and poor regulation (impulsivity; measured with Present Time Perspective, Poor Delay of Gratification, Distractibility) are theorized to be relatively independent constructs rather than opposite ends of a single continuum. The analytic sample consisted of 278 college student drinkers (68% women) who responded to a battery of surveys at a single time point. Using a structural equation model based on the two-mode model of self-control, we found that good self-control predicted increased use of three types of protective behavioral strategies (Manner of Drinking, Limiting/Stopping Drinking, and Serious Harm Reduction). Poor regulation was unrelated to use of protective behavioral strategies, but had direct effects on alcohol use and alcohol problems. Further, protective behavioral strategies mediated the relationship between good self-control and alcohol use. The clinical implications of these findings are discussed. PMID:22663345

  13. Locus of control, quality of life, anxiety, and depression among Malaysian breast cancer patients: The mediating role of uncertainty.

    Pahlevan Sharif, Saeed

    2017-04-01

    The main objective of this study was to investigate the mediating role of uncertainty in the relationship between locus of control with quality of life, anxiety, and depression. A descriptive and correlational survey was conducted in a private hospital in Kuala Lumpur, Malaysia. A convenience sample of 118 Malaysian breast cancer patients voluntarily participated in the study and responded to a set of questionnaires including: socio-demographic questionnaire, the short form of Locus of Control Scale, the Functional Assessment of Cancer Therapy-Breast (FACT-B), the Hospital Anxiety and Depression Scale (HADS), and the Short-Form Mishel Uncertainty in Illness Scale (SF-MUIS). The results revealed that breast cancer patients with higher internal locus of control and lower external locus of control experience a higher quality of life, lower anxiety, and lower depression. Also, uncertainty mediated the relationship between locus of control with quality of life and depression (quasi-significant). The findings indicated the need for early, targeted psychological interventions seeking to gradually shift cancer patients' locus of control from external to internal in order to improve their quality of life and reduce their depression and anxiety. Moreover, health care providers by providing relevant information to cancer patients, especially for externally oriented patients, can reduce their uncertainty which in turn would improve their quality of life. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Mediator effect of statistical process control between Total Quality Management (TQM) and business performance in Malaysian Automotive Industry

    Ahmad, M. F.; Rasi, R. Z.; Zakuan, N.; Hisyamudin, M. N. N.

    2015-12-01

    In today's highly competitive market, Total Quality Management (TQM) is vital management tool in ensuring a company can success in their business. In order to survive in the global market with intense competition amongst regions and enterprises, the adoption of tools and techniques are essential in improving business performance. There are consistent results between TQM and business performance. However, only few previous studies have examined the mediator effect namely statistical process control (SPC) between TQM and business performance. A mediator is a third variable that changes the association between an independent variable and an outcome variable. This study present research proposed a TQM performance model with mediator effect of SPC with structural equation modelling, which is a more comprehensive model for developing countries, specifically for Malaysia. A questionnaire was prepared and sent to 1500 companies from automotive industry and the related vendors in Malaysia, giving a 21.8 per cent rate. Attempts were made at findings significant impact of mediator between TQM practices and business performance showed that SPC is important tools and techniques in TQM implementation. The result concludes that SPC is partial correlation between and TQM and BP with indirect effect (IE) is 0.25 which can be categorised as high moderator effect.

  15. Dopamine D(1) receptor-mediated control of striatal acetylcholine release by endogenous dopamine.

    Acquas, E; Di Chiara, G

    1999-10-27

    The role of dopamine D(1) and D(2) receptors in the control of acetylcholine release in the dorsal striatum by endogenous dopamine was investigated by monitoring with microdialysis the effect of the separate or combined administration of the dopamine D(1) receptor antagonist, SCH 39166 ¿(-)-trans-6,7,7a,8,9, 13b-exahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo-[d]-nap hto-[2, 1b]-azepine hydrochloride¿ (50 microg/kg subcutaneous (s.c.)), of the dopamine D(2)/D(3) receptor agonist, quinpirole (trans-(-)-4aR, 4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo-(3,4-g)-quinoline hydrochloride) (5 and 10 microg/kg s.c.), and of the D(3) receptor selective agonist, PD 128,907 [S(+)-(4aR,10bR)-3,4,4a, 10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin -9-ol hydrochloride] (50 microg/kg s.c.), on in vivo dopamine and acetylcholine release. Microdialysis was performed with a Ringer containing low concentrations (0.01 microM) of the acetylcholinesterase inhibitor, neostigmine. Quinpirole (10 microg/kg s.c.) decreased striatal dopamine and acetylcholine release. Administration of PD 128,907 (50 microg/kg) decreased dopamine but failed to affect acetylcholine release. SCH 39166 (50 microg/kg s.c.) stimulated dopamine release and reduced acetylcholine release. Pretreatment with quinpirole reduced (5 microg/kg s.c.) or completely prevented (10 microg/kg s.c.) the stimulation of dopamine release elicited by SCH 39166 (50 microg/kg s.c.); on the other hand, pretreatment with quinpirole (5 and 10 microg/kg) potentiated the reduction of striatal acetylcholine release induced by SCH 39166 (50 microg/kg s.c.). Similarly, pretreatment with PD 128,907 (50 microg/kg) which prevented the increase of dopamine release induced by SCH 39166 (50 microg/kg), potentiated the reduction of striatal acetylcholine transmission elicited by SCH 39166. Thus, pretreatment with low doses of quinpirole or PD 128,907 influences in opposite manner the effect of SCH 39166 on striatal dopamine and

  16. Parent-mediated communication-focused treatment in children with autism (PACT): a randomised controlled trial.

    Green, Jonathan; Charman, Tony; McConachie, Helen; Aldred, Catherine; Slonims, Vicky; Howlin, Pat; Le Couteur, Ann; Leadbitter, Kathy; Hudry, Kristelle; Byford, Sarah; Barrett, Barbara; Temple, Kathryn; Macdonald, Wendy; Pickles, Andrew

    2010-06-19

    Results of small trials suggest that early interventions for social communication are effective for the treatment of autism in children. We therefore investigated the efficacy of such an intervention in a larger trial. Children with core autism (aged 2 years to 4 years and 11 months) were randomly assigned in a one-to-one ratio to a parent-mediated communication-focused (Preschool Autism Communication Trial [PACT]) intervention or treatment as usual at three specialist centres in the UK. Those assigned to PACT were also given treatment as usual. Randomisation was by use of minimisation of probability in the marginal distribution of treatment centre, age (42 months), and autism severity (Autism Diagnostic Observation Schedule-Generic [ADOS-G] algorithm score 12-17 or 18-24). Primary outcome was severity of autism symptoms (a total score of social communication algorithm items from ADOS-G, higher score indicating greater severity) at 13 months. Complementary secondary outcomes were measures of parent-child interaction, child language, and adaptive functioning in school. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN58133827. 152 children were recruited. 77 were assigned to PACT (London [n=26], Manchester [n=26], and Newcastle [n=25]); and 75 to treatment as usual (London [n=26], Manchester [n=26], and Newcastle [n=23]). At the 13-month endpoint, the severity of symptoms was reduced by 3.9 points (SD 4.7) on the ADOS-G algorithm in the group assigned to PACT, and 2.9 (3.9) in the group assigned to treatment as usual, representing a between-group effect size of -0.24 (95% CI -0.59 to 0.11), after adjustment for centre, sex, socioeconomic status, age, and verbal and non-verbal abilities. Treatment effect was positive for parental synchronous response to child (1.22, 0.85 to 1.59), child initiations with parent (0.41, 0.08 to 0.74), and for parent-child shared attention (0.33, -0.02 to

  17. The Effect of The Locus of Control on Organizational Citizenship Behavior The Mediating Role Perceived Organizationel Support : Case Study of A University

    Güçel, Cem; Tokmak, İsmail; Turgut, Hakan

    2012-01-01

    The aim of this study is to examine the effects of locus of control on organizational citizenship behaviors and the mediating effect of the perceived organizational support. For this aim, firstly, the locus of control, then organizational citizenship behaviors and, finally, the mediating effect of the perceived organizational support are explained. In the application part, a questionnaire including the measures of the locus of control, organizational support and organization...

  18. THE EFFECT OF THE LOCUS OF CONTROL ON ORGANIZATIONAL CITIZENSHIP BEHAVIOR THE MEDIATING EFFECT PERCEIVED ORGANIZATIONAL SUPPORT: CASE STUDY OF A UNIVERSITY

    GUCEL, Cem; TOKMAK, Ismail; TURGUT, Hakan

    2012-01-01

    The aim of this study is to examine the effects of locus of control on organizational citizenship behaviors and the mediating effect of the perceived organizational support. For this aim, firstly, the locus of control, then organizational citizenship behaviors and, finally, the mediating effect of the perceived organizational support are explained. In the application part, a questionnaire including the measures of the locus of control, organizational support and organizational citizenship beh...

  19. Ca2+-mediated remote control of reversible sieve tube occlusion in em>Vicia faba em>

    Furch, Alexandra C.U.; Hafke, Jens B.; Schulz, Alexander

    2007-01-01

    According to an established concept, injury of the phloem triggers local sieve plate occlusion including callose-mediated constriction and, possibly, protein plugging of the sieve pores. Sieve plate occlusion can also be achieved by distant stimuli, depends on the passage of electropotential waves...

  20. Mediation and moderation of treatment effects in randomised controlled trials of complex interventions.

    Emsley, Richard; Dunn, Graham; White, Ian R

    2010-06-01

    Complex intervention trials should be able to answer both pragmatic and explanatory questions in order to test the theories motivating the intervention and help understand the underlying nature of the clinical problem being tested. Key to this is the estimation of direct effects of treatment and indirect effects acting through intermediate variables which are measured post-randomisation. Using psychological treatment trials as an example of complex interventions, we review statistical methods which crucially evaluate both direct and indirect effects in the presence of hidden confounding between mediator and outcome. We review the historical literature on mediation and moderation of treatment effects. We introduce two methods from within the existing causal inference literature, principal stratification and structural mean models, and demonstrate how these can be applied in a mediation context before discussing approaches and assumptions necessary for attaining identifiability of key parameters of the basic causal model. Assuming that there is modification by baseline covariates of the effect of treatment (i.e. randomisation) on the mediator (i.e. covariate by treatment interactions), but no direct effect on the outcome of these treatment by covariate interactions leads to the use of instrumental variable methods. We describe how moderation can occur through post-randomisation variables, and extend the principal stratification approach to multiple group methods with explanatory models nested within the principal strata. We illustrate the new methodology with motivating examples of randomised trials from the mental health literature.

  1. TPL-2 Regulates Macrophage Lipid Metabolism and M2 Differentiation to Control TH2-Mediated Immunopathology

    Entwistle, Lewis J.; Khoury, Hania; Papoutsopoulou, Stamatia; Mahmood, Radma; Mansour, Nuha R.; Ching-Cheng Huang, Stanley; Pearce, Edward J.; Pedro S. de Carvalho, Luiz; Ley, Steven C.

    2016-01-01

    Persistent TH2 cytokine responses following chronic helminth infections can often lead to the development of tissue pathology and fibrotic scarring. Despite a good understanding of the cellular mechanisms involved in fibrogenesis, there are very few therapeutic options available, highlighting a significant medical need and gap in our understanding of the molecular mechanisms of TH2-mediated immunopathology. In this study, we found that the Map3 kinase, TPL-2 (Map3k8; Cot) regulated TH2-mediated intestinal, hepatic and pulmonary immunopathology following Schistosoma mansoni infection or S. mansoni egg injection. Elevated inflammation, TH2 cell responses and exacerbated fibrosis in Map3k8 –/–mice was observed in mice with myeloid cell-specific (LysM) deletion of Map3k8, but not CD4 cell-specific deletion of Map3k8, indicating that TPL-2 regulated myeloid cell function to limit TH2-mediated immunopathology. Transcriptional and metabolic assays of Map3k8 –/–M2 macrophages identified that TPL-2 was required for lipolysis, M2 macrophage activation and the expression of a variety of genes involved in immuno-regulatory and pro-fibrotic pathways. Taken together this study identified that TPL-2 regulated TH2-mediated inflammation by supporting lipolysis and M2 macrophage activation, preventing TH2 cell expansion and downstream immunopathology and fibrosis. PMID:27487182

  2. Testing Mediators of Intervention Effects in Randomized Controlled Trials: An Evaluation of Three Depression Prevention Programs

    Stice, Eric; Rohde, Paul; Seeley, John R.; Gau, Jeff M.

    2010-01-01

    Objective: Evaluate a new 5-step method for testing mediators hypothesized to account for the effects of depression prevention programs. Method: In this indicated prevention trial, at-risk teens with elevated depressive symptoms were randomized to a group cognitive-behavioral (CB) intervention, group supportive expressive intervention, CB…

  3. Deciphering potential mechanisms of anaerobic soil disinfestation (ASD)-mediated control of Pratylenchus penetrans

    Pratylenchus penetrans is a component of the apple replant disease (ARD) causal pathogen complex. The potential role for biological mechanisms contributing to ASD-mediated suppression of P. penetrans was examined in greenhouse study using orchard soil with a history of ARD. Populations of P. penetra...

  4. Systemic vascular function, measured with forearm flow mediated dilatation, in acute and stable cerebrovascular disease: a case-control study

    Blacker David

    2010-10-01

    Full Text Available Abstract Background Acute ischaemic stroke is associated with alteration in systemic markers of vascular function. We measured forearm vascular function (using forearm flow mediated dilatation to clarify whether recent acute ischaemic stroke/TIA is associated with impaired systemic vascular function. Methods Prospective case control study enrolling 17 patients with recent acute ischaemic stroke/TIA and 17 sex matched controls with stroke more than two years previously. Forearm vascular function was measured using flow medicated dilatation (FMD. Results Flow mediated dilatation was 6.0 ± 1.1% in acute stroke/TIA patients and 4.7 ± 1.0% among control subjects (p = 0.18. The mean paired difference in FMD between subjects with recent acute stroke and controls was 1.25% (95% CI -0.65, 3.14; p = 0.18. Endothelium independent dilatation was measured in six pairs of participants and was similar in acute stroke/TIA patients (22.6 ± 4.3% and control subjects (19.1 ± 2.6%; p = 0.43. Conclusions Despite the small size of this study, these data indicate that recent acute stroke is not necessarily associated with a clinically important reduction in FMD.

  5. The Mediator subunit MED23 couples H2B mono-ubiquitination to transcriptional control and cell fate determination.

    Yao, Xiao; Tang, Zhanyun; Fu, Xing; Yin, Jingwen; Liang, Yan; Li, Chonghui; Li, Huayun; Tian, Qing; Roeder, Robert G; Wang, Gang

    2015-12-02

    The Mediator complex orchestrates multiple transcription factors with the Pol II apparatus for precise transcriptional control. However, its interplay with the surrounding chromatin remains poorly understood. Here, we analyze differential histone modifications between WT and MED23(-/-) (KO) cells and identify H2B mono-ubiquitination at lysine 120 (H2Bub) as a MED23-dependent histone modification. Using tandem affinity purification and mass spectrometry, we find that MED23 associates with the RNF20/40 complex, the enzyme for H2Bub, and show that this association is critical for the recruitment of RNF20/40 to chromatin. In a cell-free system, Mediator directly and substantially increases H2Bub on recombinant chromatin through its cooperation with RNF20/40 and the PAF complex. Integrative genome-wide analyses show that MED23 depletion specifically reduces H2Bub on a subset of MED23-controlled genes. Importantly, MED23-coupled H2Bub levels are oppositely regulated during myogenesis and lung carcinogenesis. In sum, these results establish a mechanistic link between the Mediator complex and a critical chromatin modification in coordinating transcription with cell growth and differentiation. © 2015 The Authors.

  6. Improved confidence in performing nutrition and physical activity behaviours mediates behavioural change in young adults: Mediation results of a randomised controlled mHealth intervention.

    Partridge, Stephanie R; McGeechan, Kevin; Bauman, Adrian; Phongsavan, Philayrath; Allman-Farinelli, Margaret

    2017-01-01

    The burden of weight gain disproportionally affects young adults. Understanding the underlying behavioural mechanisms of change in mHealth nutrition and physical activity interventions designed for young adults is important for enhancing and translating effective interventions. First, we hypothesised that knowledge, self-efficacy and stage-of-change for nutrition and physical activity behaviours would improve, and second, that self-efficacy changes in nutrition and physical activity behaviours mediate the behaviour changes observed in an mHealth RCT for prevention of weight gain. Young adults, aged 18-35 years at risk of weight gain (n = 250) were randomly assigned to an mHealth-program, TXT2BFiT, consisting of a three-month intensive phase and six-month maintenance phase or to a control group. Self-reported online surveys at baseline, three- and nine-months assessed nutrition and physical activity behaviours, knowledge, self-efficacy and stage-of-change. The mediating effect of self-efficacy was assessed in multiple PROCESS macro-models for three- and nine-month nutrition and physical activity behaviour change. Young adults randomised to the intervention increased and maintained knowledge of fruit requirements (P = 0.029) compared to controls. Intervention participants' fruit and takeaway behaviours improved to meet recommendations at nine months, with a greater proportion progressing to action or maintenance stage-of-change (P behaviours did not meet recommendations, thereby halting progress to action or maintenance stage-of-change. Indirect effects of improved nutrition and physical activity behaviours at three- and nine-months in the intervention group were explained by changes in self-efficacy, accounting for 8%-37% of the total effect. This provides insights into how the mHealth intervention achieved part of its effects and the importance of improving self-efficacy to facilitate improved eating and physical activity behaviours in young adults

  7. The effects of subjective loss of control on risk-taking behavior: the mediating role of anger

    Beisswingert, Birgit M.; Zhang, Keshun; Goetz, Thomas; Fang, Ping; Fischbacher, Urs

    2015-01-01

    Based on the Appraisal Tendency Framework on the antecedents and consequences of emotions two experimental studies examined the relationship between externally caused loss of control experiences and risk-taking behavior, as well as the assumed mediation of this relationship by the emotion anger. An experimental paradigm for inducing externally caused and consequently externally attributed loss of control which should lead to experiences of anger was developed and pretested in a Pilot Study. The relationship between loss of control experiences, anger, and risk-taking behavior was investigated using two separate student samples from Germany (N = 84, 54% female) and China (N = 125; 64% female). In line with our hypotheses, results showed that anger mediated the link between subjective loss of control experiences and increasing risk-taking behavior. Multiple group comparisons revealing similar patterns in both samples affirmed the results’ cross-cultural generalizability. These results implicate that anger makes people less risk averse in the process of economic decision making. PMID:26217244

  8. The Effects of Subjective Loss of Control on Risk-taking Behavior: The Mediating Role of Anger

    Birgit M. Beisswingert

    2015-06-01

    Full Text Available Based on the Appraisal Tendency Framework on the antecedents and consequences of emotions two experimental studies examined the relationship between externally caused loss of control experiences and risk-taking behavior, as well as the assumed mediation of this relationship by the emotion anger. An experimental paradigm for inducing externally caused and consequently externally attributed loss of control which should lead to experiences of anger was developed and pretested in a Pilot Study. The relationship between loss of control experiences, anger and risk-taking behavior was investigated using two separate student samples from Germany (N = 84, 54% female and China (N = 125; 64% female. In line with our hypotheses, results showed that anger mediated the link between subjective loss of control experiences and increasing risk-taking behavior. Multiple group comparisons revealing similar patterns in both samples affirmed the results’ cross-cultural generalizability. These results implicate that anger makes people less risk averse in the process of economic decision making.

  9. Gender-specific mediational links between parenting styles, parental monitoring, impulsiveness, drinking control, and alcohol-related problems.

    Patock-Peckham, Julie A; King, Kevin M; Morgan-Lopez, Antonio A; Ulloa, Emilio C; Moses, Jennifer M Filson

    2011-03-01

    Recently, it has been suggested that traits may dynamically change as conditions change. One possible mechanism that may influence impulsiveness is parental monitoring. Parental monitoring reflects a knowledge regarding one's offspring's whereabouts and social connections. The aim of this investigation was to examine potential gender-specific parental influences to impulsiveness (general behavioral control), control over one's own drinking (specific behavioral control), and alcohol-related problems among individuals in a period of emerging adulthood. Direct and mediational links between parenting styles (permissive, authoritarian, and authoritative), parental monitoring, impulsiveness, drinking control, and alcohol-related problems were investigated. A multiple-group, SEM model with (316 women, 265 men) university students was examined. In general, the overall pattern among male and female respondents was distinct. For daughters, perceptions of a permissive father were indirectly linked to more alcohol-related problems through lower levels of monitoring by fathers and more impulsive symptoms. Perceptions of an authoritative father were also indirectly linked to fewer impulsive symptoms through higher levels of monitoring by fathers among daughters. For men, perceptions of a permissive mother were indirectly linked to more alcohol-related problems through lower levels of monitoring by mothers and more impulsive symptoms. For sons, perceptions of mother authoritativeness were indirectly linked to fewer alcohol-related problems through more monitoring by mothers and fewer impulsive symptoms. Monitoring by an opposite-gender parent mediated the link between parenting styles (i.e., permissive, authoritative) on impulsiveness.

  10. Randomized, controlled trial of TNF-α antagonist in CTL-mediated severe cutaneous adverse reactions.

    Wang, Chuang-Wei; Yang, Lan-Yan; Chen, Chun-Bing; Ho, Hsin-Chun; Hung, Shuen-Iu; Yang, Chih-Hsun; Chang, Chee-Jen; Su, Shih-Chi; Hui, Rosaline Chung-Yee; Chin, See-Wen; Huang, Li-Fang; Lin, Yang Yu-Wei; Chang, Wei-Yang; Fan, Wen-Lang; Yang, Chin-Yi; Ho, Ji-Chen; Chang, Ya-Ching; Lu, Chun-Wei; Chung, Wen-Hung

    2018-03-01

    Cytotoxic T lymphocyte-mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-α antagonist in CTL-mediated SCARs. We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-α antagonist etanercept versus traditional corticosteroids. Etanercept improved clinical outcomes in patients with SJS-TEN. Etanercept decreased the SCORTEN-based predicted mortality rate (predicted and observed rates, 17.7% and 8.3%, respectively). Compared with corticosteroids, etanercept further reduced the skin-healing time in moderate-to-severe SJS-TEN patients (median time for skin healing was 14 and 19 days for etanercept and corticosteroids, respectively; P = 0.010), with a lower incidence of gastrointestinal hemorrhage in all SJS-TEN patients (2.6% for etanercept and 18.2% for corticosteroids; P = 0.03). In the therapeutic mechanism study, etanercept decreased the TNF-α and granulysin secretions in blister fluids and plasma (45.7%-62.5% decrease after treatment; all P etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs. ClinicalTrials.gov NCT01276314. Ministry of Science and Technology of Taiwan.

  11. CRY Drives Cyclic CK2-Mediated BMAL1 Phosphorylation to Control the Mammalian Circadian Clock.

    Teruya Tamaru

    Full Text Available Intracellular circadian clocks, composed of clock genes that act in transcription-translation feedback loops, drive global rhythmic expression of the mammalian transcriptome and allow an organism to anticipate to the momentum of the day. Using a novel clock-perturbing peptide, we established a pivotal role for casein kinase (CK-2-mediated circadian BMAL1-Ser90 phosphorylation (BMAL1-P in regulating central and peripheral core clocks. Subsequent analysis of the underlying mechanism showed a novel role of CRY as a repressor for protein kinase. Co-immunoprecipitation experiments and real-time monitoring of protein-protein interactions revealed that CRY-mediated periodic binding of CK2β to BMAL1 inhibits BMAL1-Ser90 phosphorylation by CK2α. The FAD binding domain of CRY1, two C-terminal BMAL1 domains, and particularly BMAL1-Lys537 acetylation/deacetylation by CLOCK/SIRT1, were shown to be critical for CRY-mediated BMAL1-CK2β binding. Reciprocally, BMAL1-Ser90 phosphorylation is prerequisite for BMAL1-Lys537 acetylation. We propose a dual negative-feedback model in which a CRY-dependent CK2-driven posttranslational BMAL1-P-BMAL1 loop is an integral part of the core clock oscillator.

  12. Phosphorylation of the Usher syndrome 1G protein SANS controls Magi2-mediated endocytosis.

    Bauß, Katharina; Knapp, Barbara; Jores, Pia; Roepman, Ronald; Kremer, Hannie; Wijk, Erwin V; Märker, Tina; Wolfrum, Uwe

    2014-08-01

    The human Usher syndrome (USH) is a complex ciliopathy with at least 12 chromosomal loci assigned to three clinical subtypes, USH1-3. The heterogeneous USH proteins are organized into protein networks. Here, we identified Magi2 (membrane-associated guanylate kinase inverted-2) as a new component of the USH protein interactome, binding to the multifunctional scaffold protein SANS (USH1G). We showed that the SANS-Magi2 complex assembly is regulated by the phosphorylation of an internal PDZ-binding motif in the sterile alpha motif domain of SANS by the protein kinase CK2. We affirmed Magi2's role in receptor-mediated, clathrin-dependent endocytosis and showed that phosphorylated SANS tightly regulates Magi2-mediated endocytosis. Specific depletions by RNAi revealed that SANS and Magi2-mediated endocytosis regulates aspects of ciliogenesis. Furthermore, we demonstrated the localization of the SANS-Magi2 complex in the periciliary membrane complex facing the ciliary pocket of retinal photoreceptor cells in situ. Our data suggest that endocytotic processes may not only contribute to photoreceptor cell homeostasis but also counterbalance the periciliary membrane delivery accompanying the exocytosis processes for the cargo vesicle delivery. In USH1G patients, mutations in SANS eliminate Magi2 binding and thereby deregulate endocytosis, lead to defective ciliary transport modules and ultimately disrupt photoreceptor cell function inducing retinal degeneration. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Resistance Exercise and Inflammation in Breast Cancer Patients Undergoing Adjuvant Radiation Therapy: Mediation Analysis From a Randomized, Controlled Intervention Trial

    Schmidt, Martina E.; Meynköhn, Anna; Habermann, Nina; Wiskemann, Joachim; Oelmann, Jan; Hof, Holger; Wessels, Sabine; Klassen, Oliver; Debus, Jürgen; Potthoff, Karin; Steindorf, Karen; Ulrich, Cornelia M.

    2016-01-01

    Purpose: To explore the mediating role of inflammatory parameters in the development of fatigue, pain, and potentially related depressive symptoms during radiation therapy for breast cancer and its mitigation by resistance exercise. Methods and Materials: Breast cancer patients scheduled for adjuvant radiation therapy were randomized to 12-week progressive resistance exercise training (EX) or a relaxation control group. Interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) were measured in serum samples collected before, at the end, and 6 weeks after radiation therapy from 103 chemotherapy-naïve participants. Fatigue was assessed with the multidimensional Fatigue Assessment Questionnaire, pain with the European Organization for Research and Treatment of Cancer QLQ-C30, and depressive symptoms with the Center for Epidemiologic Studies Depression Scale. Analysis of covariance models, partial correlations, Freedman-Schatzkin tests, and R"2 effect-size measures for mediation were calculated. Results: The analysis of covariance models revealed a significant intervention effect on IL-6 (P=.010) and the IL-6/IL-1ra ratio (P=.018), characterized by a marked increase during radiation therapy among controls, but no significant change in EX. Interleukin-1 receptor antagonist did not change significantly in either group (P=.88). Increased IL-6 and IL-6/IL-1ra levels at the end of radiation therapy were significantly associated with increased physical fatigue and pain 6 weeks after radiation. We observed significant partial mediation by IL-6 and IL-6/IL-1ra of the effect of resistance exercise on physical fatigue (Freedman-Schatzkin P=.023 and P<.001) and pain (both P<.001). Hereby IL-6 and IL-6/IL-1ra mediated between 15% and 24% of the variance of physical fatigue and pain explained by the intervention. Conclusions: This randomized, controlled trial showed a significantly increased proinflammatory cytokine level after adjuvant radiation therapy in breast

  14. Resistance Exercise and Inflammation in Breast Cancer Patients Undergoing Adjuvant Radiation Therapy: Mediation Analysis From a Randomized, Controlled Intervention Trial

    Schmidt, Martina E., E-mail: m.schmidt@dkfz.de [Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg (Germany); Meynköhn, Anna; Habermann, Nina [Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg (Germany); Wiskemann, Joachim [Division of Medical Oncology, National Center for Tumor Diseases and University Hospital, Heidelberg (Germany); Oelmann, Jan; Hof, Holger; Wessels, Sabine [Department of Radiation Oncology, National Center for Tumor Diseases and University Hospital, Heidelberg (Germany); Klassen, Oliver [Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg (Germany); Debus, Jürgen; Potthoff, Karin [Department of Radiation Oncology, National Center for Tumor Diseases and University Hospital, Heidelberg (Germany); Steindorf, Karen; Ulrich, Cornelia M. [Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg (Germany)

    2016-02-01

    Purpose: To explore the mediating role of inflammatory parameters in the development of fatigue, pain, and potentially related depressive symptoms during radiation therapy for breast cancer and its mitigation by resistance exercise. Methods and Materials: Breast cancer patients scheduled for adjuvant radiation therapy were randomized to 12-week progressive resistance exercise training (EX) or a relaxation control group. Interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) were measured in serum samples collected before, at the end, and 6 weeks after radiation therapy from 103 chemotherapy-naïve participants. Fatigue was assessed with the multidimensional Fatigue Assessment Questionnaire, pain with the European Organization for Research and Treatment of Cancer QLQ-C30, and depressive symptoms with the Center for Epidemiologic Studies Depression Scale. Analysis of covariance models, partial correlations, Freedman-Schatzkin tests, and R{sup 2} effect-size measures for mediation were calculated. Results: The analysis of covariance models revealed a significant intervention effect on IL-6 (P=.010) and the IL-6/IL-1ra ratio (P=.018), characterized by a marked increase during radiation therapy among controls, but no significant change in EX. Interleukin-1 receptor antagonist did not change significantly in either group (P=.88). Increased IL-6 and IL-6/IL-1ra levels at the end of radiation therapy were significantly associated with increased physical fatigue and pain 6 weeks after radiation. We observed significant partial mediation by IL-6 and IL-6/IL-1ra of the effect of resistance exercise on physical fatigue (Freedman-Schatzkin P=.023 and P<.001) and pain (both P<.001). Hereby IL-6 and IL-6/IL-1ra mediated between 15% and 24% of the variance of physical fatigue and pain explained by the intervention. Conclusions: This randomized, controlled trial showed a significantly increased proinflammatory cytokine level after adjuvant radiation therapy in breast

  15. Intervening to reduce workplace sitting: mediating role of social-cognitive constructs during a cluster randomised controlled trial.

    Hadgraft, Nyssa T; Winkler, Elisabeth A H; Healy, Genevieve N; Lynch, Brigid M; Neuhaus, Maike; Eakin, Elizabeth G; Dunstan, David W; Owen, Neville; Fjeldsoe, Brianna S

    2017-03-06

    The Stand Up Victoria multi-component intervention successfully reduced workplace sitting time in both the short (three months) and long (12 months) term. To further understand how this intervention worked, we aimed to assess the impact of the intervention on four social-cognitive constructs, and examined whether these constructs mediated intervention effects on workplace sitting time at 3 and 12 months post-baseline. Two hundred and thirty one office-based workers (14 worksites, single government employer) were randomised to intervention or control conditions by worksite. The intervention comprised organisational, environmental, and individual level elements. Participant characteristics and social-cognitive constructs (perceived behavioural control, barrier self-efficacy, perceived organisational norms and knowledge) were measured through a self-administered online survey at baseline, 3 months and 12 months. Workplace sitting time (min/8 h day) was measured with the activPAL3 device. Single multi-level mediation models were performed for each construct at both time points. There were significant intervention effects at 3 months on perceived behavioural control, barrier self-efficacy and perceived organisational norms. Effects on perceived organisational norms were not significant at 12 months. Perceived behavioural control significantly mediated intervention effects at 3 months, accounting for a small portion of the total effect (indirect effect: -8.6 min/8 h day, 95% CI: -18.5, -3.6 min; 7.5% of total effect). At 12 months, barrier self-efficacy significantly mediated the intervention effects on workplace sitting time (indirect effect: -10.3 min/8 h day, 95% CI: -27.3, -2.2; 13.9% of total effect). No significant effects were observed for knowledge at either time point. Strategies that aim to increase workers' perceived control and self-efficacy over their sitting time may be helpful components of sedentary behaviour interventions in the workplace

  16. Toehold-mediated internal control to probe the near-field interaction between the metallic nanoparticle and the fluorophore

    Ang, Y. S.; Yung, L. Y. L.

    2014-10-01

    Metallic nanoparticles (MNPs) are known to alter the emission of vicinal fluorophores through the near-field interaction, leading to either fluorescence quenching or enhancement. Much ambiguity remains in the experimental outcome of such a near-field interaction, particularly for bulk colloidal solution. It is hypothesized that the strong far-field interference from the inner filter effect of the MNPs could mask the true near-field MNP-fluorophore interaction significantly. Thus, in this work, a reliable internal control capable of decoupling the near-field interaction from far-field interference is established by the use of the DNA toehold concept to mediate the in situ assembly and disassembly of the MNP-fluorophore conjugate. A model gold nanoparticle (AuNP)-Cy3 system is used to investigate our proposed toehold-mediated internal control system. The maximum fluorescence enhancement is obtained for large-sized AuNP (58 nm) separated from Cy3 at an intermediate distance of 6.8 nm, while fluorescence quenching is observed for smaller-sized AuNP (11 nm and 23 nm), which is in agreement with the theoretical values reported in the literature. This work shows that the toehold-mediated internal control design can serve as a central system for evaluating the near-field interaction of other MNP-fluorophore combinations and facilitate the rational design of specific MNP-fluorophore systems for various applications.Metallic nanoparticles (MNPs) are known to alter the emission of vicinal fluorophores through the near-field interaction, leading to either fluorescence quenching or enhancement. Much ambiguity remains in the experimental outcome of such a near-field interaction, particularly for bulk colloidal solution. It is hypothesized that the strong far-field interference from the inner filter effect of the MNPs could mask the true near-field MNP-fluorophore interaction significantly. Thus, in this work, a reliable internal control capable of decoupling the near

  17. Delay Discounting Mediates Parent-Adolescent Relationship Quality and Risky Sexual Behavior for Low Self-Control Adolescents.

    Kahn, Rachel E; Holmes, Christopher; Farley, Julee P; Kim-Spoon, Jungmeen

    2015-09-01

    Parent-adolescent relationship quality and delay discounting may play important roles in adolescents' sexual decision making processes, and levels of self-control during adolescence could act as a buffer within these factors. This longitudinal study included 219 adolescent (55 % male; mean age = 12.66 years at Wave 1; mean age = 15.10 years at Wave 2) and primary caregiver dyads. Structural equation modeling (SEM) was utilized to determine whether delay discounting mediated the association between parent-adolescent relationship quality and adolescents' risky sexual behavior and how this mediated association may differ between those with high versus low self-control. The results revealed parent-adolescent relationship quality plays a role in the development of risky sexual behavior indirectly through levels of delay discounting, but only for adolescents with low self-control. These findings could inform sex education policies and health prevention programs that address adolescent risky sexual behavior.

  18. Personal Values as a Mediator of Relations Between Perceived Parental Support and Control and Youth Substance Use.

    Borca, Gabriella; Rabaglietti, Emanuela; Roggero, Antonella; Keller, Peggy; Haak, Eric; Begotti, Tatiana

    2017-10-15

    Tobacco and marijuana smoking are very popular in adolescence and there is a high rate of comorbidity between them, even in young adulthood. Parental support and control may hinder involvement in the use of these substances by promoting conventional values among adolescents. The present study investigates the relations between family functioning (parental support and control) and psychoactive substance use (tobacco and marijuana smoking) and determines whether these relationships are mediated by personal values (in terms of disapproval of deviance and beliefs about the importance of school, health and religion). 175 Italian late adolescents (17 to 20 years old) participated in this two-wave longitudinal study. Data were collected at school through an anonymous questionnaire. Greater parental control and support were directly associated with lower adolescent tobacco and marijuana use; adolescent acceptance of conventional values mediated the association between parenting and adolescent marijuana use. Findings emphasize the influence of family relationships throughout adolescence. The transmission of conventional values to adolescents may be a critical mechanism through which parenting protects adolescents from substance use, especially marijuana use.

  19. Relational aggression and psychological control in the sibling relationship: mediators of the association between maternal psychological control and adolescents' emotional adjustment.

    Campione-Barr, Nicole; Lindell, Anna K; Greer, Kelly Bassett; Rose, Amanda J

    2014-08-01

    The association between mothers' psychological control and their children's emotional adjustment problems is well documented. However, processes that may explain this association are not well understood. The present study tested the idea that relational aggression and psychological control within the context of the sibling relationship may help to account for the relation between mothers' psychological control and adolescents' internalizing symptoms. Older (M = 16.46, SD = 1.35 years) and younger (M = 13.67, SD = 1.56 years) siblings from 101 dyads rated the psychological control they received from mothers and siblings, and the relational aggression they received from siblings. Despite some similarities between psychological control and relational aggression, confirmatory factor analyses provided evidence that the two sibling processes are distinct. Maternal psychological control was related to psychological control and relational aggression within the sibling relationship, which were related to adolescents' anxiety and depressed mood. In addition, sibling relational aggression was a more powerful mediator of the relationship between maternal psychological control and adolescent adjustment than sibling psychological control.

  20. Notch-mediated post-translational control of Ngn3 protein stability regulates pancreatic patterning and cell fate commitment

    Qu, Xiaoling; Afelik, Solomon; Jensen, Jan Nygaard

    2013-01-01

    of ducts. On one hand, Ngn3 cell-intrinsically activates endocrine target genes; on the other, Ngn3 cell-extrinsically promotes lateral signaling via the Dll1>Notch>Hes1 pathway which substantially limits its ability to sustain endocrine formation. Prior to endocrine commitment, the Ngn3-mediated...... involves transcriptional repression as previously shown, but also incorporates a novel post-translational mechanism. In addition to its ability to promote endocrine fate, we provide evidence of a competing ability of Ngn3 in the patterning of multipotent progenitor cells in turn controlling the formation...

  1. Controlled Zn-mediated grafting of thin layers of bipodal diazonium salt on gold and carbon substrates.

    Torréns, Mabel; Ortiz, Mayreli; Turner, Anthony P F; Beni, Valerio; O'Sullivan, Ciara K

    2015-01-07

    A controlled, rapid, and potentiostat-free method has been developed for grafting the diazonium salt (3,5-bis(4-diazophenoxy)benzoic acid tetrafluoroborate (DCOOH)) on gold and carbon substrates, based on a Zn-mediated chemical dediazonation. The highly stable thin layer organic platforms obtained were characterized by cyclic voltammetry, AFM, impedance, XP, and Raman spectroscopies. A dediazonation mechanism based on radical formation is proposed. Finally, DCOOH was proved as a linker to an aminated electroactive probe. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Systemic inflammatory mediators in post-traumatic complex regional pain syndrome (CRPS I) - longitudinal investigations and differences to control groups.

    Schinkel, Christian; Scherens, A; Köller, M; Roellecke, G; Muhr, G; Maier, C

    2009-03-17

    The Complex Regional Pain Syndrome I (CRPS I) is a disease that might affect an extremity after trauma or operation. The pathogenesis remains yet unclear. It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response but neurogenic dysregulation also contributes to it. Some studies investigated the role inflammatory mediators and cytokines; however, few longitudinal studies exist and control groups except healthy controls were not investigated yet. To get further insights into the role of systemic inflammatory mediators in CRPS I, we investigated a variety of pro-, anti-, or neuro-inflammatory mediators such as C-Reactive Protein (CRP), White Blood Cell Count (WBC), Interleukins 4, 6, 8, 10, 11, 12 (p70), Interferon gamma, Tumor-Necrosis-Factor alpha (TNF-a) and its soluble Receptors I/II, soluble Selectins (E,L,P), Substance-P (SP), and Calcitonin Gene-Related Peptide (CGRP) at different time points in venous blood from patients with acute (AC) and chronic (CC) CRPS I, patients with forearm fractures (FR), with neuralgia (NE), and from healthy volunteers (C). No significant changes for serum parameters investigated in CRPS compared to control groups were found except for CC/C (CGRP p = 0.007), FR/C (CGRP p = 0.048) and AC/CC (IL-12 p = 0.02; TNFRI/II p = 0.01; SP p = 0.049). High interindividual variations were observed. No intra- or interindividual correlation of parameters with clinical course (e.g. chronification) or outcome was detectable. Although clinically appearing as inflammation in acute stages, local rather than systemic inflammatory responses seem to be relevant in CRPS. Variable results from different studies might be explained by unpredictable intermittent release of mediators from local inflammatory processes into the blood combined with high interindividual variabilities. A clinically relevant difference to various control groups was not notable in this pilot study. Determination of systemic inflammatory

  3. Systemic inflammatory mediators in post-traumatic Complex Regional Pain Syndrome (CRPS I - longitudinal investigations and differences to control groups

    Schinkel Ch

    2009-03-01

    Full Text Available Abstract Objectives The Complex Regional Pain Syndrome I (CRPS I is a disease that might affect an extremity after trauma or operation. The pathogenesis remains yet unclear. It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response but neurogenic dysregulation also contributes to it. Some studies investigated the role inflammatory mediators and cytokines; however, few longitudinal studies exist and control groups except healthy controls were not investigated yet. Methods To get further insights into the role of systemic inflammatory mediators in CRPS I, we investigated a variety of pro-, anti-, or neuro-inflammatory mediators such as C-Reactive Protein (CRP, White Blood Cell Count (WBC, Interleukins 4, 6, 8, 10, 11, 12 (p70, Interferon gamma, Tumor-Necrosis-Factor alpha (TNF-α and its soluble Receptors I/II, soluble Selectins (E, L, P, Substance-P (SP, and Calcitonin Gene-Related Peptide (CGRP at different time points in venous blood from patients with acute (AC and chronic (CC CRPS I, patients with forearm fractures (FR, with neuralgia (NE, and from healthy volunteers (C. Results No significant changes for serum parameters investigated in CRPS compared to control groups were found except for CC/C (CGRP p = 0.007, FR/C (CGRP p = 0.048 and AC/CC (IL-12 p = 0.02; TNFRI/II p = 0.01; SP p = 0.049. High interindividual variations were observed. No intra-or interindividual correlation of parameters with clinical course (e.g. chronification or outcome was detectable. Conclusion Although clinically appearing as inflammation in acute stages, local rather than systemic inflammatory responses seem to be relevant in CRPS. Variable results from different studies might be explained by unpredictable intermittent release of mediators from local inflammatory processes into the blood combined with high interindividual variabilities. A clinically relevant difference to various control groups was not notable in this

  4. Nipbl and mediator cooperatively regulate gene expression to control limb development.

    Akihiko Muto

    2014-09-01

    Full Text Available Haploinsufficiency for Nipbl, a cohesin loading protein, causes Cornelia de Lange Syndrome (CdLS, the most common "cohesinopathy". It has been proposed that the effects of Nipbl-haploinsufficiency result from disruption of long-range communication between DNA elements. Here we use zebrafish and mouse models of CdLS to examine how transcriptional changes caused by Nipbl deficiency give rise to limb defects, a common condition in individuals with CdLS. In the zebrafish pectoral fin (forelimb, knockdown of Nipbl expression led to size reductions and patterning defects that were preceded by dysregulated expression of key early limb development genes, including fgfs, shha, hand2 and multiple hox genes. In limb buds of Nipbl-haploinsufficient mice, transcriptome analysis revealed many similar gene expression changes, as well as altered expression of additional classes of genes that play roles in limb development. In both species, the pattern of dysregulation of hox-gene expression depended on genomic location within the Hox clusters. In view of studies suggesting that Nipbl colocalizes with the mediator complex, which facilitates enhancer-promoter communication, we also examined zebrafish deficient for the Med12 Mediator subunit, and found they resembled Nipbl-deficient fish in both morphology and gene expression. Moreover, combined partial reduction of both Nipbl and Med12 had a strongly synergistic effect, consistent with both molecules acting in a common pathway. In addition, three-dimensional fluorescent in situ hybridization revealed that Nipbl and Med12 are required to bring regions containing long-range enhancers into close proximity with the zebrafish hoxda cluster. These data demonstrate a crucial role for Nipbl in limb development, and support the view that its actions on multiple gene pathways result from its influence, together with Mediator, on regulation of long-range chromosomal interactions.

  5. Surface control of blastospore attachment and ligand-mediated hyphae adhesion of Candida albicans.

    Varghese, Nisha; Yang, Sijie; Sejwal, Preeti; Luk, Yan-Yeung

    2013-11-14

    Adhesion on a surface via nonspecific attachment or multiple ligand-receptor interactions is a critical event for fungal infection by Candida albicans. Here, we find that the tri(ethylene glycol)- and d-mannitol-terminated monolayers do not resist the blastospore attachment, but prevent the hyphae adhesion of C. albicans. The hyphae adhesion can be facilitated by tripeptide sequences of arginine-glycine-aspartic acid (RGD) covalently decorated on a background of tri(ethylene glycol)-terminated monolayers. This adhesion mediated by selected ligands is sensitive to the scrambling of peptide sequences, and is inhibited by the presence of cyclic RGD peptides in the solution.

  6. The Mediating Role of Maladaptive Perfectionism in the Association between Psychological Control and Learned Helplessness

    Filippello, Pina; Larcan, Rosalba; Sorrenti, Luana; Buzzai, Caterina; Orecchio, Susanna; Costa, Sebastiano

    2017-01-01

    Despite the extensive research on parental psychological control, no study has explored the relation between parental and teacher psychological control, maladaptive perfectionism and learned helplessness (LH). The purpose of this study was to investigate (1) whether perceived teacher psychological control predicts positively LH, (2) whether…

  7. No mediating effects of glycemic control and inflammation on the association between vitamin D and lung function in the general population.

    Kaul, Anne; Gläser, Sven; Hannemann, Anke; Stubbe, Beate; Felix, Stefan B; Nauck, Matthias; Ewert, Ralf; Friedrich, Nele

    2017-04-01

    Vitamin D deficiency is discussed to be associated with lung health. While former studies focused on subjects suffering from pulmonary diseases, we aimed to investigate the association of 25-hydroxy vitamin D [25(OH)D] with lung function in the general population and examined whether mediating effects of inflammation, glycemic control or renal function exist. 1404 participants from the Study of Health in Pomerania with pulmonary function testing assessed by expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), total lung capacity and Krogh index were used. Adjusted analysis of variance, linear regression models and mediation analyses were performed. Significant positive associations between 25(OH)D levels and FEV 1 , FVC and Krogh index were found. Mediator analyses revealed no mediating effect of inflammation (fibrinogen), glycemic control (HbA1c) or renal function (eGFR) on associations with FEV 1 or FVC. With respect to Krogh-Index, the association to 25(OH)D was slightly mediated by fibrinogen with a proportion mediated of 9.7%. Significant positive associations of 25(OH)D with lung function were revealed in a general population. The proposed mediating effects of inflammation, glycemic control and renal function on these relations were not confirmed. Further studies examining the causality of the association between 25(OH)D and lung function are necessary. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Basic Psychological Needs Satisfaction Mediates the Association between Self-Control Skills and Subjective Well-Being

    Hod Orkibi

    2017-06-01

    Full Text Available Although studies have shown that self-control skills (SCSs are positively linked to both personal and interpersonal outcomes in adolescent students, studies on the putative mechanisms underlying this relationship are scarce. Drawing on Self-Determination Theory and previous studies, we theorized that the association between students’ SCSs and their subjective well-being (SWB in school may be mediated by students’ perceived satisfaction of their basic psychological needs for competence, relatedness, and autonomy. The sample consisted of 1576 Israeli adolescent students (54% girls in grades 10–12 (mean age 16 enrolled in 20 schools. A mediation model was tested with structural equation modeling and a robust bootstrap method for testing indirect effects, controlling for school-level variance. The findings supported the hypothesized model and a post hoc multi-group comparison analysis yielded gender invariance in the model. The findings suggest that both girls and boys with high SCSs may perceive themselves as having greater needs satisfaction in school and consequently higher school-related SWB. Implications for policy and practice are discussed.

  9. Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex.

    Hiraga, Shin-Ichiro; Alvino, Gina M; Chang, Fujung; Lian, Hui-Yong; Sridhar, Akila; Kubota, Takashi; Brewer, Bonita J; Weinreich, Michael; Raghuraman, M K; Donaldson, Anne D

    2014-02-15

    Initiation of eukaryotic DNA replication requires phosphorylation of the MCM complex by Dbf4-dependent kinase (DDK), composed of Cdc7 kinase and its activator, Dbf4. We report here that budding yeast Rif1 (Rap1-interacting factor 1) controls DNA replication genome-wide and describe how Rif1 opposes DDK function by directing Protein Phosphatase 1 (PP1)-mediated dephosphorylation of the MCM complex. Deleting RIF1 partially compensates for the limited DDK activity in a cdc7-1 mutant strain by allowing increased, premature phosphorylation of Mcm4. PP1 interaction motifs within the Rif1 N-terminal domain are critical for its repressive effect on replication. We confirm that Rif1 interacts with PP1 and that PP1 prevents premature Mcm4 phosphorylation. Remarkably, our results suggest that replication repression by Rif1 is itself also DDK-regulated through phosphorylation near the PP1-interacting motifs. Based on our findings, we propose that Rif1 is a novel PP1 substrate targeting subunit that counteracts DDK-mediated phosphorylation during replication. Fission yeast and mammalian Rif1 proteins have also been implicated in regulating DNA replication. Since PP1 interaction sites are evolutionarily conserved within the Rif1 sequence, it is likely that replication control by Rif1 through PP1 is a conserved mechanism.

  10. Identification of highly effective target genes for RNAi-mediated control of emerald ash borer, Agrilus planipennis.

    Rodrigues, Thais B; Duan, Jian J; Palli, Subba R; Rieske, Lynne K

    2018-03-22

    Recent study has shown that RNA interference (RNAi) is efficient in emerald ash borer (EAB), Agrilus planipennis, and that ingestion of double-stranded RNA (dsRNA) targeting specific genes causes gene silencing and mortality in neonates. Here, we report on the identification of highly effective target genes for RNAi-mediated control of EAB. We screened 13 candidate genes in neonate larvae and selected the most effective target genes for further investigation, including their effect on EAB adults and on a non-target organism, Tribolium castaneum. The two most efficient target genes selected, hsp (heat shock 70-kDa protein cognate 3) and shi (shibire), caused up to 90% mortality of larvae and adults. In EAB eggs, larvae, and adults, the hsp is expressed at higher levels when compared to that of shi. Ingestion of dsHSP and dsSHI caused mortality in both neonate larvae and adults. Administration of a mixture of both dsRNAs worked better than either dsRNA by itself. In contrast, injection of EAB.dsHSP and EAB.dsSHI did not cause mortality in T. castaneum. Thus, the two genes identified cause high mortality in the EAB with no apparent phenotype effects in a non-target organism, the red flour beetle, and could be used in RNAi-mediated control of this invasive pest.

  11. NARROW LEAF 7 controls leaf shape mediated by auxin in rice

    Fujino, Kenji; Matsuda, Yasuyuki; Ozawa, Kenjirou; Nishimura, Takeshi; Koshiba, Tomokazu; Fraaije, Marco W.; Sekiguchi, Hiroshi

    Elucidation of the genetic basis of the control of leaf shape could be of use in the manipulation of crop traits, leading to more stable and increased crop production. To improve our understanding of the process controlling leaf shape, we identified a mutant gene in rice that causes a significant

  12. Inhibitory Control Mediates the Association between Perceived Stress and Secure Relationship Quality

    Toria Herd; Mengjiao Li; Dominique Maciejewski; Jacob Lee; Kirby Deater-Deckard; Brooks King-Casas; Jungmeen Kim-Spoon

    2018-01-01

    Past research has demonstrated negative associations between exposure to stressors and quality of interpersonal relationships among children and adolescents. Nevertheless, underlying mechanisms of this association remain unclear. Chronic stress has been shown to disrupt prefrontal functioning in the brain, including inhibitory control abilities, and evidence is accumulating that inhibitory control may play an important role in secure interpersonal relationship quality, including peer problems...

  13. Effortless inhibition: Habit mediates the relation between self-control and unhealthy snack consumption

    Adriaanse, Marieke A.|info:eu-repo/dai/nl/304823023; Kroese, Floor M.|info:eu-repo/dai/nl/313869871; Gillebaart, Marleen|info:eu-repo/dai/nl/344390365; De Ridder, Denise T D|info:eu-repo/dai/nl/070706174

    2014-01-01

    In contrast to prevailing beliefs, recent research suggests that trait self-control promotes health behavior not because those high in self-control are more successful at resisting single temptations, but rather because they develop adaptive habits. The present paper presents a first empirical test

  14. Controlling Coaching Behaviors and Athlete Burnout: Investigating the Mediating Roles of Perfectionism and Motivation.

    Barcza-Renner, Kelly; Eklund, Robert C; Morin, Alexandre J; Habeeb, Christine M

    2016-02-01

    This investigation sought to replicate and extend earlier studies of athlete burnout by examining athlete-perceived controlling coaching behaviors and athlete perfectionism variables as, respectively, environmental and dispositional antecedents of athlete motivation and burnout. Data obtained from NCAA Division I swimmers (n = 487) within 3 weeks of conference championship meets were analyzed for this report. Significant indirect effects were observed between controlling coaching behaviors and burnout through athlete perfectionism (i.e., socially prescribed, self-oriented) and motivation (i.e., autonomous, amotivation). Controlling coaching behaviors predicted athlete perfectionism. In turn, self-oriented perfectionism was positively associated with autonomous motivation and negatively associated with amotivation, while socially prescribed perfectionism was negatively associated with autonomous motivation and positively associated with controlled motivation and amotivation. Autonomous motivation and amotivation, in turn, predicted athlete burnout in expected directions. These findings implicate controlling coaching behaviors as potentially contributing to athlete perfectionism, shaping athlete motivational regulations, and possibly increasing athlete burnout.

  15. The Mediating Roles of Primary and Secondary Control in the Relationship between Body Satisfaction and Subjective Well-Being Among Middle-Aged and Older Women.

    Watt, Ashli D; Konnert, Candace A; Speirs, Calandra E C

    2017-07-01

    This study examined primary and secondary control as mediators in the relationship between body satisfaction and subjective well-being (SWB) and explored age differences in the mediation model. Data from 362 women, aged 40-91 years, assessed (i) the relationships between body satisfaction, age, primary and secondary control strategies (body-specific social comparison, acceptance, and positive reappraisal), and three indices of SWB (positive affect, negative affect, and life satisfaction), (ii) the mediation effects of primary and secondary control on the relationship between body satisfaction and SWB, and (iii) whether mediational relationships were moderated by age. Body satisfaction was unrelated to age but positively related to positive affect and life satisfaction and negatively related to negative affect. Body satisfaction was also related to primary and secondary control strategies. There were significant indirect (mediated) effects of body satisfaction on all outcome variables through acceptance and positive reappraisal. These mediators were significant at all age levels, but exerted their strongest influence among younger women. This study provides new information about the mechanisms that influence the relationship between body satisfaction and SWB among a broad age range of women who are experiencing physical changes that are inconsistent with Western beauty standards. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Effectiveness of erythrosine-mediated photodynamic antimicrobial chemotherapy on dental plaque aerobic microorganisms: A randomized controlled trial.

    Bhat, Manohar; Acharya, Swathi; Prasad, Kakarla Veera Venkata; Kulkarni, Raghavendra; Bhat, Anithraj; Bhat, Devikripa

    2017-01-01

    Dental plaque is one of the predominant causes of major oral diseases. Although mechanical and chemical methods are extensively followed to control the development of plaque, plaque-related diseases still persist. Therefore, this necessitates for alternative measures of plaque control, one such alternative is photodynamic antimicrobial chemotherapy (PACT). Split mouth randomized clinical trial (CTRI/2017/03/008239) was conducted on 30 participants who reported to the hospital. Participants were asked to rinse their mouth for 1 min using 10 ml of 25 μM erythrosine solutions. Same tooth on both quadrants of the same jaw are selected as the test and control. Intervention used was halogen-based composite curing light with wavelength of 500-590 nm. Plaque sample from the control tooth and test tooth was collected before and after exposure, respectively, and sent to microbiological laboratory for colony count. Logarithmic mean and standard deviation of control group with 10 2 dilutions of aerobic microbial count were found to be 5.34 ± 0.94, and for experimental group, it was 4.47 ± 1.37. The statistical difference between mean CFU values between aerobic bacterial counts was significant ( P = 0.006). Erythrosine-mediated PACT reduces the extent of dental plaque microbial count and has a potential preventive and therapeutic use in day-to-day life and dental clinics.

  17. Mediating Mechanisms of Theory-Based Psychosocial Determinants on Behavioral Changes in a Middle School Obesity Risk Reduction Curriculum Intervention, Choice, Control, and Change.

    Gray, Heewon Lee; Contento, Isobel R; Koch, Pamela A; Noia, Jennifer Di

    2016-10-01

    A limited number of school-based intervention studies have explored mediating mechanisms of theory-based psychosocial variables on obesity risk behavior changes. The current study investigated how theory-based psychosocial determinants mediated changes in energy balance-related behaviors (EBRBs) among urban youth. A secondary analysis study was conducted using data from a cluster randomized controlled trial. Data from students at 10 middle schools in New York City (n = 1136) were used. The intervention, Choice, Control, and Change curriculum, was based on social cognitive and self-determination theories. Theory-based psychosocial determinants (goal intention, cognitive outcome expectations, affective outcome expectations, self-efficacy, perceived barriers, and autonomous motivation) and EBRBs were measured with self-report questionnaires. Mediation mechanisms were examined using structural equation modeling, Results: Mediating mechanisms for daily sugar-sweetened beverage (SSB) consumption and purposeful stair climbing were identified. Models with best fit indices (root mean square error of approximation = 0.039/0.045, normed fit index = 0.916/0.882; comparative fit index = 0.945/0.932; Tucker-Lewis index = 0.896/0.882, respectively) suggested that goal intention and reduced perceived barriers were significant proximal mediators for reducing SSB consumption among both boys and girls or increasing physical activity by stair climbing among boys. Cognitive outcome expectations, affective outcome expectations, self-efficacy, and autonomous motivation indirectly mediated behavioral changes through goal intention or perceived barriers (p behavioral outcome variances. Theory-based psychosocial determinants targeted in Choice, Control, and Change in fact mediated behavior changes in middle school students. Strategies targeting these mediators might benefit future success of behavioral interventions. Further studies are needed to determine other

  18. Neurogenesis and Helplessness are Mediated by Controllability in Males but not in Females

    Shors, Tracey J.; Mathew, Jason; Sisti, Helene M.; Edgecomb, Carol; Beckoff, Steven; Dalla, Christina

    2009-01-01

    Background Numerous studies have implicated neurogenesis in the hippocampus in animal models of depression, especially those related to controllability and learned helplessness. Here, we tested the hypothesis that uncontrollable, but not controllable stress would reduce cell proliferation in the hippocampus of male and female rats, and would relate to the expression of helplessness behavior. Methods To manipulate controllability, groups of male and female rats were trained in one session (acute stress) or over seven sessions (repeated stress) to escape a footshock, while yoked controls could not escape, but were exposed to the same amount of stress. Cell proliferation was assessed with immunohistochemistry of BrdU and immunofluorescence of BrdU and NeuN. Separate groups were exposed to either controllable or uncontrollable stress and their ability to learn to escape during training on a more difficult task was used as a behavioral measure of helplessness. Results Acute stress reduced cell proliferation in males, but did not affect proliferation in the female hippocampus. When animals were given the opportunity to learn to control the stress over days, males produced more cells than the yoked males without control. Repeated training with controllable stress did not influence proliferation in females. Under all conditions, males were more likely than females to express helplessness behavior, even males that were not previously stressed. Conclusions The modulation of neurogenesis by controllability was evident in males but not in females, as was the expression of helplessness behavior, despite the fact that men are less likely than women to experience depression. PMID:17306770

  19. Effectiveness of Parent-Child Mediation in Improving Family Functioning and Reducing Adolescent Problem Behavior: Results from a Pilot Randomized Controlled Trial.

    Tucker, Joan S; Edelen, Maria Orlando; Huang, Wenjing

    2017-03-01

    Parent-child mediation programs are intended to resolve or manage disputes and improve family functioning, but rigorous evaluations of their effectiveness are lacking. Families referred to a community-based mediation program (N = 111) were randomized to an intervention or wait-list control group, and completed three surveys over a 12-week period. With the exception of parent-reported child delinquency (which decreased more in the intervention group), this evaluation provides little support for the short-term effectiveness of parent-child mediation for improving family functioning and reducing child problem behaviors in general. Given that this is the first randomized controlled trial of a parent-child mediation program, additional evaluations involving larger samples and longer follow-ups are needed before firm conclusions can be drawn about the effectiveness of this intervention.

  20. Effectiveness of Parent-Child Mediation in Improving Family Functioning and Reducing Adolescent Problem Behavior: Results from a Pilot Randomized Controlled Trial

    Tucker, Joan S.; Edelen, Maria Orlando; Huang, Wenjing

    2016-01-01

    Parent-child mediation programs are intended to resolve or manage disputes and improve family functioning, but rigorous evaluations of their effectiveness are lacking. Families referred to a community-based mediation program (N=111) were randomized to an intervention or wait-list control group, and completed three surveys over a 12-week period. With the exception of parent-reported child delinquency (which decreased more in the intervention group), this evaluation provides little support for the short-term effectiveness of parent-child mediation for improving family functioning and reducing child problem behaviors in general. Given that this is the first randomized controlled trial of a parent-child mediation program, additional evaluations involving larger samples and longer follow-ups are needed before firm conclusions can be drawn about the effectiveness of this intervention. PMID:26762375

  1. Diabetes-specific emotional distress mediates the association between depressive symptoms and glycaemic control in Type 1 and Type 2 diabetes

    van Bastelaar, Kim M P; Pouwer, F; Geelhoed-Duijvestijn, P H L M

    2010-01-01

    and diabetes-specific emotional distress respectively. Linear regression was performed to examine the mediating effect of diabetes-distress. RESULTS: Complete data were available for 627 outpatients with Type 1 (n = 280) and Type 2 (n = 347) diabetes. Analyses showed that diabetes-distress mediated......OBJECTIVES: To investigate whether diabetes-specific emotional distress mediates the relationship between depression and glycaemic control in patients with Type 1 and Type 2 diabetes. RESEARCH DESIGN AND METHODS: Data were derived from the baseline assessment of a depression in diabetes screening...... and glycaemic control, diabetes-specific emotional distress appears to be an important mediator. Addressing diabetes-specific emotional problems as part of depression treatment in diabetes patients may help improve glycaemic outcomes....

  2. Unc-51/ATG1 controls axonal and dendritic development via kinesin-mediated vesicle transport in the Drosophila brain.

    Hiroaki Mochizuki

    2011-05-01

    Full Text Available Members of the evolutionary conserved Ser/Thr kinase Unc-51 family are key regulatory proteins that control neural development in both vertebrates and invertebrates. Previous studies have suggested diverse functions for the Unc-51 protein, including axonal elongation, growth cone guidance, and synaptic vesicle transport.In this work, we have investigated the functional significance of Unc-51-mediated vesicle transport in the development of complex brain structures in Drosophila. We show that Unc-51 preferentially accumulates in newly elongating axons of the mushroom body, a center of olfactory learning in flies. Mutations in unc-51 cause disintegration of the core of the developing mushroom body, with mislocalization of Fasciclin II (Fas II, an IgG-family cell adhesion molecule important for axonal guidance and fasciculation. In unc-51 mutants, Fas II accumulates in the cell bodies, calyx, and the proximal peduncle. Furthermore, we show that mutations in unc-51 cause aberrant overshooting of dendrites in the mushroom body and the antennal lobe. Loss of unc-51 function leads to marked accumulation of Rab5 and Golgi components, whereas the localization of dendrite-specific proteins, such as Down syndrome cell adhesion molecule (DSCAM and No distributive disjunction (Nod, remains unaltered. Genetic analyses of kinesin light chain (Klc and unc-51 double heterozygotes suggest the importance of kinesin-mediated membrane transport for axonal and dendritic development. Moreover, our data demonstrate that loss of Klc activity causes similar axonal and dendritic defects in mushroom body neurons, recapitulating the salient feature of the developmental abnormalities caused by unc-51 mutations.Unc-51 plays pivotal roles in the axonal and dendritic development of the Drosophila brain. Unc-51-mediated membrane vesicle transport is important in targeted localization of guidance molecules and organelles that regulate elongation and compartmentalization of

  3. Low-noise humidity controller for imaging water mediated processes in atomic force microscopy

    Gaponenko, I., E-mail: iaroslav.gaponenko@unige.ch; Gamperle, L.; Herberg, K.; Muller, S. C.; Paruch, P. [DQMP, University of Geneva, 24 Quai E. Ansermet, 1211 Geneva 4 (Switzerland)

    2016-06-15

    We demonstrate the construction of a novel low-noise continuous flow humidity controller and its integration with a commercial variable-temperature atomic force microscope fluid cell, allowing precise control of humidity and temperature at the sample during nanoscale measurements. Based on wet and dry gas mixing, the design allows a high mechanical stability to be achieved by means of an ultrasonic atomiser for the generation of water-saturated gas, improving upon previous bubbler-based architectures. Water content in the flow is measured both at the inflow and outflow of the fluid cell, enabling the monitoring of water condensation and icing, and allowing controlled variation of the sample temperature independently of the humidity. To benchmark the performance of the controller, the results of detailed noise studies and time-based imaging of the formation of ice layers on highly oriented pyrolytic graphite are shown.

  4. Low-noise humidity controller for imaging water mediated processes in atomic force microscopy

    Gaponenko, I.; Gamperle, L.; Herberg, K.; Muller, S. C.; Paruch, P.

    2016-06-01

    We demonstrate the construction of a novel low-noise continuous flow humidity controller and its integration with a commercial variable-temperature atomic force microscope fluid cell, allowing precise control of humidity and temperature at the sample during nanoscale measurements. Based on wet and dry gas mixing, the design allows a high mechanical stability to be achieved by means of an ultrasonic atomiser for the generation of water-saturated gas, improving upon previous bubbler-based architectures. Water content in the flow is measured both at the inflow and outflow of the fluid cell, enabling the monitoring of water condensation and icing, and allowing controlled variation of the sample temperature independently of the humidity. To benchmark the performance of the controller, the results of detailed noise studies and time-based imaging of the formation of ice layers on highly oriented pyrolytic graphite are shown.

  5. Low-noise humidity controller for imaging water mediated processes in atomic force microscopy

    Gaponenko, I.; Gamperle, L.; Herberg, K.; Muller, S. C.; Paruch, P.

    2016-01-01

    We demonstrate the construction of a novel low-noise continuous flow humidity controller and its integration with a commercial variable-temperature atomic force microscope fluid cell, allowing precise control of humidity and temperature at the sample during nanoscale measurements. Based on wet and dry gas mixing, the design allows a high mechanical stability to be achieved by means of an ultrasonic atomiser for the generation of water-saturated gas, improving upon previous bubbler-based architectures. Water content in the flow is measured both at the inflow and outflow of the fluid cell, enabling the monitoring of water condensation and icing, and allowing controlled variation of the sample temperature independently of the humidity. To benchmark the performance of the controller, the results of detailed noise studies and time-based imaging of the formation of ice layers on highly oriented pyrolytic graphite are shown.

  6. Month of birth, vitamin D and risk of immune-mediated disease: a case control study

    Disanto Giulio

    2012-07-01

    Full Text Available Abstract Background A season of birth effect in immune-mediated diseases (ID such as multiple sclerosis and type 1 diabetes has been consistently reported. We aimed to investigate whether season of birth influences the risk of rheumatoid arthritis, Crohn's disease, ulcerative colitis and systemic lupus erythematosus in addition to multiple sclerosis, and to explore the correlation between the risk of ID and predicted ultraviolet B (UVB light exposure and vitamin D status during gestation. Methods The monthly distribution of births of patients with ID from the UK (n = 115,172 was compared to that of the general population using the Cosinor test. Predicted UVB radiation and vitamin D status in different time windows during pregnancy were calculated for each month of birth and correlated with risk of ID using the Spearman's correlation coefficient. Results The distributions of ID births significantly differed from that of the general population (P = 5e-12 with a peak in April (odds ratio = 1.045, 95% confidence interval = 1.024, 1.067, P P P = 0.00005 and third trimester vitamin D status (Spearman's rho = -0.44, P = 0.0003. Conclusions The risk of different ID in the UK is significantly influenced by the season of birth, suggesting the presence of a shared seasonal risk factor or factors predisposing to ID. Gestational UVB and vitamin D exposure may be implicated in the aetiology of ID.

  7. Action control is mediated by prefrontal BDNF and glucocorticoid receptor binding.

    Gourley, Shannon L; Swanson, Andrew M; Jacobs, Andrea M; Howell, Jessica L; Mo, Michelle; Dileone, Ralph J; Koleske, Anthony J; Taylor, Jane R

    2012-12-11

    Stressor exposure biases decision-making strategies from those based on the relationship between actions and their consequences to others restricted by stimulus-response associations. Chronic stressor exposure also desensitizes glucocorticoid receptors (GR) and diminishes motivation to acquire food reinforcement, although causal relationships are largely not established. We show that a history of chronic exposure to the GR ligand corticosterone or acute posttraining GR blockade with RU38486 makes rodents less able to perform actions based on their consequences. Thus, optimal GR binding is necessary for the consolidation of new response-outcome learning. In contrast, medial prefrontal (but not striatal) BDNF can account for stress-related amotivation, in that selective medial prefrontal cortical Bdnf knockdown decreases break-point ratios in a progressive-ratio task. Knockdown also increases vulnerability to RU38486. Despite the role of BDNF in dendritic spine reorganization, deep-layer spine remodeling does not obviously parallel progressive-ratio response patterns, but treatment with the Na(+)-channel inhibitor riluzole reverses corticosteroid-induced motivational deficits and restores prefrontal BDNF expression after corticosterone. We argue that when prefrontal neurotrophin systems are compromised, and GR-mediated hypothalamic-pituitary-adrenal axis feedback is desensitized (as in the case of chronic stress hormone exposure), amotivation and inflexible maladaptive response strategies that contribute to stress-related mood disorders result.

  8. Detachment of Chain-Forming Neuroblasts by Fyn-Mediated Control of cell-cell Adhesion in the Postnatal Brain.

    Fujikake, Kazuma; Sawada, Masato; Hikita, Takao; Seto, Yayoi; Kaneko, Naoko; Herranz-Pérez, Vicente; Dohi, Natsuki; Homma, Natsumi; Osaga, Satoshi; Yanagawa, Yuchio; Akaike, Toshihiro; García-Verdugo, Jose Manuel; Hattori, Mitsuharu; Sobue, Kazuya; Sawamoto, Kazunobu

    2018-05-09

    In the rodent olfactory system, neuroblasts produced in the ventricular-subventricular zone of the postnatal brain migrate tangentially in chain-like cell aggregates toward the olfactory bulb (OB) through the rostral migratory stream (RMS). After reaching the OB, the chains are dissociated and the neuroblasts migrate individually and radially toward their final destination. The cellular and molecular mechanisms controlling cell-cell adhesion during this detachment remain unclear. Here we report that Fyn, a nonreceptor tyrosine kinase, regulates the detachment of neuroblasts from chains in the male and female mouse OB. By performing chemical screening and in vivo loss-of-function and gain-of-function experiments, we found that Fyn promotes somal disengagement from the chains and is involved in neuronal migration from the RMS into the granule cell layer of the OB. Fyn knockdown or Dab1 (disabled-1) deficiency caused p120-catenin to accumulate and adherens junction-like structures to be sustained at the contact sites between neuroblasts. Moreover, a Fyn and N-cadherin double-knockdown experiment indicated that Fyn regulates the N-cadherin-mediated cell adhesion between neuroblasts. These results suggest that the Fyn-mediated control of cell-cell adhesion is critical for the detachment of chain-forming neuroblasts in the postnatal OB. SIGNIFICANCE STATEMENT In the postnatal brain, newly born neurons (neuroblasts) migrate in chain-like cell aggregates toward their destination, where they are dissociated into individual cells and mature. The cellular and molecular mechanisms controlling the detachment of neuroblasts from chains are not understood. Here we show that Fyn, a nonreceptor tyrosine kinase, promotes the somal detachment of neuroblasts from chains, and that this regulation is critical for the efficient migration of neuroblasts to their destination. We further show that Fyn and Dab1 (disabled-1) decrease the cell-cell adhesion between chain-forming neuroblasts

  9. Well-being among older adults with OA: direct and mediated patterns of control beliefs, optimism and pessimism.

    Sherman, Aurora M; Cotter, Kelly A

    2013-01-01

    To assess the contribution of important psychological resources (i.e. optimism, pessimism, control beliefs) to the psychological well-being of older adults with Osteoarthritis (OA); to assess the direct and mediated association of these psychosocial resources to outcomes (depressive symptoms, life satisfaction, and self-esteem). These objectives are important because OA is a significant stressor, treatments are limited, and psychological functioning is at risk for those coping with the condition, even compared to other chronic illnesses. A cross-sectional survey of 160 community-dwelling older adults with OA (81% women). Participants were not randomly selected, but nonetheless reflected the demographic makeup of the selection area. Ordinary least squares regression analyses using the PROCESS macro revealed that optimism and pessimism were associated with higher depressive symptoms and lower self-esteem indirectly through constraints beliefs. The analysis of life satisfaction showed that optimism and pessimism were each partially mediated through mastery and constraints beliefs. These results suggest that prior research, which has assessed these psychological resources as having singular relationships to outcomes, may have underestimated the importance of the relationship between these variables. We discuss possible points of intervention for older adults with OA who may experience increasing constraints beliefs over time.

  10. RISC-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells.

    Pandolfini, Luca; Luzi, Ettore; Bressan, Dario; Ucciferri, Nadia; Bertacchi, Michele; Brandi, Rossella; Rocchiccioli, Silvia; D'Onofrio, Mara; Cremisi, Federico

    2016-05-06

    Embryonic stem cells are intrinsically unstable and differentiate spontaneously if they are not shielded from external stimuli. Although the nature of such instability is still controversial, growing evidence suggests that protein translation control may play a crucial role. We performed an integrated analysis of RNA and proteins at the transition between naïve embryonic stem cells and cells primed to differentiate. During this transition, mRNAs coding for chromatin regulators are specifically released from translational inhibition mediated by RNA-induced silencing complex (RISC). This suggests that, prior to differentiation, the propensity of embryonic stem cells to change their epigenetic status is hampered by RNA interference. The expression of these chromatin regulators is reinstated following acute inactivation of RISC and it correlates with loss of stemness markers and activation of early cell differentiation markers in treated embryonic stem cells. We propose that RISC-mediated inhibition of specific sets of chromatin regulators is a primary mechanism for preserving embryonic stem cell pluripotency while inhibiting the onset of embryonic developmental programs.

  11. Mitochondrial Dynamics Mediated by Mitofusin 1 Is Required for POMC Neuron Glucose-Sensing and Insulin Release Control.

    Ramírez, Sara; Gómez-Valadés, Alicia G; Schneeberger, Marc; Varela, Luis; Haddad-Tóvolli, Roberta; Altirriba, Jordi; Noguera, Eduard; Drougard, Anne; Flores-Martínez, Álvaro; Imbernón, Mónica; Chivite, Iñigo; Pozo, Macarena; Vidal-Itriago, Andrés; Garcia, Ainhoa; Cervantes, Sara; Gasa, Rosa; Nogueiras, Ruben; Gama-Pérez, Pau; Garcia-Roves, Pablo M; Cano, David A; Knauf, Claude; Servitja, Joan-Marc; Horvath, Tamas L; Gomis, Ramon; Zorzano, Antonio; Claret, Marc

    2017-06-06

    Proopiomelanocortin (POMC) neurons are critical sensors of nutrient availability implicated in energy balance and glucose metabolism control. However, the precise mechanisms underlying nutrient sensing in POMC neurons remain incompletely understood. We show that mitochondrial dynamics mediated by Mitofusin 1 (MFN1) in POMC neurons couple nutrient sensing with systemic glucose metabolism. Mice lacking MFN1 in POMC neurons exhibited defective mitochondrial architecture remodeling and attenuated hypothalamic gene expression programs during the fast-to-fed transition. This loss of mitochondrial flexibility in POMC neurons bidirectionally altered glucose sensing, causing abnormal glucose homeostasis due to defective insulin secretion by pancreatic β cells. Fed mice lacking MFN1 in POMC neurons displayed enhanced hypothalamic mitochondrial oxygen flux and reactive oxygen species generation. Central delivery of antioxidants was able to normalize the phenotype. Collectively, our data posit MFN1-mediated mitochondrial dynamics in POMC neurons as an intrinsic nutrient-sensing mechanism and unveil an unrecognized link between this subset of neurons and insulin release. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Translational Control Protein 80 Stimulates IRES-Mediated Translation of p53 mRNA in Response to DNA Damage

    Marie-Jo Halaby

    2015-01-01

    Full Text Available Synthesis of the p53 tumor suppressor increases following DNA damage. This increase and subsequent activation of p53 are essential for the protection of normal cells against tumorigenesis. We previously discovered an internal ribosome entry site (IRES that is located at the 5′-untranslated region (UTR of p53 mRNA and found that the IRES activity increases following DNA damage. However, the mechanism underlying IRES-mediated p53 translation in response to DNA damage is still poorly understood. In this study, we discovered that translational control protein 80 (TCP80 has increased binding to the p53 mRNA in vivo following DNA damage. Overexpression of TCP80 also leads to increased p53 IRES activity in response to DNA damage. TCP80 has increased association with RNA helicase A (RHA following DNA damage and overexpression of TCP80, along with RHA, leads to enhanced expression of p53. Moreover, we found that MCF-7 breast cancer cells with decreased expression of TCP80 and RHA exhibit defective p53 induction following DNA damage and diminished expression of its downstream target PUMA, a proapoptotic protein. Taken together, our discovery of the function of TCP80 and RHA in regulating p53 IRES and p53 induction following DNA damage provides a better understanding of the mechanisms that regulate IRES-mediated p53 translation in response to genotoxic stress.

  13. Transcriptome Analysis and Screening for Potential Target Genes for RNAi-Mediated Pest Control of the Beet Armyworm, Spodoptera exigua.

    Li, Hang; Jiang, Weihua; Zhang, Zan; Xing, Yanru; Li, Fei

    2013-01-01

    The beet armyworm, Spodoptera exigua (Hübner), is a serious pest worldwide that causes significant losses in crops. Unfortunately, genetic resources for the beet armyworm is extremely scarce. To improve these resources we sequenced the transcriptome of S. exigua representing all stages including eggs, 1(st) to 5(th) instar larvae, pupae, male and female adults using the Illumina Solexa platform. We assembled the transcriptome with Trinity that yielded 31,414 contigs. Of these contigs, 18,592 were annotated as protein coding genes by Blast searches against the NCBI nr database. It has been shown that knockdown of important insect genes by dsRNAs or siRNAs is a feasible mechanism to control insect pests. The first key step towards developing an efficient RNAi-mediated pest control technique is to find suitable target genes. To screen for effective target genes in the beet armyworm, we selected nine candidate genes. The sequences of these genes were amplified using the RACE strategy. Then, siRNAs were designed and chemically synthesized. We injected 2 µl siRNA (2 µg/µl) into the 4(th) instar larvae to knock down the respective target genes. The mRNA abundance of target genes decreased to different levels (∼20-94.3%) after injection of siRNAs. Knockdown of eight genes including chitinase7, PGCP, chitinase1, ATPase, tubulin1, arf2, tubulin2 and arf1 caused a significantly high level of mortality compared to the negative control (Ppest control.

  14. Surface-Chemistry-Mediated Control of Individual Magnetic Helical Microswimmers in a Swarm.

    Wang, Xiaopu; Hu, Chengzhi; Schurz, Lukas; De Marco, Carmela; Chen, Xiangzhong; Pané, Salvador; Nelson, Bradley J

    2018-05-31

    Magnetic helical microswimmers, also known as artificial bacterial flagella (ABFs), perform 3D navigation in various liquids under low-strength rotating magnetic fields by converting rotational motion to translational motion. ABFs have been widely studied as carriers for targeted delivery and release of drugs and cells. For in vivo/ in vitro therapeutic applications, control over individual groups of swimmers within a swarm is necessary for several biomedical applications such as drug delivery or small-scale surgery. In this work, we present the selective control of individual swimmers in a swarm of geometrically and magnetically identical ABFs by modifying their surface chemistry. We confirm experimentally and analytically that the forward/rotational velocity ratio of ABFs is independent of their surface coatings when the swimmers are operated below their step-out frequency (the frequency requiring the entire available magnetic torque to maintain synchronous rotation). We also show that ABFs with hydrophobic surfaces exhibit larger step-out frequencies and higher maximum forward velocities compared to their hydrophilic counterparts. Thus, selective control of a group of swimmers within a swarm of ABFs can be achieved by operating the selected ABFs at a frequency that is below their step-out frequencies but higher than the step-out frequencies of unselected ABFs. The feasibility of this method is investigated in water and in biologically relevant solutions. Selective control is also demonstrated inside a Y-shaped microfluidic channel. Our results present a systematic approach for realizing selective control within a swarm of magnetic helical microswimmers.

  15. Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation

    Huebsch, Nathaniel; Lippens, Evi; Lee, Kangwon; Mehta, Manav; Koshy, Sandeep T.; Darnell, Max C.; Desai, Rajiv M.; Madl, Christopher M.; Xu, Maria; Zhao, Xuanhe; Chaudhuri, Ovijit; Verbeke, Catia; Kim, Woo Seob; Alim, Karen; Mammoto, Akiko; Ingber, Donald E.; Duda, Georg N.; Mooney, David J.

    2015-12-01

    The effectiveness of stem cell therapies has been hampered by cell death and limited control over fate. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype. Stem cell behaviour can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel’s elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel’s elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem cell behaviours in situ.

  16. Controllable synthesis of metal selenide heterostructures mediated by Ag2Se nanocrystals acting as catalysts

    Zhou, Jiangcong; Huang, Feng; Xu, Ju; Wang, Yuansheng

    2013-09-01

    Ag2Se nanocrystals were demonstrated to be novel semiconductor mediators, or in other word catalysts, for the growth of semiconductor heterostructures in solution. This is a result of the unique feature of Ag2Se as a fast ion conductor, allowing foreign cations to dissolve and then to heterogrow the second phase. Using Ag2Se nanocrystals as catalysts, dimeric metal selenide heterostructures such as Ag2Se-CdSe and Ag2Se-ZnSe, and even multi-segment heterostructures such as Ag2Se-CdSe-ZnSe and Ag2Se-ZnSe-CdSe, were successfully synthesized. Several interesting features were found in the Ag2Se based heterogrowth. At the initial stage of heterogrowth, a layer of the second phase forms on the surface of an Ag2Se nanosphere, with a curved junction interface between the two phases. With further growth of the second phase, the Ag2Se nanosphere tends to flatten the junction surface by modifying its shape from sphere to hemisphere in order to minimize the conjunct area and thus the interfacial energy. Notably, the crystallographic relationship of the two phases in the heterostructure varies with the lattice parameters of the second phase, in order to reduce the lattice mismatch at the interface. Furthermore, a small lattice mismatch at the interface results in a straight rod-like second phase, while a large lattice mismatch would induce a tortuous product. The reported results may provide a new route for developing novel selenide semiconductor heterostructures which are potentially applicable in optoelectronic, biomedical, photovoltaic and catalytic fields.Ag2Se nanocrystals were demonstrated to be novel semiconductor mediators, or in other word catalysts, for the growth of semiconductor heterostructures in solution. This is a result of the unique feature of Ag2Se as a fast ion conductor, allowing foreign cations to dissolve and then to heterogrow the second phase. Using Ag2Se nanocrystals as catalysts, dimeric metal selenide heterostructures such as Ag2Se-CdSe and Ag2Se

  17. Glucose-mediated control of ghrelin release from primary cultures of gastric mucosal cells

    Sakata, Ichiro; Park, Won-Mee; Walker, Angela K.; Piper, Paul K.; Chuang, Jen-Chieh; Osborne-Lawrence, Sherri

    2012-01-01

    The peptide hormone ghrelin is released from a distinct group of gastrointestinal cells in response to caloric restriction, whereas its levels fall after eating. The mechanisms by which ghrelin secretion is regulated remain largely unknown. Here, we have used primary cultures of mouse gastric mucosal cells to investigate ghrelin secretion, with an emphasis on the role of glucose. Ghrelin secretion from these cells upon exposure to different d-glucose concentrations, the glucose antimetabolite 2-deoxy-d-glucose, and other potential secretagogues was assessed. The expression profile of proteins involved in glucose transport, metabolism, and utilization within highly enriched pools of mouse ghrelin cells and within cultured ghrelinoma cells was also determined. Ghrelin release negatively correlated with d-glucose concentration. Insulin blocked ghrelin release, but only in a low d-glucose environment. 2-Deoxy-d-glucose prevented the inhibitory effect of high d-glucose exposure on ghrelin release. mRNAs encoding several facilitative glucose transporters, hexokinases, the ATP-sensitive potassium channel subunit Kir6.2, and sulfonylurea type 1 receptor were expressed highly within ghrelin cells, although neither tolbutamide nor diazoxide exerted direct effects on ghrelin secretion. These findings suggest that direct exposure of ghrelin cells to low ambient d-glucose stimulates ghrelin release, whereas high d-glucose and glucose metabolism within ghrelin cells block ghrelin release. Also, low d-glucose sensitizes ghrelin cells to insulin. Various glucose transporters, channels, and enzymes that mediate glucose responsiveness in other cell types may contribute to the ghrelin cell machinery involved in regulating ghrelin secretion under these different glucose environments, although their exact roles in ghrelin release remain uncertain. PMID:22414807

  18. Environmental and cortisol-mediated control of Ca(2+) uptake in tilapia (Oreochromis mossambicus).

    Lin, Chia-Hao; Kuan, Wei-Chun; Liao, Bo-Kai; Deng, Ang-Ni; Tseng, Deng-Yu; Hwang, Pung-Pung

    2016-04-01

    Ca(2+) is a vital element for many physiological processes in vertebrates, including teleosts, which live in aquatic environments and acquire Ca(2+) from their surroundings. Ionocytes within the adult gills or larval skin are critical sites for transcellular Ca(2+) uptake in teleosts. The ionocytes of zebrafish were found to contain transcellular Ca(2+) transporters, epithelial Ca(2+) channel (ECaC), plasma membrane Ca(2+)-ATPase 2 (PMCA2), and Na(+)/Ca(2+) exchanger 1b (NCX1b), providing information about the molecular mechanism of transcellular Ca(2+) transports mediated by ionocytes in fish. However, more evidence is required to establish whether or not a similar mechanism of transcellular Ca(2+) transport also exists in others teleosts. In the present study, ecac, pmca2, and ncx1 were found to be expressed in the branchial ionocytes of tilapia, thereby providing further support for the mechanism of transcellular Ca(2+) transport through ionocytes previously proposed for zebrafish. In addition, we also reveal that low Ca(2+) water treatment of tilapia stimulates Ca(2+) uptake and expression of ecac and cyp11b (the latter encodes a cortisol-synthesis enzyme). Treatment of tilapia with exogenous cortisol (20 mg/l) enhanced both Ca(2+) influx and ecac expression. Therefore, increased cyp11b expression is suggested to enhance Ca(2+) uptake capacity in tilapia exposed to low Ca(2+) water. Furthermore, the application of cortisol receptor antagonists revealed that cortisol may regulate Ca(2+) uptake through glucocorticoid and/or mineralocorticoid receptor (GR and/or MR) in tilapia. Taken together, the data suggest that cortisol may activate GR and/or MR to execute its hypercalcemic action by stimulating ecac expression in tilapia.

  19. Controllable synthesis and characterization of CdS quantum dots by a microemulsion-mediated hydrothermal method

    Chen, Rongrong; Han, Boning; Yang, Lin, E-mail: yanglin@hbu.edu.cn; Yang, Yanmin; Xu, Ying; Mai, Yaohua, E-mail: yaohuamai@hbu.edu.cn

    2016-04-15

    CdS QDs were successfully synthesized through a chemical reaction between cadmium acetate dehydrate and thioacetamide by using a microemulsion-mediated hydrothermal method. The properties of as-prepared CdS QDs can be controlled by using Emulsifier OP and CTAB surfactant, which produce a universal cubic phase and an unusual hexagonal phase, respectively. As a comparison, CdS QDs prepared by CTAB exhibit a better crystallinity and dispersibility. A possible mechanism involving the critical role of surfactant in the formation of crystal structure has also been explored in this paper. It is also found that the crystal size gradually increase with the increase of temperature, and the observation of red-shift in the absorption and emission peaks gives a clear evidence of the quantum confinement effect. All the desired properties of CdS QDs synthesized in this study imply the possibility of the preparation of high quality QDs under the appropriate reaction conditions.

  20. Pulse-bandwidth dependence of coherent phase control of resonance-mediated (2+1) three-photon absorption

    Gandman, Andrey; Chuntonov, Lev; Rybak, Leonid; Amitay, Zohar

    2007-01-01

    We study in detail coherent phase control of femtosecond resonance-mediated (2+1) three-photon absorption and its dependence on the spectral bandwidth of the excitation pulse. The regime is the weak-field regime of third perturbative order. The corresponding interference mechanism involves a group of three-photon excitation pathways that are on resonance with the intermediate state and a group of three-photon excitation pathways that are near resonant with it. The model system of the study is atomic sodium (Na), for which experimental and numerical-theoretical results are obtained. Prominent among the results is our finding that with simple proper pulse shaping an increase in the excitation bandwidth leads to a corresponding increase in the enhancement of the three-photon absorption over the absorption induced by the (unshaped) transform-limited pulse. For example, here, a 40 nm bandwidth leads to an order-of-magnitude enhancement over the transform-limited absorption

  1. Incorporation of hyaluronic acid into collagen scaffolds for the control of chondrocyte-mediated contraction and chondrogenesis

    Tang Shunqing [Department of Biomedical Engineering, Jinan University, Guangzhou 510632 (China); Spector, Myron [Tissue Engineering, VA Boston Healthcare System, Boston, MA 02130 (United States)

    2007-09-15

    Hyaluronic acid (HA), a principal matrix molecule in many tissues, is present in high amounts in articular cartilage. HA contributes in unique ways to the physical behavior of the tissue, and has been shown to have beneficial effects on chondrocyte activity. The goal of this study was to incorporate graduated amounts of HA into type I collagen scaffolds for the control of chondrocyte-mediated contraction and chondrogenesis in vitro. The results demonstrated that the amount of contraction of HA/collagen scaffolds by adult canine articular chondrocytes increased with the HA content of the scaffolds. The greatest amount of chondrogenesis after two weeks was found in the scaffolds which had undergone the most contraction. HA can play a useful role in adjusting the mechanical behavior of tissue engineering scaffolds and chondrogenesis in chondrocyte-seeded scaffolds.

  2. Global efficiency of structural networks mediates cognitive control in mild cognitive impairment

    Berlot, R. (Rok); Metzler-Baddeley, C. (Claudia); M.A. Ikram (Arfan); Jones, D.K. (Derek K.); O'Sullivan, M.J. (Michael J.)

    2016-01-01

    markdownabstract__Background:__ Cognitive control has been linked to both the microstructure of individual tracts and the structure of whole-brain networks, but their relative contributions in health and disease remain unclear. __Objective:__ To determine the contribution of both localized white

  3. Agrobacterium-mediated transformation of black cherry for flowering control and insect resistance

    Ying Wang; Paula M. Pijut

    2014-01-01

    Black cherry is one of the most valuable hardwood species for cabinetry, furniture, and veneer. The goal of this study was to develop transgenic black cherry plants with reproductive sterility and enhanced insect resistance. Black cherry TERMINAL FLOWER 1 (PsTFL1) was overexpressed under the control of the CaMV 35S promoter in black cherry via

  4. Spinal sensory projection neuron responses to spinal cord stimulation are mediated by circuits beyond gate control.

    Zhang, Tianhe C; Janik, John J; Peters, Ryan V; Chen, Gang; Ji, Ru-Rong; Grill, Warren M

    2015-07-01

    Spinal cord stimulation (SCS) is a therapy used to treat intractable pain with a putative mechanism of action based on the Gate Control Theory. We hypothesized that sensory projection neuron responses to SCS would follow a single stereotyped response curve as a function of SCS frequency, as predicted by the Gate Control circuit. We recorded the responses of antidromically identified sensory projection neurons in the lumbar spinal cord during 1- to 150-Hz SCS in both healthy rats and neuropathic rats following chronic constriction injury (CCI). The relationship between SCS frequency and projection neuron activity predicted by the Gate Control circuit accounted for a subset of neuronal responses to SCS but could not account for the full range of observed responses. Heterogeneous responses were classifiable into three additional groups and were reproduced using computational models of spinal microcircuits representing other interactions between nociceptive and nonnociceptive sensory inputs. Intrathecal administration of bicuculline, a GABAA receptor antagonist, increased spontaneous and evoked activity in projection neurons, enhanced excitatory responses to SCS, and reduced inhibitory responses to SCS, suggesting that GABAA neurotransmission plays a broad role in regulating projection neuron activity. These in vivo and computational results challenge the Gate Control Theory as the only mechanism underlying SCS and refine our understanding of the effects of SCS on spinal sensory neurons within the framework of contemporary understanding of dorsal horn circuitry. Copyright © 2015 the American Physiological Society.

  5. Young-Age Gender Differences in Mathematics Mediated by Independent Control or Uncontrollability

    Zirk-Sadowski, Jan; Lamptey, Charlotte; Devine, Amy; Haggard, Mark; Szucs, Dénes

    2014-01-01

    We studied whether the origins of math anxiety can be related to a biologically supported framework of stress induction: (un)controllability perception, here indicated by self-reported independent efforts in mathematics. Math anxiety was tested in 182 children (8- to 11-year-olds). "Latent factor modeling" was used to test hypotheses on…

  6. Microbial- and isothiocyanate-mediated control of Phytophthora and Pythium species

    M.F. Cohen; E. Yamamoto; E. Condeso; B.L. Anacker; N. Rank; M. Mazzola

    2008-01-01

    Plant pathogens of the oomycete lineage share common susceptibilities to many biotic and abiotic stresses. We are investigating the potential of antagonistic bacteria, isothiocyanates, and mycophagous amoebae to control diseases caused by Phytophthora spp., including the etiologic agent of sudden oak death, Phytophthora ramorum (...

  7. Development of suicidality within socioeconomic context: mediation effect of parental control and anomie.

    Heydari, Arash; Teymoori, Ali; Nasiri, Hedayat

    Despite some scientific research on suicide as one of the most serious social and mental health problems in Iran, there is still lack of research on the effective structural and socio-familial factors contributing to the issue in Iran. The purpose of this study is to investigate some of the effective variables conditioning suicidality while also establishing a synthetic model. Three hundred-fifty university students (165 males, 185 females) were randomly chosen from Shahid Chamran University, Ahvaz, Iran. The participants were asked to complete a package of self-report questionnaires including subjective socioeconomic status (SES), feeling of anomie, perceived parental control, and suicidality. The results show that all correlations among variables are significant. For testing the theoretical model, results of standardized regression coefficients suggest that SES has direct effect on suicidality and indirect effect via anomie and parental control. In addition, parental control has direct effects on suicidality and indirect effect via anomie as well. The findings confirm the expected paths hypothesized among variables which are consistent with the theories of Durkheim, Merton, Kohn, and Agnew. It implies that the development of suicidality takes place within socioeconomic context through the influence of parental control and feeling of anomie.

  8. Home blood pressure monitoring, secure electronic messaging and medication intensification for improving hypertension control: a mediation analysis.

    Ralston, J D; Cook, A J; Anderson, M L; Catz, S L; Fishman, P A; Carlson, J; Johnson, R; Green, B B

    2014-01-01

    We evaluated the role of home monitoring, communication with pharmacists, medication intensification, medication adherence and lifestyle factors in contributing to the effectiveness of an intervention to improve blood pressure control in patients with uncontrolled essential hypertension. We performed a mediation analysis of a published randomized trial based on the Chronic Care Model delivered over a secure patient website from June 2005 to December 2007. Study arms analyzed included usual care with a home blood pressure monitor and usual care with home blood pressure monitor and web-based pharmacist care. Mediator measures included secure messaging and telephone encounters; home blood pressure monitoring; medications intensification and adherence and lifestyle factors. Overall fidelity to the Chronic Care Model was assessed with the Patient Assessment of Chronic Care (PACIC) instrument. The primary outcome was percent of participants with blood pressure (BP) <140/90 mm Hg. At 12 months follow-up, patients in the web-based pharmacist care group were more likely to have BP <140/90 mm Hg (55%) compared to patients in the group with home blood pressure monitors only (37%) (p = 0.001). Home blood pressure monitoring accounted for 30.3% of the intervention effect, secure electronic messaging accounted for 96%, and medication intensification for 29.3%. Medication adherence and self-report of fruit and vegetable intake and weight change were not different between the two study groups. The PACIC score accounted for 22.0 % of the main intervention effect. The effect of web-based pharmacist care on improved blood pressure control was explained in part through a combination of home blood pressure monitoring, secure messaging, and antihypertensive medication intensification.

  9. Determination of inmune response and inflammation mediators in tears: Changes in dry eye and glaucoma as compared to healthy controls.

    Benitez-Del-Castillo Sánchez, J; Morillo-Rojas, M D; Galbis-Estrada, C; Pinazo-Duran, M D

    2017-05-01

    To determine the expression profile of immune response and inflammation (IRI) mediator molecules in tears from patients with dry eye (DE), and those suspected of having or have primary open-angle glaucoma (POAG) under treatment and compare them with healthy controls. A prospective observational cohort study including 107 participants sub-divided into: healthy controls (CG; n=30), patients with DE (DEG; n=41) and patients suspected of having or have POAG and on hypotensive treatment (POAG-G; n=36). Tear samples were collected by capillary to be processed using a multi-immunoassay system based on flow cytometry (Luminex R-200 ®), in order to determine the interleukins (IL): 1β, 2, 4, 5, 6, and 10, and the growth factors: Tumour necrosis alpha (TNF-α), vascular endothelial (VEGF), and granulocyte-macrophage colony stimulating- (GM-CSF). Data were processed using the SPSS 20.0 program. Molecules that significantly increased in tears from DEG vs. POAG-G patients were: IL-1 (P=.01), IL-6 (P=.004), IL-10 (P=.04), whereas VEGF significantly decreased in the DEG. The POAG-G showed significantly higher IL-6 values (P<.0001) as compared to the CG. When comparing both the DEG and POAG-G, significant differences were observed in tear expression of IL-4 (P=.004), IL-6 (P=.002), TNF-α (P=.03), GM-CSF (P=.03), and VEGF (P=.002). The increased expression of IRI mediators in tears from patients with DE or POAG strongly demonstrated the importance of immune response in both pathologies. However, the different molecules involved also suggest distinct signalling pathways for these processes that still require further research. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Cross-site randomized control trial of the Social ABCs caregiver-mediated intervention for toddlers with autism spectrum disorder.

    Brian, Jessica A; Smith, Isabel M; Zwaigenbaum, Lonnie; Bryson, Susan E

    2017-10-01

    To evaluate the efficacy of the Social ABCs parent-mediated intervention for toddlers with suspected or confirmed autism spectrum disorder (ASD), through a cross-site randomized control trial, sixty-three parent-toddler dyads (toddler age: 16-30 months) were randomized into treatment (Social ABCs) or control (service-as-usual) conditions. Video data were obtained at three key time-points: Baseline; Post-training (PT; week 12); and Follow-Up (week 24). Analyses included 62 dyads. Treatment allocation significantly accounted for PT gains, all favouring the Treatment group, in (1) child functional vocal responsiveness to parent prompts (R 2  = 0.43, P social orienting (R 2  = 0.06, P = 0.054); gains in parent smiling significantly predicted increases in child smiling and social orienting. Parents in the treatment condition reported significant gains in self-efficacy following the intervention (P = 0.009). No differential effects emerged for performance on standardized measures. The Social ABCs is a relatively low-resource, efficacious intervention, with potential to be a cost-effective means of intervening at the first signs of possible ASD. Autism Res 2017, 10: 1700-1711. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Clinical Trial Title: Social ABCs for Toddlers with Signs of Autism Spectrum Disorder: RCT of a Parent-Mediated Intervention http//ClinicalTrials.gov identifier: NCT02428452. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

  11. Fluid-Mediated Stochastic Self-Assembly at Centimetric and Sub-Millimetric Scales: Design, Modeling, and Control

    Bahar Haghighat

    2016-08-01

    Full Text Available Stochastic self-assembly provides promising means for building micro-/nano-structures with a variety of properties and functionalities. Numerous studies have been conducted on the control and modeling of the process in engineered self-assembling systems constituted of modules with varied capabilities ranging from completely reactive nano-/micro-particles to intelligent miniaturized robots. Depending on the capabilities of the constituting modules, different approaches have been utilized for controlling and modeling these systems. In the quest of a unifying control and modeling framework and within the broader perspective of investigating how stochastic control strategies can be adapted from the centimeter-scale down to the (sub-millimeter-scale, as well as from mechatronic to MEMS-based technology, this work presents the outcomes of our research on self-assembly during the past few years. As the first step, we leverage an experimental platform to study self-assembly of water-floating passive modules at the centimeter scale. A dedicated computational framework is developed for real-time tracking, modeling and control of the formation of specific structures. Using a similar approach, we then demonstrate controlled self-assembly of microparticles into clusters of a preset dimension in a microfluidic chamber, where the control loop is closed again through real-time tracking customized for a much faster system dynamics. Finally, with the aim of distributing the intelligence and realizing programmable self-assembly, we present a novel experimental system for fluid-mediated programmable stochastic self-assembly of active modules at the centimeter scale. The system is built around the water-floating 3-cm-sized Lily robots specifically designed to be operative in large swarms and allows for exploring the whole range of fully-centralized to fully-distributed control strategies. The outcomes of our research efforts extend the state-of-the-art methodologies

  12. Seed-mediated growth and manipulation of Au nanorods via size-controlled synthesis of Au seeds

    Liu Juncheng; Duggan, Jennifer N.; Morgan, Joshua; Roberts, Christopher B.

    2012-01-01

    Seed-mediated growth of gold (Au) nanorods with highly controllable length, width, and aspect ratio was accomplished via carefully size-controlled synthesis of the original Au seeds. A slow dynamic growth of Au nanoparticle seeds was observed after reduction of the Au salt (i.e., hydrogen tetrachloroaurate (III) hydrate) by sodium borohydride (NaBH 4 ) in the presence of cetyltrimethyl ammonium bromide (CTAB). As such, the size of the Au nanoparticle seeds can therefore be manipulated through control over the duration of the reaction period (i.e., aging times of 2, 8, 48, 72, and 144 h were used in this study). These differently sized Au nanoparticles were subsequently used as seeds for the growth of Au nanorods, where the additions of Au salt, CTAB, AgNO 3 , and ascorbic acid were employed. Smaller Au nanoparticle seeds obtained via short growth/aging time resulted in Au nanorods with higher aspect ratio and thus longer longitudinal surface plasmon wavelength (LSPW). The larger Au nanoparticle seeds obtained via longer growth/aging time resulted in Au nanorods with lower aspect ratio and shorter LSPW.

  13. cGAS-mediated control of blood-stage malaria promotes Plasmodium-specific germinal center responses.

    Hahn, William O; Butler, Noah S; Lindner, Scott E; Akilesh, Holly M; Sather, D Noah; Kappe, Stefan Hi; Hamerman, Jessica A; Gale, Michael; Liles, W Conrad; Pepper, Marion

    2018-01-25

    Sensing of pathogens by host pattern recognition receptors is essential for activating the immune response during infection. We used a nonlethal murine model of malaria (Plasmodium yoelii 17XNL) to assess the contribution of the pattern recognition receptor cyclic GMP-AMP synthase (cGAS) to the development of humoral immunity. Despite previous reports suggesting a critical, intrinsic role for cGAS in early B cell responses, cGAS-deficient (cGAS-/-) mice had no defect in the early expansion or differentiation of Plasmodium-specific B cells. As the infection proceeded, however, cGAS-/- mice exhibited higher parasite burdens and aberrant germinal center and memory B cell formation when compared with littermate controls. Antimalarial drugs were used to further demonstrate that the disrupted humoral response was not B cell intrinsic but instead was a secondary effect of a loss of parasite control. These findings therefore demonstrate that cGAS-mediated innate-sensing contributes to parasite control but is not intrinsically required for the development of humoral immunity. Our findings highlight the need to consider the indirect effects of pathogen burden in investigations examining how the innate immune system affects the adaptive immune response.

  14. Seed-mediated synthesis of silver nanocrystals with controlled sizes and shapes in droplet microreactors separated by air.

    Zhang, Lei; Wang, Yi; Tong, Limin; Xia, Younan

    2013-12-17

    Silver nanocrystals with uniform sizes were synthesized in droplet microreactors through seed-mediated growth. The key to the success of this synthesis is the use of air as a carrier phase to generate the droplets. The air not only separates the reaction solution into droplets but also provides O2 for the generation of reducing agent (glycolaldehyde). It also serves as a buffer space for the diffusion of NO, which is formed in situ due to the oxidative etching of Ag nanocrystals with twin defects. For the first time, we were able to generate Ag nanocrystals with controlled sizes and shapes in continuous production by using droplet microreactors. For Ag nanocubes, their edge lengths could be readily controlled in the range of 30-100 nm by varying the reaction time, the amount of seeds, and the concentration of AgNO3 in the droplets. Furthermore, we demonstrated the synthesis of Ag octahedra in the droplet microreactors. We believe that the air-driven droplet generation device can be extended to other noble metals for the production of nanocrystals with controlled sizes and shapes.

  15. Neutrophil and Alveolar Macrophage-Mediated Innate Immune Control of Legionella pneumophila Lung Infection via TNF and ROS.

    Pascal Ziltener

    2016-04-01

    Full Text Available Legionella pneumophila is a facultative intracellular bacterium that lives in aquatic environments where it parasitizes amoeba. However, upon inhalation of contaminated aerosols it can infect and replicate in human alveolar macrophages, which can result in Legionnaires' disease, a severe form of pneumonia. Upon experimental airway infection of mice, L. pneumophila is rapidly controlled by innate immune mechanisms. Here we identified, on a cell-type specific level, the key innate effector functions responsible for rapid control of infection. In addition to the well-characterized NLRC4-NAIP5 flagellin recognition pathway, tumor necrosis factor (TNF and reactive oxygen species (ROS are also essential for effective innate immune control of L. pneumophila. While ROS are essential for the bactericidal activity of neutrophils, alveolar macrophages (AM rely on neutrophil and monocyte-derived TNF signaling via TNFR1 to restrict bacterial replication. This TNF-mediated antibacterial mechanism depends on the acidification of lysosomes and their fusion with L. pneumophila containing vacuoles (LCVs, as well as caspases with a minor contribution from cysteine-type cathepsins or calpains, and is independent of NLRC4, caspase-1, caspase-11 and NOX2. This study highlights the differential utilization of innate effector pathways to curtail intracellular bacterial replication in specific host cells upon L. pneumophila airway infection.

  16. Deterministic creation and stabilization of entanglement in circuit QED by homodyne-mediated feedback control

    Liu Zhuo; Kuang Luelin; Hu Kai; Xu Luting; Wei Suhua; Guo Lingzhen; Li Xinqi

    2010-01-01

    In a solid-state circuit QED system, we demonstrate that a homodyne-current-based feedback can create and stabilize highly entangled two-qubit states in the presence of a moderate noisy environment. Particularly, we present an extended analysis for the current-based Markovian feedback, which leads to an improved feedback scheme. We show that this is essential to achieve a desirable control effect by the use of dispersive measurement.

  17. Card9 mediates susceptibility to intestinal pathogens through microbiota modulation and control of bacterial virulence.

    Lamas, Bruno; Michel, Marie-Laure; Waldschmitt, Nadine; Pham, Hang-Phuong; Zacharioudaki, Vassiliki; Dupraz, Louise; Delacre, Myriam; Natividad, Jane M; Costa, Gregory Da; Planchais, Julien; Sovran, Bruno; Bridonneau, Chantal; Six, Adrien; Langella, Philippe; Richard, Mathias L; Chamaillard, Mathias; Sokol, Harry

    2017-08-08

    In association with innate and adaptive immunity, the microbiota controls the colonisation resistance against intestinal pathogens. Caspase recruitment domain 9 ( CARD9 ), a key innate immunity gene, is required to shape a normal gut microbiota. Card9 -/- mice are more susceptible to the enteric mouse pathogen Citrobacter rodentium that mimics human infections with enteropathogenic and enterohaemorrhagic Escherichia coli . Here, we examined how CARD9 controls C. rodentium infection susceptibility through microbiota-dependent and microbiota-independent mechanisms. C. rodentium infection was assessed in conventional and germ-free (GF) wild-type (WT) and Card9 -/- mice. To explore the impact of Card9 -/- microbiota in infection susceptibility, GF WT mice were colonised with WT (WT→GF) or Card9 -/- ( Card9 -/- →GF) microbiota before C. rodentium infection. Microbiota composition was determined by 16S rDNA gene sequencing. Inflammation severity was determined by histology score and lipocalin level. Microbiota-host immune system interactions were assessed by quantitative PCR analysis. CARD9 controls pathogen virulence in a microbiota-independent manner by supporting a specific humoral response. Higher susceptibility to C. rodentium -induced colitis was observed in Card9 -/- →GF mice. The microbiota of Card9 -/- mice failed to outcompete the monosaccharide-consuming C. rodentium , worsening the infection severity. A polysaccharide-enriched diet counteracted the ecological advantage of C. rodentium and the defective pathogen-specific antibody response in Card9 -/- mice. CARD9 modulates the susceptibility to intestinal infection by controlling the pathogen virulence in a microbiota-dependent and microbiota-independent manner. Genetic susceptibility to intestinal pathogens can be overridden by diet intervention that restores humoural immunity and a competing microbiota. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017

  18. CRISPR-Cas9-Mediated Genome Editing and Transcriptional Control in Yarrowia lipolytica.

    Schwartz, Cory; Wheeldon, Ian

    2018-01-01

    The discovery and adaptation of RNA-guided nucleases has resulted in the rapid development of efficient, scalable, and easily accessible synthetic biology tools for targeted genome editing and transcriptional control. In these systems, for example CRISPR-Cas9 from Streptococcus pyogenes, a protein with nuclease activity is targeted to a specific nucleotide sequence by a short RNA molecule, whereupon binding it cleaves the targeted nucleotide strand. To extend this genome-editing ability to the industrially important oleaginous yeast Yarrowia lipolytica, we developed a set of easily usable and effective CRISPR-Cas9 episomal vectors. In this protocols chapter, we first present a method by which arbitrary protein-coding genes can be disrupted via indel formation after CRISPR-Cas9 targeting. A second method demonstrates how the same CRISPR-Cas9 system can be used to induce markerless gene cassette integration into the genome by inducing homologous recombination after DNA cleavage by Cas9. Finally, we describe how a catalytically inactive form of Cas9 fused to a transcriptional repressor can be used to control transcription of native genes in Y. lipolytica. The CRISPR-Cas9 tools and strategies described here greatly increase the types of genome editing and transcriptional control that can be achieved in Y. lipolytica, and promise to facilitate more advanced engineering of this important oleaginous host.

  19. Neo-Geometric Copper Nanocrystals by Competitive, Dual Surfactant-Mediated Facet Adsorption Controlling Skin Permeation

    Karmani Murugan

    2016-11-01

    Full Text Available Neogeometric copper nanoparticles (CuNPs have various applications yet its synthesis still proves to be challenging with regards to self-assembly and uniformity control. This study aimed to synthesize shape-specific CuNPs in the biomedical application of ascertaining skin permeation and retention of the CuNPs as a drug delivery system. The approach to the shape design involved the dual control of two surfactants to direct the shape organisation of the nanoparticles (NPs while an interesting aspect of the study showed the competitive adsorption of the surfactants onto the nanocrystal facets to direct facet growth. The resulting copper nanoparticles were characterised using X-ray diffraction (XRD and electron diffraction spectra analysis (EDS for elemental and crystalline analysis. Thermogravimetric Analysis (TGA identified the degradation of the surfactant coat and the synthesis of a novel copper-polymer complex and extensive transmission electron microscopy (TEM was conducted to determine the nanoparticle morphology. Epidermal skin tissue served as the model for permeation studies of five idealistic nano-geometries and investigated its application in drug delivery with regards to cellular internalisation and transbarrier transport of the geometric CuNPs. A mechanistic consideration for shape control is discussed.

  20. Biodiversity mediates top-down control in eelgrass ecosystems: a global comparative-experimental approach.

    Duffy, J Emmett; Reynolds, Pamela L; Boström, Christoffer; Coyer, James A; Cusson, Mathieu; Donadi, Serena; Douglass, James G; Eklöf, Johan S; Engelen, Aschwin H; Eriksson, Britas Klemens; Fredriksen, Stein; Gamfeldt, Lars; Gustafsson, Camilla; Hoarau, Galice; Hori, Masakazu; Hovel, Kevin; Iken, Katrin; Lefcheck, Jonathan S; Moksnes, Per-Olav; Nakaoka, Masahiro; O'Connor, Mary I; Olsen, Jeanine L; Richardson, J Paul; Ruesink, Jennifer L; Sotka, Erik E; Thormar, Jonas; Whalen, Matthew A; Stachowicz, John J

    2015-07-01

    Nutrient pollution and reduced grazing each can stimulate algal blooms as shown by numerous experiments. But because experiments rarely incorporate natural variation in environmental factors and biodiversity, conditions determining the relative strength of bottom-up and top-down forcing remain unresolved. We factorially added nutrients and reduced grazing at 15 sites across the range of the marine foundation species eelgrass (Zostera marina) to quantify how top-down and bottom-up control interact with natural gradients in biodiversity and environmental forcing. Experiments confirmed modest top-down control of algae, whereas fertilisation had no general effect. Unexpectedly, grazer and algal biomass were better predicted by cross-site variation in grazer and eelgrass diversity than by global environmental gradients. Moreover, these large-scale patterns corresponded strikingly with prior small-scale experiments. Our results link global and local evidence that biodiversity and top-down control strongly influence functioning of threatened seagrass ecosystems, and suggest that biodiversity is comparably important to global change stressors. © 2015 John Wiley & Sons Ltd/CNRS.

  1. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo.

    Douam, Florian; Soto Albrecht, Yentli E; Hrebikova, Gabriela; Sadimin, Evita; Davidson, Christian; Kotenko, Sergei V; Ploss, Alexander

    2017-08-15

    role of type III interferon (IFN)-mediated signaling, a host immune defense mechanism, in controlling YFV-17D infection and attenuation in different mouse models. We uncovered a critical role of type III IFN-mediated signaling in preserving the integrity of the blood-brain barrier and preventing viral brain invasion. Type III IFN also played a major role in regulating the induction of a potent but balanced immune response that prevented viral evasion of the host immune system. An improved understanding of the complex mechanisms regulating YFV-17D attenuation will provide insights into the key virus-host interactions that regulate host immune responses and infection outcomes as well as open novel avenues for the development of innovative vaccine strategies. Copyright © 2017 Douam et al.

  2. Light-activated control of protein channel assembly mediated by membrane mechanics

    Miller, David M.; Findlay, Heather E.; Ces, Oscar; Templer, Richard H.; Booth, Paula J.

    2016-12-01

    Photochemical processes provide versatile triggers of chemical reactions. Here, we use a photoactivated lipid switch to modulate the folding and assembly of a protein channel within a model biological membrane. In contrast to the information rich field of water-soluble protein folding, there is only a limited understanding of the assembly of proteins that are integral to biological membranes. It is however possible to exploit the foreboding hydrophobic lipid environment and control membrane protein folding via lipid bilayer mechanics. Mechanical properties such as lipid chain lateral pressure influence the insertion and folding of proteins in membranes, with different stages of folding having contrasting sensitivities to the bilayer properties. Studies to date have relied on altering bilayer properties through lipid compositional changes made at equilibrium, and thus can only be made before or after folding. We show that light-activation of photoisomerisable di-(5-[[4-(4-butylphenyl)azo]phenoxy]pentyl)phosphate (4-Azo-5P) lipids influences the folding and assembly of the pentameric bacterial mechanosensitive channel MscL. The use of a photochemical reaction enables the bilayer properties to be altered during folding, which is unprecedented. This mechanical manipulation during folding, allows for optimisation of different stages of the component insertion, folding and assembly steps within the same lipid system. The photochemical approach offers the potential to control channel assembly when generating synthetic devices that exploit the mechanosensitive protein as a nanovalve.

  3. ATM Mediates pRB Function To Control DNMT1 Protein Stability and DNA Methylation

    Suzuki, Misa; Hayashi, Naoyuki; Kobayashi, Masahiko; Sasaki, Nobunari; Nishiuchi, Takumi; Doki, Yuichiro; Okamoto, Takahiro; Kohno, Susumu; Muranaka, Hayato; Kitajima, Shunsuke; Yamamoto, Ken-ichi

    2013-01-01

    The retinoblastoma tumor suppressor gene (RB) product has been implicated in epigenetic control of gene expression owing to its ability to physically bind to many chromatin modifiers. However, the biological and clinical significance of this activity was not well elucidated. To address this, we performed genetic and epigenetic analyses in an Rb-deficient mouse thyroid C cell tumor model. Here we report that the genetic interaction of Rb and ATM regulates DNMT1 protein stability and hence controls the DNA methylation status in the promoters of at least the Ink4a, Shc2, FoxO6, and Noggin genes. Furthermore, we demonstrate that inactivation of pRB promotes Tip60 (acetyltransferase)-dependent ATM activation; allows activated ATM to physically bind to DNMT1, forming a complex with Tip60 and UHRF1 (E3 ligase); and consequently accelerates DNMT1 ubiquitination driven by Tip60-dependent acetylation. Our results indicate that inactivation of the pRB pathway in coordination with aberration in the DNA damage response deregulates DNMT1 stability, leading to an abnormal DNA methylation pattern and malignant progression. PMID:23754744

  4. Basomedial amygdala mediates top–down control of anxiety and fear

    Adhikari, Avishek; Lerner, Talia N.; Finkelstein, Joel; Pak, Sally; Jennings, Joshua H.; Davidson, Thomas J.; Ferenczi, Emily; Gunaydin, Lisa A.; Mirzabekov, Julie J.; Ye, Li; Kim, Sung-Yon; Lei, Anna; Deisseroth, Karl

    2016-01-01

    Anxiety-related conditions are among the most difficult neuropsychiatric diseases to treat pharmacologically, but respond to cognitive therapies. There has therefore been interest in identifying relevant top-down pathways from cognitive control regions in medial prefrontal cortex (mPFC). Identification of such pathways could contribute to our understanding of the cognitive regulation of affect, and provide pathways for intervention. Previous studies have suggested that dorsal and ventral mPFC subregions exert opposing effects on fear, as do subregions of other structures. However, precise causal targets for top-down connections among these diverse possibilities have not been established. Here we show that the basomedial amygdala (BMA) represents the major target of ventral mPFC in amygdala in mice. Moreover, BMA neurons differentiate safe and aversive environments, and BMA activation decreases fear-related freezing and high-anxiety states. Lastly, we show that the ventral mPFC–BMA projection implements top-down control of anxiety state and learned freezing, both at baseline and in stress-induced anxiety, defining a broadly relevant new top-down behavioural regulation pathway. PMID:26536109

  5. Endoplasmic reticulum quality control is involved in the mechanism of endoglin-mediated hereditary haemorrhagic telangiectasia.

    Bassam R Ali

    Full Text Available Hereditary haemorrhagic telangiectasia (HHT is an autosomal dominant genetic condition affecting the vascular system and is characterised by epistaxis, arteriovenous malformations and mucocutaneous and gastrointestinal telangiectases. This disorder affects approximately 1 in 8,000 people worldwide. Significant morbidity is associated with this condition in affected individuals, and anaemia can be a consequence of repeated haemorrhages from telangiectasia in the gut and nose. In the majority of the cases reported, the condition is caused by mutations in either ACVRL1 or endoglin genes, which encode components of the TGF-beta signalling pathway. Numerous missense mutations in endoglin have been reported as causative defects for HHT but the exact underlying cellular mechanisms caused by these mutations have not been fully established despite data supporting a role for the endoplasmic reticulum (ER quality control machinery. For this reason, we examined the subcellular trafficking of twenty-five endoglin disease-causing missense mutations. The mutant proteins were expressed in HeLa and HEK293 cell lines, and their subcellular localizations were established by confocal fluorescence microscopy alongside the analysis of their N-glycosylation profiles. ER quality control was found to be responsible in eight (L32R, V49F, C53R, V125D, A160D, P165L, I271N and A308D out of eleven mutants located on the orphan extracellular domain in addition to two (C363Y and C382W out of thirteen mutants in the Zona Pellucida (ZP domain. In addition, a single intracellular domain missense mutant was examined and found to traffic predominantly to the plasma membrane. These findings support the notion of the involvement of the ER's quality control in the mechanism of a significant number, but not all, missense endoglin mutants found in HHT type 1 patients. Other mechanisms including loss of interactions with signalling partners as well as adverse effects on functional

  6. Control of room-temperature defect-mediated ferromagnetism in VO{sub 2} films

    Yang, Tsung-Han, E-mail: tyang3@ncsu.edu [NSF Center for Advanced Materials and Smart Structures, Department of Materials Science and Engineering, North Carolina State University, Raleigh, NC 27695-7907 (United States); Nori, Sudhakar; Mal, Siddhartha; Narayan, Jagdish [NSF Center for Advanced Materials and Smart Structures, Department of Materials Science and Engineering, North Carolina State University, Raleigh, NC 27695-7907 (United States)

    2011-09-15

    We report interesting ferromagnetic properties and their control in a vanadium-based oxide system driven by stoichiometric defects. Vanadium oxide (VO{sub 2}) thin films were grown on c-plane sapphire substrates by a pulsed laser deposition technique under different ambient conditions. The ferromagnetism of the epitaxial VO{sub 2} films can be switched on and off by altering the cooling ambient parameters. In addition, the saturated magnetic moments and coercivity of the VO{sub 2} films were found to be a function of the oxygen partial pressure during the growth process. The room-temperature ferromagnetic properties of VO{sub 2} films were correlated with the nature of the microstructure and the growth parameters. The origin of the induced magnetic properties are qualitatively understood to stem from intrinsic structural and stoichiometric defects.

  7. Cell Density Control of Staphylococcal Virulence Mediated by an Octapeptide Pheromone

    Ji, Guangyong; Beavis, Ronald C.; Novick, Richard P.

    1995-12-01

    Some bacterial pathogens elaborate and secrete virulence factors in response to environmental signals, others in response to a specific host product, and still others in response to no discernible cue. In this study, we have demonstrated that the synthesis of Staphylococcus aureus virulence factors is controlled by a density-sensing system that utilizes an octapeptide produced by the organism itself. The octapeptide activates expression of the agr locus, a global regulator of the virulence response. This response involves the reciprocal regulation of genes encoding surface proteins and those encoding secreted virulence factors. As cells enter the postexponential phase, surface protein genes are repressed by agr and secretory protein genes are subsequently activated. The intracellular agr effector is a regulatory RNA, RNAIII, whose transcription is activated by an agr-encoded signal transduction system for which the octapeptide is the ligand.

  8. Competitive excitation and osmotic-pressure-mediated control of lasing modes in cholesteric liquid crystal microshells

    Lin, Ya-Li; Gong, Ling-Li; Che, Kai-Jun; Li, Sen-Sen; Chu, Cheng-Xu; Cai, Zhi-Ping; Yang, Chaoyong James; Chen, Lu-Jian

    2017-05-01

    We examined the end-pumped lasing behaviors of dye doped cholesteric liquid crystal (DDCLC) microshells which were fabricated by glass capillary microfluidics. Several kinds of mode resonances, including distributed feedback, Fabry-Pérot (FP), and whispering gallery (WG) modes, can be robustly constructed in each individual DDCLC microshell by varying the beam diameter, namely, tuning the DDCLC gain area. The FP and WG modes were further confirmed experimentally, and the corresponding lasing mechanisms are clearly revealed from the unique material characteristics of DDCLC and the geometrical structure of the microshell. Additionally, we demonstrated that the osmotic pressure can be used to shrink/expand the microshell, productively tuning the excitation of lasing modes in a controlled manner. We wish our findings can provide a new insight into the design of DDCLC microlasers with tunable optical properties.

  9. Globular adiponectin controls insulin-mediated vasoreactivity in muscle through AMPKα2

    de Boer, Michiel P; Meijer, Rick I; Richter, Erik

    2016-01-01

    Decreased tissue perfusion increases the risk of developing insulin resistance and cardiovascular disease in obesity, and decreased levels of globular adiponectin (gAdn) have been proposed to contribute to this risk. We hypothesized that gAdn controls insulin's vasoactive effects through AMP......-activated protein kinase (AMPK), specifically its α2 subunit, and studied the mechanisms involved. In healthy volunteers, we found that decreased plasma gAdn levels in obese subjects associate with insulin resistance and reduced capillary perfusion during hyperinsulinemia. In cultured human microvascular...... endothelial cells (HMEC), gAdn increased AMPK activity. In isolated muscle resistance arteries gAdn uncovered insulin-induced vasodilation by selectively inhibiting insulin-induced activation of ERK1/2, and the AMPK inhibitor compound C as well as genetic deletion of AMPKα2 blunted insulin...

  10. Assertive Anger Mediates Effects of Dialectical Behaviour-informed Skills Training for Borderline Personality Disorder: A Randomized Controlled Trial.

    Kramer, Ueli; Pascual-Leone, Antonio; Berthoud, Laurent; de Roten, Yves; Marquet, Pierre; Kolly, Stéphane; Despland, Jean-Nicolas; Page, Dominique

    2016-05-01

    Dialectical behaviour therapy (DBT)-informed skills training for borderline personality disorder (BPD) aims at the development of specific emotion regulation skills in patients, particularly with regard to the regulation of problematic anger. While the effects of dialectical behaviour skills training have been shown, their processes of change are rarely examined. Neacsiu, Rizvi and Linehan (2010) found that patient's self-reported use of emotion regulation skills was a mediator of therapeutic change in these treatments; however, they found no effect for problematic anger. From an integrative perspective on anger (Pascual-Leone & Greenberg, 2007; Pascual-Leone & Paivio, 2013), there are several forms of anger, varying in their degree of therapeutic productivity. The present add-on randomized controlled trial included n = 41 patients with BPD (n = 21 DBT-informed skills training versus n = 20 treatment as usual). The first study examined the outcome of the DBT-informed skills training encompassing basic components of training in mindfulness, distress tolerance, interpersonal effectiveness and emotion regulation. Results showed that symptom reduction was significantly greater in the DBT-informed skills training, compared with the treatment as usual. The second study used process assessment, for which all patient completers underwent a 50-min-long psychological interview both early and late in treatment, which was rated using the Classification of Affective Meaning States. DBT-informed skills training produced increased levels of primary 'assertive' anger, as compared with the treatment as usual, whereas no effect was found for 'rejecting' secondary anger. Most importantly, we showed that changes in assertive anger mediated the reported symptom reduction, in particular in patient's social roles. We discuss these results in the context of underlying mechanisms of change in DBT skills group treatments, in particular towards developing more productive forms of

  11. Gibberellin mediates daylength-controlled differentiation of vegetative meristems in strawberry (Fragaria × ananassa Duch

    Moritz Thomas

    2009-02-01

    Full Text Available Abstract Background Differentiation of long and short shoots is an important developmental trait in several species of the Rosaceae family. However, the physiological mechanisms controlling this differentiation are largely unknown. We have studied the role of gibberellin (GA in regulation of shoot differentiation in strawberry (Fragaria × ananassa Duch. cv. Korona. In strawberry, differentiation of axillary buds to runners (long shoot or to crown branches (short shoot is promoted by long-day and short-day conditions, respectively. Formation of crown branches is a prerequisite for satisfactory flowering because inflorescences are formed from the apical meristems of the crown. Results We found that both prohexadione-calcium and short photoperiod inhibited runner initiation and consequently led to induction of crown branching. In both cases, this correlated with a similar decline in GA1 level. Exogenous GA3 completely reversed the effect of prohexadione-calcium in a long photoperiod, but was only marginally effective in short-day grown plants. However, transfer of GA3-treated plants from short days to long days restored the normal runner formation. This did not occur in plants that were not treated with GA3. We also studied GA signalling homeostasis and found that the expression levels of several GA biosynthetic, signalling and target genes were similarly affected by prohexadione-calcium and short photoperiod in runner tips and axillary buds, respectively. Conclusion GA is needed for runner initiation in strawberry, and the inhibition of GA biosynthesis leads to the formation of crown branches. Our findings of similar changes in GA levels and in GA signalling homeostasis after prohexadione-calcium and short-day treatments, and photoperiod-dependent responsiveness of the axillary buds to GA indicate that GA plays a role also in the photoperiod-regulated differentiation of axillary buds. We propose that tightly regulated GA activity may control

  12. A Coincidence Detection Mechanism Controls PX-BAR Domain-Mediated Endocytic Membrane Remodeling via an Allosteric Structural Switch.

    Lo, Wen-Ting; Vujičić Žagar, Andreja; Gerth, Fabian; Lehmann, Martin; Puchkov, Dymtro; Krylova, Oxana; Freund, Christian; Scapozza, Leonardo; Vadas, Oscar; Haucke, Volker

    2017-11-20

    Clathrin-mediated endocytosis occurs by bending and remodeling of the membrane underneath the coat. Bin-amphiphysin-rvs (BAR) domain proteins are crucial for endocytic membrane remodeling, but how their activity is spatiotemporally controlled is largely unknown. We demonstrate that the membrane remodeling activity of sorting nexin 9 (SNX9), a late-acting endocytic PX-BAR domain protein required for constriction of U-shaped endocytic intermediates, is controlled by an allosteric structural switch involving coincident detection of the clathrin adaptor AP2 and phosphatidylinositol-3,4-bisphosphate (PI(3,4)P 2 ) at endocytic sites. Structural, biochemical, and cell biological data show that SNX9 is autoinhibited in solution. Binding to PI(3,4)P 2 via its PX-BAR domain, and concomitant association with AP2 via sequences in the linker region, releases SNX9 autoinhibitory contacts to enable membrane constriction. Our results reveal a mechanism for restricting the latent membrane remodeling activity of BAR domain proteins to allow spatiotemporal coupling of membrane constriction to the progression of the endocytic pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Disintegration mediated controlled release supersaturating solid dispersion formulation of an insoluble drug: design, development, optimization, and in vitro evaluation.

    Verma, Sanjay; Rudraraju, Varma S

    2015-02-01

    The objective of this study was to develop a solid dispersion based controlled release system for drug substances that are poorly soluble in water. A wax-based disintegration mediated controlled release system was designed based on the fact that an amorphous drug can crystallize out from hydrophilic matrices. For this study, cilostazol (CIL) was selected as the model drug, as it exhibits poor aqueous solubility. An amorphous solid dispersion was prepared to assist the drug to attain a supersaturated state. Povidone was used as carrier for solid dispersion (spray drying technique), hydrogenated vegetable oil (HVO) as wax matrix former, and sodium carboxymethyl cellulose (NaCMC) as a disintegrant. The extreme vertices mixture design (EVMD) was applied to optimize the designed and developed composition. The optimized formulation provided a dissolution pattern which was equivalent to the predicted curve, ascertaining that the optimal formulation could be accomplished with EVMD. The release profile of CIL was described by the Higuchi's model better than zero-order, first-order, and Hixson-Crowell's model, which indicated that the supersaturation state of CIL dominated to allow drug release by diffusion rather than disintegration regulated release as is generally observed by Hixson-Crowell's model. The optimized composition was evaluated for disintegration, dissolution, XRD, and stability studies. It was found that the amorphous state as well as the dissolution profile of CIL was maintained under the accelerated conditions of 40°C/75% RH for 6 months.

  14. Foodborne Infectious Diseases Mediated by Inappropriate Infection Control in Food Service Businesses and Relevant Countermeasures in Korea.

    Park, Jong Myong; You, Young-Hyun; Cho, Hyun-Min; Hong, Ji Won; Ghim, Sa-Youl

    2017-06-01

    The objective of this review is to propose an appropriate course of action for improving the guidelines followed by food handlers for control of infection. For this purpose, previous epidemiological reports related to acute gastroenteritis in food service businesses mediated by food handlers were intensively analyzed. Relevant studies were identified in international databases. We selected eligible papers reporting foodborne infectious disease outbreaks. Among primary literature collection, the abstract of each article was investigated to find cases that absolutely identified a causative factor to be food handlers' inappropriate infection control and the taxon of causative microbial agents by epidemiological methodologies. Information about the sites (type of food business) where the outbreaks occurred was investigated. A wide variety of causative microbial agents has been investigated, using several epidemiological methods. These agents have shown diverse propagation pathways based on their own molecular pathogenesis, physiology, taxonomy, and etiology. Depending on etiology, transmission, propagation, and microbiological traits, we can predict the transmission characteristics of pathogens in food preparation areas. The infected food workers have a somewhat different ecological place in infection epidemiology as compared to the general population. However, the current Korean Food Safety Act cannot propose detailed guidelines. Therefore, different methodologies have to be made available to prevent further infections.

  15. Sutureless liver repair and hemorrhage control using laser-mediated fusion of human albumin as a solder.

    Wadia, Y; Xie, H; Kajitani, M

    2001-07-01

    Major liver trauma has a high mortality because of immediate exsanguination and a delayed morbidity from septicemia, peritonitis, biliary fistulae, and delayed secondary hemorrhage. We evaluated laser soldering using liquid albumin for welding liver injuries. Fourteen lacerations (6 x 2 cm) and 13 nonanatomic resection injuries (raw surface, 8 x 2 cm) were repaired. An 805-nm laser was used to weld 53% liquid albumin-indocyanine green solder to the liver surface, reinforcing it by welding a free autologous omental scaffold. The animals were heparinized and hepatic inflow occlusion was used for vascular control. For both laceration and resection injuries, 16 soldering repairs were evaluated acutely at 3 hours. Eleven animals were evaluated chronically, two at 2 weeks and nine at 4 weeks. All 27 laser mediated-liver repairs had minimal blood loss compared with the suture controls. No dehiscence, hemorrhage, or bile leakage was seen in any of the laser repairs after 3 hours. All 11 chronic repairs healed without complication. This modality effectively seals the liver surface, joins lacerations with minimal thermal injury, and works independently of the patient's coagulation status.

  16. The mediating effect of Mediterranean diet on the relation between smoking and colorectal cancer: a case-control study.

    Kontou, Niki; Psaltopoulou, Theodora; Soupos, Nick; Polychronopoulos, Evangelos; Xinopoulos, Dimitrios; Linos, Athena; Panagiotakos, Demosthenes B

    2013-10-01

    The protective role of Mediterranean diet (MD) and the detrimental effect of smoking on colorectal cancer (CRC) have already been shown. The aim of this work was to evaluate the potential mediating effect of MD on the association between the aforementioned factor (smoking) and CRC. It is a case-control study. Two hundred fifty consecutive patients with CRC (63 ± 12 years, 59% males) and 250 age-sex group-matched controls, both from the area of Attica, were studied. Various socio-demographic, clinical, lifestyle (including detailed smoking habits) and dietary characteristics were measured. Adherence to the MD was evaluated using the MedDietScore (theoretical range 0-55). Each unit increase in the MedDietScore was associated with 13% lower likelihood of CRC (P Smoking habits were associated with 2.9-fold the likelihood of CRC among participants who were away from the MD (i.e. MedDietScore smoking habits with CRC, suggesting indirect benefits of adherence to this dietary pattern with regards to CRC morbidity and mortality.

  17. Diffusion-controlled oxygen reduction on multi-copper oxidase-adsorbed carbon aerogel electrodes without mediator

    Tsujimura, S.; Kamitaka, Y.; Kano, K. [Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto (Japan)

    2007-12-15

    Bioelectrocatalytic reduction of O{sub 2} into water was archived at diffusion-controlled rate by using enzymes (laccase from Trametes sp. and bilirubin oxidase from Myrothecium verrucaria, which belong to the family of multi-copper oxidase) adsorbed on mesoporous carbon aerogel particle without a mediator. The current density was predominantly controlled by the diffusion of dissolved O{sub 2} in rotating-disk electrode experiments, and reached a value as large as 10 mA cm{sup -2} at 1 atm O{sub 2}, 25 C, and 8,000 rpm on the laccase-adsorbed electrode. The overpotential of the bioelectrocatalytic reduction of O{sub 2} was 0.4-0.55 V smaller than that observed on a Pt disk electrode. Without any optimization, the laccase-adsorbed biocathode showed stable current intensity of the O{sub 2} reduction in an air-saturated buffer at least for 10 days under continuous flow system. (Abstract Copyright [2007], Wiley Periodicals, Inc.)

  18. Sleep-Related Safety Behaviors and Dysfunctional Beliefs Mediate the Efficacy of Online CBT for Insomnia: A Randomized Controlled Trial.

    Lancee, Jaap; Eisma, Maarten C; van Straten, Annemieke; Kamphuis, Jan H

    2015-01-01

    Several trials have demonstrated the efficacy of online cognitive behavioral therapy (CBT) for insomnia. However, few studies have examined putative mechanisms of change based on the cognitive model of insomnia. Identification of modifiable mechanisms by which the treatment works may guide efforts to further improve the efficacy of insomnia treatment. The current study therefore has two aims: (1) to replicate the finding that online CBT is effective for insomnia and (2) to test putative mechanism of change (i.e., safety behaviors and dysfunctional beliefs). Accordingly, we conducted a randomized controlled trial in which individuals with insomnia were randomized to either online CBT for insomnia (n = 36) or a waiting-list control group (n = 27). Baseline and posttest assessments included questionnaires assessing insomnia severity, safety behaviors, dysfunctional beliefs, anxiety and depression, and a sleep diary. Three- and six-month assessments were administered to the CBT group only. Results show moderate to large statistically significant effects of the online treatment compared to the waiting list on insomnia severity, sleep measures, sleep safety behaviors, and dysfunctional beliefs. Furthermore, dysfunctional beliefs and safety behaviors mediated the effects of treatment on insomnia severity and sleep efficiency. Together, these findings corroborate the efficacy of online CBT for insomnia, and suggest that these effects were produced by changing maladaptive beliefs, as well as safety behaviors. Treatment protocols for insomnia may specifically be enhanced by more focused attention on the comprehensive fading of sleep safety behaviors, for instance through behavioral experiments.

  19. Coping Styles Mediate the Relationship Between Self-esteem, Health Locus of Control, and Health-Promoting Behavior in Chinese Patients With Coronary Heart Disease.

    Zou, Huijing; Tian, Qian; Chen, Yuxia; Cheng, Cheng; Fan, Xiuzhen

    Health-promoting behavior plays an important role in reducing the burden of coronary heart disease. Self-esteem and health locus of control may contribute to health-promoting behavior, and coping styles may mediate these associations. The aims of our study were to examine whether self-esteem and health locus of control are associated with health-promoting behavior and examine the possible mediating effect of coping styles in patients with coronary heart disease. Health-promoting behavior, self-esteem, health locus of control, and coping styles were assessed in 272 hospitalized patients (60 ± 12 years, 61% male) with coronary heart disease. Hierarchical regression analysis was conducted to analyze the relationships between health-promoting behavior and other variables. Mediation effect was examined according to the methods of Baron and Kenny. The mean score for health-promoting behavior was 2.57 ± 0.51; 38.2% of patients (n = 104) scored lower than 2.5. Self-esteem (β = .139, P locus of control and health-promoting behavior. Confrontation plays a mediating role in the association among self-esteem, internal health locus of control, and health-promoting behavior. Strategies should be undertaken to encourage the use of confrontation coping style, which will facilitate health-promoting behavior.

  20. Compartmentalized Regulation of Parkin-Mediated Mitochondrial Quality Control in the Drosophila Nervous System In Vivo

    Sung, Hyun; Tandarich, Lauren C.; Nguyen, Kenny

    2016-01-01

    In neurons, the normal distribution and selective removal of mitochondria are considered essential for maintaining the functions of the large asymmetric cell and its diverse compartments. Parkin, a E3 ubiquitin ligase associated with familial Parkinson's disease, has been implicated in mitochondrial dynamics and removal in cells including neurons. However, it is not clear how Parkin functions in mitochondrial turnover in vivo, or whether Parkin-dependent events of the mitochondrial life cycle occur in all neuronal compartments. Here, using the live Drosophila nervous system, we investigated the involvement of Parkin in mitochondrial dynamics, distribution, morphology, and removal. Contrary to our expectations, we found that Parkin-deficient animals do not accumulate senescent mitochondria in their motor axons or neuromuscular junctions; instead, they contain far fewer axonal mitochondria, and these displayed normal motility behavior, morphology, and metabolic state. However, the loss of Parkin did produce abnormal tubular and reticular mitochondria restricted to the motor cell bodies. In addition, in contrast to drug-treated, immortalized cells in vitro, mature motor neurons rarely displayed Parkin-dependent mitophagy. These data indicate that the cell body is the focus of Parkin-dependent mitochondrial quality control in neurons, and argue that a selection process allows only healthy mitochondria to pass from cell bodies to axons, perhaps to limit the impact of mitochondrial dysfunction. SIGNIFICANCE STATEMENT Parkin has been proposed to police mitochondrial fidelity by binding to dysfunctional mitochondria via PTEN (phosphatase and tensin homolog)-induced putative kinase 1 (PINK1) and targeting them for autophagic degradation. However, it is unknown whether and how the PINK1/Parkin pathway regulates the mitochondrial life cycle in neurons in vivo. Using Drosophila motor neurons, we show that parkin disruption generates an abnormal mitochondrial network in cell

  1. A Technology-Mediated Behavioral Weight Gain Prevention Intervention for College Students: Controlled, Quasi-Experimental Study.

    West, Delia Smith; Monroe, Courtney M; Turner-McGrievy, Gabrielle; Sundstrom, Beth; Larsen, Chelsea; Magradey, Karen; Wilcox, Sara; Brandt, Heather M

    2016-06-13

    Both men and women are vulnerable to weight gain during the college years, and this phenomenon is linked to an increased risk of several chronic diseases and mortality. Technology represents an attractive medium for the delivery of weight control interventions focused on college students, given its reach and appeal among this population. However, few technology-mediated weight gain prevention interventions have been evaluated for college students. This study examined a new technology-based, social media-facilitated weight gain prevention intervention for college students. Undergraduates (n =58) in two sections of a public university course were allocated to either a behavioral weight gain prevention intervention (Healthy Weight, HW; N=29) or a human papillomavirus (HPV) vaccination awareness intervention (control; N=29). All students were enrolled, regardless of initial body weight or expressed interest in weight management. The interventions delivered 8 lessons via electronic newsletters and Facebook postings over 9 weeks, which were designed to foster social support and introduce relevant educational content. The HW intervention targeted behavioral strategies to prevent weight gain and provided participants with a Wi-Fi-enabled scale and an electronic physical activity tracker to facilitate weight regulation. A repeated-measures analysis of variance was conducted to examine within- and between-group differences in measures of self-reported weight control practices and objectively measured weight. Use of each intervention medium and device was objectively tracked, and intervention satisfaction measures were obtained. Students remained weight stable (HW: -0.48+1.9 kg; control: -0.45+1.4 kg), with no significant difference between groups over 9 weeks (P =.94). However, HW students reported a significantly greater increase in the number of appropriate weight control strategies than did controls (2.1+4.5 vs -1.1+3.4, respectively; P =.003) and there was no increase in

  2. Morphological control of strontium oxalate particles by PSMA-mediated precipitation reaction

    Yu Jiaguo [State Key Laboratory of Advanced Technology for Material Synthesis and Processing, Wuhan University of Technology, Wuhan 430070 (China)]. E-mail: jiaguoyu@yahoo.com; Tang Hua [State Key Laboratory of Advanced Technology for Material Synthesis and Processing, Wuhan University of Technology, Wuhan 430070 (China); Cheng Bei [State Key Laboratory of Advanced Technology for Material Synthesis and Processing, Wuhan University of Technology, Wuhan 430070 (China)

    2005-05-15

    In this paper, strontium oxalate particles with different morphologies could be easily obtained by a precipitation reaction of sodium oxalate with strontium chloride in the absence and presence of poly-(styrene-alt-maleic acid) (PSMA). The as-prepared products were characterized with scanning electron microscopy and X-ray diffraction. The effects of pH, aging time and concentration of PSMA on the phase structures and morphologies of the as-prepared strontium oxalate particles were investigated and discussed. The results showed that strontium oxalate particles with various morphologies, such as, bi-pyramids, rods, peanuts, and spherical particles, etc., could be obtained by varying the experimental conditions. PSMA promoted the formation of strontium oxalate dihydrate (SOD) phase. Suitable pH values (pH 7 and 8) favor the formation of the peanut-shaped SrC{sub 2}O{sub 4} particles. This research may provide new insight into the control of morphologies and phase structures of strontium oxalate particles and the biomimetic synthesis of novel inorganic materials.

  3. Aven-mediated checkpoint kinase control regulates proliferation and resistance to chemotherapy in conventional osteosarcoma.

    Baranski, Zuzanna; Booij, Tijmen H; Cleton-Jansen, Anne-Marie; Price, Leo S; van de Water, Bob; Bovée, Judith V M G; Hogendoorn, Pancras C W; Danen, Erik H J

    2015-07-01

    Conventional high-grade osteosarcoma is the most common primary bone sarcoma, with relatively high incidence in young people. In this study we found that expression of Aven correlates inversely with metastasis-free survival in osteosarcoma patients and is increased in metastases compared to primary tumours. Aven is an adaptor protein that has been implicated in anti-apoptotic signalling and serves as an oncoprotein in acute lymphoblastic leukaemia. In osteosarcoma cells, silencing Aven triggered G2 cell-cycle arrest; Chk1 protein levels were attenuated and ATR-Chk1 DNA damage response signalling in response to chemotherapy was abolished in Aven-depleted osteosarcoma cells, while ATM, Chk2 and p53 activation remained intact. Osteosarcoma is notoriously difficult to treat with standard chemotherapy, and we examined whether pharmacological inhibition of the Aven-controlled ATR-Chk1 response could sensitize osteosarcoma cells to genotoxic compounds. Indeed, pharmacological inhibitors targeting Chk1/Chk2 or those selective for Chk1 synergized with standard chemotherapy in 2D cultures. Likewise, in 3D extracellular matrix-embedded cultures, Chk1 inhibition led to effective sensitization to chemotherapy. Together, these findings implicate Aven in ATR-Chk1 signalling and point towards Chk1 inhibition as a strategy to sensitize human osteosarcomas to chemotherapy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  4. A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism.

    Shah, Meera; Su, Dan; Scheliga, Judith S; Pluskal, Tomáš; Boronat, Susanna; Motamedchaboki, Khatereh; Campos, Alexandre Rosa; Qi, Feng; Hidalgo, Elena; Yanagida, Mitsuhiro; Wolf, Dieter A

    2016-08-16

    The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement

    Louie, Gordon; Noel, Joseph P.; Baran, Phil S.; Palfey, Bruce; Moore, Bradley S.

    2013-01-01

    Flavoproteins catalyze a diversity of fundamental redox reactions and are one of the most studied enzyme families1,2. As monooxygenases, they are universally thought to control oxygenation by means of a peroxyflavin species that transfers a single atom of molecular oxygen to an organic substrate1,3,4. Here we report that the bacterial flavoenzyme EncM5,6 catalyzes the peroxyflavin-independent oxygenation-dehydrogenation dual oxidation of a highly reactive poly(β-carbonyl). The crystal structure of EncM with bound substrate mimics coupled with isotope labeling studies reveal previously unknown flavin redox biochemistry. We show that EncM maintains an unanticipated stable flavin oxygenating species, proposed to be a flavin-N5-oxide, to promote substrate oxidation and trigger a rare Favorskii-type rearrangement that is central to the biosynthesis of the antibiotic enterocin. This work provides new insight into the fine-tuning of the flavin cofactor in offsetting the innate reactivity of a polyketide substrate to direct its efficient electrocyclization. PMID:24162851

  6. Topographically mediated controls on aboveground biomass across a mediterranean-type landscape

    Dahlin, K.; Asner, G. P.; Field, C. B.

    2009-12-01

    Aboveground biomass accumulation is a useful metric for evaluating habitat restoration and ecosystem services projects, in addition to being a robust measure of carbon sequestration. However, at the landscape scale non-anthropogenic controls on biomass accumulation are poorly understood. In this study we combined field measurements, high resolution data from the NASA JPL Airborne Visible/Infrared Imaging Spectrometer (AVIRIS), and the Carnegie Airborne Observatory (CAO) airborne light detection and ranging (lidar) system to create a comprehensive map of aboveground biomass across a patchy mediterranean-type landscape (Jasper Ridge Biological Preserve, Stanford, CA). Candidate explanatory variables (e.g. slope, elevation, incident solar radiation) were developed using a geologic map and a digital elevation model derived from the lidar data. Finally, candidate variables were tested, and a model was produced to predict aboveground biomass from environmental data. Though many of the explanatory variables have only indirect effects on plant growth, the model permits inferences to be made about the relative importance of light, water, temperature, and edaphic characteristics on carbon accumulation in mediterranean-type systems.

  7. A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism

    Meera Shah

    2016-08-01

    Full Text Available The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer.

  8. Control of GABARAP-mediated autophagy by the Golgi complex, centrosome and centriolar satellites.

    Joachim, Justin; Tooze, Sharon A

    2018-01-01

    Within minutes of induction of autophagy by amino-acid starvation in mammalian cells, multiple autophagosomes form throughout the cell cytoplasm. During their formation, the autophagosomes sequester cytoplasmic material and deliver it to lysosomes for degradation. How these organelles can be so rapidly formed and how their formation is acutely regulated are major questions in the autophagy field. Protein and lipid trafficking from diverse cell compartments contribute membrane to, or regulate the formation of the autophagosome. In addition, recruitment of Atg8 (in yeast), and the ATG8-family members (in mammalian cells) to autophagosomes is required for efficient autophagy. Recently, it was discovered that the centrosome and centriolar satellites regulate autophagosome formation by delivery of an ATG8-family member, GABARAP, to the forming autophagosome membrane, the phagophore. We propose that GABARAP regulates phagophore expansion by activating the ULK complex, the amino-acid controlled initiator complex. This finding reveals a previously unknown link between the centrosome, centriolar satellites and autophagy. © 2017 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

  9. NAMPT-mediated salvage synthesis of NAD+ controls morphofunctional changes of macrophages.

    Gerda Venter

    Full Text Available Functional morphodynamic behavior of differentiated macrophages is strongly controlled by actin cytoskeleton rearrangements, a process in which also metabolic cofactors ATP and NAD(H (i.e. NAD+ and NADH and NADP(H (i.e. NADP+ and NADPH play an essential role. Whereas the link to intracellular ATP availability has been studied extensively, much less is known about the relationship between actin cytoskeleton dynamics and intracellular redox state and NAD+-supply. Here, we focus on the role of nicotinamide phosphoribosyltransferase (NAMPT, found in extracellular form as a cytokine and growth factor, and in intracellular form as one of the key enzymes for the production of NAD+ in macrophages. Inhibition of NAD+ salvage synthesis by the NAMPT-specific drug FK866 caused a decrease in cytosolic NAD+ levels in RAW 264.7 and Maf-DKO macrophages and led to significant downregulation of the glycolytic flux without directly affecting cell viability, proliferation, ATP production capacity or mitochondrial respiratory activity. Concomitant with these differential metabolic changes, the capacity for phagocytic ingestion of particles and also substrate adhesion of macrophages were altered. Depletion of cytoplasmic NAD+ induced cell-morphological changes and impaired early adhesion in phagocytosis of zymosan particles as well as spreading performance. Restoration of NAD+ levels by NAD+, NMN, or NADP+ supplementation reversed the inhibitory effects of FK866. We conclude that direct coupling to local, actin-based, cytoskeletal dynamics is an important aspect of NAD+'s cytosolic role in the regulation of morphofunctional characteristics of macrophages.

  10. NAMPT-Mediated Salvage Synthesis of NAD+ Controls Morphofunctional Changes of Macrophages

    Venter, Gerda; Oerlemans, Frank T. J. J.; Willemse, Marieke; Wijers, Mietske; Fransen, Jack A. M.; Wieringa, Bé

    2014-01-01

    Functional morphodynamic behavior of differentiated macrophages is strongly controlled by actin cytoskeleton rearrangements, a process in which also metabolic cofactors ATP and NAD(H) (i.e. NAD+ and NADH) and NADP(H) (i.e. NADP+ and NADPH) play an essential role. Whereas the link to intracellular ATP availability has been studied extensively, much less is known about the relationship between actin cytoskeleton dynamics and intracellular redox state and NAD+-supply. Here, we focus on the role of nicotinamide phosphoribosyltransferase (NAMPT), found in extracellular form as a cytokine and growth factor, and in intracellular form as one of the key enzymes for the production of NAD+ in macrophages. Inhibition of NAD+ salvage synthesis by the NAMPT-specific drug FK866 caused a decrease in cytosolic NAD+ levels in RAW 264.7 and Maf-DKO macrophages and led to significant downregulation of the glycolytic flux without directly affecting cell viability, proliferation, ATP production capacity or mitochondrial respiratory activity. Concomitant with these differential metabolic changes, the capacity for phagocytic ingestion of particles and also substrate adhesion of macrophages were altered. Depletion of cytoplasmic NAD+ induced cell-morphological changes and impaired early adhesion in phagocytosis of zymosan particles as well as spreading performance. Restoration of NAD+ levels by NAD+, NMN, or NADP+ supplementation reversed the inhibitory effects of FK866. We conclude that direct coupling to local, actin-based, cytoskeletal dynamics is an important aspect of NAD+’s cytosolic role in the regulation of morphofunctional characteristics of macrophages. PMID:24824795

  11. The Mediator co-activator complex regulates Ty1 retromobility by controlling the balance between Ty1i and Ty1 promoters.

    Salinero, Alicia C; Knoll, Elisabeth R; Zhu, Z Iris; Landsman, David; Curcio, M Joan; Morse, Randall H

    2018-02-01

    The Ty1 retrotransposons present in the genome of Saccharomyces cerevisiae belong to the large class of mobile genetic elements that replicate via an RNA intermediary and constitute a significant portion of most eukaryotic genomes. The retromobility of Ty1 is regulated by numerous host factors, including several subunits of the Mediator transcriptional co-activator complex. In spite of its known function in the nucleus, previous studies have implicated Mediator in the regulation of post-translational steps in Ty1 retromobility. To resolve this paradox, we systematically examined the effects of deleting non-essential Mediator subunits on the frequency of Ty1 retromobility and levels of retromobility intermediates. Our findings reveal that loss of distinct Mediator subunits alters Ty1 retromobility positively or negatively over a >10,000-fold range by regulating the ratio of an internal transcript, Ty1i, to the genomic Ty1 transcript. Ty1i RNA encodes a dominant negative inhibitor of Ty1 retromobility that blocks virus-like particle maturation and cDNA synthesis. These results resolve the conundrum of Mediator exerting sweeping control of Ty1 retromobility with only minor effects on the levels of Ty1 genomic RNA and the capsid protein, Gag. Since the majority of characterized intrinsic and extrinsic regulators of Ty1 retromobility do not appear to effect genomic Ty1 RNA levels, Mediator could play a central role in integrating signals that influence Ty1i expression to modulate retromobility.

  12. Diabetes-specific emotional distress mediates the association between depressive symptoms and glycaemic control in Type 1 and Type 2 diabetes.

    Bastelaar, K.M. van; Pouwer, F.; Geelhoed-Duijvestijn, P.H.; Tack, C.J.J.; Bazelmans, E.; Beekman, A.T.; Heine, R.J.; Snoek, F.J.

    2010-01-01

    OBJECTIVES: To investigate whether diabetes-specific emotional distress mediates the relationship between depression and glycaemic control in patients with Type 1 and Type 2 diabetes. RESEARCH DESIGN AND METHODS: Data were derived from the baseline assessment of a depression in diabetes screening

  13. Do Different ADHD-Related Etiological Risks Involve Specific Neuropsychological Pathways? An Analysis of Mediation Processes by Inhibitory Control and Delay Aversion

    Pauli-Pott, Ursula; Dalir, Silke; Mingebach, Tanja; Roller, Alisa; Becker, Katja

    2013-01-01

    Background: Inhibitory control (IC) has been regarded as a neuropsychological basic deficit and as an endophenotype of attention deficit/hyperactivity disorder (ADHD). Implicated here are mediation processes between etiological factors and ADHD symptoms. We thus analyze whether and to what extent executive IC and delay aversion (DA; i.e.,…

  14. Self-Efficacy and Social Support Mediate the Relationship between Internal Health Locus of Control and Health Behaviors in College Students

    Marr, Joni; Wilcox, Sara

    2015-01-01

    Background: Internal health locus of control has been associated with positive health outcomes and behaviors. Understanding the mechanisms of this relationship are key to designing and implementing effective health behavior intervention programs. Purpose: The purpose was to examine whether self-efficacy and social support mediate the relationship…

  15. The coping with depression course: Short term outcomes and mediating effects of a randomized controlled trial in the treatment of subclinical depression

    Allart-van Dam, E.; Hosman, C.M.H.; Hoogduin, C.A.L.; Schaap, C.P.D.R.

    2003-01-01

    This article reports on a randomized controlled trial investigating the short-term effectiveness of the Coping With Depression course in a sample of adults seriously at risk of developing major depression. In addition, possible mediating properties of several proximal outcome variables were

  16. The Coping with Depression course : Short-term outcomes and mediating effects of a randomized controlled trial in the treatment of subclinical depression

    Allart-van Dam, E; Hosman, CMH; Hoogduin, CAL; Schaap, CPDR

    2003-01-01

    This article reports on a randomized controlled trial investigating the short-term effectiveness of the Coping With Depression course in a sample of adults seriously at risk of developing major depression. In addition, possible mediating properties of several proximal outcome variables were

  17. Child Effortful Control as a Mediator of Parenting Practices on Externalizing Behavior: Evidence for a Sex-Differentiated Pathway across the Transition from Preschool to School

    Chang, Hyein; Olson, Sheryl L.; Sameroff, Arnold J.; Sexton, Holly R.

    2011-01-01

    An explanatory model for children's development of disruptive behavior across the transition from preschool to school was tested. It was hypothesized that child effortful control would mediate the effects of parenting on children's externalizing behavior and that child sex would moderate these relations. Participants were 241 children (123 boys)…

  18. Parent-Mediated Intervention for One-Year-Olds Screened as At-Risk for Autism Spectrum Disorder: A Randomized Controlled Trial

    Watson, Linda R.; Crais, Elizabeth R.; Baranek, Grace T.; Turner-Brown, Lauren; Sideris, John; Wakeford, Linn; Kinard, Jessica; Reznick, J. Steven; Martin, Katrina L.; Nowell, Sallie W.

    2017-01-01

    Theoretically, interventions initiated with at-risk infants prior to the point in time a definitive autism spectrum disorder (ASD) diagnosis can be made will improve outcomes. Pursuing this idea, we tested the efficacy of a parent-mediated early intervention called Adapted Responsive Teaching (ART) via a randomized controlled trial with 87…

  19. An online community improves adherence in an internet-mediated walking program. Part 1: results of a randomized controlled trial.

    Richardson, Caroline R; Buis, Lorraine R; Janney, Adrienne W; Goodrich, David E; Sen, Ananda; Hess, Michael L; Mehari, Kathleen S; Fortlage, Laurie A; Resnick, Paul J; Zikmund-Fisher, Brian J; Strecher, Victor J; Piette, John D

    2010-12-17

    Approximately half of American adults do not meet recommended physical activity guidelines. Face-to-face lifestyle interventions improve health outcomes but are unlikely to yield population-level improvements because they can be difficult to disseminate, expensive to maintain, and inconvenient for the recipient. In contrast, Internet-based behavior change interventions can be disseminated widely at a lower cost. However, the impact of some Internet-mediated programs is limited by high attrition rates. Online communities that allow participants to communicate with each other by posting and reading messages may decrease participant attrition. Our objective was to measure the impact of adding online community features to an Internet-mediated walking program on participant attrition and average daily step counts. This randomized controlled trial included sedentary, ambulatory adults who used email regularly and had at least 1 of the following: overweight (body mass index [BMI] ≥ 25), type 2 diabetes, or coronary artery disease. All participants (n = 324) wore enhanced pedometers throughout the 16-week intervention and uploaded step-count data to the study server. Participants could log in to the study website to view graphs of their walking progress, individually-tailored motivational messages, and weekly calculated goals. Participants were randomized to 1 of 2 versions of a Web-based walking program. Those randomized to the "online community" arm could post and read messages with other participants while those randomized to the "no online community" arm could not read or post messages. The main outcome measures were participant attrition and average daily step counts over 16 weeks. Multiple regression analyses assessed the effect of the online community access controlling for age, sex, disease status, BMI, and baseline step counts. Both arms significantly increased their average daily steps between baseline and the end of the intervention period, but there were no

  20. Examination of mid-intervention mediating effects on objectively assessed sedentary time among children in the Transform-Us! cluster-randomized controlled trial.

    Carson, Valerie; Salmon, Jo; Arundell, Lauren; Ridgers, Nicola D; Cerin, Ester; Brown, Helen; Hesketh, Kylie D; Ball, Kylie; Chinapaw, Mai; Yildirim, Mine; Daly, Robin M; Dunstan, David W; Crawford, David

    2013-05-20

    The optimal targets and strategies for effectively reducing sedentary behavior among young people are unknown. Intervention research that explores changes in mediated effects as well as in outcome behaviors is needed to help inform more effective interventions. Therefore, the purpose of this study was to examine the mid-intervention mediating effects on children's objectively assessed classroom and total weekday sedentary time in the Transform-Us! intervention. The results are based on 293 children, aged 7- to 9-years-old at baseline, from 20 schools in Melbourne, Australia. Each school was randomly allocated to one of four groups, which targeted reducing sedentary time in the school and family settings (SB; n = 74), increasing or maintaining moderate- to vigorous-intensity physical activity in the school and family settings (PA; n = 75), combined SB and PA (SB + PA; n = 80), or the current practice control (C; n = 64). Baseline and mid-intervention data (5-9 months) were collected in 2010 and analyzed in 2012. Classroom and total weekday sedentary time was objectively assessed using ActiGraph accelerometers. The hypothesized mediators including, child enjoyment, parent and teacher outcome expectancies, and child perceived access to standing opportunities in the classroom environment, were assessed by questionnaire. The SB + PA group spent 13.3 min/day less in weekday sedentary time at mid-intervention compared to the control group. At mid-intervention, children in the SB group had higher enjoyment of standing in class (0.9 units; 5-unit scale) and all intervention groups had more positive perceptions of access to standing opportunities in the classroom environment (0.3-0.4 units; 3-unit scale), compared to the control group. However, none of the hypothesized mediator variables had an effect on sedentary time; thus, no mediating effects were observed. While beneficial intervention effects were observed on some hypothesized mediating

  1. Opening the Gender Diversity Black Box: Causality of Perceived Gender Equity & Locus of Control and Mediation of Work Engagement in Employee Well-being

    Radha R. Sharma

    2015-01-01

    The study is aimed at assessing the role of perceived gender equity and locus of control in employee well-being at the workplace and ascertaining if work engagement mediates between perceived gender equity, locus of control, and employee well-being (measured through optimism, general satisfaction with life and work, and executive burnout). Adopting a personal survey method data was collected from 373 managers (both males and females) from the public and private sectors representing manufactur...

  2. Opening the gender diversity black box: causality of perceived gender equity and locus of control and mediation of work engagement in employee well-being

    Sharma, Radha R.; Sharma, Neha P.

    2015-01-01

    The study is aimed at assessing the role of perceived gender equity and locus of control in employee well-being at the workplace and ascertaining if work engagement mediates between perceived gender equity, locus of control, and employee well-being (measured through optimism, general satisfaction with life and work, and executive burnout). Adopting a personal survey method data was collected from 373 managers (both males and females) from the public and private sectors representing manufactur...

  3. Controlled and selective placement of boron subphthalocyanines on either chain end of polymers synthesized by nitroxide mediated polymerization

    Benoît H. Lessard

    2015-10-01

    Full Text Available In previous studies, we synthesized the first organic light emitting diode (OLED using boron subphthalocyanines (BsubPcs based polymers. When designing new polymer materials for organic electronic applications such as OLEDs or organic photovoltaic (OPV devices it is important to consider not only the contribution of each monomer but also the polymer chain ends. In this paper we establish a post-polymerization strategy to couple BsubPcs onto either the α- or the ω-chain end using chemically selective BsubPc derivatives. We outline how the chain ends of two representative polymers, poly(styrene (PS and poly(n-butylacrylate (BA, synthesized by nitroxide mediated polymerization (NMP, using BlocBuilder-MA as the initiating species, can be chemically modified by the incorporation of BsubPc chromophores. The addition of the BsubPc chromophore was confirmed through the use of a photodiode array detector (PDA connected in-line with a gel permeation chromatography (GPC setup. These findings represent the first reported method for the controlled and selective placement of a BsubPc chromophores on either end of a polymer produced by NMP. This strategy will therefore be utilized to make next generation BsubPc polymers for OLEDs and OPV devices. The extremely high molar extinction coefficient of BsubPc also make these polymers ideally suited for dye-labelling of polymers.

  4. Functional electrical stimulation mediated by iterative learning control and 3D robotics reduces motor impairment in chronic stroke

    Meadmore Katie L

    2012-06-01

    Full Text Available Abstract Background Novel stroke rehabilitation techniques that employ electrical stimulation (ES and robotic technologies are effective in reducing upper limb impairments. ES is most effective when it is applied to support the patients’ voluntary effort; however, current systems fail to fully exploit this connection. This study builds on previous work using advanced ES controllers, and aims to investigate the feasibility of Stimulation Assistance through Iterative Learning (SAIL, a novel upper limb stroke rehabilitation system which utilises robotic support, ES, and voluntary effort. Methods Five hemiparetic, chronic stroke participants with impaired upper limb function attended 18, 1 hour intervention sessions. Participants completed virtual reality tracking tasks whereby they moved their impaired arm to follow a slowly moving sphere along a specified trajectory. To do this, the participants’ arm was supported by a robot. ES, mediated by advanced iterative learning control (ILC algorithms, was applied to the triceps and anterior deltoid muscles. Each movement was repeated 6 times and ILC adjusted the amount of stimulation applied on each trial to improve accuracy and maximise voluntary effort. Participants completed clinical assessments (Fugl-Meyer, Action Research Arm Test at baseline and post-intervention, as well as unassisted tracking tasks at the beginning and end of each intervention session. Data were analysed using t-tests and linear regression. Results From baseline to post-intervention, Fugl-Meyer scores improved, assisted and unassisted tracking performance improved, and the amount of ES required to assist tracking reduced. Conclusions The concept of minimising support from ES using ILC algorithms was demonstrated. The positive results are promising with respect to reducing upper limb impairments following stroke, however, a larger study is required to confirm this.

  5. Does self-efficacy mediate functional change in older adults participating in an exercise program after hip fracture? A randomized control trial

    Latham, Nancy K.; Ni, Pengsheng; Jette, Alan M.

    2015-01-01

    Objectives This study examined whether self-efficacy mediated the effect of the HIP Rehab exercise program on activity limitations in older adults after hip fracture, and whether the mediation effect was different between different gender and age groups. Design Randomized controlled trial (RCT) Setting Community Participants Two hundred and thirty two participants aged 79±9.4 years with hip fracture were randomly assigned to intervention (n=120) or attention control (n=112) groups. Interventions The 6-month intervention, the HIP Rehab, is a functionally-oriented, home-based exercise program. Data was collected at baseline, post-intervention (6 months), and follow-up (9 months). Main outcome measure Activity Measure for Post-Acute Care (AM-PAC) Results The mediation effect of the HIP Rehab exercise program on Basic Mobility function through self-efficacy for exercise was significant at 9 months (βindirect=0.21). Similarly, the mediation effect of the intervention on Daily Activity function through self-efficacy for exercise was significant at 9 months (βindirect=0.49). In subgroup analyses, the mediation effect was significant at 9 months in the younger group (≤79 years old) in comparison to the older group, and was significant in females in comparison to males. Conclusion Self-efficacy may play a partial mediating role for the effect on some longer-term functional outcomes in the HIP Rehab intervention. The results suggest that program components that target self-efficacy should be incorporated in the future hip fracture rehabilitation interventions. Age and gender of the targeted participants may also need to be considered when developing interventions. PMID:25701101

  6. Does self-efficacy mediate functional change in older adults participating in an exercise program after hip fracture? A randomized controlled trial.

    Chang, Feng-Hang; Latham, Nancy K; Ni, Pengsheng; Jette, Alan M

    2015-06-01

    To examine whether self-efficacy mediated the effect of the Home-based Post-Hip Fracture Rehabilitation program on activity limitations in older adults after hip fracture and whether the mediating effect was different between sex and age groups. Randomized controlled trial. Community. Participants with hip fracture (N=232; mean age ± SD, 79±9.4y) were randomly assigned to intervention (n=120, 51.7%) and attention control (n=112, 48.3%) groups. The 6-month intervention, the Home-based Post-Hip Fracture Rehabilitation, is a functionally oriented, home-based exercise program. Data were collected at baseline, postintervention (6mo), and follow-up (9mo). Activity Measure for Post-Acute Care. The mediating effect of the Home-based Post-Hip Fracture Rehabilitation program on Basic Mobility function through self-efficacy for exercise was significant at 9 months (βindirect=.21). Similarly, the mediating effect of the intervention on Daily Activity function through self-efficacy for exercise was significant at 9 months (βindirect=.49). In subgroup analyses, the mediating effect was significant at 9 months in the younger group (age, ≤79y) in comparison to the older group and was significant in women in comparison to men. Self-efficacy may play a partial mediating role in the effect on some longer-term functional outcomes in the Home-based Post-Hip Fracture Rehabilitation intervention. The results suggest that program components that target self-efficacy should be incorporated in future hip fracture rehabilitation interventions. Age and sex of the targeted participants may also need to be considered when developing interventions. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  7. Mediating effects of resistance training skill competency on health-related fitness and physical activity: the ATLAS cluster randomised controlled trial.

    Smith, Jordan J; Morgan, Philip J; Plotnikoff, Ronald C; Stodden, David F; Lubans, David R

    2016-01-01

    The purpose of this study was to examine the mediating effect of resistance training skill competency on percentage of body fat, muscular fitness and physical activity among a sample of adolescent boys participating in a school-based obesity prevention intervention. Participants were 361 adolescent boys taking part in the Active Teen Leaders Avoiding Screen-time (ATLAS) cluster randomised controlled trial: a school-based program targeting the health behaviours of economically disadvantaged adolescent males considered "at-risk" of obesity. Body fat percentage (bioelectrical impedance), muscular fitness (hand grip dynamometry and push-ups), physical activity (accelerometry) and resistance training skill competency were assessed at baseline and post-intervention (i.e., 8 months). Three separate multi-level mediation models were analysed to investigate the potential mediating effects of resistance training skill competency on each of the study outcomes using a product-of-coefficients test. Analyses followed the intention-to-treat principle. The intervention had a significant impact on the resistance training skill competency of the boys, and improvements in skill competency significantly mediated the effect of the intervention on percentage of body fat and the combined muscular fitness score. No significant mediated effects were found for physical activity. Improving resistance training skill competency may be an effective strategy for achieving improvements in body composition and muscular fitness in adolescent boys.

  8. HLA Class I-Mediated HIV-1 Control in Vietnamese Infected with HIV-1 Subtype A/E.

    Chikata, Takayuki; Tran, Giang Van; Murakoshi, Hayato; Akahoshi, Tomohiro; Qi, Ying; Naranbhai, Vivek; Kuse, Nozomi; Tamura, Yoshiko; Koyanagi, Madoka; Sakai, Sachiko; Nguyen, Dung Hoai; Nguyen, Dung Thi; Nguyen, Ha Thu; Nguyen, Trung Vu; Oka, Shinichi; Martin, Maureen P; Carrington, Mary; Sakai, Keiko; Nguyen, Kinh Van; Takiguchi, Masafumi

    2018-03-01

    HIV-1-specific cytotoxic T cells (CTLs) play an important role in the control of HIV-1 subtype B or C infection. However, the role of CTLs in HIV-1 subtype A/E infection still remains unclear. Here we investigated the association of HLA class I alleles with clinical outcomes in treatment-naive Vietnamese infected with subtype A/E virus. We found that HLA-C*12:02 was significantly associated with lower plasma viral loads (pVL) and higher CD4 counts and that the HLA-A*29:01-B*07:05-C*15:05 haplotype was significantly associated with higher pVL and lower CD4 counts than those for individuals without these respective genotypes. Nine Pol and three Nef mutations were associated with at least one HLA allele in the HLA-A*29:01-B*07:05-C*15:05 haplotype, with a strong negative correlation between the number of HLA-associated Pol mutations and CD4 count as well as a positive correlation with pVL for individuals with these HLA alleles. The results suggest that the accumulation of mutations selected by CTLs restricted by these HLA alleles affects HIV control. IMPORTANCE Most previous studies on HLA association with disease progression after HIV-1 infection have been performed on cohorts infected with HIV-1 subtypes B and C, whereas few such population-based studies have been reported for cohorts infected with the Asian subtype A/E virus. In this study, we analyzed the association of HLA class I alleles with clinical outcomes for 536 HIV-1 subtype A/E-infected Vietnamese individuals. We found that HLA-C*12:02 is protective, while the HLA haplotype HLA-A*29:01-B*07:05-C*15:05 is deleterious. The individuals with HIV-1 mutations associated with at least one of the HLA alleles in the deleterious HLA haplotype had higher plasma viral loads and lower CD4 counts than those of individuals without the mutations, suggesting that viral adaptation and escape from HLA-mediated immune control occurred. The present study identifies a protective allele and a deleterious haplotype for HIV-1

  9. Mediating effect of perceived overweight on the association between actual obesity and intention for weight control; role of race, ethnicity, and gender

    Shervin Assari

    2015-01-01

    Full Text Available Background: Although obesity is expected to be associated with intention to reduce weight, this effect may be through perceived overweight. This study tested if perceived overweight mediates the association between actual obesity and intention to control weight in groups based on the intersection of race and gender. For this purpose, we compared Non-Hispanic White men, Non-Hispanic White women, African American men, African American women, Caribbean Black men, and Caribbean Black women. Methods: National Survey of American Life, 2001-2003 included 5,810 American adults (3516 African Americans, 1415 Caribbean Blacks, and 879 Non-Hispanic Whites. Weight control intention was entered as the main outcome. In the first step, we fitted race/gender specific logistic regression models with the intention for weight control as outcome, body mass index as predictor and sociodemographics as covariates. In the next step, to test mediation, we added perceived weight to the model. Results: Obesity was positively associated with intention for weight control among all race × gender groups. Perceived overweight fully mediated the association between actual obesity and intention for weight control among Non-Hispanic White women, African American men, and Caribbean Black men. The mediation was only partial for Non-Hispanic White men, African American women, and Caribbean Black women. Conclusions: The complex relation between actual weight, perceived weight, and weight control intentions depends on the intersection of race and gender. Perceived overweight plays a more salient role for Non-Hispanic White women and Black men than White men and Black women. Weight loss programs may benefit from being tailored based on race and gender. This finding also sheds more light to the disproportionately high rate of obesity among Black women in US.

  10. Beyond total treatment effects in randomised controlled trials: Baseline measurement of intermediate outcomes needed to reduce confounding in mediation investigations.

    Landau, Sabine; Emsley, Richard; Dunn, Graham

    2018-06-01

    Random allocation avoids confounding bias when estimating the average treatment effect. For continuous outcomes measured at post-treatment as well as prior to randomisation (baseline), analyses based on (A) post-treatment outcome alone, (B) change scores over the treatment phase or (C) conditioning on baseline values (analysis of covariance) provide unbiased estimators of the average treatment effect. The decision to include baseline values of the clinical outcome in the analysis is based on precision arguments, with analysis of covariance known to be most precise. Investigators increasingly carry out explanatory analyses to decompose total treatment effects into components that are mediated by an intermediate continuous outcome and a non-mediated part. Traditional mediation analysis might be performed based on (A) post-treatment values of the intermediate and clinical outcomes alone, (B) respective change scores or (C) conditioning on baseline measures of both intermediate and clinical outcomes. Using causal diagrams and Monte Carlo simulation, we investigated the performance of the three competing mediation approaches. We considered a data generating model that included three possible confounding processes involving baseline variables: The first two processes modelled baseline measures of the clinical variable or the intermediate variable as common causes of post-treatment measures of these two variables. The third process allowed the two baseline variables themselves to be correlated due to past common causes. We compared the analysis models implied by the competing mediation approaches with this data generating model to hypothesise likely biases in estimators, and tested these in a simulation study. We applied the methods to a randomised trial of pragmatic rehabilitation in patients with chronic fatigue syndrome, which examined the role of limiting activities as a mediator. Estimates of causal mediation effects derived by approach (A) will be biased if one of

  11. Singlet oxygen explicit dosimetry to predict long-term local tumor control for BPD-mediated photodynamic therapy

    Kim, Michele M.; Penjweini, Rozhin; Ong, Yi Hong; Zhu, Timothy C.

    2017-02-01

    Photodynamic therapy (PDT) is a well-established treatment modality for cancer and other malignant diseases; however, quantities such as light fluence, photosensitizer photobleaching rate, and PDT dose do not fully account for all of the dynamic interactions between the key components involved. In particular, fluence rate (Φ) effects are not accounted for, which has a large effect on the oxygen consumption rate. In this preclinical study, reacted singlet oxygen [1O2]rx was investigated as a dosimetric quantity for PDT outcome. The ability of [1O2]rx to predict the long-term local tumor control rate (LCR) for BPD-mediated PDT was examined. Mice bearing radioactivelyinduced fibrosarcoma (RIF) tumors were treated with different in-air fluences (250, 300, and 350 J/cm2) and in-air ϕ (75, 100, and150 mW/cm2) with a BPD dose of 1 mg/kg and a drug-light interval of 3 hours. Treatment was delivered with a collimated laser beam of 1 cm diameter at 690 nm. Explicit dosimetry of initial tissue oxygen concentration, tissue optical properties, and BPD concentration was used to calculate [1O2]rx. Φ was calculated for the treatment volume based on Monte-Carlo simulations and measured tissue optical properties. Kaplan-Meier analyses for LCR were done for an endpoint of tumor volume defined as the product of the timeintegral of photosensitizer concentration and Φ at a 3 mm tumor depth. Preliminary studies show that [1O2]rx better correlates with LCR and is an effective dosimetric quantity that can predict treatment outcome.

  12. Singlet oxygen explicit dosimetry to predict long-term local tumor control for Photofrin-mediated photodynamic therapy

    Penjweini, Rozhin; Kim, Michele M.; Ong, Yi Hong; Zhu, Timothy C.

    2017-02-01

    Although photodynamic therapy (PDT) is an established modality for the treatment of cancer, current dosimetric quantities do not account for the variations in PDT oxygen consumption for different fluence rates (φ). In this study we examine the efficacy of reacted singlet oxygen concentration ([1O2]rx) to predict long-term local control rate (LCR) for Photofrin-mediated PDT. Radiation-induced fibrosarcoma (RIF) tumors in the right shoulders of female C3H mice are treated with different in-air fluences of 225-540 J/cm2 and in-air fluence rate (φair) of 50 and 75 mW/cm2 at 5 mg/kg Photofrin and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 630 nm wavelength. [1O2]rx is calculated by using a macroscopic model based on explicit dosimetry of Photofrin concentration, tissue optical properties, tissue oxygenation and blood flow changes during PDT. The tumor volume of each mouse is tracked for 90 days after PDT and Kaplan-Meier analyses for LCR are performed based on a tumor volume defined as a temporal integral of photosensitizer concentration and Φ at a 3 mm tumor depth. φ is calculated throughout the treatment volume based on Monte-Carlo simulation and measured tissue optical properties. Our preliminary studies show that [1O2]rx is the best dosimetric quantity that can predict tumor response and correlate with LCR. Moreover, [1O2]rx calculated using the blood flow changes was in agreement with [1O2]rx calculated based on the actual tissue oxygenation.

  13. Intercultural Mediation

    Dragos Marian Radulescu; Denisa Mitrut

    2012-01-01

    The Intercultural Mediator facilitates exchanges between people of different socio-cultural backgrounds and acts as a bridge between immigrants and national and local associations, health organizations, services and offices in order to foster integration of every single individual. As the use mediation increases, mediators are more likely to be involved in cross-cultural mediation, but only the best mediators have the opportunity to mediate cross border business disputes or international poli...

  14. Functional disability in patients with low back pain: the mediator role of suffering and beliefs about pain control in patients receiving physical and chiropractic treatment.

    Pereira, M Graça; Roios, Edite; Pereira, Marta

    Low back pain is the leading cause of disability worldwide. There is evidence that depression, anxiety, and external locus of control are negative predictors of functional disability in low back patients. This study focused on the mediator role of suffering and beliefs about pain control in the relationship between psychological morbidity and functional disability in patients receiving physical therapy and chiropractic treatment for chronic low back pain. The sample included 213 patients receiving chiropractic treatment and 125 receiving physical therapy, who answered the following instruments: Beliefs about Pain Control Questionnaire; Inventory of Subjective Experiences of Suffering in Illness; Oswestry Low Back Pain Disability Questionnaire; and the Hospital Anxiety and Depression Scales. Suffering was a mediator in the relationship between depression and functional disability in both treatment groups. Only beliefs related to external chance events mediated the relationship between depression and functional disability in the physical therapy group, but not in the chiropratic teratment group. Intervention should focus on suffering regardless of the type of treatment and target beliefs about pain control, in patients receiving physical therapy treatment since they seem to play a key role in functional disability in patients with low back pain. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

  15. MECHANISM AND REGULATION OF NONSENSE-MEDIATED MRNA DECAY (NMD, AN ESSENTIAL QUALITY CONTROL SYSTEM OF PLANTS

    D. Silhavy

    2008-09-01

    Full Text Available In eukaryotic cell, various quality control mechanisms have evolved to ensure that only perfect mRNAs could be translated. Nonsense-mediated mRNA decay (NMD is a quality control system that identifies and eliminates mRNAs containing premature termination codons, thereby preventing the accumulation of potentially harmful truncated proteins. While NMD is well-characterized in yeast, in invertebrates and in mammals, plant NMD is poorly understood. In yeast and in invertebrates unusually long 3'untranslated regions (3'UTRs render an mRNA subject to NMD, while in mammals' 3'UTR located introns trigger NMD. UPF1, 2 and 3 are the key trans-acting NMD factors in yeast as well as in animals. However, in mammals, the core components of the Exon Junction Complex (Mago, Y14, eIF4A3 and MLN51 are also required for NMD. It was proposed that long 3’UTR-induced NMD is the ancient type and that it was changed to a more complex intron-based NMD in mammals. To better understand the evolution of eukaryotic NMD systems, we have studied the NMD machinery of plants, as plants are outgroup relative to fungi and animals. We have elaborated various transient assays to analyze plant NMD. Using these assays we defined the cis elements of plant NMD and characterized several trans-acting plant NMD factors. We demonstrated that two plant NMD pathways co-exist, one pathway, as yeast or invertebrate NMD systems, eliminates mRNAs with long 3'UTRs, while a distinct pathway, like mammalian NMD, degrades mRNAs harbouring 3'UTR-located introns. We showed that UPF1, UPF2, and SMG-7 are involved in both plant NMD pathways, whereas Mago and Y14 are required only for intron-based NMD. We also provide evidence that the molecular mechanism of long 3'UTR-based plant NMD resembles yeast NMD, while the intron-based NMD is similar to mammalian NMD. Moreover we have found that the SMG-7 component of plant NMD is targeted by NMD suggesting that plant NMD is autoregulated. We propose that in

  16. SAD1, an RNA polymerase I subunit A34.5 of rice, interacts with Mediator and controls various aspects of plant development.

    Li, Weiqiang; Yoshida, Akiko; Takahashi, Megumu; Maekawa, Masahiko; Kojima, Mikiko; Sakakibara, Hitoshi; Kyozuka, Junko

    2015-01-01

    The DWARF14 (D14) gene of rice functions within the signaling pathway of strigolactones, a group of plant hormones that inhibits shoot branching. We isolated a recessive mutant named super apical dormant (sad1-1) from a suppressor screen of d14-1. The growth of tillers (vegetative shoot branches) is suppressed in both the d14-1 sad1-1 double mutant and the sad1-1 single mutant. In addition, the sad1-1 mutant shows pleiotropic defects throughout development. SAD1 encodes an ortholog of RPA34.5, a subunit of RNA polymerase I (Pol I). Consequently, the level of ribosomal RNA (rRNA) is severely reduced in the sad1-1 mutant. These results indicate that proper ribosome function is a prerequisite for normal development in plants. The Arabidopsis ortholog of SAD1 was previously isolated as a Mediator-interacting protein. Here we show that SAD1 interacts physically with the Mediator complex through direct binding with OsMED4, a component of the middle module of the Mediator complex in rice. It is known that Mediator interacts with Pol II, which transcribes mRNAs and functions as a central regulator of transcription. This study indicates a novel aspect of Mediator function in Pol I-controlled rRNA transcription. TFIIF2 and RPC53 are the counterparts of RPA34.5 in Pol II and Pol III, respectively. We demonstrate that the rice orthologs of these proteins also interact with OsMED4. Our results suggest that interaction with MED4 in the Mediator complex is a common feature of the three types of RNA polymerases. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  17. The Effect of Social Support on Glycemic Control in Patients with Type 2 Diabetes Mellitus: The Mediating Roles of Self-Efficacy and Adherence

    Yechang Shao

    2017-01-01

    Full Text Available Ample evidence suggests that social support, self-efficacy, and adherence significantly, independently, and together affect glycemic control in patients with type 2 diabetes mellitus (T2DM, but the pathway from social support to glycemic control remains unclear. This study hypothesized that the effect of social support on glycemic control was mediated sequentially by self-efficacy and adherence. Patients with T2DM were recruited from two hospitals in Guangzhou, China, from January 1 to July 31, 2014, and their sociodemographic clinical data and their assessments on social support, self-efficacy, and adherence were obtained from medical records and self-completed questionnaires. Of the 532 patients who participated, 35% achieved glycemic control (i.e., HbA1c < 7%. Social support, self-efficacy, and adherence had significant correlations with each other and with glycemic control (P<0.05. Regression analyses and structural equation modeling showed that better social support was associated to better patient self-efficacy, which, in turn, was associated with better medical adherence, which was associated with improved glycemic control, and the relationship between social support and glycemic control was sequentially and completely mediated by self-efficacy and adherence. The five goodness-of-fit indices confirmed that our data fitted the hypothesized pathway model strongly.

  18. Density- and trait-mediated top-down effects modify bottom-up control of a highly endemic tropical aquatic food web

    C. M. Dalton; A. Mokiao-Lee; T. S. Sakihara; M. G. Weber; C. A. Roco; Z. Han; B. Dudley; R. A. MacKenzie; N. G. Hairston Jr.

    2013-01-01

    Benthic invertebrates mediate bottom–up and top–down influences in aquatic food webs, and changes in the abundance or traits of invertebrates can alter the strength of top–down effects. Studies assessing the role of invertebrate abundance and behavior as controls on food web structure are rare at the whole ecosystem scale. Here we use a comparative approach to...

  19. Increased skills usage statistically mediates symptom reduction in self-guided internet-delivered cognitive-behavioural therapy for depression and anxiety: a randomised controlled trial.

    Terides, Matthew D; Dear, Blake F; Fogliati, Vincent J; Gandy, Milena; Karin, Eyal; Jones, Michael P; Titov, Nickolai

    2018-01-01

    Cognitive-behavioural therapy (CBT) is an effective treatment for clinical and subclinical symptoms of depression and general anxiety, and increases life satisfaction. Patients' usage of CBT skills is a core aspect of treatment but there is insufficient empirical evidence suggesting that skills usage behaviours are a mechanism of clinical change. This study investigated if an internet-delivered CBT (iCBT) intervention increased the frequency of CBT skills usage behaviours and if this statistically mediated reductions in symptoms and increased life satisfaction. A two-group randomised controlled trial was conducted comparing internet-delivered CBT (n = 65) with a waitlist control group (n = 75). Participants were individuals experiencing clinically significant symptoms of depression or general anxiety. Mixed-linear models analyses revealed that the treatment group reported a significantly higher frequency of skills usage, lower symptoms, and higher life satisfaction by the end of treatment compared with the control group. Results from bootstrapping mediation analyses revealed that the increased skills usage behaviours statistically mediated symptom reductions and increased life satisfaction. Although skills usage and symptom outcomes were assessed concurrently, these findings support the notion that iCBT increases the frequency of skills usage behaviours and suggest that this may be an important mechanism of change.

  20. CD4(+) T cell-mediated control of a gamma-herpesvirus in B cell-deficient mice is mediated by IFN-gamma

    Christensen, Jan Pravsgaard; Cardin, R D; Branum, K C

    1999-01-01

    The lack of B cells and antibody does not prevent mice from dealing effectively with a pathogenic gamma-herpesvirus. Both CD4(+) and CD8(+) T cells contribute to the control of virus replication in the respiratory tract, with the depletion of either lymphocyte subset leading to increased titers...... for direct interaction with virus-infected targets expressing MHC class II glycoproteins, suggesting that the IFN-gamma produced by these lymphocytes is functioning at short range. The numbers of latently infected cells in the spleens of carrier mice are also significantly increased by the concurrent...

  1. Unhealthy weight control behaviors mediate the association between weight status and weight-specific health-related quality of life in treatment-seeking youth who are obese.

    Lim, Crystal S; Gowey, Marissa A; Cohen, Megan J; Silverstein, Janet; Janicke, David M

    2017-03-01

    Examine whether unhealthy and extreme weight control behaviors (WCBs) mediate the relationship between youth weight status and disease-specific health-related quality of life (HRQOL) in treatment-seeking youth who are overweight and obese (OV/OB). 82 youth 10-17 years of age who were OV/OB and attending an outpatient obesity-related medical appointment completed measures assessing unhealthy and extreme WCBs and disease-specific HRQOL. Parents completed a demographic questionnaire and medical staff measured youth height and weight. Regression analyses revealed that unhealthy WCBs mediated the associations between youth weight status and emotional and social avoidance disease-specific HRQOL, such that higher body mass index (BMI) predicted unhealthy WCBs, which were ultimately associated with poorer emotional and social HRQOL. Mediation analyses were not significant for total, physical, teasing/marginalization, and positive attributes disease-specific HRQOL. In addition, extreme WCBs did not mediate the association between youth weight status and any subscales of the disease-specific HRQOL measure. Weight status is an important predictor of disease-specific HRQOL in OV/OB youth; however, the association with emotional and social HRQOL is partially accounted for by youth engagement in unhealthy WCBs. Clinicians and researchers should assess WCBs and further research should explore and evaluate appropriate intervention strategies to address unhealthy WCBs in pediatric weight management prevention and treatment efforts.

  2. A disposable laser print-cut-laminate polyester microchip for multiplexed PCR via infra-red-mediated thermal control

    Ouyang, Yiwen; Duarte, Gabriela R.M.; Poe, Brian L.; Riehl, Paul S.; Santos, Fernando M. dos; Martin-Didonet, Claudia C.G.; Carrilho, Emanuel; Landers, James P.

    2015-01-01

    Infrared (IR)-mediated thermal cycling system, a method proven to be a effective for sub-μL scale polymerase chain reaction (PCR) on microchips, has been integrated with DNA extraction and separation on a glass microchip in a fully integrated micro Total Analysis System by Easley et al., in 2006. IR-PCR has been demonstrated on both glass and PMMA microdevices where the fabrication (bonding) is not trivial. Polyester-toner (PeT) microfluidic devices have significant potential as cost-effective, disposable microdevices as a result of the ease of fabrication (∼$0.25 USD and <10 min per device) and availability of commercial substrates. For the first time, we demonstrate here the thermal cycling in PeT microchips on the IR-PCR system. Undesirable IR absorption by the black-toner bonding layer was eliminated with a spatial filter in the form of an aluminum foil mask. The solution heating rate for a black PeT microchip using a tungsten lamp was 10.1 ± 0.7 °C s −1 with a cooling rate of roughly −12 ± 0.9 °C s −1 assisted by forced air cooling. Dynamic surface passivation strategies allowed the successful amplification of a 520 bp fragment of the λ-phage genome (in 11 min) and a 1500 bp region of Azospirillum brasilense. Using a centrosymmetric chamber configuration in a multichamber PeT microchip, homogenous temperature distribution over all chambers was achieved with inter-chamber temperature differences at annealing, extension and denaturing steps of less than ±2 °C. The effectiveness of the multichamber system was demonstrated with the simultaneous amplification of a 390 bp amplicon of human β-globin gene in five PeT PCR microchambers. The relative PCR amplification efficiency with a human β-globin DNA fragment ranged from 70% to 90%, in comparison to conventional thermal cyclers, with an inter-chamber standard deviation of ∼10%. Development of PeT microchips for IR-PCR has the potential to provide rapid, low-volume amplification

  3. Explaining why larks are future-oriented and owls are present-oriented: self-control mediates the chronotype-time perspective relationships.

    Milfont, Taciano L; Schwarzenthal, Miriam

    2014-05-01

    Recent studies provide evidence for the chronotype-time perspective relationships. Larks are more future-oriented and owls are more present-oriented. The present study expands this initial research by examining whether the associations are replicable with other time perspective measures, and whether self-control explains the observed relationships. Chronotype was assessed with the Morningness-Eveningness Questionnaire and the basic associations with the Zimbardo Time Perspective Inventory were replicated in a sample of 142 New Zealand students, but not with other measures. Self-control mediated the influence of morningness on both future time perspective and delay of gratification. Implications of the findings are discussed.

  4. Social cognitive theory mediators of physical activity in a lifestyle program for cancer survivors and carers: findings from the ENRICH randomized controlled trial.

    Stacey, F G; James, E L; Chapman, K; Lubans, D R

    2016-04-14

    Despite increasing numbers of cancer survivors and evidence that diet and physical activity improves the health of cancer survivors, most do not meet guidelines. Some social cognitive theory (SCT)-based interventions have increased physical activity behavior, however few have used objective physical activity measures. The Exercise and Nutrition Routine Improving Cancer Health (ENRICH) randomized controlled trial reported a significant intervention effect for the primary outcome of pedometer-assessed step counts at post-test (8-weeks) and follow-up (20-weeks). The aim of this study was to test whether the SCT constructs operationalized in the ENRICH intervention were mediators of physical activity behavior change. Randomized controlled trial with 174 cancer survivors and carers assessed at baseline, post-test (8-weeks), and follow-up (20-weeks). Participants were randomized to the ENRICH six session face-to-face healthy lifestyle program, or to a wait-list control. Hypothesized SCT mediators of physical activity behavior change (self-efficacy, behavioral goal, outcome expectations, impediments, and social expectations) were assessed using valid and reliable scales. Mediation was assessed using the Preacher and Hayes SPSS INDIRECT macro. At eight weeks, there was a significant intervention effect on behavioral goal (A = 9.12, p = 0.031) and outcome expectations (A = 0.25, p = 0.042). At 20 weeks, the intervention had a significant effect on self-efficacy (A = 0.31, p = 0.049) and behavioral goal (A = 13.15, p = 0.011). Only changes in social support were significantly associated with changes in step counts at eight weeks (B = 633.81, p = 0.023). Behavioral goal was the only SCT construct that had a significant mediating effect on step counts, and explained 22 % of the intervention effect at 20 weeks (AB = 397.9, 95 % CI 81.5-1025.5). SCT constructs had limited impact on objectively-assessed step counts in a multiple health

  5. Improved eating behaviours mediate weight gain prevention of young adults: moderation and mediation results of a randomised controlled trial of TXT2BFiT, mHealth program.

    Partridge, Stephanie R; McGeechan, Kevin; Bauman, Adrian; Phongsavan, Philayrath; Allman-Farinelli, Margaret

    2016-04-02

    Explanatory evaluation of interventions for prevention of weight gain is required beyond changes in weight, to determine for whom the intervention works and the underlying mechanisms of change. It was hypothesised that participant characteristics moderate intervention effect on weight change and improved eating and physical activity behaviours during the 3-month program mediate the relationship between intervention and weight. In our randomised controlled trial, young adults at risk of weight gain (n = 250) were assigned either to an intervention group that received a 3-month mHealth (TXT2BFiT) program with 6-month maintenance or to a control group. Data were collected via online self-report surveys. Hypothesised moderators and mediators of the intervention effect on weight were independently assessed in PROCESS macro models for 3 and 9-month weight change. Males (P = 0.01), mid-20s age group (P = 0.04), and higher income earners (P = 0.02) moderated intervention effects on weight change at 3-months and males only at 9-months (P = 0.02). Weight change at 3 (-1.12 kg) and 9-months (-1.38 kg) remained significant when 3-month nutrition and physical activity behaviours were specified as mediators (P <0.01 and P = 0.01 respectively). Indirect paths explained 39% (0.72/1.85 kg) and 40 % (0.92/2.3 kg) of total effect on weight change at 3 and 9-months respectively. Increased vegetable intake by intervention group at 3-months accounted for 19 and 17% and decreased sugar-sweetened beverages accounted for 8 and 13% of indirect weight change effects at 3 and 9-months respectively. TXT2BFiT was effective for both young men and women. Small sustained behavioural changes, including increased vegetable intake and decreased sugar-sweetened beverages consumption significantly mediated the intervention's effects on weight change. Improved eating behaviours and increased physical activity accounted for approximately 40% of the weight change. The trial is

  6. Mediators of a Brief Hypnosis Intervention to Control Side Effects in Breast Surgery Patients: Response Expectancies and Emotional Distress

    Montgomery, Guy H.; Hallquist, Michael N.; Schnur, Julie B.; David, Daniel; Silverstein, Jeffrey H.; Bovbjerg, Dana H.

    2010-01-01

    Objective: The present study was designed to test the hypotheses that response expectancies and emotional distress mediate the effects of an empirically validated presurgical hypnosis intervention on postsurgical side effects (i.e., pain, nausea, and fatigue). Method: Women (n = 200) undergoing breast-conserving surgery (mean age = 48.50 years;…

  7. Catastrophizing and internal pain control as mediators of outcome in the multidisciplinary treatment of chronic low back pain.

    Spinhoven, P.; Kuile, M. ter; Kole-Snijders, A.M.J.; Hutten Mansfeld, M.; Ouden, D.J. den; Vlaeyen, J.W.S.

    2004-01-01

    The aim of the present study was to examine (a) whether a cognitive-behavioral treatment (differentially) affects pain coping and cognition; and (b) whether changes in pain coping and cognition during treatment mediate treatment outcome. Participants in this randomized clinical trial were 148

  8. The relationship between adult attachment orientation and child self-regulation in eating: The mediating role of persuasive-controlling feeding practices.

    Powell, Elisabeth M; Frankel, Leslie A; Umemura, Tomo; Hazen, Nancy

    2017-08-01

    The present study examines the hypothesis that adult attachment orientation, specifically anxious attachment, is related to children's diminished ability to self-regulate their food intake, and that this relationship is mediated by parents' persuasive-controlling feeding practices. Two hundred and sixty five mothers and fathers of preschool children completed online questionnaires that included measures of Adult Attachment Orientation, Parental Persuasive-Controlling Feeding Practices, and Child Self-Regulation of Eating. Structural equation modeling revealed a significant relationship between parental anxious attachment and child self-regulatory abilities, which was fully mediated by parental persuasive-controlling feeding. Also as predicted, parents' avoidant attachment was found to be unrelated to persuasive-controlling feeding and child self-regulated eating. Findings suggest that parents with an anxious attachment orientation may be more likely than other parents to try to use persuasive techniques to control their children's food intake, which may impair children's ability to regulate their food intake, increasing their obesity risk. Implications for intervention are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Novel Strategy to Control Transgene Expression Mediated by a Sendai Virus-Based Vector Using a Nonstructural C Protein and Endogenous MicroRNAs.

    Masayuki Sano

    Full Text Available Tissue-specific control of gene expression is an invaluable tool for studying various biological processes and medical applications. Efficient regulatory systems have been utilized to control transgene expression in various types of DNA viral or integrating viral vectors. However, existing regulatory systems are difficult to transfer into negative-strand RNA virus vector platforms because of significant differences in their transcriptional machineries. In this study, we developed a novel strategy for regulating transgene expression mediated by a cytoplasmic RNA vector based on a replication-defective and persistent Sendai virus (SeVdp. Because of the capacity of Sendai virus (SeV nonstructural C proteins to specifically inhibit viral RNA synthesis, overexpression of C protein significantly reduced transgene expression mediated by SeVdp vectors. We found that SeV C overexpression concomitantly reduced SeVdp mRNA levels and genomic RNA synthesis. To control C expression, target sequences for an endogenous microRNA were incorporated into the 3' untranslated region of the C genes. Incorporation of target sequences for miR-21 into the SeVdp vector restored transgene expression in HeLa cells by decreasing C expression. Furthermore, the SeVdp vector containing target sequences for let-7a enabled cell-specific control of transgene expression in human fibroblasts and induced pluripotent stem cells. Our findings demonstrate that SeV C can be used as an effective regulator for controlling transgene expression. This strategy will contribute to efficient and less toxic SeVdp-mediated gene transfer in various biological applications.

  10. Intrinsic religiousness and well-being among cancer patients: the mediating role of control-related religious coping and self-efficacy for coping with cancer.

    Pérez, John E; Rex Smith, Amy

    2015-04-01

    We examined the relationship between intrinsic religiousness and well-being, with control-related religious coping and self-efficacy for coping with cancer as potential mediators of this relationship among cancer patients. In a cross-sectional design, 179 ambulatory cancer patients completed measures of intrinsic religiousness, religious coping, self-efficacy for coping with cancer, well-being, and demographic variables. Type of cancer, stage of cancer, and time since diagnosis were collected from electronic medical charts. In a path model, the positive association between intrinsic religiousness and three types of well-being--physical, functional, and social-was fully mediated by active religious surrender and self-efficacy for coping with cancer. In addition, the negative association between passive religious deferral and all four types of well-being--physical, functional, social, and emotional--was fully mediated by self-efficacy for coping with cancer. Finally, there was a negative direct association between pleading for God's direct intercession and emotional well-being. These findings suggest pathways by which intrinsic religiousness and control-related religious coping are linked to various dimensions of well-being among cancer patients.

  11. Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case-Control Study in EPIC.

    Assi, Nada; Thomas, Duncan C; Leitzmann, Michael; Stepien, Magdalena; Chajès, Véronique; Philip, Thierry; Vineis, Paolo; Bamia, Christina; Boutron-Ruault, Marie-Christine; Sandanger, Torkjel M; Molinuevo, Amaia; Boshuizen, Hendriek C; Sundkvist, Anneli; Kühn, Tilman; Travis, Ruth C; Overvad, Kim; Riboli, Elio; Gunter, Marc J; Scalbert, Augustin; Jenab, Mazda; Ferrari, Pietro; Viallon, Vivian

    2018-05-01

    Background: The "meeting-in-the-middle" (MITM) is a principle to identify exposure biomarkers that are also predictors of disease. The MITM statistical framework was applied in a nested case-control study of hepatocellular carcinoma (HCC) within European Prospective Investigation into Cancer and Nutrition (EPIC), where healthy lifestyle index (HLI) variables were related to targeted serum metabolites. Methods: Lifestyle and targeted metabolomic data were available from 147 incident HCC cases and 147 matched controls. Partial least squares analysis related 7 lifestyle variables from a modified HLI to a set of 132 serum-measured metabolites and a liver function score. Mediation analysis evaluated whether metabolic profiles mediated the relationship between each lifestyle exposure and HCC risk. Results: Exposure-related metabolic signatures were identified. Particularly, the body mass index (BMI)-associated metabolic component was positively related to glutamic acid, tyrosine, PC aaC38:3, and liver function score and negatively to lysoPC aC17:0 and aC18:2. The lifetime alcohol-specific signature had negative loadings on sphingomyelins (SM C16:1, C18:1, SM(OH) C14:1, C16:1 and C22:2). Both exposures were associated with increased HCC with total effects (TE) = 1.23 (95% confidence interval = 0.93-1.62) and 1.40 (1.14-1.72), respectively, for BMI and alcohol consumption. Both metabolic signatures mediated the association between BMI and lifetime alcohol consumption and HCC with natural indirect effects, respectively, equal to 1.56 (1.24-1.96) and 1.09 (1.03-1.15), accounting for a proportion mediated of 100% and 24%. Conclusions: In a refined MITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk. Impact: The understanding of the biological basis for the relationship between modifiable exposures and cancer would pave avenues for clinical and public health interventions on metabolic mediators

  12. Mediation Analysis with Multiple Mediators.

    VanderWeele, T J; Vansteelandt, S

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

  13. Cognitive cooperation groups mediated by computers and internet present significant improvement of cognitive status in older adults with memory complaints: a controlled prospective study

    Rodrigo de Rosso Krug

    Full Text Available ABSTRACT Objective To estimate the effect of participating in cognitive cooperation groups, mediated by computers and the internet, on the Mini-Mental State Examination (MMSE percent variation of outpatients with memory complaints attending two memory clinics. Methods A prospective controlled intervention study carried out from 2006 to 2013 with 293 elders. The intervention group (n = 160 attended a cognitive cooperation group (20 sessions of 1.5 hours each. The control group (n = 133 received routine medical care. Outcome was the percent variation in the MMSE. Control variables included gender, age, marital status, schooling, hypertension, diabetes, dyslipidaemia, hypothyroidism, depression, vascular diseases, polymedication, use of benzodiazepines, exposure to tobacco, sedentary lifestyle, obesity and functional capacity. The final model was obtained by multivariate linear regression. Results The intervention group obtained an independent positive variation of 24.39% (CI 95% = 14.86/33.91 in the MMSE compared to the control group. Conclusion The results suggested that cognitive cooperation groups, mediated by computers and the internet, are associated with cognitive status improvement of older adults in memory clinics.

  14. A disposable laser print-cut-laminate polyester microchip for multiplexed PCR via infra-red-mediated thermal control

    Ouyang, Yiwen [Department of Chemistry, University of Virginia, Charlottesville, VA 22904 (United States); Duarte, Gabriela R.M. [Department of Chemistry, University of Virginia, Charlottesville, VA 22904 (United States); Universidade Federal de Goiás, Goiânia, GO 74690-900 (Brazil); Poe, Brian L.; Riehl, Paul S. [Department of Chemistry, University of Virginia, Charlottesville, VA 22904 (United States); Santos, Fernando M. dos; Martin-Didonet, Claudia C.G. [Universidade Estadual de Goiás, Anápolis, GO 75132-400 (Brazil); Carrilho, Emanuel [Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP 13566-590 (Brazil); Instituto Nacional de Ciência e Tecnologia de Bioanalítica, CP 6154, Campinas, SP 13083-970 (Brazil); Landers, James P., E-mail: landers@virginia.edu [Department of Chemistry, University of Virginia, Charlottesville, VA 22904 (United States); Department of Mechanical Engineering, University of Virginia, Charlottesville, VA 22904 (United States); Department of Pathology, University of Virginia Health Science Center, Charlottesville, VA (United States)

    2015-12-11

    Infrared (IR)-mediated thermal cycling system, a method proven to be a effective for sub-μL scale polymerase chain reaction (PCR) on microchips, has been integrated with DNA extraction and separation on a glass microchip in a fully integrated micro Total Analysis System by Easley et al., in 2006. IR-PCR has been demonstrated on both glass and PMMA microdevices where the fabrication (bonding) is not trivial. Polyester-toner (PeT) microfluidic devices have significant potential as cost-effective, disposable microdevices as a result of the ease of fabrication (∼$0.25 USD and <10 min per device) and availability of commercial substrates. For the first time, we demonstrate here the thermal cycling in PeT microchips on the IR-PCR system. Undesirable IR absorption by the black-toner bonding layer was eliminated with a spatial filter in the form of an aluminum foil mask. The solution heating rate for a black PeT microchip using a tungsten lamp was 10.1 ± 0.7 °C s{sup −1} with a cooling rate of roughly −12 ± 0.9 °C s{sup −1} assisted by forced air cooling. Dynamic surface passivation strategies allowed the successful amplification of a 520 bp fragment of the λ-phage genome (in 11 min) and a 1500 bp region of Azospirillum brasilense. Using a centrosymmetric chamber configuration in a multichamber PeT microchip, homogenous temperature distribution over all chambers was achieved with inter-chamber temperature differences at annealing, extension and denaturing steps of less than ±2 °C. The effectiveness of the multichamber system was demonstrated with the simultaneous amplification of a 390 bp amplicon of human β-globin gene in five PeT PCR microchambers. The relative PCR amplification efficiency with a human β-globin DNA fragment ranged from 70% to 90%, in comparison to conventional thermal cyclers, with an inter-chamber standard deviation of ∼10%. Development of PeT microchips for IR-PCR has the potential to provide rapid, low

  15. Formation of polyhedral ceria nanoparticles with enhanced catalytic CO oxidation activity in thermal plasma via a hydrogen mediated shape control mechanism

    Zheng Jie; Zhang Yaohua; Song Xubo; Li Xingguo

    2011-01-01

    Ceria nanoparticles with well defined facets are prepared in argon–hydrogen thermal plasma followed by controlled oxidation. With increasing hydrogen fraction in the plasma, a clear sphere-to-polyhedron shape transition is observed. The heat released during the hydrogenation of cerium, which significantly enhances the species mobility on the surface, favors the growth of well defined facets. The polyhedron ceria nanoparticles, though lower in specific surface area, exhibit superior catalytic performance for CO oxidation over the round particles, which is attributed to the higher density of the reactive {200} and {220} facets on the surface. The hydrogen mediated shape control mechanism provides new insights into the shape control of nanoparticles during thermal plasma processing.

  16. Deletion of protein tyrosine phosphatase 1b in proopiomelanocortin neurons reduces neurogenic control of blood pressure and protects mice from leptin- and sympatho-mediated hypertension.

    Bruder-Nascimento, Thiago; Butler, Benjamin R; Herren, David J; Brands, Michael W; Bence, Kendra K; Belin de Chantemèle, Eric J

    2015-12-01

    Protein tyrosine phosphatase 1b (Ptp1b), which represses leptin signaling, is a promising therapeutic target for obesity. Genome wide deletion of Ptp1b, increases leptin sensitivity, protects mice from obesity and diabetes, but alters cardiovascular function by increasing blood pressure (BP). Leptin-control of metabolism is centrally mediated and involves proopiomelanocortin (POMC) neurons. Whether these neurons contribute to leptin-mediated increases in BP remain unclear. We hypothesized that increasing leptin signaling in POMC neurons with Ptp1b deletion will sensitize the cardiovascular system to leptin and enhance neurogenic control of BP. We analyzed the cardiovascular phenotype of Ptp1b+/+ and POMC-Ptp1b-/- mice, at baseline and after 7 days of leptin infusion or sympatho-activation with phenylephrine. POMCPtp1b deletion did not alter baseline cardiovascular hemodynamics (BP, heart rate) but reduced BP response to ganglionic blockade and plasma catecholamine levels that suggests a decreased neurogenic control of BP. In contrast, POMC-Ptp1b deletion increased vascular adrenergic reactivity and aortic α-adrenergic receptors expression. Chronic leptin treatment reduced vascular adrenergic reactivity and blunted diastolic and mean BP increases in POMC-Ptp1b-/- mice only. Similarly POMC-Ptp1b-/- mice exhibited a blunted increased in diastolic and mean BP accompanied by a gradual reduction in adrenergic reactivity in response to chronic vascular sympatho-activation with phenylephrine. Together these data rule out our hypothesis but suggest that deletion of Ptp1b in POMC neurons protects from leptin- and sympatho-mediated increases in BP. Vascular adrenergic desensitization appears as a protective mechanism against hypertension, and POMC-Ptp1b as a key therapeutic target for the treatment of metabolic and cardiovascular dysfunctions associated with obesity. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Drinking water to reduce alcohol craving? A randomized controlled study on the impact of ghrelin in mediating the effects of forced water intake in alcohol addiction.

    Koopmann, Anne; Lippmann, Katharina; Schuster, Rilana; Reinhard, Iris; Bach, Patrick; Weil, Georg; Rietschel, Marcella; Witt, Stephanie H; Wiedemann, Klaus; Kiefer, Falk

    2017-11-01

    Recent data suggest that ghrelin is involved in the pathophysiology of alcohol use disorders, affecting alcohol self-administration and craving. Gastric ghrelin secretion is reduced by stomach distension. We now tested the hypothesis whether the clinically well-known effects of high-volume water intake on craving reduction in alcoholism is mediated by acute changes in ghrelin secretion. In this randomized human laboratory study, we included 23 alcohol-dependent male inpatient subjects who underwent alcohol cue exposure. Participants of the intervention group drank 1000ml of mineral water within 10min directly thereafter, compared to the participants of the control group who did not. Craving and plasma concentrations of acetylated ghrelin were measured ten times during the 120min following the alcohol cue exposure session. In the intervention group, a significant decrease in acetylated ghrelin in plasma compared to the control group was observed. This decrease was correlated to a reduction in patients' subjective level of craving. In the control group, no decrease of acetylated ghrelin in plasma and no association between alcohol craving and changes in plasma concentrations of acetylated ghrelin were observed. Our results present new evidence that the modulation in the ghrelin system by oral water intake mediates the effects of volume intake with craving reduction in alcohol use disorders. Hence, in addition to pharmacological interventions with ghrelin antagonists, the reduction of physiological ghrelin secretion might be a target for future interventions in the treatment of alcohol craving. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. The role of empowerment in youth development: a study of sociopolitical control as mediator of ecological systems' influence on developmental outcomes.

    Christens, Brian D; Peterson, N Andrew

    2012-05-01

    Empowerment has become an influential concept and theoretical framework for social policy and practice. Still, relatively little is known about the roles that empowerment plays in the ecology of human development, particularly among young people. This article reports results of a study of psychological empowerment among young people, using data from 629 high school students (65.8% female; 96.5% non-white). Using a path analysis, we examined the role of perceived sociopolitical control--an indicator of the intrapersonal component of psychological empowerment--as a mediator between ecological support systems and developmental outcomes. Findings confirmed that social support in family, peer, and school settings, and family cohesion positively predict self-esteem and perceived school importance, which, in turn, have protective effects on psychological symptoms, violent behaviors and substance use. Sociopolitical control was found to mediate the relationships between ecological supports and risk factors and developmental outcomes, leading to the conclusion that perceived efficacy in the sociopolitical domain, and youth empowerment, more generally, should be considered as core elements of the ecology of human development. Policy and practice aimed at promoting positive developmental outcomes and preventing risk behaviors should take their relationship to sociopolitical control into account.

  19. The Dutch Obesity Intervention in Teenagers (DOiT) cluster controlled implementation trial: intervention effects and mediators and moderators of adiposity and energy balance-related behaviours.

    van Nassau, Femke; Singh, Amika S; Cerin, Ester; Salmon, Jo; van Mechelen, Willem; Brug, Johannes; Chinapaw, Mai Jm

    2014-12-24

    The Dutch Obesity Intervention in Teenagers (DOiT) programme is an evidence-based obesity prevention programme tailored to adolescents attending the first two years of prevocational education in the Netherlands. The initial programme showed promising results during an effectiveness trial. The programme was adapted and prepared for nationwide dissemination. To gain more insight into the process of translating evidence-based approaches into 'real world' (i.e., 'natural') conditions, our research aims were to evaluate the impact of the DOiT-implementation programme on adolescents' adiposity and energy balance-related behaviours during natural dissemination and to explore the mediating and moderating factors underlying the DOiT intervention effects. We conducted a cluster-controlled implementation trial with 20 voluntary intervention schools (n=1002 adolescents) and 9 comparable control schools (n = 484 adolescents). We measured adolescents' body height and weight, skinfold thicknesses, and waist circumference. We assessed adolescents' dietary and physical activity behaviours by means of self-report. Data were collected at baseline and at 20-months follow-up. We used multivariable multilevel linear or logistic regression analyses to evaluate the intervention effects and to test the hypothesised behavioural mediating factors. We checked for potential effect modification by gender, ethnicity and education level. We found no significant intervention effects on any of the adiposity measures or behavioural outcomes. Furthermore, we found no mediating effects by any of the hypothesised behavioural mediators. Stratified analyses for gender showed that the intervention was effective in reducing sugar-containing beverage consumption in girls (B = -188.2 ml/day; 95% CI = -344.0; -32.3). In boys, we found a significant positive intervention effect on breakfast frequency (B = 0.29 days/week; 95% CI = 0.01; 0.58). Stratified analyses for education level showed

  20. Macrophages control vascular stem/progenitor cell plasticity through tumor necrosis factor-α-mediated nuclear factor-κB activation.

    Wong, Mei Mei; Chen, Yikuan; Margariti, Andriani; Winkler, Bernhard; Campagnolo, Paola; Potter, Claire; Hu, Yanhua; Xu, Qingbo

    2014-03-01

    Vascular lineage differentiation of stem/progenitor cells can contribute to both tissue repair and exacerbation of vascular diseases such as in vein grafts. The role of macrophages in controlling vascular progenitor differentiation is largely unknown and may play an important role in graft development. This study aims to identify the role of macrophages in vascular stem/progenitor cell differentiation and thereafter elucidate the mechanisms that are involved in the macrophage- mediated process. We provide in vitro evidence that macrophages can induce endothelial cell (EC) differentiation of the stem/progenitor cells while simultaneously inhibiting their smooth muscle cell differentiation. Mechanistically, both effects were mediated by macrophage-derived tumor necrosis factor-α (TNF-α) via TNF-α receptor 1 and canonical nuclear factor-κB activation. Although the overexpression of p65 enhanced EC (or attenuated smooth muscle cell) differentiation, p65 or TNF-α receptor 1 knockdown using lentiviral short hairpin RNA inhibited EC (or rescued smooth muscle cell) differentiation in response to TNF-α. Furthermore, TNF-α-mediated EC differentiation was driven by direct binding of nuclear factor-κB (p65) to specific VE-cadherin promoter sequences. Subsequent experiments using an ex vivo decellularized vessel scaffold confirmed an increase in the number of ECs and reduction in smooth muscle cell marker expression in the presence of TNF-α. The lack of TNF-α in a knockout mouse model of vein graft decreased endothelialization and significantly increased thrombosis formation. Our study highlights the role of macrophages in directing vascular stem/progenitor cell lineage commitment through TNF-α-mediated TNF-α receptor 1 and nuclear factor-κB activation that is likely required for endothelial repair in vascular diseases such as vein graft.

  1. Mediation Analysis with Multiple Mediators

    VanderWeele, T.J.; Vansteelandt, S.

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects throu...

  2. Far-UVC light: A new tool to control the spread of airborne-mediated microbial diseases.

    Welch, David; Buonanno, Manuela; Grilj, Veljko; Shuryak, Igor; Crickmore, Connor; Bigelow, Alan W; Randers-Pehrson, Gerhard; Johnson, Gary W; Brenner, David J

    2018-02-09

    Airborne-mediated microbial diseases such as influenza and tuberculosis represent major public health challenges. A direct approach to prevent airborne transmission is inactivation of airborne pathogens, and the airborne antimicrobial potential of UVC ultraviolet light has long been established; however, its widespread use in public settings is limited because conventional UVC light sources are both carcinogenic and cataractogenic. By contrast, we have previously shown that far-UVC light (207-222 nm) efficiently inactivates bacteria without harm to exposed mammalian skin. This is because, due to its strong absorbance in biological materials, far-UVC light cannot penetrate even the outer (non living) layers of human skin or eye; however, because bacteria and viruses are of micrometer or smaller dimensions, far-UVC can penetrate and inactivate them. We show for the first time that far-UVC efficiently inactivates airborne aerosolized viruses, with a very low dose of 2 mJ/cm 2 of 222-nm light inactivating >95% of aerosolized H1N1 influenza virus. Continuous very low dose-rate far-UVC light in indoor public locations is a promising, safe and inexpensive tool to reduce the spread of airborne-mediated microbial diseases.

  3. School climate and delinquency among Chinese adolescents: analyses of effortful control as a moderator and deviant peer affiliation as a mediator.

    Bao, Zhenzhou; Li, Dongping; Zhang, Wei; Wang, Yanhui

    2015-01-01

    School climate is the quality and character of school life and reflects the norms, goals, values, interpersonal relationships, teaching and learning practices, and the organizational structure of a school. There is substantial literature documenting the negative association between positive school climate and adolescent delinquency, but little is known about the moderating and mediating mechanisms underlying this relationship. The aim of this study was to examine whether the direct and indirect pathways between school climate and adolescent delinquency would be moderated by effortful control. A sample of 2,758 Chinese adolescents (M age = 13.53 years, SD = 1.06) from 10 middle schools completed anonymous questionnaires regarding school climate, effortful control, deviant peer affiliation, and delinquency. After gender, age, geographical area, and socioeconomic status were included as covariates, the results revealed that school climate was significantly associated with adolescent delinquent behavior. This direct association was moderated by effortful control, such that the negative relationship between positive school climate and delinquency was only significant among adolescents low in effortful control. Moreover, the indirect association between school climate and delinquency via deviant peer affiliation was also moderated by effortful control. Specifically, the moderating effect of effortful control was not only manifested in the relationship between school climate and deviant peer affiliation, but also in the relationship between deviant peer affiliation and delinquency. These findings contribute to understanding the mechanisms through which positive school climate might reduce delinquent behavior and have important implications for prevention efforts aimed at diminishing adolescent delinquency.

  4. Development of temperamental effortful control mediates the relationship between maturation of the prefrontal cortex and psychopathology during adolescence: A 4-year longitudinal study

    Nandita Vijayakumar

    2014-07-01

    Full Text Available This study investigated the relationship between the development of effortful control (EC, a temperamental measure of self-regulation, and concurrent development of three regions of the prefrontal cortex (anterior cingulate cortex, ACC; dorsolateral prefrontal cortex, dlPFC; ventrolateral prefrontal cortex, vlPFC between early- and mid-adolescence. It also examined whether development of EC mediated the relationship between cortical maturation and emotional and behavioral symptoms. Ninety-two adolescents underwent baseline assessments when they were approximately 12 years old and follow-up assessments approximately 4 years later. At each assessment, participants had MRI scans and completed the Early Adolescent Temperament Questionnaire-Revised, as well as measures of depressive and anxious symptoms, and aggressive and risk taking behavior. Cortical thicknesses of the ACC, dlPFC and vlPFC, estimated using the FreeSurfer software, were found to decrease over time. EC also decreased over time in females. Greater thinning of the left ACC was associated with less reduction in EC. Furthermore, change in effortful control mediated the relationship between greater thinning of the left ACC and improvements in socioemotional functioning, including reductions in psychopathological symptoms. These findings highlight the dynamic association between EC and the maturation of the anterior cingulate cortex, and the importance of this relationship for socioemotional functioning during adolescence.

  5. Efficacy and Mediation of a Theory-Based Physical Activity Intervention for African American Men Who Have Sex with Men: A Randomized Controlled Trial.

    Zhang, Jingwen; Jemmott, John B; O'Leary, Ann; Stevens, Robin; Jemmott, Loretta Sweet; Icard, Larry D; Hsu, Janet; Rutledge, Scott E

    2017-02-01

    Few trials have tested physical-activity interventions among sexual minorities, including African American men who have sex with men (MSM). We examined the efficacy and mediation of the Being Responsible for Ourselves (BRO) physical-activity intervention among African American MSM. African American MSM were randomized to the physical-activity intervention consisting of three 90-min one-on-one sessions or an attention-matched control intervention and completed pre-intervention, immediately post-intervention, and 6- and 12-month post-intervention audio computer-based surveys. Of the 595 participants, 503 completed the 12-month follow-up. Generalized estimating equation models revealed that the intervention increased self-reported physical activity compared with the control intervention, adjusted for pre-intervention physical activity. Mediation analyses suggested that the intervention increased reasoned action approach variables, subjective norm and self-efficacy, increasing intention immediately post-intervention, which increased physical activity during the follow-up period. Interventions targeting reasoned action approach variables may contribute to efforts to increase African American MSM's physical activity. The trial was registered with the ClinicalTrials.gov Identifier NCT02561286 .

  6. Sox17-Mediated XEN Cell Conversion Identifies Dynamic Networks Controlling Cell-Fate Decisions in Embryo-Derived Stem Cells

    Angela C.H. McDonald

    2014-10-01

    Full Text Available Little is known about the gene regulatory networks (GRNs distinguishing extraembryonic endoderm (ExEn stem (XEN cells from those that maintain the extensively characterized embryonic stem cell (ESC. An intriguing network candidate is Sox17, an essential transcription factor for XEN derivation and self-renewal. Here, we show that forced Sox17 expression drives ESCs toward ExEn, generating XEN cells that contribute to ExEn when placed back into early mouse embryos. Transient Sox17 expression is sufficient to drive this fate change during which time cells transit through distinct intermediate states prior to the generation of functional XEN-like cells. To orchestrate this conversion process, Sox17 acts in autoregulatory and feedforward network motifs, regulating dynamic GRNs directing cell fate. Sox17-mediated XEN conversion helps to explain the regulation of cell-fate changes and reveals GRNs regulating lineage decisions in the mouse embryo.

  7. Self-control and problematic mobile phone use in Chinese college students: the mediating role of mobile phone use patterns

    Jiang, Zhaocai; Zhao, Xiuxin

    2016-01-01

    Background With the popularity of mobile phones, problematic mobile phone use is getting increasing attention in recent years. Although self-control was found to be a critical predictor of problematic mobile phone use, no study has ever explored the association between self-control and mobile phone use patterns as well as the possible pathway how self-control affects problematic mobile phone use. Methods Four hundred sixty-eight college students were randomly selected in this study. Data were...

  8. The MEDIATOR genes MED12 and MED13 control Arabidopsis root system configuration influencing sugar and auxin responses.

    Raya-González, Javier; López-Bucio, Jesús Salvador; Prado-Rodríguez, José Carlos; Ruiz-Herrera, León Francisco; Guevara-García, Ángel Arturo; López-Bucio, José

    2017-09-01

    Arabidopsis med12 and med13 mutants exhibit shoot and root phenotypes related to an altered auxin homeostasis. Sucrose supplementation reactivates both cell division and elongation in primary roots as well as auxin-responsive and stem cell niche gene expression in these mutants. An analysis of primary root growth of WT, med12, aux1-7 and med12 aux1 single and double mutants in response to sucrose and/or N-1-naphthylphthalamic acid (NPA) placed MED12 upstream of auxin transport for the sugar modulation of root growth. The MEDIATOR (MED) complex plays diverse functions in plant development, hormone signaling and biotic and abiotic stress tolerance through coordination of transcription. Here, we performed genetic, developmental, molecular and pharmacological analyses to characterize the role of MED12 and MED13 on the configuration of root architecture and its relationship with auxin and sugar responses. Arabidopsis med12 and med13 single mutants exhibit shoot and root phenotypes consistent with altered auxin homeostasis including altered primary root growth, lateral root development, and root hair elongation. MED12 and MED13 were required for activation of cell division and elongation in primary roots, as well as auxin-responsive and stem cell niche gene expression. Remarkably, most of these mutant phenotypes were rescued by supplying sucrose to the growth medium. The growth response of primary roots of WT, med12, aux1-7 and med12 aux1 single and double mutants to sucrose and application of auxin transport inhibitor N-1-naphthylphthalamic acid (NPA) revealed the correlation of med12 phenotype with the activity of the auxin intake permease and suggests that MED12 acts upstream of AUX1 in the root growth response to sugar. These data provide compelling evidence that MEDIATOR links sugar sensing to auxin transport and distribution during root morphogenesis.

  9. A control systems approach to quantify wall shear stress normalization by flow-mediated dilation in the brachial artery.

    Frank C G van Bussel

    Full Text Available Flow-mediated dilation is aimed at normalization of local wall shear stress under varying blood flow conditions. Blood flow velocity and vessel diameter are continuous and opposing influences that modulate wall shear stress. We derived an index FMDv to quantify wall shear stress normalization performance by flow-mediated dilation in the brachial artery. In 22 fasting presumed healthy men, we first assessed intra- and inter-session reproducibilities of two indices pFMDv and mFMDv, which consider the relative peak and relative mean hyperemic change in flow velocity, respectively. Second, utilizing oral glucose loading, we evaluated the tracking performance of both FMDv indices, in comparison with existing indices [i.e., the relative peak diameter increase (%FMD, the peak to baseline diameter ratio (Dpeak/Dbase, and the relative peak diameter increase normalized to the full area under the curve of blood flow velocity with hyperemia (FMD/shearAUC or with area integrated to peak hyperemia (FMD/shearAUC_peak]. Inter-session and intra-session reproducibilities for pFMDv, mFMDv and %FMD were comparable (intra-class correlation coefficients within 0.521-0.677 range. Both pFMDv and mFMDv showed more clearly a reduction after glucose loading (reduction of ~45%, p≤0.001 than the other indices (% given are relative reductions: %FMD (~11%, p≥0.074; Dpeak/Dbase (~11%, p≥0.074; FMD/shearAUC_peak (~20%, p≥0.016 and FMD/shearAUC (~38%, p≤0.038. Further analysis indicated that wall shear stress normalization under normal (fasting conditions is already far from ideal (FMDv << 1, which (therefore does not materially change with glucose loading. Our approach might be useful in intervention studies to detect intrinsic changes in shear stress normalization performance in conduit arteries.

  10. Analysis of the siRNA-Mediated Gene Silencing Process Targeting Three Homologous Genes Controlling Soybean Seed Oil Quality.

    Lu, Sha; Yin, Xiaoyan; Spollen, William; Zhang, Ning; Xu, Dong; Schoelz, James; Bilyeu, Kristin; Zhang, Zhanyuan J

    2015-01-01

    In the past decade, RNA silencing has gained significant attention because of its success in genomic scale research and also in the genetic improvement of crop plants. However, little is known about the molecular basis of siRNA processing in association with its target transcript. To reveal this process for improving hpRNA-mediated gene silencing in crop plants, the soybean GmFAD3 gene family was chosen as a test model. We analyzed RNAi mutant soybean lines in which three members of the GmFAD3 gene family were silenced. The silencing levels of FAD3A, FAD3B and FAD3C were correlated with the degrees of sequence homology between the inverted repeat of hpRNA and the GmFAD3 transcripts in the RNAi lines. Strikingly, transgenes in two of the three RNAi lines were heavily methylated, leading to a dramatic reduction of hpRNA-derived siRNAs. Small RNAs corresponding to the loop portion of the hairpin transcript were detected while much lower levels of siRNAs were found outside of the target region. siRNAs generated from the 318-bp inverted repeat were found to be diced much more frequently at stem sequences close to the loop and associated with the inferred cleavage sites on the target transcripts, manifesting "hot spots". The top candidate hpRNA-derived siRNA share certain sequence features with mature miRNA. This is the first comprehensive and detailed study revealing the siRNA-mediated gene silencing mechanism in crop plants using gene family GmFAD3 as a test model.

  11. Analysis of the siRNA-Mediated Gene Silencing Process Targeting Three Homologous Genes Controlling Soybean Seed Oil Quality.

    Sha Lu

    Full Text Available In the past decade, RNA silencing has gained significant attention because of its success in genomic scale research and also in the genetic improvement of crop plants. However, little is known about the molecular basis of siRNA processing in association with its target transcript. To reveal this process for improving hpRNA-mediated gene silencing in crop plants, the soybean GmFAD3 gene family was chosen as a test model. We analyzed RNAi mutant soybean lines in which three members of the GmFAD3 gene family were silenced. The silencing levels of FAD3A, FAD3B and FAD3C were correlated with the degrees of sequence homology between the inverted repeat of hpRNA and the GmFAD3 transcripts in the RNAi lines. Strikingly, transgenes in two of the three RNAi lines were heavily methylated, leading to a dramatic reduction of hpRNA-derived siRNAs. Small RNAs corresponding to the loop portion of the hairpin transcript were detected while much lower levels of siRNAs were found outside of the target region. siRNAs generated from the 318-bp inverted repeat were found to be diced much more frequently at stem sequences close to the loop and associated with the inferred cleavage sites on the target transcripts, manifesting "hot spots". The top candidate hpRNA-derived siRNA share certain sequence features with mature miRNA. This is the first comprehensive and detailed study revealing the siRNA-mediated gene silencing mechanism in crop plants using gene family GmFAD3 as a test model.

  12. The role of GαO-mediated signaling in the rostral ventrolateral medulla oblongata in cardiovascular reflexes and control of cardiac ventricular excitability.

    Ang, Richard; Abramowitz, Joel; Birnbaumer, Lutz; Gourine, Alexander V; Tinker, Andrew

    2016-08-01

    The heart is controlled by the sympathetic and parasympathetic limbs of the autonomic nervous system with inhibitory signaling mechanisms recruited in both limbs. The aim of this study was to determine the role of inhibitory heterotrimeric G proteins in the central nervous mechanisms underlying autonomic control of the heart and its potential role in arrhythmogenesis. Mice with conditional deletion of the inhibitory heterotrimeric G protein GαO in the presympathetic area of the rostral ventral lateral medulla (RVLM) were generated to determine the role of GαO-mediated signalling in autonomic control and electrophysiological properties of the heart. GαO deletion within the RVLM was not associated with changes in heart rate (HR) or the arterial blood pressure at rest (home cage, normal behavior). However, exposure to stressful conditions (novel environment, hypoxia, or hypercapnia) in these mice was associated with abnormal HR responses and an increased baroreflex gain when assessed under urethane anesthesia. This was associated with shortening of the ventricular effective refractory period. This phenotype was reversed by systemic beta-adrenoceptor blockade, suggesting that GαO depletion in the RVLM increases central sympathetic drive. The data obtained support the hypothesis that GαO-mediated signaling within the presympathetic circuits of the RVLM contributes to the autonomic control of the heart. GαO deficiency in the RVLM has a significant impact on cardiovascular responses to stress, cardiovascular reflexes and electrical properties of the heart. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  13. Dispositional Flow as a Mediator of the Relationships between Attentional Control and Approaches to Studying during Academic Examination Preparation

    Cermakova, Lucie; Moneta, Giovanni B.; Spada, Marcantonio M.

    2010-01-01

    This study investigated how attentional control and study-related dispositional flow influence students' approaches to studying when preparing for academic examinations. Based on information-processing theories, it was hypothesised that attentional control would be positively associated with deep and strategic approaches to studying, and…

  14. Mother-Child Interactions and Externalizing Behavior Problems in Preschoolers over Time : Inhibitory Control as a Mediator

    van Dijk, Rianne; Dekovic, Maja; Bunte, Tessa L; Schoemaker, Kim; Zondervan-Zwijnenburg, Mariëlle; Espy, Kimberly A; Matthys, Walter

    2017-01-01

    Previous research has shown links between parenting and externalizing behavior problems in young children over time. Associations between inhibitory control, one of the executive functions, and externalizing behavior problems are widely established as well. Yet, the role of inhibitory control in the

  15. Circadian control of kisspeptin and a gated GnRH response mediate the preovulatory luteinizing hormone surge

    Williams, Wilbur P; Jarjisian, Stephan G; Mikkelsen, Jens D

    2011-01-01

    In spontaneously ovulating rodents, the preovulatory LH surge is initiated on the day of proestrus by a timed, stimulatory signal originating from the circadian clock in the suprachiasmatic nucleus (SCN). The present studies explored whether kisspeptin is part of the essential neural circuit...... linking the SCN to the GnRH system to stimulate ovulation in Syrian hamsters (Mesocricetus auratus). Kisspeptin neurons exhibit an estrogen-dependent, daily pattern of cellular activity consistent with a role in the circadian control of the LH surge. The SCN targets kisspeptin neurons via vasopressinergic...... of ovulatory control with interactions among the circadian system, kisspeptin signaling, and a GnRH gating mechanism of control....

  16. The GPCR membrane receptor, DopEcR, mediates the actions of both dopamine and ecdysone to control sex pheromone perception in an insect

    Antoine eAbrieux

    2014-09-01

    Full Text Available Olfactory information mediating sexual behavior is crucial for reproduction in many animals, including insects. In male moths, the macroglomerular complex of the primary olfactory center, the antennal lobe (AL is specialized in the treatment of information on the female-emitted sex pheromone. Evidence is accumulating that modulation of behavioral pheromone responses occurs through neuronal plasticity via the action of hormones and/or catecholamines. We recently showed that a G-protein-coupled receptor (GPCR, AipsDopEcR, with its homologue known in Drosophila for its double affinity to the main insect steroid hormone 20-hydroxyecdysone (20E, and dopamine (DA, present in the ALs, is involved in the behavioral response to pheromone in the moth, Agrotis ipsilon. Here we tested the role of AipsDopEcR as compared to nuclear 20E receptors in central pheromone processing combining receptor inhibition with intracellular recordings of AL neurons. We show that the sensitivity of AL neurons for the pheromone in males decreases strongly after AipsDopEcR-dsRNA injection but also after inhibition of nuclear 20E receptors. Moreover we tested the involvement of 20E and DA in the receptor-mediated behavioral modulation in wind tunnel experiments, using ligand applications and receptor inhibition treatments. We show that both ligands are necessary and act on AipsDopEcR-mediated behavior. Altogether these results indicate that the GPCR membrane receptor, AipsDopEcR, controls sex pheromone perception through the action of both 20E and DA in the central nervous system, probably in concert with 20E action through nuclear receptors.

  17. Reports of Wins and Risk Taking : An Investigation of the Mediating Effect of the Illusion of Control.

    Martinez , Frederic; Le Floch , Valérie; Gaffié , Bernard; Villejoubert , Gaëlle

    2011-01-01

    International audience; Two experiments examined the relationships between the knowledge that another person has won in a gamble, the illusion of control and risk taking. Participants played a computer-simulated French roulette game individually. Before playing, some participants learnt that another person won a large amount of money. Results from a first experiment (n=24) validated a causal model where the knowledge of another person's win increased the illusion of control, measured with bet...

  18. Relationship of perceived stress with depression: complete mediation by perceived control and anxiety in Iran and the United States.

    Ghorbani, Nima; Krauss, Stephen W; Watson, P J; Lebreton, Daniel

    2008-12-01

    This study sought to clarify the importance and cross-cultural relevance of associations between generalized perceived stress and depression. Also tested was the hypothesis that perceived stress would correlate more strongly with anxiety than with depression, whereas control would be more predictive of depression than of anxiety. Relationships between perceived stress, anxiety, depression, and perceived control were examined in samples of Iranian (n = 191) and American (n = 197) undergraduates. Correlations among these variables were generally similar across the two societies. Perceived stress did predict anxiety better than depression, but perceptions of control predicted depression significantly better than anxiety only in the United States. Best fitting structural equation models revealed that anxiety and perceived control completely accounted for the linkage between perceived stress and depression in both societies. An equally acceptable and more parsimonious model described perceived stress as a consequence rather than as an antecedent of anxiety and perceived control. Structural equation models were essentially identical across the two cultures except that internal control displayed a significant negative relationship with anxiety only in Iran. This result seemed to disconfirm any possible suggestion that a supposedly individualistic process like internal control could have no noteworthy role within a presumably more collectivistic Muslim society like Iran. Overall, these data documented the importance of anxiety and perceived control in explaining the perceived stress-depression relationship cross-culturally and therefore questioned the usefulness of perceived stress in predicting depression. Whether this understanding of the stress-depression relationship deserves general acceptance will require additional studies that measure the frequency of stressful life events and that utilize a longitudinal design.

  19. Seed-mediated synthesis of gold nanorods: control of the aspect ratio by variation of the reducing agent

    Koeppl, Susanne; Ghielmetti, Nico; Caseri, Walter; Spolenak, Ralph

    2013-01-01

    Seed-mediated growth methods involving reduction of tetrachloroaurate(III) with ascorbic acid are common for the synthesis of gold nanorods. This study shows, however, that simply by appropriate choice of the reducing agent a drastic influence on the aspect ratio can be attained. Weaker reducing agents, such as dihydroxybenzene isomers (hydroquinone, catechol or resorcinol) or glucose can increase the aspect ratio of the nanorods by an order of magnitude, up to values as high as 100 (nanowires). The increase in aspect ratio is mainly a consequence of an increase in length of the particles (up to 1–3 μm). This effect is probably associated with a decrease in the reduction rate of gold(III) species by dihydroxybenzenes or glucose compared to ascorbic acid. The reduction potential of the reducing agents strongly depends on the pH value, and related effects on the dimensions of the nanoparticles are also reflected in this study. The nanorods exhibited penta-twinned nature without noteworthy defects (e.g. stacking faults and dislocations).

  20. DNA-mediated dimerization on a compact sequence signature controls enhancer engagement and regulation by FOXA1.

    Wang, Xuecong; Srivastava, Yogesh; Jankowski, Aleksander; Malik, Vikas; Wei, Yuanjie; Del Rosario, Ricardo C H; Cojocaru, Vlad; Prabhakar, Shyam; Jauch, Ralf

    2018-04-14

    FOXA1 is a transcription factor capable to bind silenced chromatin to direct context-dependent cell fate conversion. Here, we demonstrate that a compact palindromic DNA element (termed 'DIV' for its diverging half-sites) induces the homodimerization of FOXA1 with strongly positive cooperativity. Alternative structural models are consistent with either an indirect DNA-mediated cooperativity or a direct protein-protein interaction. The cooperative homodimer formation is strictly constrained by precise half-site spacing. Re-analysis of chromatin immunoprecipitation sequencing data indicates that the DIV is effectively targeted by FOXA1 in the context of chromatin. Reporter assays show that FOXA1-dependent transcriptional activity declines when homodimeric binding is disrupted. In response to phosphatidylinositol-3 kinase inhibition DIV sites pre-bound by FOXA1 such as at the PVT1/MYC locus exhibit a strong increase in accessibility suggesting a role of the DIV configuration in the chromatin closed-open dynamics. Moreover, several disease-associated single nucleotide polymorphisms map to DIV elements and show allelic differences in FOXA1 homodimerization, reporter gene expression and are annotated as quantitative trait loci. This includes the rs541455835 variant at the MAPT locus encoding the Tau protein associated with Parkinson's disease. Collectively, the DIV guides chromatin engagement and regulation by FOXA1 and its perturbation could be linked to disease etiologies.

  1. The role of calcium in the receptor mediated control of potassium permeability in the rat lacrimal gland

    Parod, R.J.; Putney, J.W. Jr.

    1978-01-01

    In the presence of extracellular Ca, adrenaline stimulated by a large increase in the rate of K ( 86 Rb) release from rat lacrimal slices, followed by a lower, more sustained rate. In the absence of extracellular Ca, adrenaline elicited only a transient release of 86 Rb. The artificial introduction of Ca into the cytosol by the ionophore A-23187 could also initiate the release of 86 Rb. In a zero-Ca medium, if either adrenaline or carbachol produced a transient release of 86 Rb, the tissue could not respond to the other agonist with a transient release unless Ca was momentarily reintroduced to the medium. If Ca was present in a limiting concentration, the Ca-dependent rate of 86 Rb release elicited from a lacrimal slice exposed simultaneously to carbachol and adrenaline was not significantly different from the release seen with carbachol alone. It is concluded that the agonist-induced release of K from the lacrimal gland consists of both a Ca-independent phase which is initiated by the release of a limited pool of Ca, and a Ca-dependent phase which is mediated by the influx of extracellular Ca. It is also concluded that both α-adrenergic and muscarinic receptors occupation activate a common, post-receptor mechanism which may be responsible for both phases of K release. (author)

  2. The effect of HMB supplementation on body composition, fitness, hormonal and inflammatory mediators in elite adolescent volleyball players: a prospective randomized, double-blind, placebo-controlled study.

    Portal, Shawn; Zadik, Zvi; Rabinowitz, Jonathan; Pilz-Burstein, Ruty; Adler-Portal, Dana; Meckel, Yoav; Cooper, Dan M; Eliakim, Alon; Nemet, Dan

    2011-09-01

    The use of ergogenic nutritional supplements is becoming inseparable from competitive sports. β-Hydroxy-β-Methylbutyric acid (HMB) has recently been suggested to promote fat-free mass (FFM) and strength gains during resistance training in adults. In this prospective randomized, double-blind, placebo-controlled study, we studied the effect of HMB (3 g/day) supplementation on body composition, muscle strength, anaerobic and aerobic capacity, anabolic/catabolic hormones and inflammatory mediators in elite, national team level adolescent volleyball players (13.5-18 years, 14 males, 14 females, Tanner stage 4-5) during the first 7 weeks of the training season. HMB led to a significant greater increase in FFM by skinfold thickness (56.4 ± 10.2 to 56.3 ± 8.6 vs. 59.3 ± 11.3 to 61.6 ± 11.3 kg in the control and HMB group, respectively, p HMB led to a significant greater increase in both dominant and non-dominant knee flexion isokinetic force/FFM, measured at fast (180°/sec) and slow (60°/sec) angle speeds, but had no significant effect on knee extension and elbow flexion and extension. HMB led to a significant greater increase in peak and mean anaerobic power determined by the Wingate anaerobic test (peak power: 15.5 ± 1.6 to 16.2 ± 1.2 vs. 15.4 ± 1.6 to 17.2 ± 1.2 watts/FFM, mean power: 10.6 ± 0.9 to 10.8 ± 1.1 vs. 10.7 ± 0.8 to 11.8 ± 1.0 watts/FFM in control and HMB group, respectively, p HMB had no significant effect on aerobic fitness or on anabolic (growth hormone, IGF-I, testosterone), catabolic (cortisol) and inflammatory mediators (IL-6 and IL-1 receptor antagonist). HMB supplementation was associated with greater increases in muscle mass, muscle strength and anaerobic properties with no effect on aerobic capacity suggesting some advantage for its use in elite adolescent volleyball players during the initial phases of the training season. These effects were not accompanied by hormonal and inflammatory mediator changes.

  3. MPK6 controls H2 O2-induced root elongation by mediating Ca2+ influx across the plasma membrane of root cells in Arabidopsis seedlings.

    Han, Shuan; Fang, Lin; Ren, Xuejian; Wang, Wenle; Jiang, Jing

    2015-01-01

    Mitogen-activated protein kinases (MPKs) play critical roles in signalling and growth, and Ca(2+) and H2 O2 control plant growth processes associated with abscisic acid (ABA). However, it remains unclear how MPKs are involved in H2 O2 - and Ca(2+) -mediated root elongation. Root elongation in seedlings of the loss-of-function mutant Atmpk6 (Arabidopsis thaliana MPK6) was less sensitive to moderate H2 O2 or ABA than that in wild-type (WT) plants. The enhanced elongation was a result of root cell expansion. This effect disappeared when ABA-induced H2 O2 accumulation or the cytosolic Ca(2+) increase were defective. Molecular and biochemical evidence showed that increased expression of the cell wall peroxidase PRX34 in Atmpk6 root cells enhanced apoplastic H2 O2 generation; this promoted a cytosolic Ca(2+) increase and Ca(2+) influx across the plasma membrane. The plasma membrane damage caused by high levels of H2 O2 was ameliorated in a Ca(2+) -dependent manner. These results suggested that there was intensified PRX34-mediated H2 O2 generation in the apoplast and increased Ca(2+) flux into the cytosol of Atmpk6 root cells; that is, the spatial separation of apoplastic H2 O2 from cytosolic Ca(2+) in root cells prevented H2 O2 -induced inhibition of root elongation in Atmpk6 seedlings. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

  4. Laboratory, semi-pilot and room scale study of nitrite and molybdate mediated control of H(2)S emission from swine manure.

    Moreno, Lyman; Predicala, Bernardo; Nemati, Mehdi

    2010-04-01

    The effects of manure age on emission of H(2)S and required level of nitrite or molybdate to control these emissions were investigated in the present work. Molybdate mediated control of H(2)S emission was also studied in semi-pilot scale open systems, and in specifically designed chambers which simulated swine production rooms. With fresh 1-, 3- and 6-month old manures average H(2)S concentration in the headspace gas of the closed systems were 4856+/-460, 3431+/-208, 1037+/-98 ppm and non-detectable, respectively. Moreover, the level of nitrite or molybdate required to control the emission of H(2)S decreased as manure age increased. In the semi-pilot scale open system and chambers, average H(2)S concentration at the surface of agitated fresh manure were 831+/-26 and 88.4+/-5.7 ppm, respectively. Furthermore, 0.1-0.25 mM molybdate was sufficient to control the emission of H(2)S. A cost study for an average size swine operation showed that the cost of treatment with molybdate was less than 1% of the overall production cost for each market hog. Copyright 2009 Elsevier Ltd. All rights reserved.

  5. Evaluating Change in Beliefs About the Importance/Control of Thoughts as a Mediator of CBM-I and Responses to an ICT Stressor.

    Clerkin, Elise M; Magee, Joshua C; Parsons, E Marie

    2014-10-01

    This study evaluated an adaptation of a Cognitive Bias Modification-Interpretation (CBM-I) procedure designed to shift interpretations of intrusive thoughts related to beliefs about the Importance and Control of Thoughts (ICT). Individuals high in the ICT belief domain were randomly assigned to one of two conditions: (a) a positive (n = 38) condition in which scenarios about intrusive thoughts were repeatedly paired with benign interpretations; or (b) a control (n = 39) condition in which scenarios about intrusive thoughts were paired with 50% benign and 50% threatening interpretations. Further, participants engaged in an ICT stressor task. Structural equation modeling with bias-corrected bootstrapping was used to examine the effects of training on ICT-relevant interpretations, beliefs, and ICT stressor responding. As predicted, individuals in a positive (vs. control) training condition reported decreases in ICT-relevant interpretations and beliefs. Further, there was a small, statistically significant indirect (i.e., mediated) effect of training on measures of ICT stressor responding, which occurred via decreases in ICT-relevant beliefs. In sum, results indicate that training was effective in influencing interpretations and beliefs tied to Importance/Control of Thoughts and that there may be clinical utility to shifting this belief domain.

  6. Why are people with high self-control happier? The effect of trait self-control on happiness as mediated by regulatory focus

    Cheung, Tracy T L|info:eu-repo/dai/nl/371747546; Gillebaart, Marleen|info:eu-repo/dai/nl/344390365; Kroese, Floor|info:eu-repo/dai/nl/313869871; De Ridder, Denise|info:eu-repo/dai/nl/070706174

    2014-01-01

    Background: While self-control has often been related to positive outcomes in life such as higher academic achievements and better health, recent insights reveal that people with high trait self-control (TSC) may even experience greater life satisfaction or happiness. Objective: The current study

  7. Complex Mediation

    Bødker, Susanne; Andersen, Peter Bøgh

    2005-01-01

    This article has its starting point in a large number of empirical findings regarding computer-mediated work. These empirical findings have challenged our understanding of the role of mediation in such work; on the one hand as an aspect of communication and cooperation at work and on the other hand...... as an aspect of human engagement with instruments of work. On the basis of previous work in activity-theoretical and semiotic human—computer interaction, we propose a model to encompass both of these aspects. In a dialogue with our empirical findings we move on to propose a number of types of mediation...... that have helped to enrich our understanding of mediated work and the design of computer mediation for such work....

  8. Interventional Effects for Mediation Analysis with Multiple Mediators.

    Vansteelandt, Stijn; Daniel, Rhian M

    2017-03-01

    The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator-outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that involve repeatedly measured mediators, or multiple correlated mediators. VanderWeele, Vansteelandt, and Robins introduced so-called interventional (in)direct effects. These can be identified under much weaker conditions than natural (in)direct effects, but have the drawback of not adding up to the total effect. In this article, we adapt their proposal to achieve an exact decomposition of the total effect, and extend it to the multiple mediator setting. Interestingly, the proposed effects capture the path-specific effects of an exposure on an outcome that are mediated by distinct mediators, even when-as often-the structural dependence between the multiple mediators is unknown, for instance, when the direction of the causal effects between the mediators is unknown, or there may be unmeasured common causes of the mediators.

  9. H(2 enhances arabidopsis salt tolerance by manipulating ZAT10/12-mediated antioxidant defence and controlling sodium exclusion.

    Yanjie Xie

    Full Text Available BACKGROUND: The metabolism of hydrogen gas (H(2 in bacteria and algae has been extensively studied for the interesting of developing H(2-based fuel. Recently, H(2 is recognized as a therapeutic antioxidant and activates several signalling pathways in clinical trials. However, underlying physiological roles and mechanisms of H(2 in plants as well as its signalling cascade remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this report, histochemical, molecular, immunological and genetic approaches were applied to characterize the participation of H(2 in enhancing Arabidopsis salt tolerance. An increase of endogenous H(2 release was observed 6 hr after exposure to 150 mM NaCl. Arabidopsis pretreated with 50% H(2-saturated liquid medium, mimicking the induction of endogenous H(2 release when subsequently exposed to NaCl, effectively decreased salinity-induced growth inhibition. Further results showed that H(2 pretreatment modulated genes/proteins of zinc-finger transcription factor ZAT10/12 and related antioxidant defence enzymes, thus significantly counteracting the NaCl-induced reactive oxygen species (ROS overproduction and lipid peroxidation. Additionally, H(2 pretreatment maintained ion homeostasis by regulating the antiporters and H(+ pump responsible for Na(+ exclusion (in particular and compartmentation. Genetic evidence suggested that SOS1 and cAPX1 might be the target genes of H(2 signalling. CONCLUSIONS: Overall, our findings indicate that H(2 acts as a novel and cytoprotective regulator in coupling ZAT10/12-mediated antioxidant defence and maintenance of ion homeostasis in the improvement of Arabidopsis salt tolerance.

  10. Regulation of protein quality control by UBE4B and LSD1 through p53-mediated transcription.

    Goran Periz

    2015-04-01

    Full Text Available Protein quality control is essential for clearing misfolded and aggregated proteins from the cell, and its failure is associated with many neurodegenerative disorders. Here, we identify two genes, ufd-2 and spr-5, that when inactivated, synergistically and robustly suppress neurotoxicity associated with misfolded proteins in Caenorhabditis elegans. Loss of human orthologs ubiquitination factor E4 B (UBE4B and lysine-specific demethylase 1 (LSD1, respectively encoding a ubiquitin ligase and a lysine-specific demethylase, promotes the clearance of misfolded proteins in mammalian cells by activating both proteasomal and autophagic degradation machineries. An unbiased search in this pathway reveals a downstream effector as the transcription factor p53, a shared substrate of UBE4B and LSD1 that functions as a key regulator of protein quality control to protect against proteotoxicity. These studies identify a new protein quality control pathway via regulation of transcription factors and point to the augmentation of protein quality control as a wide-spectrum antiproteotoxicity strategy.

  11. Changes in Frontal EEG Coherence across Infancy Predict Cognitive Abilities at Age 3: The Mediating Role of Attentional Control

    Whedon, Margaret; Perry, Nicole B.; Calkins, Susan D.; Bell, Martha Ann

    2016-01-01

    Theoretical perspectives of cognitive development have maintained that functional integration of the prefrontal cortex across infancy underlies the emergence of attentional control and higher cognitive abilities in early childhood. To investigate these proposed relations, we tested whether functional integration of prefrontal regions across the…

  12. Ability of nitrones of various structures to control the radical polymerization of styrene mediated by in situ formed nitroxides.

    Sciannamea, V.; Guerrero-Sanchez, C.A.; Schubert, U.S.; Catala, J.-M.; Jerome, R.; Detrembleur, C.

    2005-01-01

    The ability of several nitrones to control the radical polymerization of styrene at 110 °C has been investigated by high-throughput experimentation. The nitrone/free radical initiator pair dictates the structure of the nitroxide and the alkoxyamine formed in situ, which determines the position of

  13. Reports of wins and risk taking: an investigation of the mediating effect of the illusion of control.

    Martinez, Frédéric; Le Floch, Valérie; Gaffié, Bernard; Villejoubert, Gaëlle

    2011-06-01

    Two experiments examined the relationships between the knowledge that another person has won in a gamble, the illusion of control and risk taking. Participants played a computer-simulated French roulette game individually. Before playing, some participants learnt that another person won a large amount of money. Results from a first experiment (n = 24) validated a causal model where the knowledge of another person's win increased the illusion of control, measured with betting times, expectancy and self-reports on scales, which in turn encourages risk taking. In the second experiment (n = 36), some participants were told the previous player acknowledged the win to be fortuitous. The suppression of the belief that the previous winner had himself exerted control over the outcome resulted in lower rates of risk-taking behaviors. This suggests that it was not the knowledge of another person's win in itself that increased risk taking, but rather, the belief that the other person had some control over the gamble's outcome. Theoretical implications for the study of social mechanisms involved in gambling behavior are discussed.

  14. Genetically designed biomolecular capping system for mesoporous silica nanoparticles enables receptor-mediated cell uptake and controlled drug release

    Datz, S.; Argyo, C.; Gattner, M.; Weiss, V.; Brunner, K.; Bretzler, J.; von Schirnding, C.; Torrano, A. A.; Spada, F.; Vrábel, Milan; Engelke, H.; Bräuchle, C.; Carell, T.; Bein, T.

    2016-01-01

    Roč. 8, č. 15 (2016), s. 8101-8110 ISSN 2040-3364 Institutional support: RVO:61388963 Keywords : responsive controlled release * Diels-Alder reactions * human carbonic anhydrase Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 7.367, year: 2016 http://pubs.rsc.org/en/content/articlehtml/2016/nr/c5nr08163g

  15. Policy-relevant behaviours predict heavier drinking and mediate the relationship with age, gender and education status: Analysis from the International Alcohol Control study.

    Casswell, Sally; Huckle, Taisia; Wall, Martin; Parker, Karl; Chaiyasong, Surasak; Parry, Charles D H; Viet Cuong, Pham; Gray-Phillip, Gaile; Piazza, Marina

    2018-02-21

    To investigate behaviours related to four alcohol policy variables (policy-relevant behaviours) and demographic variables in relation to typical quantities of alcohol consumed on-premise in six International Alcohol Control study countries. General population surveys with drinkers using a comparable survey instrument and data analysed using path analysis in an overall model and for each country. typical quantities per occasion consumed on-premise; gender, age; years of education, prices paid, time of purchase, time to access alcohol and liking for alcohol advertisements. In the overall model younger people, males and those with fewer years of education consumed larger typical quantities. Overall lower prices paid, later time of purchase and liking for alcohol ads predicted consuming larger typical quantities; this was found in the high-income countries, less consistently in the high-middle-income countries and not in the low middle-income country. Three policy-relevant behaviours (prices paid, time of purchase, liking for alcohol ads) mediated the relationships between age, gender, education and consumption in high-income countries. International Alcohol Control survey data showed a relationship between policy-relevant behaviours and typical quantities consumed and support the likely effect of policy change (trading hours, price and restrictions on marketing) on heavier drinking. The path analysis also revealed policy-relevant behaviours were significant mediating variables between the effect of age, gender and educational status on consumption. However, this relationship is clearest in high-income countries. Further research is required to understand better how circumstances in low-middle-income countries impact effects of policies. © 2018 The Authors Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.

  16. The Long-Term Effectiveness of the Family Check-up on Peer Preference: Parent-Child Interaction and Child Effortful Control as Sequential Mediators.

    Chang, Hyein; Shaw, Daniel S; Shelleby, Elizabeth C; Dishion, Thomas J; Wilson, Melvin N

    2017-05-01

    We examined the longitudinal effects of the Family Check-Up (FCU) intervention beginning in toddlerhood on children's peer preference at school-age. Specifically, a sequential mediational model was proposed in which the FCU was hypothesized to promote peer preference (i.e., higher acceptance and lower rejection by peers) in middle childhood through its positive effects on parent-child interaction and child effortful control in early childhood. Participants were 731 low-income families (49 % female). Qualities of parent-child interaction were observed during structured activities at 2 to 5 years, child effortful control was assessed using behavioral tasks at 5 years, and peer acceptance and rejection were rated by teachers at 7.5 to 10.5 years. Results indicated that the FCU indirectly predicted peer preference by sequentially improving parent-child interaction and child effortful control. The findings are discussed with respect to implications for understanding mechanisms by which early parenting-focused programs may enhance child functioning across time and context.

  17. Mediation effect of perceived behavioural control on intended condom use: applicability of the theory of planned behaviour to money boys in China.

    Liu, Hongjie; Kennedy, May; Liu, Hui; Hong, Fuchang; Ha, Toan; Ning, Zheng

    2013-12-01

    Money boys (MBs) are male sex workers who sell sex to men who have sex with men. The objectives of this study were to assess (a) the sexual HIV risk of MBs; (b) the ability of the theory of planned behaviour (TPB) to predict MBs' intentions to use condoms; and (c) the manner in which TPB constructs (attitudes towards condom use, subjective norms and perceived behavioural control) combine to influence condom use intentions. Participants came from 10 MB-frequented clubs in two cities in China. Multiple regression and path analytic models were used to test inter-relationships among the TPB constructs. Seventy-eight percent of the 122 MB participants reported having used condoms for every anal sex act. About one-third reported having had female sexual partners in the past 2 months; of these MBs, half (53%) used condoms for every sex act. A revised model using TPB constructs accounted for 52% of the variance of condom use intentions and revealed that perceived behavioural control was a mediator in pathways beginning with attitudes and ending with condom use intentions, and beginning with subjective norms and ending with intentions. The findings suggest that a revised model of TPB applies to condom use intentions among Chinese MBs. It may be appropriate to adapt HIV interventions that are grounded in TPB and that have been shown to be effective elsewhere for use with Chinese MBs. HIV interventions for this population should give perceived behavioural control and its predictors special consideration.

  18. Effect of sports participation on Internet addiction mediated by self-control: A case of Korean adolescents

    Jae-Ahm Park; Mi-Hyang Park; Ji-Hye Shin; Bo Li; David Thomas Rolfe; Jong-Yeol Yoo; Stephen W. Dittmore

    2016-01-01

    Internet addiction among adolescents has become a major social problem. Thus, more effective Internet addiction treatment programs through sports are required. This study tried to identify the relationship among sports participation, self-control, and Internet addiction among Korean adolescents. In total, 345 students (aged 15–18 years) from two middle schools and two high schools in South Korea were analyzed using Confirmatory Factor Analysis (CFA) and Structural Equation Modeling (SEM). ...

  19. Direct and indirect influences of fate control belief, gambling expectancy bias, and self-efficacy on problem gambling and negative mood among Chinese college students: a multiple mediation analysis.

    Tang, Catherine So-Kum; Wu, Anise M S

    2010-12-01

    A multiple mediation model was proposed to integrate core concepts of the social axioms framework and the social cognitive theory in order to understand gambling behavior. It was hypothesized that the influence of general fate control belief on problem gambling and negative mood would be mediated by gambling-specific beliefs. Data from 773 Chinese college recreational gamblers were collected. The bootstrapping procedure was used to test the multiple mediation hypotheses. Significant indirect effects of fate control belief on problem gambling and negative mood through two gambling-specific mediators were found. Gambling expectancy bias was a more salient mediator than gambling self-efficacy. Fate control belief was also found to have a significant direct effect on negative mood. In general, a high level of general fate control belief was related to greater gambling expectancy bias and lower self-efficacy in resisting gambling, which were in turn related to problem gambling and negative mood. Limitations and implications of the study were discussed.

  20. Using Functional Electrical Stimulation Mediated by Iterative Learning Control and Robotics to Improve Arm Movement for People With Multiple Sclerosis.

    Sampson, Patrica; Freeman, Chris; Coote, Susan; Demain, Sara; Feys, Peter; Meadmore, Katie; Hughes, Ann-Marie

    2016-02-01

    Few interventions address multiple sclerosis (MS) arm dysfunction but robotics and functional electrical stimulation (FES) appear promising. This paper investigates the feasibility of combining FES with passive robotic support during virtual reality (VR) training tasks to improve upper limb function in people with multiple sclerosis (pwMS). The system assists patients in following a specified trajectory path, employing an advanced model-based paradigm termed iterative learning control (ILC) to adjust the FES to improve accuracy and maximise voluntary effort. Reaching tasks were repeated six times with ILC learning the optimum control action from previous attempts. A convenience sample of five pwMS was recruited from local MS societies, and the intervention comprised 18 one-hour training sessions over 10 weeks. The accuracy of tracking performance without FES and the amount of FES delivered during training were analyzed using regression analysis. Clinical functioning of the arm was documented before and after treatment with standard tests. Statistically significant results following training included: improved accuracy of tracking performance both when assisted and unassisted by FES; reduction in maximum amount of FES needed to assist tracking; and less impairment in the proximal arm that was trained. The system was well tolerated by all participants with no increase in muscle fatigue reported. This study confirms the feasibility of FES combined with passive robot assistance as a potentially effective intervention to improve arm movement and control in pwMS and provides the basis for a follow-up study.

  1. Interventional effects for mediation analysis with multiple mediators

    Vansteelandt, Stijn; Daniel, Rhian M.

    2017-01-01

    The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator–outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that...

  2. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo

    Florian Douam

    2017-08-01

    Full Text Available Yellow fever virus (YFV is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β signaling and type II interferon (IFN-γ signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection. However, it remains unclear how type III IFN (IFN-λ integrates into this antiviral system. Here, we report that while wild-type (WT and IFN-λ receptor knockout (λR−/− mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. Although IFN-α/β receptor knockout (α/βR−/− mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. Mortality was associated with viral neuroinvasion and increased permeability of the blood-brain barrier (BBB. α/βR−/− λR−/− mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication. Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity.

  3. Can Allowance, Personal Budgeting and Self Control as Mediating Role Manage Compulsive Buying Behavior Among College Students?

    Alce Mariani Labito

    2017-12-01

    Full Text Available Compulsive Buying Behavior seemed to be increasing, especially among college students. The aim of this study was to explain some factors that influence compulsive buying behavior. This study involved 189 undergraduate students and data collected by distributing questionnaires. The result showed that allowance, personal budgeting, were related to compulsive buying behavior. The other results indicated that self-control was able to weaken the influence of allowance on compulsive buying behavior. Also, the outcome empirically showed that college students are knowledgeable with some alternative methods for overcoming compulsive buying behavior.

  4. Autonomous control of metabolic state by a quorum sensing (QS)-mediated regulator for bisabolene production in engineered E. coli

    Kim, Eun-Mi; Min Woo, Han; Tian, Tian

    2017-01-01

    as it is self-regulated and does not require the addition of inducer compounds, which reduce operational costs for inducer. In this study, a QS system was developed for inducer-free production of the biofuel compound bisabolene from engineered E. coli. Seven variants of the Sensor plasmid, which carry the lux......I-luxR genes, and four variants of the Response plasmid, which carry bisabolene producing pathway genes under the control of the PluxI promoter, were designed for optimization of bisabolene production. Furthermore, a chromosome-integrated QS strain was engineered with the best combination of Sensor...

  5. The Relationship Between Poor Quality of Life and Desire to Hasten Death: A Multiple Mediation Model Examining the Contributions of Depression, Demoralization, Loss of Control, and Low Self-worth.

    Robinson, Sophie; Kissane, David W; Brooker, Joanne; Hempton, Courtney; Burney, Susan

    2017-02-01

    The risk of suicide is elevated in palliative care patients compared with the general population. Various psychological factors, including depression, demoralization, loss of control, and low self-worth, have been associated with a desire to hasten death. The aim of this study was to investigate whether depression, demoralization, loss of control, and low self-worth mediated the relationship between global quality of life and desire to hasten death. A sample of 162 palliative care patients completed measures of global quality of life, depression, demoralization, perceived control, self-worth, and desire to hasten death. A multiple mediation model with bootstrapping sampling tested the total (combined) indirect effect and individual indirect effects of depression, the two subscales of demoralization (Meaning and Purpose, and Distress and Coping Ability), perceived control, and self-worth. Depressive symptoms, loss of meaning and purpose, loss of control, and low self-worth mediated the direct effect of global quality of life on desire to hasten death. The Distress and Coping Ability component of demoralization was not a significant mediator. Depression, loss of meaning and purpose, loss of control, and low self-worth are strong clinical markers for desire to hasten death. Targeting these symptoms through existentially oriented therapies, such as meaning-centered therapy, may ameliorate suicidal thinking. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  6. The tuberal lateral hypothalamus is a major target for GABAA--but not GABAB-mediated control of food intake.

    Turenius, Christine I; Charles, Jonathan R; Tsai, Donna H; Ebersole, Priscilla L; Htut, Myat H; Ngo, Phuong T; Lara, Raul N; Stanley, B Glenn

    2009-08-04

    The lateral hypothalamus (LH) is a site of integration for control mechanisms of feeding behavior as it has extensive reciprocal connections with multiple intrahypothalamic and extrahypothalamic brain areas. Evidence suggests that blockade of ionotropric gamma-aminobutyric acid (GABA) receptors in the LH elicits eating in satiated rats. To determine whether this GABA(A) receptor antagonist effect is specific to the LH, the antagonist picrotoxin was injected into one of six nearby sites and food intake was measured. Picrotoxin at 133 pmol elicited eating in the LH, but not in surrounding sites (thalamus, lateral preoptic area, ventral tegmental area, dorsomedial hypothalamus, and entopeduncular nucleus). More specifically, picrotoxin injected into the tuberal LH (tLH) elicited eating, but was ineffective when injected into the anterior or posterior LH. We also investigated whether GABA(B) receptors in the LH participated in the control of food intake and found that neither blockade nor activation of these receptors under multiple conditions changed food intake. Collectively, our findings suggest that GABA(A) but not GABA(B) receptors in the tLH act to suppress feeding behavior.

  7. Fear-of-intimacy-mediated zinc transport controls the function of zinc-finger transcription factors involved in myogenesis.

    Carrasco-Rando, Marta; Atienza-Manuel, Alexandra; Martín, Paloma; Burke, Richard; Ruiz-Gómez, Mar

    2016-06-01

    Zinc is a component of one-tenth of all human proteins. Its cellular concentration is tightly regulated because its dyshomeostasis has catastrophic health consequences. Two families of zinc transporters control zinc homeostasis in organisms, but there is little information about their specific developmental roles. We show that the ZIP transporter Fear-of-intimacy (Foi) is necessary for the formation of Drosophila muscles. In foi mutants, myoblasts segregate normally, but their specification is affected, leading to the formation of a misshapen muscle pattern and distorted midgut. The observed phenotypes could be ascribed to the inactivation of specific zinc-finger transcription factors (ZFTFs), supporting the hypothesis that they are a consequence of intracellular depletion of zinc. Accordingly, foi phenotypes can be rescued by mesodermal expression of other ZIP members with similar subcellular localization. We propose that Foi acts mostly as a transporter to regulate zinc intracellular homeostasis, thereby impacting on the activity of ZFTFs that control specific developmental processes. Our results additionally suggest a possible explanation for the presence of large numbers of zinc transporters in organisms based on differences in ion transport specificity and/or degrees of activity among transporters. © 2016. Published by The Company of Biologists Ltd.

  8. Nitric oxide–mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection

    Nairz, Manfred; Schleicher, Ulrike; Schroll, Andrea; Sonnweber, Thomas; Theurl, Igor; Ludwiczek, Susanne; Talasz, Heribert; Brandacher, Gerald; Moser, Patrizia L.; Muckenthaler, Martina U.; Fang, Ferric C.; Bogdan, Christian

    2013-01-01

    Nitric oxide (NO) generated by inducible NO synthase 2 (NOS2) affects cellular iron homeostasis, but the underlying molecular mechanisms and implications for NOS2-dependent pathogen control are incompletely understood. In this study, we found that NO up-regulated the expression of ferroportin-1 (Fpn1), the major cellular iron exporter, in mouse and human cells. Nos2−/− macrophages displayed increased iron content due to reduced Fpn1 expression and allowed for an enhanced iron acquisition by the intracellular bacterium Salmonella typhimurium. Nos2 gene disruption or inhibition of NOS2 activity led to an accumulation of iron in the spleen and splenic macrophages. Lack of NO formation resulted in impaired nuclear factor erythroid 2-related factor-2 (Nrf2) expression, resulting in reduced Fpn1 transcription and diminished cellular iron egress. After infection of Nos2−/− macrophages or mice with S. typhimurium, the increased iron accumulation was paralleled by a reduced cytokine (TNF, IL-12, and IFN-γ) expression and impaired pathogen control, all of which were restored upon administration of the iron chelator deferasirox or hyperexpression of Fpn1 or Nrf2. Thus, the accumulation of iron in Nos2−/− macrophages counteracts a proinflammatory host immune response, and the protective effect of NO appears to partially result from its ability to prevent iron overload in macrophages PMID:23630227

  9. A NIN-LIKE PROTEIN mediates nitrate-induced control of root nodule symbiosis in Lotus japonicus.

    Nishida, Hanna; Tanaka, Sachiko; Handa, Yoshihiro; Ito, Momoyo; Sakamoto, Yuki; Matsunaga, Sachihiro; Betsuyaku, Shigeyuki; Miura, Kenji; Soyano, Takashi; Kawaguchi, Masayoshi; Suzaki, Takuya

    2018-02-05

    Legumes and rhizobia establish symbiosis in root nodules. To balance the gains and costs associated with the symbiosis, plants have developed two strategies for adapting to nitrogen availability in the soil: plants can regulate nodule number and/or stop the development or function of nodules. Although the former is accounted for by autoregulation of nodulation, a form of systemic long-range signaling, the latter strategy remains largely enigmatic. Here, we show that the Lotus japonicus NITRATE UNRESPONSIVE SYMBIOSIS 1 (NRSYM1) gene encoding a NIN-LIKE PROTEIN transcription factor acts as a key regulator in the nitrate-induced pleiotropic control of root nodule symbiosis. NRSYM1 accumulates in the nucleus in response to nitrate and directly regulates the production of CLE-RS2, a root-derived mobile peptide that acts as a negative regulator of nodule number. Our data provide the genetic basis for how plants respond to the nitrogen environment and control symbiosis to achieve proper plant growth.

  10. In vivo real-time monitoring system of electroporation mediated control of transdermal and topical drug delivery.

    Blagus, Tanja; Markelc, Bostjan; Cemazar, Maja; Kosjek, Tina; Preat, Veronique; Miklavcic, Damijan; Sersa, Gregor

    2013-12-28

    Electroporation (EP) is a physical method for the delivery of molecules into cells and tissues, including the skin. In this study, in order to control the degree of transdermal and topical drug delivery, EP at different amplitudes of electric pulses was evaluated. A new in vivo real-time monitoring system based on fluorescently labeled molecules was developed, for the quantification of transdermal and topical drug delivery. EP of the mouse skin was performed with new non-invasive multi-array electrodes, delivering different amplitudes of electric pulses ranging from 70 to 570 V, between the electrode pin pairs. Patches, soaked with 4 kDa fluorescein-isothiocyanate labeled dextran (FD), doxorubicin (DOX) or fentanyl (FEN), were applied to the skin before and after EP. The new monitoring system was developed based on the delivery of FD to and through the skin. FD relative quantity was determined with fluorescence microscopy imaging, in the treated region of the skin for topical delivery and in a segment of the mouse tail for transdermal delivery. The application of electric pulses for FD delivery resulted in enhanced transdermal delivery. Depending on the amplitude of electric pulses, it increased up to the amplitude of 360 V, and decreased at higher amplitudes (460 and 570 V). Topical delivery steadily enhanced with increasing the amplitude of the delivered electric pulses, being even higher than after tape stripping used as a positive control. The non-invasive monitoring of the delivery of DOX, a fluorescent chemotherapeutic drug, qualitatively and quantitatively confirmed the effects of EP at 360 and 570 V pulse amplitudes on topical and transdermal drug delivery. Delivery of FEN at 360 and 570 V pulse amplitudes verified the observed effects as obtained with FD and DOX, by the measured physiological responses of the mice as well as FEN plasma concentration. This study demonstrates that with the newly developed non-invasive multi-array electrodes and with the

  11. Cognitive issues in autonomous spacecraft-control operations: An investigation of software-mediated decision making in a scaled environment

    Murphy, Elizabeth Drummond

    As advances in technology are applied in complex, semi-automated domains, human controllers are distanced from the controlled process. This physical and psychological distance may both facilitate and degrade human performance. To investigate cognitive issues in spacecraft ground-control operations, the present experimental research was undertaken. The primary issue concerned the ability of operations analysts who do not monitor operations to make timely, accurate decisions when autonomous software calls for human help. Another key issue involved the potential effects of spatial-visualization ability (SVA) in environments that present data in graphical formats. Hypotheses were derived largely from previous findings and predictions in the literature. Undergraduate psychology students were assigned at random to a monitoring condition or an on-call condition in a scaled environment. The experimental task required subjects to decide on the veracity of a problem diagnosis delivered by a software process on-board a simulated spacecraft. To support decision-making, tabular and graphical data displays presented information on system status. A level of software confidence in the problem diagnosis was displayed, and subjects reported their own level of confidence in their decisions. Contrary to expectations, the performance of on-call subjects did not differ significantly from that of continuous monitors. Analysis yielded a significant interaction of sex and condition: Females in the on-call condition had the lowest mean accuracy. Results included a preference for bar charts over line graphs and faster performance with tables than with line graphs. A significant correlation was found between subjective confidence and decision accuracy. SVA was found to be predictive of accuracy but not speed; and SVA was found to be a stronger predictor of performance for males than for females. Low-SVA subjects reported that they relied more on software confidence than did medium- or high

  12. Pulse-mediated chemotherapy enhances local control and survival in a spontaneous canine model of primary mucosal melanoma.

    Spugnini, Enrico P; Dragonetti, Emanuele; Vincenzi, Bruno; Onori, Nicoletta; Citro, Gennaro; Baldi, Alfonso

    2006-02-01

    Mucosal melanomas account for 1% of all malignant melanomas in humans. Treatment options include surgery, chemotherapy, immunotherapy and radiation therapy; however, local recurrence and distant dissemination are still frequent. We treated locally aggressive spontaneous canine oral melanomas that, because of their advanced stage, were not treatable with conventional strategies. A cohort of 10 dogs with oral melanoma was enrolled over a 4-year period. The dogs received two sessions of local bleomycin, followed by the application of trains of biphasic pulses. The treatment was well tolerated and resulted in an overall response rate of 80% with 50% long-term control. Of interest, only one of the dogs died of metastatic disease, and four of the long-term survivors showed a vitiligo-like discoloration at the site of treatment, potentially suggesting a recruitment of the immune system by the therapy. Further studies are needed to characterize this approach and to determine its suitability for head and neck mucosal melanoma.

  13. Post-translational control of RIPK3 and MLKL mediated necroptotic cell death [version 1; referees: 4 approved

    James M. Murphy

    2015-11-01

    Full Text Available Several programmed lytic and necrotic-like cell death mechanisms have now been uncovered, including the recently described receptor interacting protein kinase-3 (RIPK3-mixed lineage kinase domain-like (MLKL-dependent necroptosis pathway. Genetic experiments have shown that programmed necrosis, including necroptosis, can play a pivotal role in regulating host-resistance against microbial infections. Alternatively, excess or unwarranted necroptosis may be pathological in autoimmune and autoinflammatory diseases. This review highlights the recent advances in our understanding of the post-translational control of RIPK3-MLKL necroptotic signaling. We discuss the critical function of phosphorylation in the execution of necroptosis, and highlight the emerging regulatory roles for several ubiquitin ligases and deubiquitinating enzymes. Finally, based on current evidence, we discuss the potential mechanisms by which the essential, and possibly terminal, necroptotic effector, MLKL, triggers the disruption of cellular membranes to cause cell lysis.

  14. Receptor protein tyrosine phosphatase alpha activates Src-family kinases and controls integrin-mediated responses in fibroblasts

    Su, J; Muranjan, M; Sap, J

    1999-01-01

    of tyrosine kinases, the activity of which is tightly controlled by inhibitory phosphorylation of a carboxyterminal tyrosine residue (Tyr527 in chicken c-Src); this phosphorylation induces the kinases to form an inactive conformation. Whereas the identity of such inhibitory Tyr527 kinases has been well...... established, no corresponding phosphatases have been identified that, under physiological conditions, function as positive regulators of c-Src and Fyn in fibroblasts. RESULTS: Receptor protein tyrosine phosphatase alpha (RPTPalpha) was inactivated by homologous recombination. Fibroblasts derived from...... these RPTPalpha-/- mice had impaired tyrosine kinase activity of both c-Src and Fyn, and this was accompanied by a concomitant increase in c-Src Tyr527 phosphorylation. RPTPalpha-/- fibroblasts also showed a reduction in the rate of spreading on fibronectin substrates, a trait that is a phenocopy of the effect...

  15. Copper mediated controlled radical copolymerization of styrene and2-ethylhexyl acrylate and determination of their reactivity ratios.

    Bishnu Prasad Koiry

    2014-10-01

    Full Text Available Copolymerization is an important synthetic tool to prepare polymers with desirable combination of properties which are difficult to achieve from the different homopolymers concerned. This investigation reports the copolymerization of 2-ethylhexyl acrylate (EHA and styrene using copper bromide (CuBr as catalyst in combination with N,N,N’,N,N- pentamethyldiethylenetriamine (PMDETA as ligand and 1-phenylethyl bromide (PEBr as initiator. Linear kinetic plot and linear increase in molecular weights versus conversion indicate that copolymerization reactions were controlled. The copolymer composition was calculated using 1H NMR studies. The reactivity ratio of styrene and EHA (r1 and r2 were determined using the Finemann-Ross (FR, inverted Finemann-Ross (FR and Kelen-Tudos (KT methods. Thermal properties of the copolymers were also studied by using TGA and DSC analysis.

  16. Extracellular signal-regulated kinase 2 (ERK-2) mediated phosphorylation regulates nucleo-cytoplasmic shuttling and cell growth control of Ras-associated tumor suppressor protein, RASSF2

    Kumari, Gita; Mahalingam, S.

    2009-01-01

    Ras GTPase controls the normal cell growth through binding with an array of effector molecules, such as Raf and PI3-kinase in a GTP-dependent manner. RASSF2, a member of the Ras association domain family, is known to be involved in the suppression of cell growth and is frequently down-regulated in various tumor tissues by promoter hypermethylation. In the present study, we demonstrate that RASSF2 shuttles between nucleus and cytoplasm by a signal-mediated process and its export from the nucleus is sensitive to leptomycin B. Amino acids between 240 to 260 in the C-terminus of RASSF2 harbor a functional nuclear export signal (NES), which is necessary and sufficient for efficient export of RASSF2 from the nucleus. Substitution of conserved Ile254, Val257 and Leu259 within the minimal NES impaired RASSF2 export from the nucleus. In addition, wild type but not the nuclear export defective RASSF2 mutant interacts with export receptor, CRM-1 and exported from the nucleus. Surprisingly, we observed nucleolar localization for the nuclear export defective mutant suggesting the possibility that RASSF2 may localize in different cellular compartments transiently in a cell cycle dependent manner and the observed nuclear localization for wild type protein may be due to faster export kinetics from the nucleolus. Furthermore, our data suggest that RASSF2 is specifically phosphorylated by MAPK/ERK-2 and the inhibitors of MAPK pathway impair the phosphorylation and subsequently block the export of RASSF2 from the nucleus. These data clearly suggest that ERK-2 mediated phosphorylation plays an important role in regulating the nucleo-cytoplasmic shuttling of RASSF2. Interestingly, nuclear import defective mutant of RASSF2 failed to induce cell cycle arrest at G1/S phase and apoptosis suggesting that RASSF2 regulates cell growth in a nuclear localization dependent manner. Collectively, these data provided evidence for the first time that MAPK/ERK-2 mediated phosphorylation regulates

  17. Extracellular signal-regulated kinase 2 (ERK-2) mediated phosphorylation regulates nucleo-cytoplasmic shuttling and cell growth control of Ras-associated tumor suppressor protein, RASSF2

    Kumari, Gita [Laboratory of Molecular Virology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500076 (India); Mahalingam, S., E-mail: mahalingam@iitm.ac.in [Laboratory of Molecular Virology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500076 (India); Department of Biotechnology, Laboratory of Molecular Virology and Cell Biology, Indian Institute of Technology-Madras, Chennai 600 036 (India)

    2009-10-01

    Ras GTPase controls the normal cell growth through binding with an array of effector molecules, such as Raf and PI3-kinase in a GTP-dependent manner. RASSF2, a member of the Ras association domain family, is known to be involved in the suppression of cell growth and is frequently down-regulated in various tumor tissues by promoter hypermethylation. In the present study, we demonstrate that RASSF2 shuttles between nucleus and cytoplasm by a signal-mediated process and its export from the nucleus is sensitive to leptomycin B. Amino acids between 240 to 260 in the C-terminus of RASSF2 harbor a functional nuclear export signal (NES), which is necessary and sufficient for efficient export of RASSF2 from the nucleus. Substitution of conserved Ile254, Val257 and Leu259 within the minimal NES impaired RASSF2 export from the nucleus. In addition, wild type but not the nuclear export defective RASSF2 mutant interacts with export receptor, CRM-1 and exported from the nucleus. Surprisingly, we observed nucleolar localization for the nuclear export defective mutant suggesting the possibility that RASSF2 may localize in different cellular compartments transiently in a cell cycle dependent manner and the observed nuclear localization for wild type protein may be due to faster export kinetics from the nucleolus. Furthermore, our data suggest that RASSF2 is specifically phosphorylated by MAPK/ERK-2 and the inhibitors of MAPK pathway impair the phosphorylation and subsequently block the export of RASSF2 from the nucleus. These data clearly suggest that ERK-2 mediated phosphorylation plays an important role in regulating the nucleo-cytoplasmic shuttling of RASSF2. Interestingly, nuclear import defective mutant of RASSF2 failed to induce cell cycle arrest at G1/S phase and apoptosis suggesting that RASSF2 regulates cell growth in a nuclear localization dependent manner. Collectively, these data provided evidence for the first time that MAPK/ERK-2 mediated phosphorylation regulates

  18. Identification of a Novel TGFβ/PKA Signaling Transduceome in Mediating Control of Cell Survival and Metastasis in Colon Cancer

    Rajput, Ashwani; Teggart, Carol A.; Brattain, Lisa E.; Weber, Hannah R.; Chowdhury, Aparajita; Brattain, Michael G.

    2011-01-01

    Background Understanding drivers for metastasis in human cancer is important for potential development of therapies to treat metastases. The role of loss of TGFβ tumor suppressor activities in the metastatic process is essentially unknown. Methodology/Principal Findings Utilizing in vitro and in vivo techniques, we have shown that loss of TGFβ tumor suppressor signaling is necessary to allow the last step of the metastatic process - colonization of the metastatic site. This work demonstrates for the first time that TGFβ receptor reconstitution leads to decreased metastatic colonization. Moreover, we have identified a novel TGFβ/PKA tumor suppressor pathway that acts directly on a known cell survival mechanism that responds to stress with the survivin/XIAP dependent inhibition of caspases that effect apoptosis. The linkage between the TGFβ/PKA transduceome signaling and control of metastasis through induction of cell death was shown by TGFβ receptor restoration with reactivation of the TGFβ/PKA pathway in receptor deficient metastatic colon cancer cells leading to control of aberrant cell survival. Conclusion/Significance This work impacts our understanding of the possible mechanisms that are critical to the growth and maintenance of metastases as well as understanding of a novel TGFβ function as a metastatic suppressor. These results raise the possibility that regeneration of attenuated TGFβ signaling would be an effective target in the treatment of metastasis. Our work indicates the clinical potential for developing anti-metastasis therapy based on inhibition of this very important aberrant cell survival mechanism by the multifaceted TGFβ/PKA transduceome induced pathway. Development of effective treatments for metastatic disease is a pressing need since metastases are the major cause of death in solid tumors. PMID:21559296

  19. Identification of a novel TGFβ/PKA signaling transduceome in mediating control of cell survival and metastasis in colon cancer.

    Sanjib Chowdhury

    2011-05-01

    Full Text Available Understanding drivers for metastasis in human cancer is important for potential development of therapies to treat metastases. The role of loss of TGFβ tumor suppressor activities in the metastatic process is essentially unknown.Utilizing in vitro and in vivo techniques, we have shown that loss of TGFβ tumor suppressor signaling is necessary to allow the last step of the metastatic process - colonization of the metastatic site. This work demonstrates for the first time that TGFβ receptor reconstitution leads to decreased metastatic colonization. Moreover, we have identified a novel TGFβ/PKA tumor suppressor pathway that acts directly on a known cell survival mechanism that responds to stress with the survivin/XIAP dependent inhibition of caspases that effect apoptosis. The linkage between the TGFβ/PKA transduceome signaling and control of metastasis through induction of cell death was shown by TGFβ receptor restoration with reactivation of the TGFβ/PKA pathway in receptor deficient metastatic colon cancer cells leading to control of aberrant cell survival.This work impacts our understanding of the possible mechanisms that are critical to the growth and maintenance of metastases as well as understanding of a novel TGFβ function as a metastatic suppressor. These results raise the possibility that regeneration of attenuated TGFβ signaling would be an effective target in the treatment of metastasis. Our work indicates the clinical potential for developing anti-metastasis therapy based on inhibition of this very important aberrant cell survival mechanism by the multifaceted TGFβ/PKA transduceome induced pathway. Development of effective treatments for metastatic disease is a pressing need since metastases are the major cause of death in solid tumors.

  20. SAD-A kinase controls islet β-cell size and function as a mediator of mTORC1 signaling.

    Nie, Jia; Liu, Xiaolei; Lilley, Brendan N; Zhang, Hai; Pan, Y Albert; Kimball, Scot R; Zhang, Jun; Zhang, Weiping; Wang, Li; Jefferson, Leonard S; Sanes, Joshua R; Han, Xiao; Shi, Yuguang

    2013-08-20

    The mammalian target of rapamycin (mTOR) plays an important role in controlling islet β-cell function. However, the underlying molecular mechanisms remain poorly elucidated. Synapses of amphids defective kinase-A (SAD-A) is a 5' adenosine monophosphate-activated protein kinase-related protein kinase that is exclusively expressed in pancreas and brain. In this study, we investigated a role of the kinase in regulating pancreatic β-cell morphology and function as a mediator of mTOR complex 1 (mTORC1) signaling. We show that global SAD-A deletion leads to defective glucose-stimulated insulin secretion and petite islets, which are reminiscent of the defects in mice with global deletion of ribosomal protein S6 kinase 1, a downstream target of mTORC1. Consistent with these findings, selective deletion of SAD-A in pancreas decreased islet β-cell size, whereas SAD-A overexpression significantly increased the size of mouse insulinomas cell lines β-cells. In direct support of SAD-A as a unique mediator of mTORC1 signaling in islet β-cells, we demonstrate that glucose dramatically stimulated SAD-A protein translation in isolated mouse islets, which was potently inhibited by rapamycin, an inhibitor of mTORC1. Moreover, the 5'-untranslated region of SAD-A mRNA is highly structured and requires mTORC1 signaling for its translation initiation. Together, these findings identified SAD-A as a unique pancreas-specific effector protein of mTORC1 signaling.

  1. Controlled extracellular biosynthesis of ZnS quantum dots by sulphate reduction bacteria in the presence of hydroxypropyl starch as a mediator

    Qi, Shiyue; Zhang, Mi; Guo, Xingming; Yue, Lei; Wang, Jia; Shao, Ziqiang; Xin, Baoping

    2017-06-01

    Metal sulphide quantum dots (QDs) have broad applications. Sulphate-reducing bacteria (SRB) have been recognized as synthesizers of metal sulphides, with the characteristics of a high-production efficiency and easy product harvest. However, SRB are incapable of synthesizing metal sulphide QDs. In the present study, cheap hydroxypropyl starch (HPS) was used to assist SRB in manufacturing the ZnS QDs. The results exhibited that the HPS accelerated the growth of SRB and reduction of SO4 2+ into S2-, while it blocked the precipitation between S2- and Zn2+ to control the nucleation and growth of ZnS, resulting in the formation of ZnS QDs. When the HPS concentration increased from 0.2 to 1.6 g/L, the average crystal size (ACS) of ZnS QDs dropped from 5.95 to 3.34 nm, demonstrating the controlled biosynthesis of ZnS QDs. The ZnS QDs were coated or adhered to by both HPS and proteins, which played an important role in the controlled biosynthesis of ZnS QDs. The remarkable blue shift of the narrow UV absorption peak was due to the quantum confinement effect. The sequential variation in the colour of the photoluminescence spectrum (PL) from red to yellow suggested a tunable PL of the ZnS QDs. The current work demonstrated that SRB can fabricate the formation of ZnS QDs with a controlled size and tunable PL at a high-production rate of approximately 8.7 g/(L × week) through the simple mediation of HPS, with the yield being 7.46 times the highest yield in previously reported studies. The current work is of great importance to the commercialization of the biosynthesis of ZnS QDs.

  2. Effects of supplementation with the fat-soluble vitamins E and D on fasting flow-mediated vasodilation in adults: a meta-analysis of randomized controlled trials.

    Joris, Peter J; Mensink, Ronald P

    2015-03-10

    The effects of fat-soluble vitamin supplementation on cardiovascular disease (CVD) risk are not clear. Therefore, we performed a meta-analysis to quantify effects of fat-soluble vitamin supplements on fasting flow-mediated vasodilation (FMD) of the brachial artery, a validated marker to assess CVD risk. Randomized placebo-controlled trials (RCTs) were identified by a systematic search till July 2014. Seven RCTs studying the effects of vitamin E supplements (range: 300 to 1800 IU per day) and nine RCTs examining the effects of vitamin D supplements, that involved, respectively, 303 and 658 adults, were included. No studies with carotenoid or vitamin K supplements were found. Vitamin E supplementation increased FMD vs. control by 2.42% (95% CI: 0.46% to 4.37%; p = 0.015). No effects of vitamin D supplementation were found (0.15%; 95% CI: -0.21% to 0.51%; p = 0.41). These effects did not depend on subject characteristics, treatment characteristics or technical aspects of the FMD measurement. However, no dose-response relationship was evident for vitamin E, statistical significance depended on one study, while the levels of supplement were far above recommended intakes. The current meta-analysis, therefore, does not provide unambiguous evidence to support the use of fat-soluble vitamin supplements to improve fasting FMD in adults.

  3. Evaluation of an Internally Controlled Multiplex Tth Endonuclease Cleavage Loop-Mediated Isothermal Amplification (TEC-LAMP Assay for the Detection of Bacterial Meningitis Pathogens

    Owen Higgins

    2018-02-01

    Full Text Available Bacterial meningitis infection is a leading global health concern for which rapid and accurate diagnosis is essential to reduce associated morbidity and mortality. Loop-mediated isothermal amplification (LAMP offers an effective low-cost diagnostic approach; however, multiplex LAMP is difficult to achieve, limiting its application. We have developed novel real-time multiplex LAMP technology, TEC-LAMP, using Tth endonuclease IV and a unique LAMP primer/probe. This study evaluates the analytical specificity, limit of detection (LOD and clinical application of an internally controlled multiplex TEC-LAMP assay for detection of leading bacterial meningitis pathogens: Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae. Analytical specificities were established by testing 168 bacterial strains, and LODs were determined using Probit analysis. The TEC-LAMP assay was 100% specific, with LODs for S. pneumoniae, N. meningitidis and H. influenzae of 39.5, 17.3 and 25.9 genome copies per reaction, respectively. Clinical performance was evaluated by testing 65 archived PCR-positive samples. Compared to singleplex real-time PCR, the multiplex TEC-LAMP assay demonstrated diagnostic sensitivity and specificity of 92.3% and 100%, respectively. This is the first report of a single-tube internally controlled multiplex LAMP assay for bacterial meningitis pathogen detection, and the first report of Tth endonuclease IV incorporation into nucleic acid amplification diagnostic technology.

  4. Evaluation of an Internally Controlled Multiplex Tth Endonuclease Cleavage Loop-Mediated Isothermal Amplification (TEC-LAMP) Assay for the Detection of Bacterial Meningitis Pathogens

    Clancy, Eoin; Cormican, Martin; Boo, Teck Wee; Cunney, Robert

    2018-01-01

    Bacterial meningitis infection is a leading global health concern for which rapid and accurate diagnosis is essential to reduce associated morbidity and mortality. Loop-mediated isothermal amplification (LAMP) offers an effective low-cost diagnostic approach; however, multiplex LAMP is difficult to achieve, limiting its application. We have developed novel real-time multiplex LAMP technology, TEC-LAMP, using Tth endonuclease IV and a unique LAMP primer/probe. This study evaluates the analytical specificity, limit of detection (LOD) and clinical application of an internally controlled multiplex TEC-LAMP assay for detection of leading bacterial meningitis pathogens: Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae. Analytical specificities were established by testing 168 bacterial strains, and LODs were determined using Probit analysis. The TEC-LAMP assay was 100% specific, with LODs for S. pneumoniae, N. meningitidis and H. influenzae of 39.5, 17.3 and 25.9 genome copies per reaction, respectively. Clinical performance was evaluated by testing 65 archived PCR-positive samples. Compared to singleplex real-time PCR, the multiplex TEC-LAMP assay demonstrated diagnostic sensitivity and specificity of 92.3% and 100%, respectively. This is the first report of a single-tube internally controlled multiplex LAMP assay for bacterial meningitis pathogen detection, and the first report of Tth endonuclease IV incorporation into nucleic acid amplification diagnostic technology. PMID:29425124

  5. Opening the Gender Diversity Black Box: Causality of Perceived Gender Equity & Locus of Control and Mediation of Work Engagement in Employee Well-being

    Radha R. Sharma

    2015-10-01

    Full Text Available The study is aimed at assessing the role of perceived gender equity and locus of control in employee well-being at the workplace and ascertaining if work engagement mediates between perceived gender equity, locus of control, and employee well-being (measured through optimism, general satisfaction with life and work, and executive burnout. Adopting a personal survey method data was collected from 373 managers (both males and females from the public and private sectors representing manufacturing and service industry in India. The study bridges the knowledge gap by operationalising the construct of perceived gender equity and studying its role in the work engagement and employee well-being. Conceptualization of the well-being in an unconventional way covering both the positive and the negative aspects extends the understanding of the emerging concept of well-being. It has practical implications for talent management and work engagement besides promoting gender equity at the workplace for employee well-being. It opens vistas for the gender based theory and cross cultural research on gender equity.

  6. Opening the gender diversity black box: causality of perceived gender equity and locus of control and mediation of work engagement in employee well-being.

    Sharma, Radha R; Sharma, Neha P

    2015-01-01

    The study is aimed at assessing the role of perceived gender equity and locus of control in employee well-being at the workplace and ascertaining if work engagement mediates between perceived gender equity, locus of control, and employee well-being (measured through optimism, general satisfaction with life and work, and executive burnout). Adopting a personal survey method data was collected from 373 managers (both males and females) from the public and private sectors representing manufacturing and service industry in India. The study bridges the knowledge gap by operationalizing the construct of perceived gender equity and studying its role in the work engagement and employee well-being. Conceptualization of the well-being in an unconventional way covering both the positive and the negative aspects extends the understanding of the emerging concept of well-being. It has practical implications for talent management and work engagement besides promoting gender equity at the workplace for employee well-being. It opens vistas for the gender based theory and cross cultural research on gender equity.

  7. Effect of Short-Term Fasting on Systemic Cytochrome P450-Mediated Drug Metabolism in Healthy Subjects: A Randomized, Controlled, Crossover Study Using a Cocktail Approach.

    Lammers, Laureen A; Achterbergh, Roos; van Schaik, Ron H N; Romijn, Johannes A; Mathôt, Ron A A

    2017-10-01

    Short-term fasting can alter drug exposure but it is unknown whether this is an effect of altered oral bioavailability and/or systemic clearance. Therefore, the aim of our study was to assess the effect of short-term fasting on oral bioavailability and systemic clearance of different drugs. In a randomized, controlled, crossover trial, 12 healthy subjects received a single administration of a cytochrome P450 (CYP) probe cocktail, consisting of caffeine (CYP1A2), metoprolol (CYP2D6), midazolam (CYP3A4), omeprazole (CYP2C19) and warfarin (CYP2C9), on four occasions: an oral (1) and intravenous (2) administration after an overnight fast (control) and an oral (3) and intravenous (4) administration after 36 h of fasting. Pharmacokinetic parameters of the probe drugs were analyzed using the nonlinear mixed-effects modeling software NONMEM. Short-term fasting increased systemic caffeine clearance by 17% (p = 0.04) and metoprolol clearance by 13% (p < 0.01), whereas S-warfarin clearance decreased by 19% (p < 0.01). Fasting did not affect bioavailability. The study demonstrates that short-term fasting alters CYP-mediated drug metabolism in a non-uniform pattern without affecting oral bioavailability.

  8. Identification of genes involved in the ACC-mediated control of root cell elongation in Arabidopsis thaliana

    Markakis Marios

    2012-11-01

    Full Text Available Abstract Background Along the root axis of Arabidopsis thaliana, cells pass through different developmental stages. In the apical meristem repeated cycles of division increase the numbers of cells. Upon leaving the meristem, these cells pass the transition zone where they are physiologically and mechanically prepared to undergo subsequent rapid elongation. During the process of elongation epidermal cells increase their length by 300% in a couple of hours. When elongation ceases, the cells acquire their final size, shape and functions (in the differentiation zone. Ethylene administered as its precursor 1-aminocyclopropane-1-carboxylic acid (ACC is capable of inhibiting elongation in a concentration-dependent way. Using a microarray analysis, genes and/or processes involved in this elongation arrest are identified. Results Using a CATMA-microarray analysis performed on control and 3h ACC-treated roots, 240 differentially expressed genes were identified. Quantitative Real-Time RT-PCR analysis of the 10 most up and down regulated genes combined with literature search confirmed the accurateness of the analysis. This revealed that inhibition of cell elongation is, at least partly, caused by restricting the events that under normal growth conditions initiate elongation and by increasing the processes that normally stop cellular elongation at the end of the elongation/onset of differentiation zone. Conclusions ACC interferes with cell elongation in the Arabidopsis thaliana roots by inhibiting cells from entering the elongation process and by immediately stimulating the formation of cross-links in cell wall components, diminishing the remaining elongation capacity. From the analysis of the differentially expressed genes, it becomes clear that many genes identified in this response, are also involved in several other kind of stress responses. This suggests that many responses originate from individual elicitors, but that somewhere in the downstream

  9. Arthrobotrys oligospora-mediated biological control of diseases of tomato (Lycopersicon esculentum Mill.) caused by Meloidogyne incognita and Rhizoctonia solani.

    Singh, U B; Sahu, A; Sahu, N; Singh, R K; Renu, S; Singh, D P; Manna, M C; Sarma, B K; Singh, H B; Singh, K P

    2013-01-01

    To study the biocontrol potential of nematode-trapping fungus Arthrobotrys oligospora in protecting tomato (Lycopersicon esculentum Mill.) against Meloidogyne incognita and Rhizoctonia solani under greenhouse and field conditions. Five isolates of the nematode-trapping fungus Arthrobotrys oligospora isolated from different parts of India were tested against Meloidogyne incognita and Rhizoctonia solani in tomato (Lycopersicon esculentum Mill.) plants grown under greenhouse and field conditions. Arthrobotrys oligospora-treated plants showed enhanced growth in terms of shoot and root length and biomass, chlorophyll and total phenolic content and high phenylalanine ammonia lyase activity in comparison with M. incognita- and R. solani-inoculated plants. Biochemical profiling when correlated with disease severity and intensity in A. oligospora-treated and untreated plants indicate that A. oligospora VNS-1 offered significant disease reduction in terms of number of root galls, seedling mortality, lesion length, disease index, better plant growth and fruit yield as compared to M. incognita- and R. solani-challenged plants. The result established that A. oligospora VNS-1 has the potential to provide bioprotection agents against M. incognita and R. solani. Arthrobotrys oligospora can be a better environment friendly option and can be incorporated in the integrated disease management module of crop protection. Application of A. oligospora not only helps in the control of nematodes but also increases plant growth and enhances nutritional value of tomato fruits. Thus, it proves to be an excellent biocontrol as well as plant growth promoting agent. © 2012 The Society for Applied Microbiology.

  10. A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control

    Gang Xin

    2015-11-01

    Full Text Available Control of chronic viral infections by CD8 T cells is critically dependent on CD4 help. In particular, helper-derived IL-21 plays a key role in sustaining the CD8 T cell response; however, the molecular pathways by which IL-21 sustains CD8 T cell immunity remain unclear. We demonstrate that IL-21 causes a phenotypic switch of transcription factor expression in CD8 T cells during chronic viral infection characterized by sustained BATF expression. Importantly, BATF expression during chronic infection is both required for optimal CD8 T cell persistence and anti-viral effector function and sufficient to rescue “unhelped” CD8 T cells. Mechanistically, BATF sustains the response by cooperating with IRF4, an antigen-induced transcription factor that is also critically required for CD8 T cell maintenance, to preserve Blimp-1 expression and thereby sustain CD8 T cell effector function. Collectively, these data suggest that CD4 T cells “help” the CD8 response during chronic infection via IL-21-induced BATF expression.

  11. Exploring individual cognitions, self-regulation skills, and environmental-level factors as mediating variables of two versions of a Web-based computer-tailored nutrition education intervention aimed at adults: A randomized controlled trial.

    Springvloet, Linda; Lechner, Lilian; Candel, Math J J M; de Vries, Hein; Oenema, Anke

    2016-03-01

    This study explored whether the determinants that were targeted in two versions of a Web-based computer-tailored nutrition education intervention mediated the effects on fruit, high-energy snack, and saturated fat intake among adults who did not comply with dietary guidelines. A RCT was conducted with a basic (tailored intervention targeting individual cognitions and self-regulation), plus (additionally targeting environmental-level factors), and control group (generic nutrition information). Participants were recruited from the general Dutch adult population and randomly assigned to one of the study groups. Online self-reported questionnaires assessed dietary intake and potential mediating variables (behavior-specific cognitions, action- and coping planning, environmental-level factors) at baseline and one (T1) and four (T2) months post-intervention (i.e. four and seven months after baseline). The joint-significance test was used to establish mediating variables at different time points (T1-mediating variables - T2-intake; T1-mediating variables - T1-intake; T2-mediating variables - T2-intake). Educational differences were examined by testing interaction terms. The effect of the plus version on fruit intake was mediated (T2-T2) by intention and fruit availability at home and for high-educated participants also by attitude. Among low/moderate-educated participants, high-energy snack availability at home mediated (T1-T1) the effect of the basic version on high-energy snack intake. Subjective norm mediated (T1-T1) the effect of the basic version on fat intake among high-educated participants. Only some of the targeted determinants mediated the effects of both intervention versions on fruit, high-energy snack, and saturated fat intake. A possible reason for not finding a more pronounced pattern of mediating variables is that the educational content was tailored to individual characteristics and that participants only received feedback for relevant and not for all

  12. Prenatal Internal Locus of Control Is Positively Associated with Offspring IQ, Mediated through Parenting Behavior, Prenatal Lifestyle and Social Circumstances

    Jean Golding

    2017-08-01

    Full Text Available Locus of control (LOC is a measure that identifies the likelihood as to whether an individual considers what happens to him is largely a matter of luck or fate (known as externally oriented or whether it is something that the individual can influence (internality. Here we have used data collected as part of the Avon Longitudinal Study of Parents and Children (ALSPAC to determine the associations between the mothers’ LOC orientation before the birth of the child and her child’s cognition measured at age 8. Using results from 6801 children we show that maternal internal LOC is associated with increased ability in offspring IQ, as measured using the WISC, with children of internally oriented mothers having an advantage of approximately 7 IQ points at age 8. As a sensitivity analysis we used the IQ test results of a sample of 986 preschool children tested using the WPSSI at age 4. A similar advantage was found among the offspring of the internally oriented mothers. We investigated mechanistic explanations for these results firstly by determining the extent to which three separate sets of factors known to be influenced by the LOC orientation might explain these findings. We showed that (a perinatal life-style exposures, (b parenting attitudes and strategies and (c socio-economic circumstances, largely explain the mechanism through which the internality of the mother influences the cognition of the child. Similar effects were found using the smaller sample tested at age 4. The results indicate that efforts made to foster internality in adolescents and young adults prior to parenthood may result in improvements in the cognitive development of the next generation. Intervention studies are urgently needed.

  13. Nitric Oxide Mediates the Hormonal Control of Crassulacean Acid Metabolism Expression in Young Pineapple Plants1[W][OA

    Freschi, Luciano; Rodrigues, Maria Aurineide; Domingues, Douglas Silva; Purgatto, Eduardo; Van Sluys, Marie-Anne; Magalhaes, Jose Ronaldo; Kaiser, Werner M.; Mercier, Helenice

    2010-01-01

    Genotypic, developmental, and environmental factors converge to determine the degree of Crassulacean acid metabolism (CAM) expression. To characterize the signaling events controlling CAM expression in young pineapple (Ananas comosus) plants, this photosynthetic pathway was modulated through manipulations in water availability. Rapid, intense, and completely reversible up-regulation in CAM expression was triggered by water deficit, as indicated by the rise in nocturnal malate accumulation and in the expression and activity of important CAM enzymes. During both up- and down-regulation of CAM, the degree of CAM expression was positively and negatively correlated with the endogenous levels of abscisic acid (ABA) and cytokinins, respectively. When exogenously applied, ABA stimulated and cytokinins repressed the expression of CAM. However, inhibition of water deficit-induced ABA accumulation did not block the up-regulation of CAM, suggesting that a parallel, non-ABA-dependent signaling route was also operating. Moreover, strong evidence revealed that nitric oxide (NO) may fulfill an important role during CAM signaling. Up-regulation of CAM was clearly observed in NO-treated plants, and a conspicuous temporal and spatial correlation was also evident between NO production and CAM expression. Removal of NO from the tissues either by adding NO scavenger or by inhibiting NO production significantly impaired ABA-induced up-regulation of CAM, indicating that NO likely acts as a key downstream component in the ABA-dependent signaling pathway. Finally, tungstate or glutamine inhibition of the NO-generating enzyme nitrate reductase completely blocked NO production during ABA-induced up-regulation of CAM, characterizing this enzyme as responsible for NO synthesis during CAM signaling in pineapple plants. PMID:20147491

  14. Prenatal Internal Locus of Control Is Positively Associated with Offspring IQ, Mediated through Parenting Behavior, Prenatal Lifestyle and Social Circumstances.

    Golding, Jean; Gregory, Steven; Ellis, Genette L; Iles-Caven, Yasmin; Nowicki, Stephen

    2017-01-01

    Locus of control (LOC) is a measure that identifies the likelihood as to whether an individual considers what happens to him is largely a matter of luck or fate (known as externally oriented) or whether it is something that the individual can influence (internality). Here we have used data collected as part of the Avon Longitudinal Study of Parents and Children (ALSPAC) to determine the associations between the mothers' LOC orientation before the birth of the child and her child's cognition measured at age 8. Using results from 6801 children we show that maternal internal LOC is associated with increased ability in offspring IQ, as measured using the WISC, with children of internally oriented mothers having an advantage of approximately 7 IQ points at age 8. As a sensitivity analysis we used the IQ test results of a sample of 986 preschool children tested using the WPSSI at age 4. A similar advantage was found among the offspring of the internally oriented mothers. We investigated mechanistic explanations for these results firstly by determining the extent to which three separate sets of factors known to be influenced by the LOC orientation might explain these findings. We showed that (a) perinatal life-style exposures, (b) parenting attitudes and strategies and (c) socio-economic circumstances, largely explain the mechanism through which the internality of the mother influences the cognition of the child. Similar effects were found using the smaller sample tested at age 4. The results indicate that efforts made to foster internality in adolescents and young adults prior to parenthood may result in improvements in the cognitive development of the next generation. Intervention studies are urgently needed.

  15. Regulated binding of PTP1B-like phosphatase to N-cadherin: control of cadherin-mediated adhesion by dephosphorylation of beta-catenin

    1996-01-01

    Cadherins are a family of cell-cell adhesion molecules which play a central role in controlling morphogenetic movements during development. Cadherin function is regulated by its association with the actin containing cytoskeleton, an association mediated by a complex of cytoplasmic proteins, the catenins: alpha, beta, and gamma. Phosphorylated tyrosine residues on beta-catenin are correlated with loss of cadherin function. Consistent with this, we find that only nontyrosine phosphorylated beta-catenin is associated with N-cadherin in E10 chick retina tissue. Moreover, we demonstrate that a PTP1B-like tyrosine phosphatase associates with N-cadherin and may function as a regulatory switch controlling cadherin function by dephosphorylating beta-catenin, thereby maintaining cells in an adhesion-competent state. The PTP1B-like phosphatase is itself tyrosine phosphorylated. Moreover, both direct binding experiments performed with phosphorylated and dephosphorylated molecules, and treatment of cells with tyrosine kinase inhibitors indicate that the interaction of the PTP1B-like phosphatase with N-cadherin depends on its tyrosine phosphorylation. Concomitant with the tyrosine kinase inhibitor-induced loss of the PTP1B-like phosphatase from its association with N-cadherin, phosphorylated tyrosine residues are retained on beta-catenin, the association of N- cadherin with the actin containing cytoskeleton is lost and N-cadherin- mediated cell adhesion is prevented. Tyrosine phosphatase inhibitors also result in the accumulation of phosphorylated tyrosine residues on beta-catenin, loss of the association of N-cadherin with the actin- containing cytoskeleton, and prevent N-cadherin mediated adhesion, presumably by directly blocking the function of the PTP1B-like phosphatase. We previously showed that the binding of two ligands to the cell surface N-acetylgalactosaminylphosphotransferase (GalNAcPTase), the monoclonal antibody 1B11 and a proteoglycan with a 250-kD core protein

  16. Latency of Epstein-Barr virus is stabilized by antisense-mediated control of the viral immediate-early gene BZLF-1.

    Prang, N; Wolf, H; Schwarzmann, F

    1999-12-01

    The ability of the Epstein-Barr virus (EBV) to avoid lytic replication and to establish a latent infection in B-lymphocytes is fundamental for its lifelong persistence and the pathogenesis of various EBV-associated diseases. The viral immediate-early gene BZLF-1 plays a key role for the induction of lytic replication and its activity is strictly regulated on different levels of gene expression. Recently, it was demonstrated that BZLF-1 is also controlled by a posttranscriptional mechanism. Transient synthesis of a mutated competitor RNA saturated this mechanism and caused both expression of the BZLF-1 protein and the induction of lytic viral replication. Using short overlapping fragments of the competitor, it is shown that this control acts on the unspliced primary transcript. RT-PCR demonstrated unspliced BZLF-1 RNA in latently infected B-lymphocytes in the absence of BZLF-1 protein. Due to the complementarity of the gene BZLF-1 and the latency-associated gene EBNA-1 on the opposite strand of the genome, we propose an antisense-mediated mechanism. RNase protection assays demonstrated transcripts in antisense orientation to the BZLF-1 transcript during latency, which comprise a comparable constellation to other herpesviruses. A combined RNAse protection/RT-PCR assay detected the double-stranded hybrid RNA, consisting of the unspliced BZLF-1 transcript and a noncoding intron of the EBNA-1 gene. Binding of BZLF-1 transcripts is suggested to be an important backup control mechanism in addition to transcriptional regulation, stabilizing latency and preventing inappropriate lytic viral replication in vivo. Copyright 1999 Wiley-Liss, Inc.

  17. Phosphorescence Control Mediated by Molecular Rotation and Aurophilic Interactions in Amphidynamic Crystals of 1,4-Bis[tri-(p-fluorophenyl)phosphane-gold(I)-ethynyl]benzene.

    Jin, Mingoo; Chung, Tim S; Seki, Tomohiro; Ito, Hajime; Garcia-Garibay, Miguel A

    2017-12-13

    Here we present a structural design aimed at the control of phosphorescence emission as the result of changes in molecular rotation in a crystalline material. The proposed strategy includes the use of aurophilic interactions, both as a crystal engineering tool and as a sensitive emission probe, and the use of a dumbbell-shaped architecture intended to create a low packing density region that permits the rotation of a central phenylene. Molecular rotor 1, with a central 1,4-diethynylphenylene rotator linked to two gold(I) triphenylphosphane complexes, was prepared and its structure confirmed by single-crystal X-ray diffraction, which revealed chains mediated by dimeric aurophilic interactions. We showed that green-emitting crystals exhibit reversible luminescent color changes between 298 and 193 K, which correlate with changes in rotational motion determined by variable-temperature solid-state 2 H NMR spin-echo experiments. Fast two-fold rotation with a frequency of ca. 4.00 MHz (τ = 0.25 μs) at 298 K becomes essentially static below 193 K as emission steadily changes from green to yellow in this temperature interval. A correlation between phosphorescence lifetimes and rotational frequencies is interpreted in terms of conformational changes arising from rotation of the central phenylene, which causes a change in electronic communication between the gold-linked rotors, as suggested by DFT studies. These results and control experiments with analogue 2, possessing a hindered tetramethylphenylene that is unable to rotate in the crystal, suggest that the molecular rotation can be a useful tool for controlling luminescence in the crystalline state.

  18. "What Goes Around Comes Around": Antecedents, Mediators, and Consequences of Controlling vs. Need-Supportive Motivational Strategies Used by Exercise Professionals.

    Silva, Marlene N; Sánchez-Oliva, David; Brunet, Jennifer; Williams, Geoffrey C; Teixeira, Pedro J; Palmeira, Antonio L

    2017-10-01

    Research into the factors associated with the use of different motivational strategies by exercise professionals is of empirical and practical utility. Grounded in self-determination theory, this study sought to analyze putative antecedents, mediators, and work-related well- and ill-being consequences of two types of motivational strategies reported by exercise professionals. Participants were 366 exercise professionals (193 males; experience = 7.7 ± 5.8 years). Questionnaires assessing psychological need satisfaction frustration, self-determined work motivation, motivational strategies (need-supportive vs. controlling), emotional exhaustion, and personal accomplishment were completed online. Path analysis was used to test the hypothesized model. Model with good fit [χ 2 (5) = 9.174, p> .05; CFI = .984; TLI = .936; RMSEA = .048; SRMR = .022] showed need satisfaction as positively associated with supportive strategies and personal accomplishment (β between .267 and .399) and negatively with emotional exhaustion (β = -.145). Need frustration was negatively associated with work motivation and personal accomplishment (β = -.315; -.176), and positively with controlling strategies and emotional exhaustion (β = .195; .226). Furthermore, supportive strategies and work motivation were positively associated with personal accomplishment (β = .134; .184), whereas controlling strategies were positively associated with emotional exhaustion (β = .178). Findings have theoretical implications, providing evidence of need satisfaction and frustration as being differently associated with work-related motivation, type of strategies used, and work-related emotional outcomes. Practical implications convey the importance of these variables in relation to the standard of motivational strategies provided and their role on work-related well- and ill-being indicators.

  19. Coping strategies as mediators of the effect of the START (strategies for RelaTives) intervention on psychological morbidity for family carers of people with dementia in a randomised controlled trial.

    Li, Ryan; Cooper, Claudia; Barber, Julie; Rapaport, Penny; Griffin, Mark; Livingston, Gill

    2014-10-01

    Family carers of people with dementia frequently become depressed or anxious. In observational studies, more emotion-focused and less dysfunctional coping predict fewer psychological symptoms, but no randomised controlled trial (RCT) has directly investigated emotion-focused coping as mediator of effectiveness of a successful psychological intervention. We hypothesised that emotion-focused coping would mediate the START psychological intervention׳s effects in an RCT. We tested whether mediated effects were moderated by severity of baseline symptoms. 260 family carers from NHS dementia services were randomised to START (manualised coping skills intervention), or treatment-as-usual (TAU). Blinded raters administered the Hospital Anxiety and Depression Scale (HADS-T) and Brief COPE inventory at baseline, 4 and 8 months. HADS-T improved in the intervention group when compared to TAU at all levels of psychological distress. We tested whether coping was a mediator and for moderated mediation, and (post-hoc) subgroup treatment effects on coping. Data were available for 187 carers (71.9%) for the mediation analysis. The reduced HADS-T score in the intervention group was mediated by increased emotion-focused coping only among carers with higher (16+) baseline HADS-T scores (mediated effect=-0.63 [-1.11, -0.15]; proportion of overall effect=33% [3%, 64%]). We did not measure plausible psychosocial treatment mechanisms other than coping. START benefited family carers both in preventing and treating psychological morbidity, through different mechanisms of action. The most psychologically distressed carers increased their emotion-focused coping and did not decrease their dysfunctional coping, while others benefited but not through this mechanism. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Mediatized play

    Johansen, Stine Liv

    Children’s play must nowadays be understood as a mediatized field in society and culture. Media – understood in a very broad sense - holds severe explanatory power in describing and understanding the practice of play, since play happens both with, through and inspired by media of different sorts........ In this presentation the case of ‘playing soccer’ will be outlined through its different mediated manifestations, including soccer games and programs on TV, computer games, magazines, books, YouTube videos and soccer trading cards....

  1. Mediating Business

    "Mediating Business" is a study of the expansion of business journalism. Building on evidence from Denmark, Finland, Norway and Sweden, "Mediating Business" is a comparative and multidisciplinary study of one of the major transformations of the mass media and the realm of business - nationally...... and globally. The book explores the history of key innovations and innovators in the business press. It analyzes changes in the discourse of business journalism associated with the growth in business news and the development of new ways of framing business issues and events. Finally, it examines...... the organizational implications of the increased media visibility of business and, in particular, the development of corporate governance and media relations....

  2. Hyperosmotic stress regulates the distribution and stability of myocardin-related transcription factor, a key modulator of the cytoskeleton

    Ly, Donald L.; Waheed, Faiza; Lodyga, Monika

    2013-01-01

    Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin-regulated coactiv......Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin......-regulated coactivator of serum response factor, is a major link between the actin skeleton and transcriptional control. We therefore investigated whether MRTF is regulated by hyperosmotic stress. Here we show that hypertonicity induces robust, rapid, and transient translocation of MRTF from the cytosol to the nucleus...... in kidney tubular cells. We found that the hyperosmolarity-triggered MRTF translocation is mediated by the RhoA/Rho kinase (ROK) pathway. Moreover, the Rho guanine nucleotide exchange factor GEF-H1 is activated by hyperosmotic stress, and it is a key contributor to the ensuing RhoA activation and MRTF...

  3. Mediation Analysis: A Practitioner's Guide.

    VanderWeele, Tyler J

    2016-01-01

    This article provides an overview of recent developments in mediation analysis, that is, analyses used to assess the relative magnitude of different pathways and mechanisms by which an exposure may affect an outcome. Traditional approaches to mediation in the biomedical and social sciences are described. Attention is given to the confounding assumptions required for a causal interpretation of direct and indirect effect estimates. Methods from the causal inference literature to conduct mediation in the presence of exposure-mediator interactions, binary outcomes, binary mediators, and case-control study designs are presented. Sensitivity analysis techniques for unmeasured confounding and measurement error are introduced. Discussion is given to extensions to time-to-event outcomes and multiple mediators. Further flexible modeling strategies arising from the precise counterfactual definitions of direct and indirect effects are also described. The focus throughout is on methodology that is easily implementable in practice across a broad range of potential applications.

  4. Cultured Mast Cells from Patients with Asthma and Controls Respond with Similar Sensitivity to Recombinant Der P2-Induced, IgE-Mediated Activation

    Krohn, I K; Sverrild, A; Lund, G

    2013-01-01

    for mite allergen Der p2. The sensitivity of IgE-mediated activation of mast cells was investigated as FcεRI-mediated upregulation of CD63. Ten subjects were atopic, defined as a positive skin prick test (>3 mm) to at least one of ten common allergens. After activation with recombinant Der p2, the maximum...

  5. Synthetic Influenza vaccine (FLU-v) stimulates cell mediated immunity in a double-blind, randomised, placebo-controlled Phase I trial.

    Pleguezuelos, Olga; Robinson, Stuart; Stoloff, Gregory A; Caparrós-Wanderley, Wilson

    2012-06-29

    Current Influenza vaccines elicit antibody mediated prophylactic immunity targeted to viral capsid antigens. Despite their global use these vaccines must be administered yearly to the population, cannot be manufactured until the circulating viral strain(s) have been identified and have limited efficacy. A need remains for Influenza vaccines addressing these issues and here we report the results of a Phase Ib trial of a novel synthetic Influenza vaccine (FLU-v) targeting T cell responses to NP, M1 and M2. Forty-eight healthy males aged 18-40 were recruited for this single-centre, randomised, double blind study. Volunteers received one single low (250 μg) or high (500 μg) dose of FLU-v, either alone or adjuvanted. Safety, tolerability and basic immunogenicity (IgG and IFN-γ responses) parameters were assessed pre-vaccination and for 21 days post-vaccination. FLU-v was found to be safe and well tolerated with no vaccine associated severe adverse events. Dose-dependent IFN-γ responses >2-fold the pre-vaccination level were detected in 80% and 100% of volunteers receiving, respectively, the low and high dose adjuvanted FLU-v formulations. No formulation tested induced any significant FLU-v antibody response. FLU-v is safe and induces a vaccine-specific cellular immunity. Cellular immune responses are historically known to control and mitigate infection and illness during natural infection. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Light-Mediated Kinetic Control Reveals the Temporal Effect of the Raf/MEK/ERK Pathway in PC12 Cell Neurite Outgrowth

    Zhang, Kai; Duan, Liting; Ong, Qunxiang; Lin, Ziliang; Varman, Pooja Mahendra; Sung, Kijung; Cui, Bianxiao

    2014-01-01

    It has been proposed that differential activation kinetics allows cells to use a common set of signaling pathways to specify distinct cellular outcomes. For example, nerve growth factor (NGF) and epidermal growth factor (EGF) induce different activation kinetics of the Raf/MEK/ERK signaling pathway and result in differentiation and proliferation, respectively. However, a direct and quantitative linkage between the temporal profile of Raf/MEK/ERK activation and the cellular outputs has not been established due to a lack of means to precisely perturb its signaling kinetics. Here, we construct a light-gated protein-protein interaction system to regulate the activation pattern of the Raf/MEK/ERK signaling pathway. Light-induced activation of the Raf/MEK/ERK cascade leads to significant neurite outgrowth in rat PC12 pheochromocytoma cell lines in the absence of growth factors. Compared with NGF stimulation, light stimulation induces longer but fewer neurites. Intermittent on/off illumination reveals that cells achieve maximum neurite outgrowth if the off-time duration per cycle is shorter than 45 min. Overall, light-mediated kinetic control enables precise dissection of the temporal dimension within the intracellular signal transduction network. PMID:24667437

  7. Growth of PbTe nanorods controlled by polymerized tellurium anions and metal(II) amides via composite-hydroxide-mediated approach

    Wan Buyong [Department of Applied Physics, Chongqing University, 174 Shapingba Street, Chongqing 400044 (China); College of Physics and Information Technology, Chongqing Normal University, Chongqing 400047 (China); Hu Chenguo, E-mail: hucg@cqu.edu.cn [Department of Applied Physics, Chongqing University, 174 Shapingba Street, Chongqing 400044 (China); Liu Hong [State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100 (China); Xiong Yufeng [National Center for Nanoscience and Technology, Beijing 100080 (China); Li Feiyun; Xi Yi; He Xiaoshan [Department of Applied Physics, Chongqing University, 174 Shapingba Street, Chongqing 400044 (China)

    2009-09-15

    The pure face-centered-cubic PbTe nanorods have been synthesized by the composite-hydroxide-mediated approach using hydrazine as a reducing agent. The method is based on reaction among reactants in the melts of potassium hydroxide and sodium hydroxide eutectic at 170-220 deg. C and normal atmosphere without using any organic dispersant or surface-capping agent. Scanning electron microscopy, X-ray diffraction, transmission electron microscopy, and energy dispersive X-ray spectroscopy were used to characterize the structure, morphology and composition of the samples. The diameters of nanorods are almost fixed, while the lengths can be tunable under different growth time and temperatures. The growth mechanism of PbTe nanorods is investigated via UV-vis absorption, demonstrating that polymerized tellurium anions and metal(II) amides in the hydrazine hydroxide melts could control the crystallization and growth process of PbTe nanostructures. The band gap of as-synthesized PbTe nanorods has been calculated based on UV-vis-NIR optical diffuse reflectance spectra data.

  8. Growth of PbTe nanorods controlled by polymerized tellurium anions and metal(II) amides via composite-hydroxide-mediated approach

    Wan Buyong; Hu Chenguo; Liu Hong; Xiong Yufeng; Li Feiyun; Xi Yi; He Xiaoshan

    2009-01-01

    The pure face-centered-cubic PbTe nanorods have been synthesized by the composite-hydroxide-mediated approach using hydrazine as a reducing agent. The method is based on reaction among reactants in the melts of potassium hydroxide and sodium hydroxide eutectic at 170-220 deg. C and normal atmosphere without using any organic dispersant or surface-capping agent. Scanning electron microscopy, X-ray diffraction, transmission electron microscopy, and energy dispersive X-ray spectroscopy were used to characterize the structure, morphology and composition of the samples. The diameters of nanorods are almost fixed, while the lengths can be tunable under different growth time and temperatures. The growth mechanism of PbTe nanorods is investigated via UV-vis absorption, demonstrating that polymerized tellurium anions and metal(II) amides in the hydrazine hydroxide melts could control the crystallization and growth process of PbTe nanostructures. The band gap of as-synthesized PbTe nanorods has been calculated based on UV-vis-NIR optical diffuse reflectance spectra data.

  9. Black Tea Increases Circulating Endothelial Progenitor Cells and Improves Flow Mediated Dilatation Counteracting Deleterious Effects from a Fat Load in Hypertensive Patients: A Randomized Controlled Study

    Grassi, Davide; Draijer, Richard; Schalkwijk, Casper; Desideri, Giovambattista; D’Angeli, Anatolia; Francavilla, Sandro; Mulder, Theo; Ferri, Claudio

    2016-01-01

    (1) Background: Endothelial dysfunction predicts cardiovascular events. Circulating angiogenic cells (CACs) maintain and repair the endothelium regulating its function. Tea flavonoids reduce cardiovascular risk. We investigated the effects of black tea on the number of CACs and on flow-mediated dilation (FMD) before and after an oral fat in hypertensives; (2) Methods: In a randomized, double-blind, controlled, cross-over study, 19 patients were assigned to black tea (150 mg polyphenols) or a placebo twice a day for eight days. Measurements were obtained in a fasted state and after consuming whipping cream, and FMD was measured at baseline and after consumption of the products; (3) Results: Compared with the placebo, black tea ingestion increased functionally active CACs (36 ± 22 vs. 56 ± 21 cells per high-power field; p = 0.006) and FMD (5.0% ± 0.3% vs. 6.6% ± 0.3%, p FMD 1, 2, 3, and 4 h after consumption, with maximal response 2 h after intake (p FMD, while tea consumption counteracted FMD impairment (p < 0.0001); (4) Conclusions: We demonstrated the vascular protective properties of black tea by increasing the number of CACs and preventing endothelial dysfunction induced by acute oral fat load in hypertensive patients. Considering that tea is the most consumed beverage after water, our findings are of clinical relevance and interest. PMID:27854314

  10. IgE-dependent activation of human mast cells and fMLP-mediated activation of human eosinophils is controlled by the circadian clock.

    Baumann, Anja; Feilhauer, Katharina; Bischoff, Stephan C; Froy, Oren; Lorentz, Axel

    2015-03-01

    Symptoms of allergic attacks frequently exhibit diurnal variations. Accordingly, we could recently demonstrate that mast cells and eosinophils - known as major effector cells of allergic diseases - showed an intact circadian clock. Here, we analyzed the role of the circadian clock in the functionality of mast cells and eosinophils. Human intestinal mast cells (hiMC) were isolated from intestinal mucosa; human eosinophils were isolated from peripheral blood. HiMC and eosinophils were synchronized by dexamethasone before stimulation every 4h around the circadian cycle by FcɛRI crosslinking or fMLP, respectively. Signaling molecule activation was examined using Western blot, mRNA expression by real-time RT-PCR, and mediator release by multiplex analysis. CXCL8 and CCL2 were expressed and released in a circadian manner by both hiMC and eosinophils in response to activation. Moreover, phosphorylation of ERK1/2, known to be involved in activation of hiMC and eosinophils, showed circadian rhythms in both cell types. Interestingly, all clock genes hPer1, hPer2, hCry1, hBmal1, and hClock were expressed in a similar circadian pattern in activated and unstimulated cells indicating that the local clock controls hiMC and eosinophils and subsequently allergic reactions but not vice versa. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Black Tea Increases Circulating Endothelial Progenitor Cells and Improves Flow Mediated Dilatation Counteracting Deleterious Effects from a Fat Load in Hypertensive Patients: A Randomized Controlled Study

    Davide Grassi

    2016-11-01

    Full Text Available (1 Background: Endothelial dysfunction predicts cardiovascular events. Circulating angiogenic cells (CACs maintain and repair the endothelium regulating its function. Tea flavonoids reduce cardiovascular risk. We investigated the effects of black tea on the number of CACs and on flow-mediated dilation (FMD before and after an oral fat in hypertensives; (2 Methods: In a randomized, double-blind, controlled, cross-over study, 19 patients were assigned to black tea (150 mg polyphenols or a placebo twice a day for eight days. Measurements were obtained in a fasted state and after consuming whipping cream, and FMD was measured at baseline and after consumption of the products; (3 Results: Compared with the placebo, black tea ingestion increased functionally active CACs (36 ± 22 vs. 56 ± 21 cells per high-power field; p = 0.006 and FMD (5.0% ± 0.3% vs. 6.6% ± 0.3%, p < 0.0001. Tea further increased FMD 1, 2, 3, and 4 h after consumption, with maximal response 2 h after intake (p < 0.0001. Fat challenge decreased FMD, while tea consumption counteracted FMD impairment (p < 0.0001; (4 Conclusions: We demonstrated the vascular protective properties of black tea by increasing the number of CACs and preventing endothelial dysfunction induced by acute oral fat load in hypertensive patients. Considering that tea is the most consumed beverage after water, our findings are of clinical relevance and interest.

  12. Optimization of intrinsic and extrinsic tendon healing through controllable water-soluble mitomycin-C release from electrospun fibers by mediating adhesion-related gene expression.

    Zhao, Xin; Jiang, Shichao; Liu, Shen; Chen, Shuai; Lin, Zhi Yuan William; Pan, Guoqing; He, Fan; Li, Fengfeng; Fan, Cunyi; Cui, Wenguo

    2015-08-01

    To balance intrinsic and extrinsic healing during tendon repair is challenging in tendon surgery. We hypothesized that by mediating apoptotic gene and collagen synthesis of exogenous fibroblasts, the adhesion formation induced by extrinsic healing could be inhibited. With the maintenance of intrinsic healing, the tendon could be healed with proper function with no adhesion. In this study, we loaded hydrophilic mitomycin-C (MMC) into hyaluronan (HA) hydrosols, which were then encapsulated in poly(L-lactic acid) (PLLA) fibers by micro-sol electrospinning. This strategy successfully provided a controlled release of MMC to inhibit adhesion formations with no detrimental effect on intrinsic healing. We found that micro-sol electrospinning was an effective and facile approach to incorporate and control hydrophilic drug release from hydrophobic polyester fibers. MMC exhibited an initially rapid, and gradually steadier release during 40 days, and the release rates could be tuned by its concentration. In vitro studies revealed that low concentrations of MMC could inhibit fibroblast adhesion and proliferation. When lacerate tendons were healed using the MMC-HA loaded PLLA fibers in vivo, they exhibited comparable mechanical strength to the naturally healed tendons but with no significant presence of adhesion formation. We further identified the up-regulation of apoptotic protein Bax expression and down-regulation of proteins Bcl2, collage I, collagen III and α-SMA during the healing process associated with minimum adhesion formations. This approach presented here leverages new advances in drug delivery and nanotechnology and offers a promising strategy to balance intrinsic and extrinsic tendon healing through modulating genes associated with fibroblast apoptosis and collagen synthesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Vaccine-Mediated Mechanisms Controlling Replication of Francisella tularensis in Human Peripheral Blood Mononuclear Cells Using a Co-culture System

    Kjell Eneslätt

    2018-02-01

    Full Text Available Cell-mediated immunity (CMI is normally required for efficient protection against intracellular infections, however, identification of correlates is challenging and they are generally lacking. Francisella tularensis is a highly virulent, facultative intracellular bacterium and CMI is critically required for protection against the pathogen, but how this is effectuated in humans is poorly understood. To understand the protective mechanisms, we established an in vitro co-culture assay to identify how control of infection of F. tularensis is accomplished by human cells and hypothesized that the model will mimic in vivo immune mechanisms. Non-adherent peripheral blood mononuclear cells (PBMCs were expanded with antigen and added to cultures with adherent PBMC infected with the human vaccine strain, LVS, or the highly virulent SCHU S4 strain. Intracellular numbers of F. tularensis was followed for 72 h and secreted and intracellular cytokines were analyzed. Addition of PBMC expanded from naïve individuals, i.e., those with no record of immunization to F. tularensis, generally resulted in little or no control of intracellular bacterial growth, whereas addition of PBMC from a majority of F. tularensis-immune individuals executed static and sometimes cidal effects on intracellular bacteria. Regardless of infecting strain, statistical differences between the two groups were significant, P < 0.05. Secretion of 11 cytokines was analyzed after 72 h of infection and significant differences with regard to secretion of IFN-γ, TNF, and MIP-1β was observed between immune and naïve individuals for LVS-infected cultures. Also, in LVS-infected cultures, CD4 T cells from vaccinees, but not CD8 T cells, showed significantly higher expression of IFN-γ, MIP-1β, TNF, and CD107a than cells from naïve individuals. The co-culture system appears to identify correlates of immunity that are relevant for the understanding of mechanisms of the protective host immunity to

  14. Direct control of peripheral lipid deposition by CNS GLP-1 receptor signaling is mediated by the sympathetic nervous system and blunted in diet-induced obesity.

    Nogueiras, Ruben; Pérez-Tilve, Diego; Veyrat-Durebex, Christelle; Morgan, Donald A; Varela, Luis; Haynes, William G; Patterson, James T; Disse, Emmanuel; Pfluger, Paul T; López, Miguel; Woods, Stephen C; DiMarchi, Richard; Diéguez, Carlos; Rahmouni, Kamal; Rohner-Jeanrenaud, Françoise; Tschöp, Matthias H

    2009-05-06

    We investigated a possible role of the central glucagon-like peptide (GLP-1) receptor system as an essential brain circuit regulating adiposity through effects on nutrient partitioning and lipid metabolism independent from feeding behavior. Both lean and diet-induced obesity mice were used for our experiments. GLP-1 (7-36) amide was infused in the brain for 2 or 7 d. The expression of key enzymes involved in lipid metabolism was measured by real-time PCR or Western blot. To test the hypothesis that the sympathetic nervous system may be responsible for informing adipocytes about changes in CNS GLP-1 tone, we have performed direct recording of sympathetic nerve activity combined with experiments in genetically manipulated mice lacking beta-adrenergic receptors. Intracerebroventricular infusion of GLP-1 in mice directly and potently decreases lipid storage in white adipose tissue. These effects are independent from nutrient intake. Such CNS control of adipocyte metabolism was found to depend partially on a functional sympathetic nervous system. Furthermore, the effects of CNS GLP-1 on adipocyte metabolism were blunted in diet-induced obese mice. The CNS GLP-1 system decreases fat storage via direct modulation of adipocyte metabolism. This CNS GLP-1 control of adipocyte lipid metabolism appears to be mediated at least in part by the sympathetic nervous system and is independent of parallel changes in food intake and body weight. Importantly, the CNS GLP-1 system loses the capacity to modulate adipocyte metabolism in obese states, suggesting an obesity-induced adipocyte resistance to CNS GLP-1.

  15. Loop-Mediated Isothermal Amplification for Detection of Endogenous Sad1 Gene in Cotton: An Internal Control for Rapid Onsite GMO Testing.

    Singh, Monika; Bhoge, Rajesh K; Randhawa, Gurinderjit

    2018-04-20

    Background : Confirming the integrity of seed samples in powdered form is important priorto conducting a genetically modified organism (GMO) test. Rapid onsite methods may provide a technological solution to check for genetically modified (GM) events at ports of entry. In India, Bt cotton is the commercialized GM crop with four approved GM events; however, 59 GM events have been approved globally. GMO screening is required to test for authorized GM events. The identity and amplifiability of test samples could be ensured first by employing endogenous genes as an internal control. Objective : A rapid onsite detection method was developed for an endogenous reference gene, stearoyl acyl carrier protein desaturase ( Sad1 ) of cotton, employing visual and real-time loop-mediated isothermal amplification (LAMP). Methods : The assays were performed at a constant temperature of 63°C for 30 min for visual LAMP and 62ºC for 40 min for real-time LAMP. Positive amplification was visualized as a change in color from orange to green on addition of SYBR ® Green or detected as real-time amplification curves. Results : Specificity of LAMP assays was confirmed using a set of 10 samples. LOD for visual LAMP was up to 0.1%, detecting 40 target copies, and for real-time LAMP up to 0.05%, detecting 20 target copies. Conclusions : The developed methods could be utilized to confirm the integrity of seed powder prior to conducting a GMO test for specific GM events of cotton. Highlights : LAMP assays for the endogenous Sad1 gene of cotton have been developed to be used as an internal control for onsite GMO testing in cotton.

  16. Controlling human corneal stromal stem cell contraction to mediate rapid cell and matrix organization of real architecture for 3-dimensional tissue equivalents.

    Mukhey, Dev; Phillips, James B; Daniels, Julie T; Kureshi, Alvena K

    2018-02-01

    The architecture of the human corneal stroma consists of a highly organized extracellular matrix (ECM) interspersed with keratocytes. Their progenitor cells; corneal stromal stem cells (CSSC) are located at the periphery, in the limbal stroma. A highly organized corneal ECM is critical for effective transmission of light but this structure may be compromised during injury or disease, resulting in loss of vision. Re-creating normal organization in engineered tissue equivalents for transplantation often involves lengthy culture times that are inappropriate for clinical use or utilisation of synthetic substrates that bring complications such as corneal melting. CSSC have great therapeutic potential owing to their ability to reorganize a disorganized matrix, restoring transparency in scarred corneas. We examined CSSC contractile behavior to assess whether this property could be exploited to rapidly generate cell and ECM organization in Real Architecture For 3D Tissues (RAFT) tissue equivalents (TE) for transplantation. Free-floating collagen gels were characterized to assess contractile behavior of CSSC and establish optimum cell density and culture times. To mediate cell and collagen organization, tethered collagen gels seeded with CSSC were cultured and subsequently stabilized with the RAFT process. We demonstrated rapid creation of biomimetic RAFT TE with tunable structural properties. These displayed three distinct regions of varying degrees of cellular and collagen organization. Interestingly, increased organization coincided with a dramatic loss of PAX6 expression in CSSC, indicating rapid differentiation into keratocytes. The organized RAFT TE system could be a useful bioengineering tool to rapidly create an organized ECM while simultaneously controlling cell phenotype. For the first time, we have demonstrated that human CSSC exhibit the phenomenon of cellular self-alignment in tethered collagen gels. We found this mediated rapid co-alignment of collagen fibrils

  17. Post-intervention effects on screen behaviours and mediating effect of parental regulation: the HEalth In Adolescents study - a multi-component school-based randomized controlled trial

    Bergh, I.H.; van Stralen, M.M.; Bjelland, M.; Grydeland, M.; Lien, N.; Klepp, K.I.; Anderssen, S.A.; Ommundsen, Y.

    2014-01-01

    Background: To improve effectiveness of future screen behaviour interventions, one needs to know whether an intervention works via the proposed mediating mechanisms and whether the intervention is equally effective among subgroups. Parental regulation is identified as a consistent correlate of

  18. C/EBPα regulates CRL4Cdt2-mediated degradation of p21 in response to UVB-induced DNA damage to control the G1/S checkpoint

    Hall, Jonathan R; Bereman, Michael S; Nepomuceno, Angelito I; Thompson, Elizabeth A; Muddiman, David C; Smart, Robert C

    2014-01-01

    The bZIP transcription factor, C/EBPα is highly inducible by UVB and other DNA damaging agents in keratinocytes. C/EBPα-deficient keratinocytes fail to undergo cell cycle arrest in G1 in response to UVB-induced DNA damage and mice lacking epidermal C/EBPα are highly susceptible to UVB-induced skin cancer. The mechanism through which C/EBPα regulates the cell cycle checkpoint in response to DNA damage is unknown. Here we report untreated C/EBPα-deficient keratinocytes have normal levels of the cyclin-dependent kinase inhibitor, p21, however, UVB-treated C/EBPα-deficient keratinocytes fail to up-regulate nuclear p21 protein levels despite normal up-regulation of Cdkn1a mRNA levels. UVB-treated C/EBPα-deficient keratinocytes displayed a 4-fold decrease in nuclear p21 protein half-life due to the increased proteasomal degradation of p21 via the E3 ubiquitin ligase CRL4Cdt2. Cdt2 is the substrate recognition subunit of CRL4Cdt2 and Cdt2 mRNA and protein levels were up-regulated in UVB-treated C/EBPα-deficient keratinocytes. Knockdown of Cdt2 restored p21 protein levels in UVB-treated C/EBPα-deficient keratinocytes. Lastly, the failure to accumulate p21 in response to UVB in C/EBPα-deficient keratinocytes resulted in decreased p21 interactions with critical cell cycle regulatory proteins, increased CDK2 activity, and inappropriate entry into S-phase. These findings reveal C/EBPα regulates G1/S cell cycle arrest in response to DNA damage via the control of CRL4Cdt2 mediated degradation of p21. PMID:25483090

  19. Parental control, nurturance, self-efficacy, and screen viewing among 5- to 6-year-old children: a cross-sectional mediation analysis to inform potential behavior change strategies.

    Jago, Russell; Wood, Lesley; Zahra, Jesmond; Thompson, Janice L; Sebire, Simon J

    2015-04-01

    Children's screen viewing (SV) is associated with higher levels of childhood obesity. Many children exceed the American Academy of Pediatrics guideline of 2 hours of television (TV) per day. There is limited information about how parenting styles and parental self-efficacy to limit child screen time are associated with children's SV. This study examined whether parenting styles were associated with the SV of young children and whether any effects were mediated by parental self-efficacy to limit screen time. Data were from a cross-sectional survey conducted in 2013. Child and parent SV were reported by a parent, who also provided information about their parenting practices and self-efficacy to restrict SV. A four-step regression method examined whether parenting styles were associated with the SV of young children. Mediation by parental self-efficacy to limit screen time was examined using indirect effects. On a weekday, 90% of children watched TV for mediated associations between parental control and SV. Parental control was associated with lower levels of SV among 5- to 6-year-old children. This association was partially mediated by parental self-efficacy to limit screen time. The development of strategies to increase parental self-efficacy to limit screen-time may be useful.

  20. Internet-mediated physiotherapy and pain coping skills training for people with persistent knee pain (IMPACT - knee pain): a randomised controlled trial protocol.

    Dobson, Fiona; Hinman, Rana S; French, Simon; Rini, Christine; Keefe, Francis; Nelligan, Rachel; Abbott, J Haxby; Bryant, Christina; Staples, Margaret P; Dalwood, Andrew; Bennell, Kim L

    2014-08-13

    Persistent knee pain in people over 50 years of age is often attributable to knee osteoarthritis (OA), a common joint condition that causes physical and psychological dysfunction. Exercise and pain coping skills training (PCST) can help reduce the impact of persistent knee pain, however, access to health professionals who deliver these services can be challenging. With increasing access to the Internet, remotely delivered Internet-based treatment approaches may provide alternatives for healthcare delivery. This pragmatic randomised controlled trial will investigate whether an Internet-delivered intervention that combines PCST and physiotherapist-guided exercise (PCST + Ex) is more effective than online educational material (educational control) in people with persistent knee pain. We will recruit 148 people over 50 years of age with self-reported persistent knee pain consistent with knee OA from the Australian community. Following completion of baseline questionnaires, participants will be randomly allocated to access a 3-month intervention of either (i) online educational material, or (ii) the same online material plus an 8-module (once per week) Internet-based PCST program and seven Internet-delivered physiotherapy sessions with a home exercise programs to be performed 3 times per week. Outcomes will be measured at baseline, 3 months and 9 months with the primary time point at 3 months. Primary outcomes are average knee pain on walking (11-point numeric rating scale) and self-reported physical function (Western Ontario and McMaster Universities Osteoarthritis Index subscale). Secondary outcomes include additional measures of knee pain, health-related quality-of-life, perceived global change in symptoms, and potential moderators and mediators of outcomes including self-efficacy for pain management and function, pain coping attempts and pain catastrophising. Other measures of adherence, adverse events, harms, use of health services/co-interventions, and process

  1. The pathway by which the yeast protein kinase Snf1p controls acquisition of sodium tolerance is different from that mediating glucose regulation.

    Ye, Tian; Elbing, Karin; Hohmann, Stefan

    2008-09-01

    It recently became apparent that the highly conserved Snf1p protein kinase plays roles in controlling different cellular processes in the yeast Saccharomyces cerevisiae, in addition to its well-known function in glucose repression/derepression. We have previously reported that Snf1p together with Gis4p controls ion homeostasis by regulating expression of ENA1, which encodes the Ena1p Na(+) extrusion system. In this study we found that Snf1p is rapidly phosphorylated when cells are exposed to NaCl and this phosphorylation is required for the role of Snf1p in Na(+) tolerance. In contrast to activation by low glucose levels, the salt-induced phosphorylation of Snf1p promoted neither phosphorylation nor nuclear export of the Mig1p repressor. The mechanism that prevents Mig1p phosphorylation by active Snf1p under salt stress does not involve either hexokinase PII or the Gis4p regulator. Instead, Snf1p may mediate upregulation of ENA1 expression via the repressor Nrg1p. Activation of Snf1p in response to glucose depletion requires any of the three upstream protein kinases Sak1p, Tos3p and Elm1p, with Sak1p playing the most prominent role. The same upstream kinases were required for salt-induced Snf1p phosphorylation, and also under these conditions Sak1p played the most prominent role. Unexpectedly, however, it appears that Elm1p plays a dual role in acquisition of salt tolerance by activating Snf1p and in a presently unknown parallel pathway. Together, these results indicate that under salt stress Snf1p takes part in a different pathway from that during glucose depletion and this role is performed together as well as in parallel with its upstream kinase Elm1p. Snf1p appears to be part of a wider functional network than previously anticipated and the full complexity of this network remains to be elucidated.

  2. Examination of mid-intervention mediating effects on objectively assessed sedentary time among children in the Transform-Us! cluster-randomized controlled trial

    Carson, V.; Salmon, J.; Arundell, L.; Ridgers, N.D.; Cerin, E.; Brown, H.; Hesketh, K.D.; Ball, K.; Chin A Paw, M.J.M.; Yildirim, M.; Daly, R.M.; Dunstan, D.W.; Crawford, D.

    2013-01-01

    Background: The optimal targets and strategies for effectively reducing sedentary behavior among young people are unknown. Intervention research that explores changes in mediated effects as well as in outcome behaviors is needed to help inform more effective interventions. Therefore, the purpose of

  3. Parent-mediated social communication therapy for young children with autism (PACT): long-term follow-up of a randomised controlled trial.

    Pickles, Andrew; Le Couteur, Ann; Leadbitter, Kathy; Salomone, Erica; Cole-Fletcher, Rachel; Tobin, Hannah; Gammer, Isobel; Lowry, Jessica; Vamvakas, George; Byford, Sarah; Aldred, Catherine; Slonims, Vicky; McConachie, Helen; Howlin, Patricia; Parr, Jeremy R; Charman, Tony; Green, Jonathan

    2016-11-19

    It is not known whether early intervention can improve long-term autism symptom outcomes. We aimed to follow-up the Preschool Autism Communication Trial (PACT), to investigate whether the PACT intervention had a long-term effect on autism symptoms and continued effects on parent and child social interaction. PACT was a randomised controlled trial of a parent-mediated social communication intervention for children aged 2-4 years with core autism. Follow-up ascertainment was done at three specialised clinical services centres in the UK (London, Manchester, and Newcastle) at a median of 5·75 years (IQR 5·42-5·92) from the original trial endpoint. The main blinded outcomes were the comparative severity score (CSS) from the Autism Diagnostic Observation Schedule (ADOS), the Dyadic Communication Assessment Measure (DCMA) of the proportion of child initiatiations when interacting with the parent, and an expressive-receptive language composite. All analyses followed the intention-to-treat principle. PACT is registered with the ISRCTN registry, number ISRCTN58133827. 121 (80%) of the 152 trial participants (59 [77%] of 77 assigned to PACT intervention vs 62 [83%] of 75 assigned to treatment as usual) were traced and consented to be assessed between July, 2013, and September, 2014. Mean age at follow-up was 10·5 years (SD 0·8). Group difference in favour of the PACT intervention based on ADOS CSS of log-odds effect size (ES) was 0·64 (95% CI 0·07 to 1·20) at treatment endpoint and ES 0·70 (95% CI -0·05 to 1·47) at follow-up, giving an overall reduction in symptom severity over the course of the whole trial and follow-up period (ES 0·55, 95% CI 0·14 to 0·91, p=0·004). Group difference in DCMA child initiations at follow-up showed a Cohen's d ES of 0·29 (95% CI -0.02 to 0.57) and was significant over the course of the study (ES 0·33, 95% CI 0·11 to 0·57, p=0·004). There were no group differences in the language composite at follow-up (ES 0·15, 95% CI -0

  4. mediation: R package for causal mediation analysis

    Tingley, Dustin; Yamamoto, Teppei; Hirose, Kentaro; Keele, Luke; Imai, Kosuke

    2012-01-01

    In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting su...

  5. MiR-192-Mediated Positive Feedback Loop Controls the Robustness of Stress-Induced p53 Oscillations in Breast Cancer Cells.

    Richard Moore

    2015-12-01

    Full Text Available The p53 tumor suppressor protein plays a critical role in cellular stress and cancer prevention. A number of post-transcriptional regulators, termed microRNAs, are closely connected with the p53-mediated cellular networks. While the molecular interactions among p53 and microRNAs have emerged, a systems-level understanding of the regulatory mechanism and the role of microRNAs-forming feedback loops with the p53 core remains elusive. Here we have identified from literature that there exist three classes of microRNA-mediated feedback loops revolving around p53, all with the nature of positive feedback coincidentally. To explore the relationship between the cellular performance of p53 with the microRNA feedback pathways, we developed a mathematical model of the core p53-MDM2 module coupled with three microRNA-mediated positive feedback loops involving miR-192, miR-34a, and miR-29a. Simulations and bifurcation analysis in relationship to extrinsic noise reproduce the oscillatory behavior of p53 under DNA damage in single cells, and notably show that specific microRNA abrogation can disrupt the wild-type cellular phenotype when the ubiquitous cell-to-cell variability is taken into account. To assess these in silico results we conducted microRNA-perturbation experiments in MCF7 breast cancer cells. Time-lapse microscopy of cell-population behavior in response to DNA double-strand breaks, together with image classification of single-cell phenotypes across a population, confirmed that the cellular p53 oscillations are compromised after miR-192 perturbations, matching well with the model predictions. Our study via modeling in combination with quantitative experiments provides new evidence on the role of microRNA-mediated positive feedback loops in conferring robustness to the system performance of stress-induced response of p53.

  6. Hypoxia induces cancer-associated cAMP/PKA signalling through HIF-mediated transcriptional control of adenylyl cyclases VI and VII.

    Simko, Veronika; Iuliano, Filippo; Sevcikova, Andrea; Labudova, Martina; Barathova, Monika; Radvak, Peter; Pastorekova, Silvia; Pastorek, Jaromir; Csaderova, Lucia

    2017-08-31

    Hypoxia is a phenomenon often arising in solid tumours, linked to aggressive malignancy, bad prognosis and resistance to therapy. Hypoxia-inducible factor-1 has been identified as a key mediator of cell and tissue adaptation to hypoxic conditions through transcriptional activation of many genes involved in glucose metabolism and other cancer-related processes, such as angiogenesis, cell survival and cell invasion. Cyclic adenosine 3'5'-monophosphate is one of the most ancient and evolutionarily conserved signalling molecules and the cAMP/PKA signalling pathway plays an important role in cellular adaptation to hypoxia. We have investigated possible new mechanisms behind hypoxic activation of the cAMP/PKA pathway. For the first time, we have shown that hypoxia induces transcriptional up-regulation of the system of adenylyl cyclases, enzymes responsible for cAMP production, in a panel of carcinoma cell lines of various origin. Our data prove functional relevance of the hypoxic increase of adenylyl cyclases VI and VII at least partially mediated by HIF-1 transcription factor. We have identified adenylyl cyclase VI and VII isoforms as mediators of cellular response to hypoxia, which led to the elevation of cAMP levels and enhanced PKA activity, with an impact on cell migration and pH regulation.

  7. Time perspective as a determinant of smoking cessation in four countries: Direct and mediated effects from the International Tobacco Control (ITC) 4-Country Surveys.

    Hall, Peter A; Fong, Geoffrey T; Meng, Gang

    2014-07-01

    Future oriented time perspective predicts a number of important health behaviors and outcomes, including smoking cessation. However, it is not known how future orientation exerts its effects on such outcomes, and no large scale cross-national studies have examined the question prospectively. The aim of the current investigation was to examine the relationship between time perspective and success in smoking cessation, and social cognitive mediators of the association. The ITC-4 is a multi-wave, four country survey (Australia, Canada, United States, United Kingdom) of current smokers (N=9772); the survey includes baseline measurements of time perspective, intentions, quit attempts, and self-reported quit status at follow-up over 8 years. We examined the predictive power of time perspective for smoking cessation, as mediated through strength of quit intentions and prior history of quit attempts. Findings indicated that those smokers with a stronger future orientation at baseline were more likely to have successfully quit at follow-up. This effect was partially explained by intention-mediated effects of future orientation on quit attempts. Future orientation predicts smoking cessation across four English-speaking countries; the cessation-facilitating effects of future orientation may be primarily due to future oriented individuals' motivated and sustained involvement in the quit cycle over time. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Micro dynamics in mediation

    Boserup, Hans

    2014-01-01

    The author has identified a number of styles in mediation, which lead to different processes and different outcomes. Through discourse and conversation analysis he examines the micro dynamics in three of these, the postmodern styles: systemic, transformative and narrative mediation. The differences between the three mediation ideologies and practice is illustrated through role play scripts enacted in each style. Mediator and providers of mediation and trainers in mediation are encouraged to a...

  9. Biologically mediated dissolution of volcanic glass in seawater

    Staudigel, H; Yayanos, A; Chastain, R; Davies, G.T.; Verdurmen, E.A Th; Schiffmann, P; Bourcier, R; de Baar, H.J.W.

    1998-01-01

    We studied the effects of biological mediation on the dissolution of basaltic glass in seawater. Experiments with typical seawater microbial populations were contrasted with a sterile control, and reactions were monitored chemically and isotopically. Biologically mediated experiments produce twice

  10. On the Efficacy and Mediation of a One-on-One HIV Risk-Reduction Intervention for African American Men Who Have Sex with Men: A Randomized Controlled Trial.

    Jemmott, John B; Jemmott, Loretta Sweet; O'Leary, Ann; Icard, Larry D; Rutledge, Scott E; Stevens, Robin; Hsu, Janet; Stephens, Alisa J

    2015-07-01

    We examined the efficacy and mediation of Being Responsible for Ourselves (BRO), an HIV/STI risk-reduction intervention for African American men who have sex with men (MSM), the population with the highest HIV-diagnosis rate in the US. We randomized African American MSM to one of two interventions: BRO HIV/STI risk-reduction, targeting condom use; or attention-matched control, targeting physical activity and healthy diet. The interventions were based on social cognitive theory, the reasoned-action approach, and qualitative research. Men reporting anal intercourse with other men in the past 90 days were eligible and completed pre-intervention, immediately post-intervention, and 6 and 12 months post-intervention surveys. Of 595 participants, 503 (85 %) completed the 12-month follow-up. Generalized-estimating-equations analysis indicated that, compared with the attention-matched control intervention, the BRO intervention did not increase consistent condom use averaged over the 6- and 12-month follow-ups, which was the primary outcome. Although BRO did not affect the proportion of condom-protected intercourse acts, unprotected sexual intercourse, multiple partners, or insertive anal intercourse, it did reduce receptive anal intercourse compared with the control, a behavior linked to incident HIV infection. Mediation analysis using the product-of-coefficients approach revealed that although BRO increased seven of nine theoretical constructs it was designed to affect, it increased only one of three theoretical constructs that predicted consistent condom use: condom-use impulse-control self-efficacy. Thus, BRO indirectly increased consistent condom use through condom-use impulse-control self-efficacy. In conclusion, although BRO increased several theoretical constructs, most of those constructs did not predict consistent condom use; hence, the intervention did not increase it. Theoretical constructs that interventions should target to increase African American MSM

  11. Parent Mediation Empowers Sibling Conflict Resolution

    Ross, Hildy S.; Lazinski, Marysia J.

    2014-01-01

    Research Findings: For the current study, formal mediation procedures were adapted for families and parents were trained and asked to mediate their children's disputes; control group parents intervened as they normally would. Conflict negotiations with parents and their children (ages 3½-11 years) occurring 3 and 7 weeks following training, and…

  12. Priming B cell-mediated anti-HIV envelope responses by vaccination allows for the long-term control of infection in macaques exposed to a R5-tropic SHIV

    Buckner, Clarisa; Gines, Leoned G.; Saunders, Cheryl J.; Vojtech, Lucia; Srivastava, Indresh; Gettie, Agegnehu; Bohm, Rudolph; Blanchard, James; Barnett, Susan W.; Safrit, Jeffrey T.; Stamatatos, Leonidas

    2004-01-01

    The potential of vaccine-elicited anti-HIV envelope antibodies to control HIV-infection was evaluated by immunizing macaques with the HIV envelope protein and transiently depleting them of their CD8+ cells before intravenous challenge with the pathogenic CCR5-tropic SIV/HIV chimeric virus, SHIV SF162P4 . Although sterilizing immunity was not achieved, all vaccinated animals effectively controlled infection and remained free of disease for the duration of observation (over 3 years). In contrast, during the same period, the control animals progressed to disease. Both the vaccinees and the controls developed robust cell-mediated antiviral and neutralizing antibody responses following infection. A comparative analysis of these responses suggests that the more effective long-term control of infection by the vaccinated animals is due to the more rapid development of anti-HIV envelope antibodies. These studies suggest that priming by vaccination of B cell anti-HIV envelope responses maybe crucial for the long-term control of HIV infection

  13. Bone Marrow-Derived Mesenchymal Stem Cells Attenuate Immune-Mediated Liver Injury and Compromise Virus Control During Acute Hepatitis B Virus Infection in Mice.

    Qu, Mengmeng; Yuan, Xu; Liu, Dan; Ma, Yuhong; Zhu, Jun; Cui, Jun; Yu, Mengxue; Li, Changyong; Guo, Deyin

    2017-06-01

    Mesenchymal stem cells (MSCs) have been used as therapeutic tools not only for their ability to differentiate toward different cells, but also for their unique immunomodulatory properties. However, it is still unknown how MSCs may affect immunity during hepatitis B virus (HBV) infection. This study was designed to explore the effect of bone marrow-derived MSCs (BM-MSCs) on hepatic natural killer (NK) cells in a mouse model of acute HBV infection. Mice were injected with 1 × 10 6 BM-MSCs, which stained with chloromethyl derivatives of fluorescein diacetate fluorescent probe, 24 h before hydrodynamic injection of viral DNA (pHBV1.3) through the tail vein. In vivo imaging system revealed that BM-MSCs were accumulated in the injured liver, and they attenuated immune-mediated liver injury during HBV infection, as shown by lower alanine aminotransferase levels, reduced proinflammatory cytokine production, and decreased inflammatory cell infiltration in the liver. Importantly, administration of BM-MSCs restrained the increased expression of natural-killer group 2, member D (NKG2D), an important receptor required for NK cell activation in the liver from HBV-infected mice. BM-MSCs also reduced NKG2D expression on NK cells and suppressed the cytotoxicity of NK cells in vitro. Furthermore, BM-MSC-derived transforming growth factor-β1 suppressed NKG2D expression on NK cells. As a consequence, BM-MSC treatment enhanced HBV gene expression and replication in vivo. These results demonstrate that adoptive transfer of BM-MSCs influences innate immunity and limits immune-mediated liver injury during acute HBV infection by suppressing NK cell activity. Meanwhile, the effect of BM-MSCs on prolonging virus clearance needs to be considered in the future.

  14. Transcription regulation by the Mediator complex.

    Soutourina, Julie

    2018-04-01

    Alterations in the regulation of gene expression are frequently associated with developmental diseases or cancer. Transcription activation is a key phenomenon in the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase II transcription (Mediator), a large complex with modular organization, is generally required for transcription by RNA polymerase II, and it regulates various steps of this process. The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation. Recent functional studies of Mediator with the use of structural biology approaches and functional genomics have revealed new insights into Mediator activity and its regulation during transcription initiation, including how Mediator is recruited to transcription regulatory regions and how it interacts and cooperates with PIC components to assist in PIC assembly. Novel roles of Mediator in the control of gene expression have also been revealed by showing its connection to the nuclear pore and linking Mediator to the regulation of gene positioning in the nuclear space. Clear links between Mediator subunits and disease have also encouraged studies to explore targeting of this complex as a potential therapeutic approach in cancer and fungal infections.

  15. The Mediator complex and transcription regulation

    Poss, Zachary C.; Ebmeier, Christopher C.

    2013-01-01

    The Mediator complex is a multi-subunit assembly that appears to be required for regulating expression of most RNA polymerase II (pol II) transcripts, which include protein-coding and most non-coding RNA genes. Mediator and pol II function within the pre-initiation complex (PIC), which consists of Mediator, pol II, TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH and is approximately 4.0 MDa in size. Mediator serves as a central scaffold within the PIC and helps regulate pol II activity in ways that remain poorly understood. Mediator is also generally targeted by sequence-specific, DNA-binding transcription factors (TFs) that work to control gene expression programs in response to developmental or environmental cues. At a basic level, Mediator functions by relaying signals from TFs directly to the pol II enzyme, thereby facilitating TF-dependent regulation of gene expression. Thus, Mediator is essential for converting biological inputs (communicated by TFs) to physiological responses (via changes in gene expression). In this review, we summarize an expansive body of research on the Mediator complex, with an emphasis on yeast and mammalian complexes. We focus on the basics that underlie Mediator function, such as its structure and subunit composition, and describe its broad regulatory influence on gene expression, ranging from chromatin architecture to transcription initiation and elongation, to mRNA processing. We also describe factors that influence Mediator structure and activity, including TFs, non-coding RNAs and the CDK8 module. PMID:24088064

  16. The Prevention Program for Externalizing Problem Behavior (PEP) Improves Child Behavior by Reducing Negative Parenting: Analysis of Mediating Processes in a Randomized Controlled Trial

    Hanisch, Charlotte; Hautmann, Christopher; Plück, Julia; Eichelberger, Ilka; Döpfner, Manfred

    2014-01-01

    Background: Our indicated Prevention program for preschool children with Externalizing Problem behavior (PEP) demonstrated improved parenting and child problem behavior in a randomized controlled efficacy trial and in a study with an effectiveness design. The aim of the present analysis of data from the randomized controlled trial was to identify…

  17. Two-Stage Translational Control of Dentate Gyrus LTP Consolidation Is Mediated by Sustained BDNF-TrkB Signaling to MNK

    Debabrata Panja

    2014-11-01

    Full Text Available BDNF signaling contributes to protein-synthesis-dependent synaptic plasticity, but the dynamics of TrkB signaling and mechanisms of translation have not been defined. Here, we show that long-term potentiation (LTP consolidation in the dentate gyrus of live rodents requires sustained (hours BDNF-TrkB signaling. Surprisingly, this sustained activation maintains an otherwise labile signaling pathway from TrkB to MAP-kinase-interacting kinase (MNK. MNK activity promotes eIF4F translation initiation complex formation and protein synthesis in mechanistically distinct early and late stages. In early-stage translation, MNK triggers release of the CYFIP1/FMRP repressor complex from the 5′-mRNA cap. In late-stage translation, MNK regulates the canonical translational repressor 4E-BP2 in a synapse-compartment-specific manner. This late stage is coupled to MNK-dependent enhanced dendritic mRNA translation. We conclude that LTP consolidation in the dentate gyrus is mediated by sustained BDNF signaling to MNK and MNK-dependent regulation of translation in two functionally and mechanistically distinct stages.

  18. Paramecium tetraurelia chromatin assembly factor-1-like protein PtCAF-1 is involved in RNA-mediated control of DNA elimination.

    Ignarski, Michael; Singh, Aditi; Swart, Estienne C; Arambasic, Miroslav; Sandoval, Pamela Y; Nowacki, Mariusz

    2014-10-29

    Genome-wide DNA remodelling in the ciliate Paramecium is ensured by RNA-mediated trans-nuclear crosstalk between the germline and the somatic genomes during sexual development. The rearrangements include elimination of transposable elements, minisatellites and tens of thousands non-coding elements called internally eliminated sequences (IESs). The trans-nuclear genome comparison process employs a distinct class of germline small RNAs (scnRNAs) that are compared against the parental somatic genome to select the germline-specific subset of scnRNAs that subsequently target DNA elimination in the progeny genome. Only a handful of proteins involved in this process have been identified so far and the mechanism of DNA targeting is unknown. Here we describe chromatin assembly factor-1-like protein (PtCAF-1), which we show is required for the survival of sexual progeny and localizes first in the parental and later in the newly developing macronucleus. Gene silencing shows that PtCAF-1 is required for the elimination of transposable elements and a subset of IESs. PTCAF-1 depletion also impairs the selection of germline-specific scnRNAs during development. We identify specific histone modifications appearing during Paramecium development which are strongly reduced in PTCAF-1 depleted cells. Our results demonstrate the importance of PtCAF-1 for the epigenetic trans-nuclear cross-talk mechanism. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Co-ordinate regulation of Salmonella typhimurium invasion genes by environmental and regulatory factors is mediated by control of hilA expression.

    Bajaj, V; Lucas, R L; Hwang, C; Lee, C A

    1996-11-01

    During infection of their hosts, salmonellae enter intestinal epithelial cells. It has been proposed that when Salmonella typhimurium is present in the intestinal lumen, several environmental and regulatory conditions modulate the expression of invasion factors required for bacterial entry into host cells. We report here that the expression of six different S. typhimurium invasion genes encoded on SPI1 (Salmonella pathogenicity island 1) is co-ordinately regulated by oxygen, osmolarity, pH, PhoPQ, and HilA. HilA is a transcriptional activator of the OmpR/ToxR family that is also encoded on SPI1. We have found that HilA plays a central role in the co-ordinated regulation of invasion genes by environmental and regulatory conditions. HilA can activate the expression of two invasion gene-lacZY fusions on reporter plasmids in Escherichia coll, suggesting that HilA acts directly at invasion-gene promoters in S. typhimurium. We have found that the regulation of invasion genes by oxygen, osmolarity, pH, and PhoPQ is indirect and is mediated by regulation of hilA expression by these environmental and regulatory factors. We hypothesize that the complex and co-ordinate regulation of Invasion genes by HilA is an important feature of salmonella pathogenesis and allows salmonellae to enter intestinal epithelial cells.

  20. Nordic Mediation Reseach

    A presentation of 12 studies on mediation from researchers from Denmark, Finland, Norway and Sweden.......A presentation of 12 studies on mediation from researchers from Denmark, Finland, Norway and Sweden....

  1. Bayesian Mediation Analysis

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    This article proposes Bayesian analysis of mediation effects. Compared to conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian mediation analysis, inference is straightforward and exact, which makes it appealing for studies with small samples. Third, the Bayesian approach is conceptua...

  2. mediation: R Package for Causal Mediation Analysis

    Dustin Tingley

    2014-09-01

    Full Text Available In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting such an analysis. The package is organized into two distinct approaches. Using the model-based approach, researchers can estimate causal mediation effects and conduct sensitivity analysis under the standard research design. Furthermore, the design-based approach provides several analysis tools that are applicable under different experimental designs. This approach requires weaker assumptions than the model-based approach. We also implement a statistical method for dealing with multiple (causally dependent mediators, which are often encountered in practice. Finally, the package also offers a methodology for assessing causal mediation in the presence of treatment noncompliance, a common problem in randomized trials.

  3. Bayesian Mediation Analysis

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    In this article, we propose Bayesian analysis of mediation effects. Compared with conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian…

  4. Mediating the effect of self-care management intervention in type 2 diabetes: A meta-analysis of 47 randomised controlled trials

    Minet, Lisbeth; Møller, Sine; Vach, Werner

    2010-01-01

    OBJECTIVE: To perform a meta-analysis assessing the effects of self-care management interventions in improving glycaemic control in type 2 diabetes by analysing the impact of different study characteristics on the effect size. METHODS: A literature search in eight scientific databases up...... to November 2007 included original studies of randomised controlled trials involving adult patients diagnosed with type 2 diabetes and evaluating a self-care management intervention. RESULTS: The 47 included studies yielded 7677 participants. The analysis showed a 0.36% (95% CI 0.21-0.51) improvement...... in glycaemic control in people who received self-care management treatment. In the univariate meta-regression sample size (effect size 0.42%, p=0.007) and follow-up period (effect size 0.49%, p=0.017) were identified to have significant effect on the effect size in favour of small studies and short follow...

  5. Controllable architecture of CdS and CuS by single-source precursor-mediated approach and their photocatalytic activity

    Sahoo, Ashish K.; Srivastava, Suneel K.

    2013-01-01

    The present work deals with the preparation of hexagonal CdS and CuS by solvothermal decomposition of the morpholine-4-carbdithioate (MCDT) complexes of Cd and Cu in a water/THF mixture at 140–180 °C for 24 h and characterization. Scanning electron microscopy, field emission scanning electron microscopy and high resolution transmission electron microscopy show that CdS exhibits a hierarchical star- and lotus flower-like morphology in the presence of disodium salt of ethylenediamine tetraaceticacid and sodium dodecyl benzene sulphonate as soft templates at 140 and 160 °C, respectively. However, Cu complex of MCDT forms CuS nanoparticles in the temperature range of 140–180 °C. On the contrary, CdS nanoparticles and CuS microparticles are formed in the absence of any template under the identical experimental conditions. Raman studies show the characteristic peak of CdS and CuS, irrespective of their size and morphology. Finally, CdS and CuS of varying morphology have successfully been used as catalysts in UV photocatalytic decomposition of methylene blue dye. These findings show that CdS lotus-like microflowers are more effective catalysts than hierarchical stars, though the latter is found to have better reusability.Graphical AbstractA simple soft template-assisted and single complex source precursor-mediated solvothermal synthesis of CdS and CuS with a diverse set of morphology has been reported. In addition, the morphology and application in photocatalysis are also discussed.

  6. Controllable architecture of CdS and CuS by single-source precursor-mediated approach and their photocatalytic activity

    Sahoo, Ashish K.; Srivastava, Suneel K., E-mail: sunil111954@yahoo.co.uk [Indian Institute of Technology Kharagpur, Department of Chemistry (India)

    2013-04-15

    The present work deals with the preparation of hexagonal CdS and CuS by solvothermal decomposition of the morpholine-4-carbdithioate (MCDT) complexes of Cd and Cu in a water/THF mixture at 140-180 Degree-Sign C for 24 h and characterization. Scanning electron microscopy, field emission scanning electron microscopy and high resolution transmission electron microscopy show that CdS exhibits a hierarchical star- and lotus flower-like morphology in the presence of disodium salt of ethylenediamine tetraaceticacid and sodium dodecyl benzene sulphonate as soft templates at 140 and 160 Degree-Sign C, respectively. However, Cu complex of MCDT forms CuS nanoparticles in the temperature range of 140-180 Degree-Sign C. On the contrary, CdS nanoparticles and CuS microparticles are formed in the absence of any template under the identical experimental conditions. Raman studies show the characteristic peak of CdS and CuS, irrespective of their size and morphology. Finally, CdS and CuS of varying morphology have successfully been used as catalysts in UV photocatalytic decomposition of methylene blue dye. These findings show that CdS lotus-like microflowers are more effective catalysts than hierarchical stars, though the latter is found to have better reusability.Graphical AbstractA simple soft template-assisted and single complex source precursor-mediated solvothermal synthesis of CdS and CuS with a diverse set of morphology has been reported. In addition, the morphology and application in photocatalysis are also discussed.

  7. Clustering the mediators between the sales control systems and the sales performance using the AMO model: A narrative systematic literature review

    Alejandro Benet-Zepf

    2018-05-01

    Originality/value: As academic result, the review highlights that all three groups from the AMO model evidence positive impacts on sales performance when a behavioral control system (mostly from the capability part is in use, by enhancing salesperson’s skills, motivation, and organizational conditions and support, fostering as a result, a salesperson relational approach and a customer orientation, which generate the best outcomes in the long term. These findings suggest as a managerial contribution, that coaching and leading -rather than commanding- to be a more appropriate control attitude, especially when the salesperson is younger or unexperienced.

  8. Impaired virus control and severe CD8+ T-cell-mediated immunopathology in chimeric mice deficient in gamma interferon receptor expression on both parenchymal and hematopoietic cells

    Henrichsen, Pernille; Bartholdy, Christina; Christensen, Jan Pravsgaard

    2005-01-01

    be capable of responding to IFN-gamma, but expression of the relevant receptor on non-T cells could be experimentally controlled. Only when the IFN-gamma receptor is absent on both radioresistant parenchymal and bone marrow-derived cells will chimeric mice challenged with a highly invasive, noncytolytic...

  9. Are metabolic signatures mediating the relationship between lifestyle factors and hepatocellular carcinoma risk? Results from a nested case-control study in EPIC.

    Assi, Nada; Thomas, Duncan C; Leitzman, Michael; Stepien, Magdalena; Chajes, Veronique; Philip, Thierry; Vineis, Paolo; Bamia, Christina; Boutron-Ruault, Marie-Christine; Sandanger, Torkjel M; Molinuevo, Amaia; Boshuizen, Hendriek C; Sundkvist, Anneli; Kühn, Tilman; Travis, Ruth C; Overvad, Kim; Riboli, Elio; Gunter, Marc J; Scalbert, Augustin; Jenab, Mazda; Ferrari, Pietro; Viallon, Vivian

    2018-01-01

    The "meeting-in-the-middle" (MITM) is a principle to identify exposure biomarkers that are also predictors of disease. The MITM statistical framework was applied in a nested case-control study of hepatocellular carcinoma (HCC) within EPIC where healthy lifestyle index (HLI) variables were related to

  10. Intervention for children exposed to interparental violence : A randomized controlled trial of effectiveness of specific factors, moderators and mediators in community-based intervention

    Overbeek, M.M.

    2014-01-01

    The main aim of this thesis was to evaluate the added benefit of applying specific factors in community-based intervention for child witnesses of interparental violence (IPV) and their parents, by means of a randomized controlled trial (RCT). The results of this RCT showed no additional benefits of

  11. Trade-offs in parasitism efficiency and brood size mediate parasitoid coexistence, with implications for biological control of the invasive emerald ash borer

    Parasitoids often are selected for use as biological control agents because of their high host specificity, yet such host specificity can result in strong interspecific competition. However, few studies have examined if and how various extrinsic factors (such as parasitism efficiency) influence the ...

  12. Mediational effects of self-efficacy dimensions in the relationship between knowledge of dengue and dengue preventive behaviour with respect to control of dengue outbreaks: a structural equation model of a cross-sectional survey.

    Affendi Isa

    Full Text Available Dengue fever is endemic in Malaysia, with frequent major outbreaks in urban areas. The major control strategy relies on health promotional campaigns aimed at encouraging people to reduce mosquito breeding sites close to people's homes. However, such campaigns have not always been 100% effective. The concept of self-efficacy is an area of increasing research interest in understanding how health promotion can be most effective. This paper reports on a study of the impact of self-efficacy on dengue knowledge and dengue preventive behaviour.We recruited 280 adults from 27 post-outbreak villages in the state of Terengganu, east coast of Malaysia. Measures of health promotion and educational intervention activities and types of communication during outbreak, level of dengue knowledge, level and strength of self-efficacy and dengue preventive behaviour were obtained via face-to-face interviews and questionnaires. A structural equation model was tested and fitted the data well (χ(2 = 71.659, df = 40, p = 0.002, RMSEA = 0.053, CFI = 0.973, TLI = 0.963. Mass media, local contact and direct information-giving sessions significantly predicted level of knowledge of dengue. Level and strength of self-efficacy fully mediated the relationship between knowledge of dengue and dengue preventive behaviours. Strength of self-efficacy acted as partial mediator in the relationship between knowledge of dengue and dengue preventive behaviours.To control and prevent dengue outbreaks by behavioural measures, health promotion and educational interventions during outbreaks should now focus on those approaches that are most likely to increase the level and strength of self-efficacy.

  13. The Rice Enhancer of Zeste [E(z] Genes SDG711 and SDG718 are respectively involved in Long Day and Short Day Signaling to Mediate the Accurate Photoperiod Control of Flowering time

    Xiaoyun eLiu

    2014-10-01

    Full Text Available Recent advances in rice flowering studies have shown that the accurate control of flowering by photoperiod is regulated by key mechanisms that involve the regulation of flowering genes including Hd1, Ehd1, Hd3a, and RFT1. The chromatin mechanism involved in the regulation of rice flowering genes is presently not well known. Here we show that the rice E(z genes SDG711 and SDG718, which encode the Polycomb Repressive Complex2 (PRC2 key subunit that is required for trimethylation of histone H3 lysine 27 (H3K27me3, are respectively involved in long day (LD and short day (SD regulation of key flowering genes. The expression of SDG711 and SDG718 is induced by LD and SD, respectively. Over-expression and down-regulation of SDG711 respectively repressed and promoted flowering in LD, but had no effect in SD. By contrast, down-regulation of SDG718 had no effect in LD but delayed flowering in SD. SDG711 and SDG718 repressed OsLF (a repressor of Hd1 respectively in LD and SD, leading to a higher expression of Hd1 thus late flowering in LD and early flowering in SD. SDG711 was also found to be involved in the repression of Ehd1 in LD. SDG711 was shown to directly target to OsLF and Ehd1 loci to mediate H3K27me3 and gene repression. The function of the rice E(z genes in LD repression and SD promotion of flowering suggests that PRC2-mediated epigenetic repression of gene expression is involved in the accurate photoperiod control of rice flowering.

  14. Mediational Effects of Self-Efficacy Dimensions in the Relationship between Knowledge of Dengue and Dengue Preventive Behaviour with Respect to Control of Dengue Outbreaks: A Structural Equation Model of a Cross-Sectional Survey

    Isa, Affendi; Loke, Yoon K.; Smith, Jane R.; Papageorgiou, Alexia; Hunter, Paul R.

    2013-01-01

    Background Dengue fever is endemic in Malaysia, with frequent major outbreaks in urban areas. The major control strategy relies on health promotional campaigns aimed at encouraging people to reduce mosquito breeding sites close to people's homes. However, such campaigns have not always been 100% effective. The concept of self-efficacy is an area of increasing research interest in understanding how health promotion can be most effective. This paper reports on a study of the impact of self-efficacy on dengue knowledge and dengue preventive behaviour. Methods and Findings We recruited 280 adults from 27 post-outbreak villages in the state of Terengganu, east coast of Malaysia. Measures of health promotion and educational intervention activities and types of communication during outbreak, level of dengue knowledge, level and strength of self-efficacy and dengue preventive behaviour were obtained via face-to-face interviews and questionnaires. A structural equation model was tested and fitted the data well (χ2 = 71.659, df = 40, p = 0.002, RMSEA = 0.053, CFI = 0.973, TLI = 0.963). Mass media, local contact and direct information-giving sessions significantly predicted level of knowledge of dengue. Level and strength of self-efficacy fully mediated the relationship between knowledge of dengue and dengue preventive behaviours. Strength of self-efficacy acted as partial mediator in the relationship between knowledge of dengue and dengue preventive behaviours. Conclusions To control and prevent dengue outbreaks by behavioural measures, health promotion and educational interventions during outbreaks should now focus on those approaches that are most likely to increase the level and strength of self-efficacy. PMID:24086777

  15. General gauge mediation

    Meade, Patrick; Seiberg, Nathan; Shih, David

    2009-01-01

    We give a general definition of gauge mediated supersymmetry breaking which encompasses all the known gauge mediation models. In particular, it includes both models with messengers as well as direct mediation models. A formalism for computing the soft terms in the generic model is presented. Such a formalism is necessary in strongly-coupled direct mediation models where perturbation theory cannot be used. It allows us to identify features of the entire class of gauge mediation models and to distinguish them from specific signatures of various subclasses. (author)

  16. Bayesian dynamic mediation analysis.

    Huang, Jing; Yuan, Ying

    2017-12-01

    Most existing methods for mediation analysis assume that mediation is a stationary, time-invariant process, which overlooks the inherently dynamic nature of many human psychological processes and behavioral activities. In this article, we consider mediation as a dynamic process that continuously changes over time. We propose Bayesian multilevel time-varying coefficient models to describe and estimate such dynamic mediation effects. By taking the nonparametric penalized spline approach, the proposed method is flexible and able to accommodate any shape of the relationship between time and mediation effects. Simulation studies show that the proposed method works well and faithfully reflects the true nature of the mediation process. By modeling mediation effect nonparametrically as a continuous function of time, our method provides a valuable tool to help researchers obtain a more complete understanding of the dynamic nature of the mediation process underlying psychological and behavioral phenomena. We also briefly discuss an alternative approach of using dynamic autoregressive mediation model to estimate the dynamic mediation effect. The computer code is provided to implement the proposed Bayesian dynamic mediation analysis. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  17. Impact of EPA ingestion on COX- and LOX-mediated eicosanoid synthesis in skin with and without a pro-inflammatory UVR challenge – Report of a randomised controlled study in humans

    Pilkington, Suzanne M; Rhodes, Lesley E; Al-Aasswad, Naser M I; Massey, Karen A; Nicolaou, Anna

    2014-01-01

    Scope Eicosapentaenoic acid (EPA), abundant in oily fish, is reported to reduce skin inflammation and provide photoprotection, potential mechanisms include competition with arachidonic acid (AA) for metabolism by cyclooxygenases/lipoxygenases to less pro-inflammatory mediators. We thus examine impact of EPA intake on levels of AA, EPA and their resulting eicosanoids in human skin with or without ultraviolet radiation (UVR) challenge. Methods and results In a double-blind randomised controlled study, 79 females took 5 g EPA-rich or control lipid for 12 wk. Pre- and post-supplementation, red blood cell and skin polyunsaturated fatty acids were assessed by GC, and eicosanoids from unexposed and UVR-exposed skin by LC-MS/MS. Active supplementation increased red blood cell and dermal EPA versus control (both p skin (p skin; 12-hydroxyeicosatetraenoic acids:12-HEPE was lower in UVR-exposed skin (3:1 versus 11:1; p skin EPA:AA content, shifting eicosanoid synthesis towards less pro-inflammatory species, and promoting a regulatory milieu under basal conditions and in response to inflammatory insult. PMID:24311515

  18. Single-pulse terahertz coherent control of spin resonance in the canted antiferromagnet YFeO3, mediated by dielectric anisotropy

    Jin, Zuanming; Mics, Zoltán; Ma, Guohong

    2013-01-01

    We report on the coherent control of terahertz (THz) spin waves in a canted antiferromagnet yttrium orthoferrite, YFeO3, associated with a quasiferromagnetic (quasi-FM) spin resonance at a frequency of 0.3 THz, using a single-incident THz pulse. The spin resonance is excited impulsively by the ma...... polarization of the THz oscillation at the spin resonance frequency, suggests a key role of magnon–phonon coupling in spin-wave energy dissipation....

  19. Seed-Mediated Synthesis of Ag Nanocubes with Controllable Edge Lengths in the Range of 30–200 nm and Comparison of Their Optical Properties

    Zhang, Qiang; Li, Weiyang; Moran, Christine; Zeng, Jie; Chen, Jingyi; Wen, Long-Ping; Xia, Younan

    2010-01-01

    Silver nanocubes with edge lengths controllable in the range of 30–200 nm were synthesized using an approach based on seeded growth. The key to the success of this synthesis is the use of single-crystal Ag seeds to direct the growth and the use of AgNO3 as a precursor to elemental Ag where the by-product HNO3 can block both the homogeneous nucleation and evolution of single-crystal seeds into twinned nanoparticles. Either spherical (in the shape of cubooctahedron) or cubic seeds could be employed for this growth process. The edge length of resultant Ag nanocubes can be readily controlled by varying the amount of Ag seeds used, the amount of AgNO3 added, or both. For the first time, we could obtain Ag nanocubes with uniform edge lengths controllable in the range of 30–200 nm and then compare their localized surface plasmon resonance and surface-enhanced Raman scattering properties. PMID:20698704

  20. Seed-mediated synthesis of Ag nanocubes with controllable edge lengths in the range of 30-200 nm and comparison of their optical properties.

    Zhang, Qiang; Li, Weiyang; Moran, Christine; Zeng, Jie; Chen, Jingyi; Wen, Long-Ping; Xia, Younan

    2010-08-18

    Silver nanocubes with edge lengths controllable in the range of 30-200 nm were synthesized using an approach based on seeded growth. The keys to the success of this synthesis are the use of single-crystal Ag seeds to direct the growth and the use of AgNO(3) as a precursor to elemental Ag, where the byproduct HNO(3) can block both the homogeneous nucleation and evolution of single-crystal seeds into twinned nanoparticles. Either spherical (in the shape of a cuboctahedron) or cubic seeds could be employed for this growth process. The edge length of the resultant Ag nanocubes can be readily controlled by varying the amount of Ag seeds used, the amount of AgNO(3) added, or both. For the first time, we could obtain Ag nanocubes with uniform edge lengths controllable in the range of 30-200 nm and then compare their localized surface plasmon resonance and surface-enhanced Raman scattering properties.

  1. Supraphysiologic control over HIV-1 replication mediated by CD8 T cells expressing a re-engineered CD4-based chimeric antigen receptor.

    Rachel S Leibman

    2017-10-01

    Full Text Available HIV is adept at avoiding naturally generated T cell responses; therefore, there is a need to develop HIV-specific T cells with greater potency for use in HIV cure strategies. Starting with a CD4-based chimeric antigen receptor (CAR that was previously used without toxicity in clinical trials, we optimized the vector backbone, promoter, HIV targeting moiety, and transmembrane and signaling domains to determine which components augmented the ability of T cells to control HIV replication. This re-engineered CAR was at least 50-fold more potent in vitro at controlling HIV replication than the original CD4 CAR, or a TCR-based approach, and substantially better than broadly neutralizing antibody-based CARs. A humanized mouse model of HIV infection demonstrated that T cells expressing optimized CARs were superior at expanding in response to antigen, protecting CD4 T cells from infection, and reducing viral loads compared to T cells expressing the original, clinical trial CAR. Moreover, in a humanized mouse model of HIV treatment, CD4 CAR T cells containing the 4-1BB costimulatory domain controlled HIV spread after ART removal better than analogous CAR T cells containing the CD28 costimulatory domain. Together, these data indicate that potent HIV-specific T cells can be generated using improved CAR design and that CAR T cells could be important components of an HIV cure strategy.

  2. eIF2β is critical for eIF5-mediated GDP-dissociation inhibitor activity and translational control.

    Jennings, Martin D; Kershaw, Christopher J; White, Christopher; Hoyle, Danielle; Richardson, Jonathan P; Costello, Joseph L; Donaldson, Ian J; Zhou, Yu; Pavitt, Graham D

    2016-11-16

    In protein synthesis translation factor eIF2 binds initiator tRNA to ribosomes and facilitates start codon selection. eIF2 GDP/GTP status is regulated by eIF5 (GAP and GDI functions) and eIF2B (GEF and GDF activities), while eIF2α phosphorylation in response to diverse signals is a major point of translational control. Here we characterize a growth suppressor mutation in eIF2β that prevents eIF5 GDI and alters cellular responses to reduced eIF2B activity, including control of GCN4 translation. By monitoring the binding of fluorescent nucleotides and initiator tRNA to purified eIF2 we show that the eIF2β mutation does not affect intrinsic eIF2 affinities for these ligands, neither does it interfere with eIF2 binding to 43S pre-initiation complex components. Instead we show that the eIF2β mutation prevents eIF5 GDI stabilizing nucleotide binding to eIF2, thereby altering the off-rate of GDP from eIF2•GDP/eIF5 complexes. This enables cells to grow with reduced eIF2B GEF activity but impairs activation of GCN4 targets in response to amino acid starvation. These findings provide support for the importance of eIF5 GDI activity in vivo and demonstrate that eIF2β acts in concert with eIF5 to prevent premature release of GDP from eIF2γ and thereby ensure tight control of protein synthesis initiation. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Effect of periodontal therapy on metabolic control and an inflammatory mediator in type 2 diabetic subjects: a report on 17 consecutive cases.

    Serrano, Carlos; Pérez, Clara; Sabogal, Diego

    2012-04-01

    A reciprocal relationship between diabetes mellitus and chronic periodontitis has been described, whereby chronic periodontal infection could affect diabetic metabolic control. Therefore, periodontal therapy could influence metabolic control or systemic inflammation leading to diabetic complications. This case report series presents the effect of therapy on periodontal indices, glycated hemoglobin (HbA1c) and high-sensitivity C-reactive protein (hs-CRP) in a group of type 2 diabetic patients. Seventeen diabetic patients diagnosed with moderate to severe chronic periodontitis received periodontal therapy. All patients received a hygienic phase of treatment and were re-examined 3 months later. At re-examination, subjects judged to need periodontal surgery were treated and re-examined after a further 3 months. A complete clinical examination and measurements of HbA1c and hs-CRP were evaluated. Periodontal treatment led to a significant improvement in periodontal indices; only five patients required periodontal surgery. The percentage of bleeding on probing was reduced by nearly 40%; percentage of pockets > or = 5 mm was less than half baseline values; mean pocket depth reduction was 1.21 mm (0.58) and attachment level gain was 0.74 mm (0.69). Nevertheless, no changes were present for HbA1c; a reduction in hs-CRP of 1.37 mg/L (2.67) was present. Periodontal therapy in this case series group produced a significant improvement in the clinical condition, butdid not affect metabolic control. It led to a decrease in hs-CRP.

  4. Altered β1-3-adrenoceptor influence on α2-adrenoceptor-mediated control of catecholamine release and vascular tension in hypertensive rats

    Torill eBerg

    2015-04-01

    Full Text Available α2- and β-adrenoceptors (AR reciprocally control catecholamine release and vascular tension. Disorders in these functions are present in spontaneously hypertensive rats (SHR. The present study tested if α2AR dysfunctions resulted from altered α2AR/βAR interaction. Blood pressure was recorded through a femoral artery catheter and cardiac output by an ascending aorta flow probe. Total peripheral vascular resistance (TPR was calculated. Norepinephrine release was stimulated by a 15-min tyramine-infusion, which allows presynaptic release-control to be reflected as differences in overflow to plasma. Surgical stress activated some secretion of epinephrine. L-659,066 (α2AR-antagonist enhanced norepinephrine overflow in normotensive controls (WKY but not SHR. Nadolol (β1+2 and ICI-118551 (β2, but not atenolol (β1 or SR59230A (β(3/1L prevented this increase. All βAR antagonists allowed L-659,066 to augment tyramine-induced norepinephrine overflow in SHR and epinephrine secretion in both strains. Inhibition of cAMP-degradation with milrinone and β3AR agonist (BRL37344 enhanced the effect of L-659,066 on release of both catecholamines in SHR and epinephrine in WKY. β1/2AR antagonists and BRL37344 opposed the L-659,066-dependent elimination of the TPR-response to tyramine in WKY. α2AR/βAR antagonists had little influence on the TPR-response in SHR. Milrinone potentiated the L-659,066-dependent reduction of the TPR-response to tyramine. Conclusions: β2AR activity was a required substrate for α2AR auto inhibition of norepinephrine release in WKY. β1+2AR opposed α2AR inhibition of norepinephrine release in SHR and epinephrine secretion in both strains. βAR-α2AR reciprocal control of vascular tension was absent in SHR. Selective agonist provoked β3AR-Gi signaling and influenced the tyramine-induced TPR-response in WKY and catecholamine release in SHR.

  5. Seed-Mediated Synthesis of Ag Nanocubes with Controllable Edge Lengths in the Range of 30–200 nm and Comparison of Their Optical Properties

    Zhang, Qiang; Li, Weiyang; Moran, Christine; Zeng, Jie; Chen, Jingyi; Wen, Long-Ping; Xia, Younan

    2010-01-01

    Silver nanocubes with edge lengths controllable in the range of 30–200 nm were synthesized using an approach based on seeded growth. The key to the success of this synthesis is the use of single-crystal Ag seeds to direct the growth and the use of AgNO3 as a precursor to elemental Ag where the by-product HNO3 can block both the homogeneous nucleation and evolution of single-crystal seeds into twinned nanoparticles. Either spherical (in the shape of cubooctahedron) or cubic seeds could be empl...

  6. Green coconut ( Cocos nucifera Linn) shell extract mediated size controlled green synthesis of polyshaped gold nanoparticles and its application in catalysis

    Paul, Koushik; Bag, Braja Gopal; Samanta, Kousik

    2014-08-01

    The shell extract of green coconut ( Cocos nucifera Linn) has been utilized for the synthesis of gold nanoparticles at room temperature under very mild condition without any extra stabilizing or capping agents. The size of the synthesized gold nanoparticles could be controlled by varying the concentration of the shell extract. The stabilized gold nanoparticles were analyzed by surface plasmon resonance spectroscopy, HRTEM, Energy dispersive X-ray spectroscopy and X-ray diffraction studies. The catalytic activity of the freshly synthesized gold nanoparticles was studied for the sodium borohydride reduction of 4-nitrophenol and the kinetics of the reduction reaction were studied spectrophotometrically.

  7. Minimal ancilla mediated quantum computation

    Proctor, Timothy J.; Kendon, Viv

    2014-01-01

    Schemes of universal quantum computation in which the interactions between the computational elements, in a computational register, are mediated by some ancillary system are of interest due to their relevance to the physical implementation of a quantum computer. Furthermore, reducing the level of control required over both the ancillary and register systems has the potential to simplify any experimental implementation. In this paper we consider how to minimise the control needed to implement universal quantum computation in an ancilla-mediated fashion. Considering computational schemes which require no measurements and hence evolve by unitary dynamics for the global system, we show that when employing an ancilla qubit there are certain fixed-time ancilla-register interactions which, along with ancilla initialisation in the computational basis, are universal for quantum computation with no additional control of either the ancilla or the register. We develop two distinct models based on locally inequivalent interactions and we then discuss the relationship between these unitary models and the measurement-based ancilla-mediated models known as ancilla-driven quantum computation. (orig.)

  8. Multi-layered control of Galectin-8 mediated autophagy during adenovirus cell entry through a conserved PPxY motif in the viral capsid.

    Charlotte Montespan

    2017-02-01

    Full Text Available Cells employ active measures to restrict infection by pathogens, even prior to responses from the innate and humoral immune defenses. In this context selective autophagy is activated upon pathogen induced membrane rupture to sequester and deliver membrane fragments and their pathogen contents for lysosomal degradation. Adenoviruses, which breach the endosome upon entry, escape this fate by penetrating into the cytosol prior to autophagosome sequestration of the ruptured endosome. We show that virus induced membrane damage is recognized through Galectin-8 and sequesters the autophagy receptors NDP52 and p62. We further show that a conserved PPxY motif in the viral membrane lytic protein VI is critical for efficient viral evasion of autophagic sequestration after endosomal lysis. Comparing the wildtype with a PPxY-mutant virus we show that depletion of Galectin-8 or suppression of autophagy in ATG5-/- MEFs rescues infectivity of the PPxY-mutant virus while depletion of the autophagy receptors NDP52, p62 has only minor effects. Furthermore we show that wildtype viruses exploit the autophagic machinery for efficient nuclear genome delivery and control autophagosome formation via the cellular ubiquitin ligase Nedd4.2 resulting in reduced antigenic presentation. Our data thus demonstrate that a short PPxY-peptide motif in the adenoviral capsid permits multi-layered viral control of autophagic processes during entry.

  9. Ultraviolet-Mediated Activation of Photo toxins from Peganum Harmala L. Seedlings to Control both Human-and Phyto-Pathogenic Microorganisms and Tumor Cells

    Kord, M.; Khafagi, I.; Dewedar, A.

    2003-01-01

    The medicinal plant Peganum harmala L. (zygophyllaceae) contains a number of Beta-carboline alkaloids, which are photosensitizers to bacteria, yeasts and eukaryotic cells in the presence of sunlight and artificial sources of long-wave UV radiation (365 nm). Ultraviolet irradiation of ten-day old aseptically germinated Peganum harmala inoculated on bacterial and yeast bioassay plates elicits strong phototoxic antimicrobials. Callus as well as crude methanol extracts of in vitro cultures were also investigated for the accumulation of photosensitizers. High performance liquid chromatographic analyses of irradiated and control tissues followed by fluorescent detection at 302 nm revealed the formation of serotonin (5-hydroxytryptamine) in irradiated tissues only. Eluted compounds detected at 330 nm revealed more than ten-fold accumulation of harmine, isoharmine and harmol in irradiated tissues. Moreover, several simple beta-carboline alkaloids were produced through irradiation with UV such as harmalanine and harmalacidine. UV-induced phototoxicity was proven against phyto pathogenic bacteria and human-pathogenic bacteria and yeasts. Photo-induced cytotoxicity was observed from two different toxicity bioassays, which are Artemia saline and potato discs tumor assay. The selective UV-dependent biological activities may imply a pharmacological potential of Peganum harmala in the control of infectious diseases and tumor tissues

  10. Age-related changes in overcoming proactive interference in associative memory: The role of PFC-mediated executive control processes at retrieval.

    Dulas, Michael R; Duarte, Audrey

    2016-05-15

    Behavioral evidence has shown age-related impairments in overcoming proactive interference in memory, but it is unclear what underlies this deficit. Imaging studies in the young suggest overcoming interference may require several executive control processes supported by the ventrolateral prefrontal cortex (VLPFC) and dorsolateral PFC (DLPFC). The present functional magnetic resonance imaging (fMRI) study investigated whether age-related changes in dissociable executive control processes underlie deficits in overcoming proactive interference in associative memory during retrieval. Participants were tasked with remembering which associate (face or scene) objects were paired with most recently during study, under conditions of high or low proactive interference. Behavioral results demonstrated that, as interference increased, memory performance decreased similarly across groups, with slight associative memory deficits in older adults. Imaging results demonstrated that, across groups, left mid-VLPFC showed increasing activity with increasing interference, though activity did not distinguish correct from incorrect associative memory responses, suggesting this region may not directly serve in successful resolution of proactive interference, per se. Under conditions of high interference, older adults showed reduced associative memory accuracy effects in the DLPFC and anterior PFC. These results suggest that age-related PFC dysfunction may not be ubiquitous. Executive processes supported by ventral regions that detect mnemonic interference may be less affected than processes supported by dorsal and anterior regions that directly resolve interference. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Time-varying auditory gain control in response to double-pulse stimuli in harbour porpoises is not mediated by a stapedial reflex

    Asger Emil Munch Schrøder

    2017-04-01

    Full Text Available Echolocating animals reduce their output level and hearing sensitivity with decreasing echo delays, presumably to stabilize the perceived echo intensity during target approaches. In bats, this variation in hearing sensitivity is formed by a call-induced stapedial reflex that tapers off over time after the call. Here, we test the hypothesis that a similar mechanism exists in toothed whales by subjecting a trained harbour porpoise to a series of double sound pulses varying in delay and frequency, while measuring the magnitudes of the evoked auditory brainstem responses (ABRs. We find that the recovery of the ABR to the second pulse is frequency dependent, and that a stapedial reflex therefore cannot account for the reduced hearing sensitivity at short pulse delays. We propose that toothed whale auditory time-varying gain control during echolocation is not enabled by the middle ear as in bats, but rather by frequency-dependent mechanisms such as forward masking and perhaps higher-order control of efferent feedback to the outer hair cells.

  12. Causal mediation analysis with multiple mediators.

    Daniel, R M; De Stavola, B L; Cousens, S N; Vansteelandt, S

    2015-03-01

    In diverse fields of empirical research-including many in the biological sciences-attempts are made to decompose the effect of an exposure on an outcome into its effects via a number of different pathways. For example, we may wish to separate the effect of heavy alcohol consumption on systolic blood pressure (SBP) into effects via body mass index (BMI), via gamma-glutamyl transpeptidase (GGT), and via other pathways. Much progress has been made, mainly due to contributions from the field of causal inference, in understanding the precise nature of statistical estimands that capture such intuitive effects, the assumptions under which they can be identified, and statistical methods for doing so. These contributions have focused almost entirely on settings with a single mediator, or a set of mediators considered en bloc; in many applications, however, researchers attempt a much more ambitious decomposition into numerous path-specific effects through many mediators. In this article, we give counterfactual definitions of such path-specific estimands in settings with multiple mediators, when earlier mediators may affect later ones, showing that there are many ways in which decomposition can be done. We discuss the strong assumptions under which the effects are identified, suggesting a sensitivity analysis approach when a particular subset of the assumptions cannot be justified. These ideas are illustrated using data on alcohol consumption, SBP, BMI, and GGT from the Izhevsk Family Study. We aim to bridge the gap from "single mediator theory" to "multiple mediator practice," highlighting the ambitious nature of this endeavor and giving practical suggestions on how to proceed. © 2014 The Authors Biometrics published by Wiley Periodicals, Inc. on behalf of International Biometric Society.

  13. A short review of radiation-induced raft-mediated graft copolymerization: A powerful combination for modifying the surface properties of polymers in a controlled manner

    Barsbay, Murat; Güven, Olgun

    2009-12-01

    Surface grafting of polymeric materials is attracting increasing attention as it enables the preparation of new materials from known and commercially available polymers having desirable bulk properties such as thermal stability, elasticity, permeability, etc., in conjunction with advantageous newly tailored surface properties such as biocompatibility, biomimicry, adhesion, etc. Ionizing radiation, particularly γ radiation is one of the most powerful tools for preparing graft copolymers as it generates radicals on most substrates. With the advent of living free-radical polymerization techniques, application of γ radiation has been extended to a new era of grafting; grafting in a controlled manner to achieve surfaces with tailored and well-defined properties. This report presents the current use of γ radiation in living free-radical polymerization and highlights the use of both techniques together as a combination to present an advance in the ability to prepare surfaces with desired, tunable and well-defined properties.

  14. A short review of radiation-induced raft-mediated graft copolymerization: A powerful combination for modifying the surface properties of polymers in a controlled manner

    Barsbay, Murat; Gueven, Olgun

    2009-01-01

    Surface grafting of polymeric materials is attracting increasing attention as it enables the preparation of new materials from known and commercially available polymers having desirable bulk properties such as thermal stability, elasticity, permeability, etc., in conjunction with advantageous newly tailored surface properties such as biocompatibility, biomimicry, adhesion, etc. Ionizing radiation, particularly γ radiation is one of the most powerful tools for preparing graft copolymers as it generates radicals on most substrates. With the advent of living free-radical polymerization techniques, application of γ radiation has been extended to a new era of grafting; grafting in a controlled manner to achieve surfaces with tailored and well-defined properties. This report presents the current use of γ radiation in living free-radical polymerization and highlights the use of both techniques together as a combination to present an advance in the ability to prepare surfaces with desired, tunable and well-defined properties.

  15. A short review of radiation-induced raft-mediated graft copolymerization: A powerful combination for modifying the surface properties of polymers in a controlled manner

    Barsbay, Murat [Department of Chemistry, Hacettepe University, 06800 Beytepe, Ankara (Turkey)], E-mail: mbarsbay@hacettepe.edu.tr; Gueven, Olgun [Department of Chemistry, Hacettepe University, 06800 Beytepe, Ankara (Turkey)], E-mail: guven@hacettepe.edu.tr

    2009-12-15

    Surface grafting of polymeric materials is attracting increasing attention as it enables the preparation of new materials from known and commercially available polymers having desirable bulk properties such as thermal stability, elasticity, permeability, etc., in conjunction with advantageous newly tailored surface properties such as biocompatibility, biomimicry, adhesion, etc. Ionizing radiation, particularly {gamma} radiation is one of the most powerful tools for preparing graft copolymers as it generates radicals on most substrates. With the advent of living free-radical polymerization techniques, application of {gamma} radiation has been extended to a new era of grafting; grafting in a controlled manner to achieve surfaces with tailored and well-defined properties. This report presents the current use of {gamma} radiation in living free-radical polymerization and highlights the use of both techniques together as a combination to present an advance in the ability to prepare surfaces with desired, tunable and well-defined properties.

  16. Precise single-qubit control of the reflection phase of a photon mediated by a strongly-coupled ancilla–cavity system

    Motzoi, F.; Mølmer, K.

    2018-05-01

    We propose to use the interaction between a single qubit atom and a surrounding ensemble of three level atoms to control the phase of light reflected by an optical cavity. Our scheme employs an ensemble dark resonance that is perturbed by the qubit atom to yield a single-atom single photon gate. We show here that off-resonant excitation towards Rydberg states with strong dipolar interactions offers experimentally-viable regimes of operations with low errors (in the 10‑3 range) as required for fault-tolerant optical-photon, gate-based quantum computation. We also propose and analyze an implementation within microwave circuit-QED, where a strongly-coupled ancilla superconducting qubit can be used in the place of the atomic ensemble to provide high-fidelity coupling to microwave photons.

  17. In vivo electroporation enhances vaccine-mediated therapeutic control of human papilloma virus-associated tumors by the activation of multifunctional and effector memory CD8+ T cells.

    Sales, Natiely S; Silva, Jamile R; Aps, Luana R M M; Silva, Mariângela O; Porchia, Bruna F M M; Ferreira, Luís Carlos S; Diniz, Mariana O

    2017-12-19

    In vivo electroporation (EP) has reignited the clinical interest on DNA vaccines as immunotherapeutic approaches to control different types of cancer. EP has been associated with increased immune response potency, but its capacity in influencing immunomodulation remains unclear. Here we evaluated the impact of in vivo EP on the induction of cellular immune responses and therapeutic effects of a DNA vaccine targeting human papillomavirus-induced tumors. Our results demonstrate that association of EP with the conventional intramuscular administration route promoted a more efficient activation of multifunctional and effector memory CD8 + T cells with enhanced cytotoxic activity. Furthermore, EP increased tumor infiltration of CD8 + T cells and avoided tumor recurrences. Finally, our results demonstrated that EP promotes local migration of antigen presenting cells that enhances with vaccine co-delivery. Altogether the present evidences shed further light on the in vivo electroporation action and its impact on the immunogenicity of DNA vaccines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. GABAA Receptor-Mediated Bidirectional Control of Synaptic Activity, Intracellular Ca2+, Cerebral Blood Flow, and Oxygen Consumption in Mouse Somatosensory Cortex In Vivo

    Jessen, Sanne Barsballe; Brazhe, Alexey; Lind, Barbara Lykke

    2015-01-01

    Neural activity regulates local increases in cerebral blood flow (ΔCBF) and the cortical metabolic rate of oxygen (ΔCMRO2) that constitutes the basis of BOLD functional neuroimaging signals. Glutamate signaling plays a key role in brain vascular and metabolic control; however, the modulatory effect...... of GABA is incompletely understood. Here we performed in vivo studies in mice to investigate how THIP (which tonically activates extrasynaptic GABAARs) and Zolpidem (a positive allosteric modulator of synaptic GABAARs) impact stimulation-induced ΔCBF, ΔCMRO2, local field potentials (LFPs), and fluorescent...... cytosolic Ca2+ transients in neurons and astrocytes. Low concentrations of THIP increased ΔCBF and ΔCMRO2 at low stimulation frequencies. These responses were coupled to increased synaptic activity as indicated by LFP responses, and to Ca2+ activities in neurons and astrocytes. Intermediate and high...

  19. Basal activity of voltage-gated Ca(2+) channels controls the IP3-mediated contraction by α(1)-adrenoceptor stimulation of mouse aorta segments.

    Leloup, Arthur J; Van Hove, Cor E; De Meyer, Guido R Y; Schrijvers, Dorien M; Fransen, Paul

    2015-08-05

    α1-Adrenoceptor stimulation of mouse aorta causes intracellular Ca(2+) release from sarcoplasmic reticulum Ca(2+) stores via stimulation of inositoltriphosphate (IP3) receptors. It is hypothesized that this Ca(2+) release from the contractile and IP3-sensitive Ca(2+) store is under the continuous dynamic control of time-independent basal Ca(2+) influx via L-type voltage-gated Ca(2+) channels (LCC) residing in their window voltage range. Mouse aortic segments were α1-adrenoceptor stimulated with phenylephrine in the absence of external Ca(2+) (0Ca) to measure phasic isometric contractions. They gradually decreased with time in 0Ca, were inhibited with 2-aminoethoxydiphenyl borate, and declined with previous membrane potential hyperpolarization (levcromakalim) or with previous inhibition of LCC (diltiazem). Former basal stimulation of LCC with depolarization (15 mM K(+)) or with BAY K8644 increased the subsequent phasic contractions by phenylephrine in 0Ca. Although exogenous NO (diethylamine NONOate) reduced the phasic contractions by phenylephrine, stimulation of endothelial cells with acetylcholine in 0Ca failed to attenuate these phasic contractions. Finally, inhibition of the basal release of NO with N(Ω)-nitro-L-arginine methyl ester also attenuated the phasic contractions by phenylephrine. Results indicated that α1-adrenoceptor stimulation with phenylephrine causes phasic contractions, which are controlled by basal LCC and endothelial NO synthase activity. Endothelial NO release by acetylcholine was absent in 0Ca. Given the growing interest in the active regulation of arterial compliance, the dependence of contractile SR Ca(2+) store-refilling in basal conditions on the activity of LCC and basal eNOS may contribute to a more thorough understanding of physiological mechanisms leading to arterial stiffness. Copyright © 2015. Published by Elsevier B.V.

  20. Mediator: A key regulator of plant development.

    Buendía-Monreal, Manuel; Gillmor, C Stewart

    2016-11-01

    Mediator is a multiprotein complex that regulates transcription at the level of RNA pol II assembly, as well as through regulation of chromatin architecture, RNA processing and recruitment of epigenetic marks. Though its modular structure is conserved in eukaryotes, its subunit composition has diverged during evolution and varies in response to environmental and tissue-specific inputs, suggesting different functions for each subunit and/or Mediator conformation. In animals, Mediator has been implicated in the control of differentiation and morphogenesis through modulation of numerous signaling pathways. In plants, studies have revealed roles for Mediator in regulation of cell division, cell fate and organogenesis, as well as developmental timing and hormone responses. We begin this review with an overview of biochemical mechanisms of yeast and animal Mediator that are likely to be conserved in all eukaryotes, as well as a brief discussion of the role of Mediator in animal development. We then present a comprehensive review of studies of the role of Mediator in plant development. Finally, we point to important questions for future research on the role of Mediator as a master coordinator of development. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Flexible Mediation Analysis With Multiple Mediators.

    Steen, Johan; Loeys, Tom; Moerkerke, Beatrijs; Vansteelandt, Stijn

    2017-07-15

    The advent of counterfactual-based mediation analysis has triggered enormous progress on how, and under what assumptions, one may disentangle path-specific effects upon combining arbitrary (possibly nonlinear) models for mediator and outcome. However, current developments have largely focused on single mediators because required identification assumptions prohibit simple extensions to settings with multiple mediators that may depend on one another. In this article, we propose a procedure for obtaining fine-grained decompositions that may still be recovered from observed data in such complex settings. We first show that existing analytical approaches target specific instances of a more general set of decompositions and may therefore fail to provide a comprehensive assessment of the processes that underpin cause-effect relationships between exposure and outcome. We then outline conditions for obtaining the remaining set of decompositions. Because the number of targeted decompositions increases rapidly with the number of mediators, we introduce natural effects models along with estimation methods that allow for flexible and parsimonious modeling. Our procedure can easily be implemented using off-the-shelf software and is illustrated using a reanalysis of the World Health Organization's Large Analysis and Review of European Housing and Health Status (WHO-LARES) study on the effect of mold exposure on mental health (2002-2003). © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Technology-Use Mediation

    Bansler, Jørgen P.; Havn, Erling C.

    2003-01-01

    This study analyzes how a group of ‘mediators’ in a large, multinational company adapted a computer-mediated communication technology (a ‘virtual workspace’) to the organizational context (and vice versa) by modifying features of the technology, providing ongoing support for users, and promoting...... appropriate conventions of use. Our findings corroborate earlier research on technology-use mediation, which suggests that such mediators can exert considerable influence on how a particular technology will be established and used in an organization. However, this study also indicates that the process...... of technology-use mediation is more complex and indeterminate than earlier literature suggests. In particular, we want to draw attention to the fact that advanced computer-mediated communication technologies are equivocal and that technology-use mediation consequently requires ongoing sensemaking (Weick 1995)....

  3. The Schizosaccharomyces pombe Mediator

    Venturi, Michela

    , Schizosaccharomyces pombe and mammalian Mediator. In our study, we have taken the S. pombe Mediator into consideration and characterized genetically and biochemically two subunits already know in S. cerevisiae, Med9 and Med11, but still not identified in the S. pombe Mediator. Genetic analysis has shown that med9......In the past several years great attention has been dedicated to the characterization of the Mediator complex in a different range of model organisms. Mediator is a conserved co-activator complex involved in transcriptional regulation and it conveys signals from regulatory transcription factors...... to the basal transcription machinery. Mediator was initially isolated from Saccharomyces cerevisiae based on its ability to render a RNA polymerase II in vitro transcription system responsive to activators. Additionally, structural studies have revealed striking structural similarities between S. cerevisiae...

  4. Applied mediation analyses

    Lange, Theis; Hansen, Kim Wadt; Sørensen, Rikke

    2017-01-01

    In recent years, mediation analysis has emerged as a powerful tool to disentangle causal pathways from an exposure/treatment to clinically relevant outcomes. Mediation analysis has been applied in scientific fields as diverse as labour market relations and randomized clinical trials of heart...... disease treatments. In parallel to these applications, the underlying mathematical theory and computer tools have been refined. This combined review and tutorial will introduce the reader to modern mediation analysis including: the mathematical framework; required assumptions; and software implementation...

  5. Immunologically mediated oral diseases

    Jimson, Sudha; Balachader, N.; Anita, N.; Babu, R.

    2015-01-01

    Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect imm...

  6. Translational Control of the SigR-Directed Oxidative Stress Response in Streptomyces via IF3-Mediated Repression of a Noncanonical GTC Start Codon.

    Feeney, Morgan A; Chandra, Govind; Findlay, Kim C; Paget, Mark S B; Buttner, Mark J

    2017-06-13

    The major oxidative stress response in Streptomyces is controlled by the sigma factor SigR and its cognate antisigma factor RsrA, and SigR activity is tightly controlled through multiple mechanisms at both the transcriptional and posttranslational levels. Here we show that sigR has a highly unusual GTC start codon and that this leads to another level of SigR regulation, in which SigR translation is repressed by translation initiation factor 3 (IF3). Changing the GTC to a canonical start codon causes SigR to be overproduced relative to RsrA, resulting in unregulated and constitutive expression of the SigR regulon. Similarly, introducing IF3* mutations that impair its ability to repress SigR translation has the same effect. Thus, the noncanonical GTC sigR start codon and its repression by IF3 are critical for the correct and proper functioning of the oxidative stress regulatory system. sigR and rsrA are cotranscribed and translationally coupled, and it had therefore been assumed that SigR and RsrA are produced in stoichiometric amounts. Here we show that RsrA can be transcribed and translated independently of SigR, present evidence that RsrA is normally produced in excess of SigR, and describe the factors that determine SigR-RsrA stoichiometry. IMPORTANCE In all sigma factor-antisigma factor regulatory switches, the relative abundance of the two proteins is critical to the proper functioning of the system. Many sigma-antisigma operons are cotranscribed and translationally coupled, leading to a generic assumption that the sigma and antisigma factors are produced in a fixed 1:1 ratio. In the case of sigR - rsrA , we show instead that the antisigma factor is produced in excess over the sigma factor, providing a buffer to prevent spurious release of sigma activity. This excess arises in part because sigR has an extremely rare noncanonical GTC start codon, and as a result, SigR translation initiation is repressed by IF3. This finding highlights the potential significance

  7. Implementing general gauge mediation

    Carpenter, Linda M.; Dine, Michael; Festuccia, Guido; Mason, John D.

    2009-01-01

    Recently there has been much progress in building models of gauge mediation, often with predictions different than those of minimal gauge mediation. Meade, Seiberg, and Shih have characterized the most general spectrum which can arise in gauge-mediated models. We discuss some of the challenges of building models of general gauge mediation, especially the problem of messenger parity and issues connected with R symmetry breaking and CP violation. We build a variety of viable, weakly coupled models which exhibit some or all of the possible low energy parameters.

  8. Nanoparticle mediated micromotor motion

    Liu, Mei; Liu, Limei; Gao, Wenlong; Su, Miaoda; Ge, Ya; Shi, Lili; Zhang, Hui; Dong, Bin; Li, Christopher Y.

    2015-03-01

    In this paper, we report the utilization of nanoparticles to mediate the motion of a polymer single crystal catalytic micromotor. Micromotors have been fabricated by directly self-assembling functional nanoparticles (platinum and iron oxide nanoparticles) onto one or both sides of two-dimensional polymer single crystals. We show that the moving velocity of these micromotors in fluids can be readily tuned by controlling the nanoparticles' surface wettability and catalytic activity. A 3 times velocity increase has been achieved for a hydrophobic micromotor as opposed to the hydrophilic ones. Furthermore, we demonstrate that the catalytic activity of platinum nanoparticles inside the micromotor can be enhanced by their synergetic interactions with iron oxide nanoparticles and an electric field. Both strategies lead to dramatically increased moving velocities, with the highest value reaching ~200 μm s-1. By decreasing the nanoparticles' surface wettability and increasing their catalytic activity, a maximum of a ~10-fold increase in the moving speed of the nanoparticle based micromotor can be achieved. Our results demonstrate the advantages of using nanoparticles in micromotor systems.In this paper, we report the utilization of nanoparticles to mediate the motion of a polymer single crystal catalytic micromotor. Micromotors have been fabricated by directly self-assembling functional nanoparticles (platinum and iron oxide nanoparticles) onto one or both sides of two-dimensional polymer single crystals. We show that the moving velocity of these micromotors in fluids can be readily tuned by controlling the nanoparticles' surface wettability and catalytic activity. A 3 times velocity increase has been achieved for a hydrophobic micromotor as opposed to the hydrophilic ones. Furthermore, we demonstrate that the catalytic activity of platinum nanoparticles inside the micromotor can be enhanced by their synergetic interactions with iron oxide nanoparticles and an electric