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Sample records for cognitive reactivity mediates

  1. Processes of change in a school-based mindfulness programme: cognitive reactivity and self-coldness as mediators.

    Science.gov (United States)

    Van der Gucht, Katleen; Takano, Keisuke; Raes, Filip; Kuppens, Peter

    2018-05-01

    The underlying mechanisms of the effectiveness of mindfulness-based interventions for emotional well-being remain poorly understood. Here, we examined the potential mediating effects of cognitive reactivity and self-compassion on symptoms of depression, anxiety and stress using data from an earlier randomised controlled school trial. A moderated time-lagged mediation model based on multilevel modelling was used to analyse the data. The findings showed that post-treatment changes in cognitive reactivity and self-coldness, an aspect of self-compassion, mediated subsequent changes in symptoms of depression, anxiety and stress. These results suggest that cognitive reactivity and self-coldness may be considered as transdiagnostic mechanisms of change of a mindfulness-based intervention programme for youth.

  2. The mediating effect of mindful non-reactivity in exposure-based cognitive behavior therapy for severe health anxiety.

    Science.gov (United States)

    Hedman, Erik; Hesser, Hugo; Andersson, Erik; Axelsson, Erland; Ljótsson, Brjánn

    2017-08-01

    Exposure-based cognitive behavior therapy (CBT) has been shown to be effective in the treatment of severe health anxiety, but little is known about mediators of treatment effect. The aim of the present study was to investigate mindful non-reactivity as a putative mediator of health anxiety outcome using data from a large scale randomized controlled trial. We assessed mindful non-reactivity using the Five Facets Mindfulness Questionnaire-Non-Reactivity scale (FFMQ-NR) and health anxiety with the Short Health Anxiety Inventory (SHAI). Participants with severe health anxiety (N=158) were randomized to internet-delivered exposure-based CBT or behavioral stress management (BSM) and throughout the treatment, both the mediator and outcome were measured weekly. As previously reported, exposure-based CBT was more effective than BSM in reducing health anxiety. In the present study, latent process growth modeling showed that treatment condition had a significant effect on the FFMQ-NR growth trajectory (α-path), estimate=0.18, 95% CI [0.04, 0.32], p=.015, indicating a larger increase in mindful non-reactivity among participants receiving exposure-based CBT compared to the BSM group. The FFMQ-NR growth trajectory was significantly correlated with the SHAI trajectory (β-path estimate=-1.82, 95% CI [-2.15, -1.48], panxiety. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. AAV-mediated overexpression of the CB1 receptor in the mPFC of adult rats alters cognitive flexibility, social behavior and emotional reactivity

    Directory of Open Access Journals (Sweden)

    Matthias eKlugmann

    2011-07-01

    Full Text Available The endocannabinoid (ECB system is strongly involved in the regulation of cognitive processing and emotional behavior and evidence indicates that ECB signaling might affect these behavioral abilities by modulations of prefrontal cortical functions. The aim of the present study was to examine the role of the CB1 receptor in the medial prefrontal cortex (mPFC on cognitive flexibility and emotional behavior. Therefore, the CB1 receptor was overexpressed by adeno-associated virus (AAV vector-mediated gene transfer specifically in the mPFC of adult Wistar rats. Animals were then tested in different anxiety-related paradigms for emotional reactivity (e.g. elevated plus maze (EPM, light/dark emergence test (EMT, social interaction and the attentional set shift task (ASST - an adaptation of the human Wisconsin card sorting test - for cognitive abilities and behavioral flexibility. A subtle increase in exploratory behavior was found in CB1 receptor overexpressing animals (CB1-R compared to empty vector injected controls (Empty in the EMT and EPM, although general locomotor activity did not differ between the groups. During social interaction testing, social contact behavior towards the unknown conspecific was found to be decreased, whereas social withdrawal was increased in CB1-R animals and they showed an inadequate increase in exploratory behavior compared to control animals. In the ASST, impaired reversal learning abilities were detected in CB1-R animals compared to controls, indicating reduced behavioral flexibility. In conclusion, upregulation of the CB1 receptor specifically in the rat mPFC induces alterations in emotional reactivity, leads to inadequate social behavior and impairs cognitive flexibility. These findings might be relevant for neuropsychiatric disorders, since higher cortical CB1 receptor expression levels as well as similar behavioral impairments as observed in the present study have been described in schizophrenic patients.

  4. A Hybrid Cognitive-Reactive Multi-Agent Controller

    National Research Council Canada - National Science Library

    Bugajska, Magdalena D; Schultz, Alan C; Trafton, J. G; Taylor, Matthew; Mintz, Farilee E

    2002-01-01

    ...). In this system, the learning algorithm handles reactive aspects of the task and provides an adaptation mechanism, while the cognitive model handles cognitive aspects of the task and ensures the realism of the behavior...

  5. Affective and cognitive reactivity to mood induction in chronic depression.

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    Guhn, Anne; Sterzer, Philipp; Haack, Friderike H; Köhler, Stephan

    2018-03-15

    Chronic depression (CD) is strongly associated with childhood maltreatment, which has been proposed to lead to inefficient coping styles that are characterized by abnormal affective responsiveness and dysfunctional cognitive attitudes. However, while this notion forms an important basis for psychotherapeutic strategies in the treatment of CD, there is still little direct empirical evidence for a role of altered affective and cognitive reactivity in CD. The present study therefore experimentally investigated affective and cognitive reactivity to two forms of negative mood induction in CD patients versus a healthy control sample (HC). For the general mood induction procedure, a combination of sad pictures and sad music was used, while for individualized mood induction, negative mood was induced by individualized scripts with autobiographical content. Both experiments included n = 15 CD patients versus n = 15 HC, respectively. Interactions between affective or cognitive reactivity and group were analyzed by repeated measurements ANOVAs. General mood induction neither revealed affective nor cognitive reactivity in the patient group while the control group reported the expected decrease of positive affect [interaction (IA) affective reactivity x group: p = .011, cognitive reactivity x group: n.s.]. In contrast, individualized mood induction specifically increased affective reactivity (IA: p = .037) as well as the amount of dysfunctional cognitions in patients versus controls (IA: p = .014). The experiments were not balanced in a crossover design, causal conclusions are thus limited. Additionally, the differences to non-chronic forms of depression are still outstanding. The results suggest that in patients with CD, specific emotional activation through autobiographical memories is a key factor in dysfunctional coping styles. Psychotherapeutic interventions aimed at modifying affective and cognitive reactivity are thus of high relevance in the treatment of CD. Copyright

  6. COMMUNITY VIOLENCE AND REACTIVE AND PROACTIVE AGGRESSION: THE MEDIATING ROLE OF COGNITIVE AND EMOTIONAL VARIABLES/ VIOLENCIA COMUNITARIA Y AGRESIÓN REACTIVA Y PROACTIVA: EL PAPEL MEDIACIONAL DE LAS VARIABLES COGNITIVAS Y EMOCIONALES/ VIOLÊNCIA COMUNITÁRIA E AGRESSÃO REATIVA E PROATIVA: O PAPEL MEDIACIONAL DAS VARIÁVEIS COGNITIVAS E EMOCIONAIS

    Directory of Open Access Journals (Sweden)

    Claudia Rincón

    2012-12-01

    Full Text Available Children exposed to higher levels of violence tend to be more aggressive. Specific mechanisms explaining this relationship are still being uncovered. This study sought to identify the relationship between exposure to community violence and reactive and proactive aggression, as well as cognitive and emotional variables mediating this relationship. Participants were 1,235 students (from fifth to ninth grade from localities of Bogotá, Colombia, with varying levels of community violence. Analyses of self-reported measures confirmed significant associations between exposure to community violence and both reactive and proactive aggression. Normative beliefs supporting aggression, hostile attribution of intent, positive expectations for aggression, and lack of guilt after aggression, partially mediated these relationships, suggesting strategies for prevention.

  7. Cognitive Mentorship: Mediating Protege Performance

    Science.gov (United States)

    2013-03-01

    and a child or adolescent, which is important for personal, emotional , cognitive, and psychological growth (Rhodes, 2002). Academic mentoring...Using mentoring and storytelling to transfer knowledge in the workplace. Journal of management information systems, 18(1), 95-114. Uecker, M. E...Air Force Base, OH. Wyatt, J. C. (2001). Management of explicit and tacit knowledge. JRSM, 94(1), 6-9. Zey, M. G. (1984). The mentor connection

  8. Identifying cognitive predictors of reactive and proactive aggression

    NARCIS (Netherlands)

    Brugman, S.; Lobbestael, J.; Arntz, A.R.; Cima, M.; Schumann, T.; Dambacher, F.

    2015-01-01

    The aim of this study was to identify implicit cognitive predictors of aggressive behavior. Specifically, the predictive value of an attentional bias for aggressive stimuli and automatic association of the self and aggression was examined for reactive and proactive aggressive behavior in a

  9. Peer victimization (and harsh parenting) as developmental correlates of cognitive reactivity, a diathesis for depression.

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    Cole, David A; Martin, Nina C; Sterba, Sonya K; Sinclair-McBride, Keneisha; Roeder, Kathryn M; Zelkowitz, Rachel; Bilsky, Sarah A

    2014-05-01

    Prior research has shown cognitive reactivity to be a diathesis for depression. Seeking evidence for the developmental origins of such diatheses, the current study examined peer victimization and harsh parenting as developmental correlates of cognitive reactivity in 571 children and adolescents (ages 8-13 years). Four major findings emerged. First, a new method for assessing cognitive reactivity in children and adolescents showed significant reliability and demonstrated construct validity vis-à-vis its relation to depression. Second, history of more severe peer victimization was significantly related to cognitive reactivity, with verbal victimization being more strongly tied to cognitive reactivity than other subtypes of peer victimization. Third, harsh parenting was also significantly related to cognitive reactivity. Fourth, both peer victimization and harsh parenting made unique statistical contributions to cognitive reactivity, after controlling for the effects of the other. Taken together, these findings provide preliminary support for a developmental model pertaining to origins of cognitive reactivity in children and adolescents.

  10. Mood reactivity rather than cognitive reactivity is predictive of depressive relapse: a randomized study with 5.5-year follow-up

    NARCIS (Netherlands)

    van Rijsbergen, Gerard D.; Bockting, Claudi L. H.; Burger, Huibert; Spinhoven, Philip; Koeter, Maarten W. J.; Ruhé, Henricus G.; Hollon, Steven D.; Schene, Aart H.

    2013-01-01

    The current study examined whether cognitive reactivity, cognitive extremity reactivity, and mood reactivity following mood provocation predicted relapse in depression over 5.5 years. Additionally, this study was the 1st to examine whether changes in cognitive reactivity and mood reactivity

  11. Mechanisms and neuronal networks involved in reactive and proactive cognitive control of interference in working memory.

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    Irlbacher, Kerstin; Kraft, Antje; Kehrer, Stefanie; Brandt, Stephan A

    2014-10-01

    Cognitive control can be reactive or proactive in nature. Reactive control mechanisms, which support the resolution of interference, start after its onset. Conversely, proactive control involves the anticipation and prevention of interference prior to its occurrence. The interrelation of both types of cognitive control is currently under debate: Are they mediated by different neuronal networks? Or are there neuronal structures that have the potential to act in a proactive as well as in a reactive manner? This review illustrates the way in which integrating knowledge gathered from behavioral studies, functional imaging, and human electroencephalography proves useful in answering these questions. We focus on studies that investigate interference resolution at the level of working memory representations. In summary, different mechanisms are instrumental in supporting reactive and proactive control. Distinct neuronal networks are involved, though some brain regions, especially pre-SMA, possess functions that are relevant to both control modes. Therefore, activation of these brain areas could be observed in reactive, as well as proactive control, but at different times during information processing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Neural Reactivity to Emotional Faces Mediates the Relationship Between Childhood Empathy and Adolescent Prosocial Behavior

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    Flournoy, John C.; Pfeifer, Jennifer H.; Moore, William E.; Tackman, Allison; Masten, Carrie L.; Mazziotta, John C.; Iacoboni, Marco; Dapretto, Mirella

    2017-01-01

    Reactivity to others' emotions can result in empathic concern (EC), an important motivator of prosocial behavior, but can also result in personal distress (PD), which may hinder prosocial behavior. Examining neural substrates of emotional reactivity may elucidate how EC and PD differentially influence prosocial behavior. Participants (N=57) provided measures of EC, PD, prosocial behavior, and neural responses to emotional expressions at age 10 and 13. Initial EC predicted subsequent prosocial behavior. Initial EC and PD predicted subsequent reactivity to emotions in the inferior frontal gyrus (IFG) and inferior parietal lobule, respectively. Activity in the IFG, a region linked to mirror neuron processes, as well as cognitive control and language, mediated the relation between initial EC and subsequent prosocial behavior. PMID:28262939

  13. Mood reactivity rather than cognitive reactivity is predictive of depressive relapse : a randomized study with 5.5-year follow-up

    NARCIS (Netherlands)

    van Rijsbergen, Gerard D; Bockting, Claudi L H; Burger, Huibert; Spinhoven, Philip; Koeter, Maarten W J; Ruhe, Eric; Hollon, Steven D; Schene, Aart H

    OBJECTIVE: The current study examined whether cognitive reactivity, cognitive extremity reactivity, and mood reactivity following mood provocation predicted relapse in depression over 5.5 years. Additionally, this study was the 1st to examine whether changes in cognitive reactivity and mood

  14. Parental Depression and Child Cognitive Vulnerability Predict Children’s Cortisol Reactivity

    Science.gov (United States)

    Hayden, Elizabeth P.; Hankin, Benjamin L.; Mackrell, Sarah V.M.; Sheikh, Haroon I.; Jordan, Patricia L.; Dozois, David J.A.; Singh, Shiva M.; Olino, Thomas M.; Badanes, Lisa S.

    2015-01-01

    Risk for depression is expressed across multiple levels of analysis. For example, parental depression and cognitive vulnerability are known markers of depression risk, but no study has examined their interactive effects on children’s cortisol reactivity, a likely mediator of early depression risk. We examined relations across these different levels of vulnerability using cross-sectional and longitudinal methods in two community samples of children. Children were assessed for cognitive vulnerability using self-reports (Study 1; n = 244) and tasks tapping memory and attentional bias (Study 2; n = 205), and their parents were assessed for depression history using structured clinical interviews. In both samples, children participated in standardized stress tasks and cortisol reactivity was assessed. Cross-sectionally and longitudinally, parental depression history and child cognitive vulnerability interacted to predict children’s cortisol reactivity; specifically, associations between parent depression and elevated child cortisol activity were found when children also showed elevated depressotypic attributions, as well as attentional and memory biases. Findings indicate that models of children’s emerging depression risk may benefit from the examination of the interactive effects of multiple sources of vulnerability across levels of analysis. PMID:25422972

  15. Cognitive and Affective Empathy as Predictors of Proactive and Reactive Aggression

    Science.gov (United States)

    Gordon, Gina M.

    2013-01-01

    This study examined cognitive and affective empathy as predictors of proactive and reactive aggression. This study also explored whether levels of cognitive and affective empathy differed among children who use proactive and reactive aggression. Cognitive and affective empathy were measured by the Basic Empathy Scale (Jolliffe & Farrington,…

  16. Late-Onset Cognitive Impairments after Early-Life Stress Are Shaped by Inherited Differences in Stress Reactivity

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    McIlwrick, Silja; Pohl, Tobias; Chen, Alon; Touma, Chadi

    2017-01-01

    Early-life stress (ELS) has been associated with lasting cognitive impairments and with an increased risk for affective disorders. A dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis, the body’s main stress response system, is critically involved in mediating these long-term consequences of adverse early-life experience. It remains unclear to what extent an inherited predisposition for HPA axis sensitivity or resilience influences the relationship between ELS and cognitive impairments, and which neuroendocrine and molecular mechanisms may be involved. To investigate this, we exposed animals of the stress reactivity mouse model, consisting of three independent lines selectively bred for high (HR), intermediate (IR), or low (LR) HPA axis reactivity to a stressor, to ELS and assessed their cognitive performance, neuroendocrine function and hippocampal gene expression in early and in late adulthood. Our results show that HR animals that were exposed to ELS exhibited an HPA axis hyper-reactivity in early and late adulthood, associated with cognitive impairments in hippocampus-dependent tasks, as well as molecular changes in transcript levels involved in the regulation of HPA axis activity (Crh) and in neurotrophic action (Bdnf). In contrast, LR animals showed intact cognitive function across adulthood, with no change in stress reactivity. Intriguingly, LR animals that were exposed to ELS even showed significant signs of enhanced cognitive performance in late adulthood, which may be related to late-onset changes observed in the expression of Crh and Crhr1 in the dorsal hippocampus of these animals. Collectively, our findings demonstrate that the lasting consequences of ELS at the level of cognition differ as a function of inherited predispositions and suggest that an innate tendency for low stress reactivity may be protective against late-onset cognitive impairments after ELS. PMID:28261058

  17. Does white matter structure or hippocampal volume mediate associations between cortisol and cognitive ageing?

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    Cox, Simon R.; MacPherson, Sarah E.; Ferguson, Karen J.; Royle, Natalie A.; Maniega, Susana Muñoz; Hernández, Maria del C. Valdés; Bastin, Mark E.; MacLullich, Alasdair M.J.; Wardlaw, Joanna M.; Deary, Ian J.

    2015-01-01

    Elevated glucocorticoid (GC) levels putatively damage specific brain regions, which in turn may accelerate cognitive ageing. However, many studies are cross-sectional or have relatively short follow-up periods, making it difficult to relate GCs directly to changes in cognitive ability with increasing age. Moreover, studies combining endocrine, MRI and cognitive variables are scarce, measurement methods vary considerably, and formal tests of the underlying causal hypothesis (cortisol → brain → cognition) are absent. In this study, 90 men, aged 73 years, provided measures of fluid intelligence, processing speed and memory, diurnal and reactive salivary cortisol and two measures of white matter (WM) structure (WM hyperintensity volume from structural MRI and mean diffusivity averaged across 12 major tracts from diffusion tensor MRI), hippocampal volume, and also cognitive ability at age 11. We tested whether negative relationships between cognitive ageing differences (over more than 60 years) and salivary cortisol were significantly mediated by WM and hippocampal volume. Significant associations between reactive cortisol at 73 and cognitive ageing differences between 11 and 73 (r = −.28 to −.36, p cognition associations (cognitive ageing differences from childhood to the early 70s, partly via brain WM structure. PMID:26298692

  18. Daily stressors and emotional reactivity in individuals with mild cognitive impairment and cognitively healthy controls.

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    Rickenbach, Elizabeth Hahn; Condeelis, Kristen L; Haley, William E

    2015-06-01

    Daily experiences of stress are common and have been associated with worse affect among older adults. People with mild cognitive impairment (PWMCI) have measurable memory deficits in between normal cognition and dementia and have been identified as having greater psychological distress than cognitively healthy older adults (CHOAs). Little is known about whether daily stressors contribute to distress among PWMCI. We hypothesized that compared with CHOAs, PWMCI would have higher daily negative affect and lower daily positive affect, report greater numbers and severity of daily stressors, and experience greater emotional reactivity to daily stressors. Fifteen clinically diagnosed PWMCI and 25 CHOAs completed daily reports of stressors, stressor severity, and positive and negative affect over an 8-day period. PWMCI reported higher daily negative affect, lower daily positive affect, and higher numbers and greater severity of memory stressors but did not differ from CHOAs in numbers or severity of general stressors. Cognitive status was a moderator of the daily stress-affect relationship. Days with greater numbers and severity of general daily stressors were associated with higher negative affect only for PWMCI. The numbers and severity of memory stressors were not associated with negative affect. In addition, more severe general daily stressors and memory stressors were associated with lower positive affect for all participants. Results suggest that PWMCI are less resilient in the face of daily stress than are CHOAs in terms of negative affect, perhaps because of declines in reserve capacity. The study presents a promising approach to understanding stress and coping in predementia states of cognition. (c) 2015 APA, all rights reserved.

  19. Social cognitive mediators of parent-child sexual communication.

    Science.gov (United States)

    Evans, W Douglas; Blitstein, Jonathan L; Davis, Kevin C

    2011-07-01

    To test a social cognitive behavior change model and identify mediators of the effects of the Parents Speak Up National Campaign (PSUNC) on parent-child sexual communication. Investigators used 5 waves of data from an online randomized controlled trial. Latent variables were developed based on item response theory and confirmatory factor analysis. Structural equation modeling was used to test mediation. Outcome expectations mediated effects of social norms and self-efficacy on sexual communication. Other hypothesized mediators were not confirmed. Interventions to promote parent-child sexual communication should target outcome expectations. Future research should investigate parents' health information seeking.

  20. Cognitive mediators of treatment outcomes in pediatric functional abdominal pain.

    Science.gov (United States)

    Levy, Rona L; Langer, Shelby L; Romano, Joan M; Labus, Jennifer; Walker, Lynn S; Murphy, Tasha B; Tilburg, Miranda A L van; Feld, Lauren D; Christie, Dennis L; Whitehead, William E

    2014-12-01

    Cognitive-behavioral (CB) interventions improve outcomes for many pediatric health conditions, but little is known about which mechanisms mediate these outcomes. The goal of this study was to identify whether changes in targeted process variables from baseline to 1 week posttreatment mediate improvement in outcomes in a randomized controlled trial of a brief CB intervention for idiopathic childhood abdominal pain. Two hundred children with persistent functional abdominal pain and their parents were randomly assigned to 1 of 2 conditions: a 3-session social learning and CB treatment (N=100), or a 3-session educational intervention controlling for time and attention (N=100). Outcomes were assessed at 3-, 6-, and 12-month follow-ups. The intervention focused on altering parental responses to pain and on increasing adaptive cognitions and coping strategies related to pain in both parents and children. Multiple mediation analyses were applied to examine the extent to which the effects of the social learning and CB treatment condition on child gastrointestinal (GI) symptom severity and pain as reported by children and their parents were mediated by changes in targeted cognitive process variables and parents' solicitous responses to their child's pain symptoms. Reductions in parents' perceived threat regarding their child's pain mediated reductions in both parent-reported and child-reported GI symptom severity and pain. Reductions in children's catastrophic cognitions mediated reductions in child-reported GI symptom severity but no other outcomes. Reductions in parental solicitousness did not mediate outcomes. Results suggest that reductions in reports of children's pain and GI symptoms after a social learning and CB intervention were mediated at least in part by decreasing maladaptive parent and child cognitions.

  1. The role of self-serving cognitive distortions in reactive and proactive aggression.

    Science.gov (United States)

    Oostermeijer, Sanne; Smeets, Kirsten C; Jansen, Lucres M C; Jambroes, Tijs; Rommelse, Nanda N J; Scheepers, Floor E; Buitelaar, Jan K; Popma, Arne

    2017-12-01

    Aggression is often divided into reactive and proactive forms. Reactive aggression is typically thought to encompass 'blaming others' and 'assuming the worst', while proactive aggression relates to 'self-centeredness' and 'minimising/mislabelling'. Our aim was to evaluate relationships between reactive and proactive aggression and cognitive distortions and to test whether changes in these cognitions relate to changes in aggression. A total of 151 adolescents (60% boys; mean age 15.05 years, standard deviation 1.28) were enrolled in an evidence-based intervention to reduce aggression. Due to attrition and anomalous responses, the post-intervention sample involved 80 adolescents. Correlation and linear regression analyses were used to investigate the relationship between cognitive distortions and aggression. Blaming others was related to reactive aggression before the intervention, while all cognitive distortions were related to proactive aggression both pre- and post-intervention. Changes in reactive aggression were uniquely predicted by blaming others, while changes in proactive aggression were predicted by changes in cognitive distortions overall. To our knowledge, this study is the first to show a relationship between changes in cognitive distortions and changes in aggression. Treatment of reactive aggression may benefit from focusing primarily on reducing cognitive distortions involving misattribution of blame to others. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  2. Developing models of how cognitive improvements change functioning: Mediation, moderation and moderated mediation

    Science.gov (United States)

    Wykes, Til; Reeder, Clare; Huddy, Vyv; Taylor, Rumina; Wood, Helen; Ghirasim, Natalia; Kontis, Dimitrios; Landau, Sabine

    2012-01-01

    Background Cognitive remediation (CRT) affects functioning but the extent and type of cognitive improvements necessary are unknown. Aim To develop and test models of how cognitive improvement transfers to work behaviour using the data from a current service. Method Participants (N49) with a support worker and a paid or voluntary job were offered CRT in a Phase 2 single group design with three assessments: baseline, post therapy and follow-up. Working memory, cognitive flexibility, planning and work outcomes were assessed. Results Three models were tested (mediationcognitive improvements drive functioning improvement; moderation — post treatment cognitive level affects the impact of CRT on functioning; moderated mediationcognition drives functioning improvements only after a certain level is achieved). There was evidence of mediation (planning improvement associated with improved work quality). There was no evidence that cognitive flexibility (total Wisconsin Card Sorting Test errors) and working memory (Wechsler Adult Intelligence Scale III digit span) mediated work functioning despite significant effects. There was some evidence of moderated mediation for planning improvement if participants had poorer memory and/or made fewer WCST errors. The total CRT effect on work quality was d = 0.55, but the indirect (planning-mediated CRT effect) was d = 0.082 Conclusion Planning improvements led to better work quality but only accounted for a small proportion of the total effect on work outcome. Other specific and non-specific effects of CRT and the work programme are likely to account for some of the remaining effect. This is the first time complex models have been tested and future Phase 3 studies need to further test mediation and moderated mediation models. PMID:22503640

  3. Brain structure mediates the association between height and cognitive ability.

    Science.gov (United States)

    Vuoksimaa, Eero; Panizzon, Matthew S; Franz, Carol E; Fennema-Notestine, Christine; Hagler, Donald J; Lyons, Michael J; Dale, Anders M; Kremen, William S

    2018-05-11

    Height and general cognitive ability are positively associated, but the underlying mechanisms of this relationship are not well understood. Both height and general cognitive ability are positively associated with brain size. Still, the neural substrate of the height-cognitive ability association is unclear. We used a sample of 515 middle-aged male twins with structural magnetic resonance imaging data to investigate whether the association between height and cognitive ability is mediated by cortical size. In addition to cortical volume, we used genetically, ontogenetically and phylogenetically distinct cortical metrics of total cortical surface area and mean cortical thickness. Height was positively associated with general cognitive ability and total cortical volume and cortical surface area, but not with mean cortical thickness. Mediation models indicated that the well-replicated height-general cognitive ability association is accounted for by individual differences in total cortical volume and cortical surface area (highly heritable metrics related to global brain size), and that the genetic association between cortical surface area and general cognitive ability underlies the phenotypic height-general cognitive ability relationship.

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

    Directory of Open Access Journals (Sweden)

    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

  5. Mediators and treatment matching in behavior therapy, cognitive therapy and cognitive behavior therapy for chronic insomnia.

    Science.gov (United States)

    Harvey, Allison G; Dong, Lu; Bélanger, Lynda; Morin, Charles M

    2017-10-01

    To examine the mediators and the potential of treatment matching to improve outcome for cognitive behavior therapy (CBT) for insomnia. Participants were 188 adults (117 women; Mage = 47.4 years, SD = 12.6) meeting the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; text rev.; DSM-IV-TR; American Psychiatric Association [APA], 2000) diagnostic criteria for chronic insomnia (Mduration: 14.5 years, SD: 12.8). Participants were randomized to behavior therapy (BT; n = 63), cognitive therapy (CT; n = 65), or CBT (n = 60). The outcome measure was the Insomnia Severity Index (ISI). Hypothesized BT mediators were sleep-incompatible behaviors, bedtime variability (BTv), risetime variability (RTv) and time in bed (TIB). Hypothesized CT mediators were worry, unhelpful beliefs, and monitoring for sleep-related threat. The behavioral processes mediated outcome for BT but not CT. The cognitive processes mediated outcome in both BT and CT. The subgroup scoring high on both behavioral and cognitive processes had a marginally significant better outcome if they received CBT relative to BT or CT. The subgroup scoring relatively high on behavioral but low on cognitive processes and received BT or CBT did not differ from those who received CT. The subgroup scoring relatively high on cognitive but low on behavioral processes and received CT or CBT did not differ from those who received BT. The behavioral mediators were specific to BT relative to CT. The cognitive mediators were significant for both BT and CT outcomes. Patients exhibiting high levels of both behavioral and cognitive processes achieve better outcome if they receive CBT relative to BT or CT alone. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  6. Cognitive Load Mediates the Effect of Emotion on Analytical Thinking.

    Science.gov (United States)

    Trémolière, Bastien; Gagnon, Marie-Ève; Blanchette, Isabelle

    2016-11-01

    Although the detrimental effect of emotion on reasoning has been evidenced many times, the cognitive mechanism underlying this effect remains unclear. In the present paper, we explore the cognitive load hypothesis as a potential explanation. In an experiment, participants solved syllogistic reasoning problems with either neutral or emotional contents. Participants were also presented with a secondary task, for which the difficult version requires the mobilization of cognitive resources to be correctly solved. Participants performed overall worse and took longer on emotional problems than on neutral problems. Performance on the secondary task, in the difficult version, was poorer when participants were reasoning about emotional, compared to neutral contents, consistent with the idea that processing emotion requires more cognitive resources. Taken together, the findings afford evidence that the deleterious effect of emotion on reasoning is mediated by cognitive load.

  7. Cognitive reactivity: investigation of a potentially treatable marker of suicide risk in depression

    NARCIS (Netherlands)

    Antypa, N.; van der Does, A.; Penninx, B.W.J.H.

    2010-01-01

    Background: Suicidal ideation is the most stable symptom of depression across episodes. This relative stability may be brought about by increased cognitive reactivity to sad mood (CR) during periods of remission. The idea is that a network of depressive cognitions, which include suicidal ideation,

  8. Physiological Reactivity to Cognitive Stressors: Variations by Age and Socioeconomic Status

    Science.gov (United States)

    Neupert, Shevaun D.; Miller, Lisa M. Soederberg; Lachman, Margie E.

    2006-01-01

    The present study focused on age and SES differences in stress reactivity in response to cognitively challenging tasks. Specifically, we assessed within-person trajectories of cortisol, a steroid hormone released by the adrenal gland in response to stressors, before, during, and after exposure to cognitively challenging tasks. We extend the…

  9. Why is discrimination stressful? The mediating role of cognitive appraisal.

    Science.gov (United States)

    King, Kimberly R

    2005-08-01

    This study attempts to shed light on past findings that experiences of racial and gender discrimination are associated with poor psychological and physical health outcomes by investigating the role of cognitive appraisal as a mediator of the relationship between experiences of discrimination and affective stress reactions. African American female college students (N = 115) imagined themselves in an audiotaped scenario in which they overheard 2 European American male classmates make negative evaluations of them. Participants then completed measures of causal attributions, cognitive appraisal, and affective stress reactions. Multiple regression analyses supported the hypotheses that attributions to racism and to discrimination that combines racism and sexism were associated with increased stress reactions. This relationship was mediated by cognitive appraisals of centrality. (c) 2005 APA

  10. Sleep and cognitive performance: the role of income and respiratory sinus arrhythmia reactivity.

    Science.gov (United States)

    Staton, Lori; Hinnant, J Benjamin; Buckhalt, Joseph; El-Sheikh, Mona

    2014-11-01

    A health disparities view suggests that low family income status acts as a risk factor for poor cognitive functioning. A biosystems view suggests that poor sleep and poor stress response system functioning are also risk factors. These views are rarely integrated to test multiplicative risk or protective effects from social-cultural and biological variables. We investigated interactions among familial income, children's sleep and respiratory sinus arrhythmia reactivity (RSA reactivity, indexing parasympathetic nervous system reactivity) in the prediction of cognitive performance of school-aged children. Participants were 282 children (146 boys; 35% African American and 65% European American; M age = 9.42 years, SD = .71). Mothers reported on family income. Children's sleep quality (efficiency) and duration (minutes) were assessed via a week of actigraphy. Children's RSA reactivity to an attention demanding and frustrating star tracing challenge was assessed in the lab. Children completed standardized cognitive assessments examining attention, processing speed, and crystallized cognitive functioning. Findings show that more optimal sleep efficiency and RSA reactivity interact to confer protection against poor cognitive performance, particularly for children from lower income homes. Results build on the literature and suggest that interactions between biological systems and socioeconomic variables are key for understanding children's cognitive performance. © 2014 Wiley Periodicals, Inc.

  11. Ginseng and Ginkgo Biloba Effects on Cognition as Modulated by Cardiovascular Reactivity: A Randomised Trial.

    Directory of Open Access Journals (Sweden)

    Derek Ong Lai Teik

    Full Text Available There is some evidence to suggest that ginseng and Ginkgo biloba can improve cognitive performance, however, very little is known about the mechanisms associated with such improvement. Here, we tested whether cardiovascular reactivity to a task is associated with cognitive improvement.Using a double-blind, placebo controlled, crossover design, participants (N = 24 received two doses of Panax Ginseng (500, 1000 mg or Ginkgo Biloba (120, 240 mg (N = 24, and underwent a series of cognitive tests while systolic, diastolic, and heart rate readings were taken. Ginkgo Biloba improved aspects of executive functioning (Stroop and Berg tasks in females but not in males. Ginseng had no effect on cognition. Ginkgo biloba in females reversed the initial (i.e. placebo increase in cardiovascular reactivity (systolic and diastolic readings increased compared to baseline to cognitive tasks. This effect (reversal was most notable after those tasks (Stroop and Iowa that elicited the greatest cardiovascular reactivity during placebo. In males, although ginkgo also decreased cardiovascular readings, it did so from an initial (placebo blunted response (i.e. decrease or no change from baseline to cognitive tasks. Ginseng, on the contrary, increased cardiovascular readings compared to placebo.These results suggest that cardiovascular reactivity may be a mechanism by which ginkgo but not ginseng, in females is associated with certain forms of cognitive improvement.ClinicalTrials.gov NCT02386852.

  12. The influence of physical and cognitive factors on reactive agility performance in men basketball players.

    Science.gov (United States)

    Scanlan, Aaron; Humphries, Brendan; Tucker, Patrick S; Dalbo, Vincent

    2014-01-01

    This study explored the influence of physical and cognitive measures on reactive agility performance in basketball players. Twelve men basketball players performed multiple sprint, Change of Direction Speed Test, and Reactive Agility Test trials. Pearson's correlation analyses were used to determine relationships between the predictor variables (stature, mass, body composition, 5-m, 10-m and 20-m sprint times, peak speed, closed-skill agility time, response time and decision-making time) and reactive agility time (response variable). Simple and stepwise regression analyses determined the individual influence of each predictor variable and the best predictor model for reactive agility time. Morphological (r = -0.45 to 0.19), sprint (r = -0.40 to 0.41) and change-of-direction speed measures (r = 0.43) had small to moderate correlations with reactive agility time. Response time (r = 0.76, P = 0.004) and decision-making time (r = 0.58, P = 0.049) had large to very large relationships with reactive agility time. Response time was identified as the sole predictor variable for reactive agility time in the stepwise model (R(2) = 0.58, P = 0.004). In conclusion, cognitive measures had the greatest influence on reactive agility performance in men basketball players. These findings suggest reaction and decision-making drills should be incorporated in basketball training programmes.

  13. Cognitive vulnerabilities as mediators between emotional abuse and depressive symptoms.

    Science.gov (United States)

    Padilla Paredes, Patricia; Calvete, Esther

    2014-01-01

    This study tested whether childhood parental emotional abuse and peer emotional bullying serve as antecedents of depression in adolescence and identified the cognitive mechanisms involved in this process. It was hypothesized that the experience of emotional abuse would predict depressive symptoms via development of rumination and negative inferences. A 3-wave longitudinal study was carried out with 998 adolescents (471 girls and 526 boys) between 13 and 17 years of age. Results showed that emotional abuse by parents and peers at Time 1 predicted a worsening of several cognitive vulnerabilities at Time 2. In addition, brooding mediated between the experiences of abuse and the increase of depressive symptoms at Time 3. Thus, findings suggest that the experiences of childhood emotional abuse by parents and peers serve as antecedents to develop a negative cognitive style, vulnerability that, once developed, is a risk factor for the onset of depressive symptoms in adolescence.

  14. Cognition and HPA axis reactivity in mildly to moderately depressed outpatients

    DEFF Research Database (Denmark)

    Krogh, Jesper; Videbech, Poul; Renvillard, Signe Groth

    2012-01-01

    Background: Patients with depression display neurobiological changes of the hypothalamic-pituitary axis as well as cognitive disturbances. Aims: To assess any association between hypothalamus-pituitary-adrenal (HPA) axis reactivity and memory-related cognitive functions. Methods: Depressed...... the following day at the same times. Results: Patients and controls did not differ on any memory-related cognitive skills. After dexamethasone the cortisol level was 1.7 nmol/l higher (95% CI 0.0-2.8, P =¿0.05) in depressed patients compared with controls. In the control group, but not in the patients...... after dexamethasone and visuo-spatial memory primarily driven by the healthy controls. Otherwise, no association were found between HPA axis reactivity and memory-related cognitive function....

  15. Laccase/Mediator Systems: Their Reactivity toward Phenolic Lignin Structures.

    Science.gov (United States)

    Hilgers, Roelant; Vincken, Jean-Paul; Gruppen, Harry; Kabel, Mirjam A

    2018-02-05

    Laccase-mediator systems (LMS) have been widely studied for their capacity to oxidize the nonphenolic subunits of lignin (70-90% of the polymer). The phenolic subunits (10-30% of the polymer), which can also be oxidized without mediators, have received considerably less attention. Consequently, it remains unclear to what extent the presence of a mediator influences the reactions of the phenolic subunits of lignin. To get more insight in this, UHPLC-MS was used to study the reactions of a phenolic lignin dimer (GBG), initiated by a laccase from Trametes versicolor , alone or in combination with the mediators HBT and ABTS. The role of HBT was negligible, as its oxidation by laccase occurred slowly in comparison to that of GBG. Laccase and laccase/HBT oxidized GBG at a comparable rate, resulting in extensive polymerization of GBG. In contrast, laccase/ABTS converted GBG at a higher rate, as GBG was oxidized both directly by laccase but also by ABTS radical cations, which were rapidly formed by laccase. The laccase/ABTS system resulted in Cα oxidation of GBG and coupling of ABTS to GBG, rather than polymerization of GBG. Based on these results, we propose reaction pathways of phenolic lignin model compounds with laccase/HBT and laccase/ABTS.

  16. Mediating the distal crime-drug relationship with proximal reactive criminal thinking.

    Science.gov (United States)

    Walters, Glenn D

    2016-02-01

    This article describes the results of a study designed to test whether reactive criminal thinking (RCT) does a better job of mediating the crime → drug relationship than it does mediating the drug → crime relationship after the direct effects of crime on drug use/dependency and of drug use/dependency on crime have been rendered nonsignificant by control variables. All 1,170 male members of the Pathways to Desistance study (Mulvey, 2012) served as participants in the current investigation. As predicted, the total (unmediated) effects of crime on substance use/dependence and of substance use/dependence on crime were nonsignificant when key demographic and third variables were controlled, although the indirect (RCT-mediated) effect of crime on drug use was significant. Proactive criminal thinking (PCT), by comparison, failed to mediate either relationship. The RCT continued to mediate the crime → drug relationship and the PCT continued to not mediate either relationship when more specific forms of offending (aggressive, income) and substance use/dependence (drug use, substance-use dependency symptoms) were analyzed. This offers preliminary support for the notion that even when the total crime-drug effect is nonsignificant the indirect path from crime to reactive criminal thinking to drugs can still be significant. Based on these results, it is concluded that mediation by proximal reactive criminal thinking is a mechanism by which distal measures of crime and drug use/dependence are connected. (c) 2016 APA, all rights reserved).

  17. Hedonic orientation moderates the association between cognitive control and affect reactivity to daily hassles in adolescent boys.

    Science.gov (United States)

    Klipker, Kathrin; Wrzus, Cornelia; Rauers, Antje; Riediger, Michaela

    2017-04-01

    People often seek to regulate their affective reactions when confronted with hassles. Hassle reactivity is lower for people with higher cognitive control, presumably because of better affect regulation. Many adolescents, however, show higher hassle reactivity than children, despite better cognitive control. The present study aims to understand whether motivational differences when seeking to regulate affective experiences moderate the association between cognitive control and hassle reactivity in adolescence. We hypothesized that higher cognitive control is related to lower hassle reactivity only for adolescents with a strong hedonic orientation, that is, for adolescents who seek to maintain or enhance positive or to dampen negative affect. We investigated 149 boys' (age range: 10-20 years) hedonic orientation and affect reactivity toward daily hassles during 2 weeks of experience sampling. Higher cognitive control, assessed with a working memory battery in the laboratory, was associated with stronger hassle reactivity in individuals with low hedonic orientation. The more hedonic-oriented individuals were, the lower was their hassle reactivity, but only in combination with high cognitive control. Our findings illustrate that higher cognitive control is not always related to lower hassle reactivity. Rather, when daily hassles compromise affect balance, hedonic orientation is equally important to understand affect reactivity in adolescent boys. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  18. Prototype Willingness Model Drinking Cognitions Mediate Personalized Normative Feedback Efficacy.

    Science.gov (United States)

    Lewis, Melissa A; Litt, Dana M; Tomkins, Mary; Neighbors, Clayton

    2017-05-01

    Personalized normative feedback (PNF) interventions have been shown to be efficacious at reducing college student drinking. Because descriptive norms have been shown to mediate PNF efficacy, the current study focused on examining additional prototype willingness model social reaction cognitions, namely, prototypes and willingness, as mediators of intervention efficacy. We expected the PNF interventions to be associated with increased prototype favorability of students who do not drink, which would in turn be associated with decreased willingness to drink and subsequently, less drinking. The current study included 622 college students (53.2% women; 62% Caucasian) who reported one or more heavy drinking episodes in the past month and completed baseline and three-month follow-up assessments. As posited by the framework of the prototype willingness model, sequential mediation analyses were conducted to evaluate increases in abstainer prototype favorability on willingness on drinking, and subsequently willingness to drink on drinking behavior. Mediation results revealed significant indirect effects of PNF on three-month drinking through three-month prototypes and willingness, indicating that the social reaction pathway of the prototype willingness model was supported. Findings have important implications for PNF interventions aiming to reduce high-risk drinking among college students. Study findings suggest that we should consider looking at additional socially-based mediators of PNF efficacy in addition to perceived descriptive norms.

  19. The Cognitive Mediation Hypothesis Revisited: An Empirical Response to Methodological and Theoretical Criticism.

    Science.gov (United States)

    Romero, Anna A.; And Others

    1996-01-01

    In order to address criticisms raised against the cognitive mediation hypothesis, three experiments were conducted to develop a more direct test of the hypothesis. Taken together, the three experiments provide converging support for the cognitive mediation hypothesis, reconfirming the central role of cognition in the persuasion process.…

  20. Cognitive reactivity to success and failure relate uniquely to manic and depression tendencies and combine in bipolar tendencies.

    Science.gov (United States)

    Raes, Filip; Ghesquière, Ine; Van Gucht, Dinska

    2012-01-01

    The present study examined simultaneously the relations between cognitive reactivity to success and failure, on the one hand, and depression, manic, and bipolar tendencies, on the other hand. Participants (161 students) completed measures of success and failure reactivity, current manic and depressive symptoms, and tendencies towards depression, mania, and bipolarity. Results showed that respondents with a greater tendency towards depression evidenced greater (negative) reactivity to failure, whereas those with a greater tendency toward mania evidenced greater (positive) reactivity to success. Depression vulnerability was unrelated to success reactivity, and manic vulnerability was unrelated to failure reactivity. Tendencies toward bipolarity correlated significantly with both failure and success reactivity in a negative and positive manner, respectively. These findings add to the growing body of literature, suggesting that different features or cognitive tendencies are related to depression vulnerability versus manic vulnerability and imply that these "mirrored" cognitive features both form part of vulnerability to bipolar disorder.

  1. Cognitive Reactivity to Success and Failure Relate Uniquely to Manic and Depression Tendencies and Combine in Bipolar Tendencies

    Directory of Open Access Journals (Sweden)

    Filip Raes

    2012-01-01

    Full Text Available The present study examined simultaneously the relations between cognitive reactivity to success and failure, on the one hand, and depression, manic, and bipolar tendencies, on the other hand. Participants (161 students completed measures of success and failure reactivity, current manic and depressive symptoms, and tendencies towards depression, mania, and bipolarity. Results showed that respondents with a greater tendency towards depression evidenced greater (negative reactivity to failure, whereas those with a greater tendency toward mania evidenced greater (positive reactivity to success. Depression vulnerability was unrelated to success reactivity, and manic vulnerability was unrelated to failure reactivity. Tendencies toward bipolarity correlated significantly with both failure and success reactivity in a negative and positive manner, respectively. These findings add to the growing body of literature, suggesting that different features or cognitive tendencies are related to depression vulnerability versus manic vulnerability and imply that these “mirrored” cognitive features both form part of vulnerability to bipolar disorder.

  2. Language Mediated Concept Activation in Bilingual Memory Facilitates Cognitive Flexibility

    Directory of Open Access Journals (Sweden)

    Anatoliy V. Kharkhurin

    2017-06-01

    Full Text Available This is the first attempt of empirical investigation of language mediated concept activation (LMCA in bilingual memory as a cognitive mechanism facilitating divergent thinking. Russian–English bilingual and Russian monolingual college students were tested on a battery of tests including among others Abbreviated Torrance Tests for Adults assessing divergent thinking traits and translingual priming (TLP test assessing the LMCA. The latter was designed as a lexical decision priming test, in which a prime and a target were not related in Russian (language of testing, but were related through their translation equivalents in English (spoken only by bilinguals. Bilinguals outperformed their monolingual counterparts on divergent thinking trait of cognitive flexibility, and bilinguals’ performance on this trait could be explained by their TLP effect. Age of second language acquisition and proficiency in this language were found to relate to the TLP effect, and therefore were proposed to influence the directionality and strength of connections in bilingual memory.

  3. Cortisol Reactivity to Social Stress as a Mediator of Early Adversity on Risk and Adaptive Outcomes

    Science.gov (United States)

    Conradt, Elisabeth; Abar, Beau; Lester, Barry M.; LaGasse, Linda L.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles R.; Whitaker, Toni M.; Hammond, Jane A.

    2014-01-01

    Children chronically exposed to stress early in life are at increased risk for maladaptive outcomes, though the physiological mechanisms driving these effects are unknown. Cortisol reactivity was tested as a mediator of the relation between prenatal substance exposure and/or early adversity on adaptive and maladaptive outcomes. Data were drawn…

  4. Social Problems as a Mediator of the Link between Reactive Aggression and Withdrawn/Depressed Symptoms

    Science.gov (United States)

    Fite, Paula J.; Rathert, Jamie L.; Stoppelbein, Laura; Greening, Leilani

    2012-01-01

    The current study examined whether social problems accounted for the relation between reactive aggression and withdrawn/depressed symptoms in a sample of 147 children (54.4% male) ranging from 5 to 13 years of age (M = 8.22 years) who attended a community based after-school program. Findings suggested that indeed social problems mediated the link…

  5. Abnormal proactive and reactive cognitive control during conflict processing in major depression.

    Science.gov (United States)

    Vanderhasselt, Marie-Anne; De Raedt, Rudi; De Paepe, Annick; Aarts, Kristien; Otte, Georges; Van Dorpe, Jan; Pourtois, Gilles

    2014-02-01

    According to the Dual Mechanisms of Control framework, cognitive control consists of two complementary components: proactive control refers to anticipatory maintenance of goal-relevant information, whereas reactive control acts as a correction mechanism that is activated when a conflict occurs. Possibly, the well-known diminished inhibitory control in response to negative stimuli in Major Depressive Disorder (MDD) patients stems from a breakdown in proactive control, and/or anomalies in reactive cognitive control. In our study, MDD patients specifically showed increased response latencies when actively inhibiting a dominant response to a sad compared with a happy face. This condition was associated with a longer duration of a dominant ERP topography (800-900 ms poststimulus onset) and a stronger activity in the bilateral dorsal anterior cingulate cortex, reflecting abnormal reactive control when inhibiting attention to a negative stimulus. Moreover, MDD patients showed abnormalities in proactive cognitive control when preparing for the upcoming imperative stimulus (abnormal modulation of the contingent negative variation component), accompanied by more activity in brain regions belonging to the default mode network. All together, deficits to inhibit attention to negative information in MDD might originate from an abnormal use of both proactive resources and reactive control processes. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  6. Anxiety and burnout in young athletes: The mediating role of cognitive appraisal.

    Science.gov (United States)

    Gomes, A R; Faria, S; Vilela, C

    2017-12-01

    This study tested the relationship between trait anxiety, cognitive appraisal, and athletes' burnout proposing two hypotheses: (a) there is a direct relationship between athletes' trait anxiety and cognitive appraisal and burnout, and (b) cognitive appraisal mediates the relationship between trait anxiety and burnout, and this mediation occurs despite the competitive level and sport records of athletes. The study included 673 young athletes and provided measures of trait anxiety, cognitive appraisal, and burnout. Structural equation modeling indicated that cognitive appraisal mediates the relationship between trait anxiety and burnout, confirming hypothesis 2, and this model provided better fit than the direct model of hypothesis 1. However, the mediation also indicated that the direct relationship between trait anxiety and burnout should be considered. The mediating model was invariant according to competitive levels and sport records. In conclusion, cognitive appraisal is an important variable in explaining athletes' burnout. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Reactivity to Social Stress in Subclinical Social Anxiety: Emotional Experience, Cognitive Appraisals, Behavior, and Physiology

    OpenAIRE

    Crişan, Liviu G.; Vulturar, Romana; Miclea, Mircea; Miu, Andrei C.

    2016-01-01

    Recent research indicates that subclinical social anxiety is associated with dysfunctions at multiple psychological and biological levels, in a manner that seems reminiscent of social anxiety disorder (SAD). This study aimed to describe multidimensional responses to laboratory-induced social stress in an analog sample selected for social anxiety symptoms. State anxiety, cognitive biases related to negative social evaluation, speech anxiety behaviors, and cortisol reactivity were assessed in t...

  8. Reactivity to Social Stress in Subclinical Social Anxiety: Emotional Experience, Cognitive Appraisals, Behavior, and Physiology

    Science.gov (United States)

    Crişan, Liviu G.; Vulturar, Romana; Miclea, Mircea; Miu, Andrei C.

    2016-01-01

    Recent research indicates that subclinical social anxiety is associated with dysfunctions at multiple psychological and biological levels, in a manner that seems reminiscent of social anxiety disorder (SAD). This study aimed to describe multidimensional responses to laboratory-induced social stress in an analog sample selected for social anxiety symptoms. State anxiety, cognitive biases related to negative social evaluation, speech anxiety behaviors, and cortisol reactivity were assessed in the Trier Social Stress Test (TSST). Results showed that social anxiety symptoms were associated with increased state anxiety, biased appraisals related to the probability and cost of negative social evaluations, behavioral changes in facial expression that were consistent with speech anxiety, and lower cortisol reactivity. In addition, multiple interrelations between responses in the TSST were found, with positive associations between subjective experience, cognitive appraisals, and observable behavior, as well as negative associations between each of the former two types of response and cortisol reactivity. These results show that in response to social stressors, subclinical social anxiety is associated with significant changes in emotional experience, cognitive appraisals, behaviors, and physiology that could parallel those previously found in SAD samples. PMID:26858658

  9. Cognitive Impairments in Occupational Burnout – Error Processing and Its Indices of Reactive and Proactive Control

    Directory of Open Access Journals (Sweden)

    Krystyna Golonka

    2017-05-01

    Full Text Available The presented study refers to cognitive aspects of burnout as the effects of long-term work-related stress. The purpose of the study was to investigate electrophysiological correlates of burnout to explain the mechanisms of the core burnout symptoms: exhaustion and depersonalization/cynicism. The analyzed error-related electrophysiological markers shed light on impaired cognitive mechanisms and the specific changes in information-processing in burnout. In the EEG study design (N = 80, two components of error-related potential (ERP, error-related negativity (ERN, and error positivity (Pe, were analyzed. In the non-clinical burnout group (N = 40, a significant increase in ERN amplitude and a decrease in Pe amplitude were observed compared to controls (N = 40. Enhanced error detection, indexed by increased ERN amplitude, and diminished response monitoring, indexed by decreased Pe amplitude, reveal emerging cognitive problems in the non-clinical burnout group. Cognitive impairments in burnout subjects relate to both reactive and unconscious (ERN and proactive and conscious (Pe aspects of error processing. The results indicate a stronger ‘reactive control mode’ that can deplete resources for proactive control and the ability to actively maintain goals. The analysis refers to error processing and specific task demands, thus should not be extended to cognitive processes in general. The characteristics of ERP patterns in burnout resemble psychophysiological indexes of anxiety (increased ERN and depressive symptoms (decreased Pe, showing to some extent an overlapping effect of burnout and related symptoms and disorders. The results support the scarce existing data on the psychobiological nature of burnout, while extending and specifying its cognitive characteristics.

  10. Youth Experiences of Family Violence and Teen Dating Violence Perpetration: Cognitive and Emotional Mediators

    Science.gov (United States)

    Jouriles, Ernest N.; McDonald, Renee; Mueller, Victoria; Grych, John H.

    2012-01-01

    This article describes a conceptual model of cognitive and emotional processes proposed to mediate the relation between youth exposure to family violence and teen dating violence perpetration. Explicit beliefs about violence, internal knowledge structures, and executive functioning are hypothesized as cognitive mediators, and their potential…

  11. Cognitive Reappraisal Self-Efficacy Mediates the Effects of Individual Cognitive-Behavioral Therapy for Social Anxiety Disorder

    Science.gov (United States)

    Goldin, Philippe R.; Ziv, Michal; Jazaieri, Hooria; Werner, Kelly; Kraemer, Helena; Heimberg, Richard G.; Gross, James J.

    2012-01-01

    Objective: To examine whether changes in cognitive reappraisal self-efficacy (CR-SE) mediate the effects of individually administered cognitive-behavioral therapy (I-CBT) for social anxiety disorder (SAD) on severity of social anxiety symptoms. Method: A randomized controlled trial in which 75 adult patients (21-55 years of age; 53% male; 57%…

  12. Cognitive reactivity to sad mood provocation and the prediction of depressive relapse.

    Science.gov (United States)

    Segal, Zindel V; Kennedy, Sidney; Gemar, Michael; Hood, Karyn; Pedersen, Rebecca; Buis, Tom

    2006-07-01

    Episode remission in unipolar major depression, while distinguished by minimal symptom burden, can also be a period of marked sensitivity to emotional stress as well as an increased risk of relapse. To examine whether mood-linked changes in dysfunctional thinking predict relapse in recovered patients who were depressed. In phase 1 of this study, patients with major depressive disorder were randomly assigned to receive either antidepressant medication or cognitive behavior therapy. In phase 2, patients who achieved clinical remission underwent sad mood provocation and were then observed with regular clinical assessments for 18 months. Outpatient psychiatric clinics at the Centre for Addiction and Mental Health, Toronto, Ontario. A total of 301 outpatients with major depressive disorder, aged 18 to 65 years, participated in phase 1 of this study and 99 outpatients with major depressive disorder in remission, aged 18 to 65 years, participated in phase 2. Occurrence of a relapse meeting DSM-IV criteria for a major depressive episode as assessed by the longitudinal interval follow-up evaluation and a Hamilton Depression Rating Scale score of 16 or greater. Patients who recovered through antidepressant medication showed greater cognitive reactivity following the mood provocation than those who received cognitive behavior therapy. Regardless of type of prior treatment, the magnitude of mood-linked cognitive reactivity was a significant predictor of relapse over the subsequent 18 months. Patients whose mood-linked endorsement of dysfunctional attitudes increased by a minimum of 8 points had a significantly shorter time to relapse than those whose scores were not as elevated. The vulnerability of remitted depressed patients for illness relapse may be related to the (re)activation of depressive thinking styles triggered by temporary dysphoric states. This is the first study to link such differences to prognosis following successful treatment for depression. Further

  13. Cognitive deficits develop 1month after diffuse brain injury and are exaggerated by microglia-associated reactivity to peripheral immune challenge.

    Science.gov (United States)

    Muccigrosso, Megan M; Ford, Joni; Benner, Brooke; Moussa, Daniel; Burnsides, Christopher; Fenn, Ashley M; Popovich, Phillip G; Lifshitz, Jonathan; Walker, Fredrick Rohan; Eiferman, Daniel S; Godbout, Jonathan P

    2016-05-01

    Traumatic brain injury (TBI) elicits immediate neuroinflammatory events that contribute to acute cognitive, motor, and affective disturbance. Despite resolution of these acute complications, significant neuropsychiatric and cognitive issues can develop and progress after TBI. We and others have provided novel evidence that these complications are potentiated by repeated injuries, immune challenges and stressors. A key component to this may be increased sensitization or priming of glia after TBI. Therefore, our objectives were to determine the degree to which cognitive deterioration occurred after diffuse TBI (moderate midline fluid percussion injury) and ascertain if glial reactivity induced by an acute immune challenge potentiated cognitive decline 30 days post injury (dpi). In post-recovery assessments, hippocampal-dependent learning and memory recall were normal 7 dpi, but anterograde learning was impaired by 30 dpi. Examination of mRNA and morphological profiles of glia 30 dpi indicated a low but persistent level of inflammation with elevated expression of GFAP and IL-1β in astrocytes and MHCII and IL-1β in microglia. Moreover, an acute immune challenge 30 dpi robustly interrupted memory consolidation specifically in TBI mice. These deficits were associated with exaggerated microglia-mediated inflammation with amplified (IL-1β, CCL2, TNFα) and prolonged (TNFα) cytokine/chemokine expression, and a marked reactive morphological profile of microglia in the CA3 of the hippocampus. Collectively, these data indicate that microglia remain sensitized 30 dpi after moderate TBI and a secondary inflammatory challenge elicits robust microglial reactivity that augments cognitive decline. Traumatic brain injury (TBI) is a major risk factor in development of neuropsychiatric problems long after injury, negatively affecting quality of life. Mounting evidence indicates that inflammatory processes worsen with time after a brain injury and are likely mediated by glia. Here

  14. The Effect of Aging on the Dynamics of Reactive and Proactive Cognitive Control of Response Interference.

    Science.gov (United States)

    Xiang, Ling; Zhang, Baoqiang; Wang, Baoxi; Jiang, Jun; Zhang, Fenghua; Hu, Zhujing

    2016-01-01

    A prime-target interference task was used to investigate the effects of cognitive aging on reactive and proactive control after eliminating frequency confounds and feature repetitions from the cognitive control measures. We used distributional analyses to explore the dynamics of the two control functions by distinguishing the strength of incorrect response capture and the efficiency of suppression control. For reactive control, within-trial conflict control and between-trial conflict adaption were analyzed. The statistical analysis showed that there were no reliable between-trial conflict adaption effects for either young or older adults. For within-trial conflict control, the results revealed that older adults showed larger interference effects on mean RT and mean accuracy. Distributional analyses showed that the decline mainly stemmed from inefficient suppression rather than from stronger incorrect responses. For proactive control, older adults showed comparable proactive conflict resolution to young adults on mean RT and mean accuracy. Distributional analyses showed that older adults were as effective as younger adults in adjusting their responses based on congruency proportion information to minimize automatic response capture and actively suppress the direct response activation. The results suggest that older adults were less proficient at suppressing interference after conflict was detected but can anticipate and prevent inference in response to congruency proportion manipulation. These results challenge earlier views that older adults have selective deficits in proactive control but intact reactive control.

  15. The effect of aging on the dynamics of reactive and proactive cognitive control of response interference

    Directory of Open Access Journals (Sweden)

    Ling Xiang

    2016-11-01

    Full Text Available A prime-target interference task was used to investigate the effects of cognitive aging on reactive and proactive control in which frequency confounds and feature repetitions were eliminated from the cognitive control measures. We used distributional analyses to explore the dynamics of the two control functions by distinguishing the strength of incorrect response capture and the efficiency of suppression control. For reactive control, within-trial conflict control and between-trial conflict adaption were analyzed. The statistical analysis showed that there were no reliable between-trial conflict adaption effects for both young and older adults. For within-trial conflict control, the results revealed that older adults showed larger interference effects on mean RT and mean accuracy. Distributional analyses showed that the decline mainly stemmed from inefficient suppression rather than from stronger incorrect responses. For proactive control, older adults showed comparable proactive conflict resolution than young adults on mean RT and mean accuracy. Distributional analyses showed older adults were as effective as younger adults in adjusting their responses to minimize automatic response capture and actively suppress the direct response activation based on congruency proportion information. The results suggest that older adults were less proficient at suppressing interference after conflict was detected but can anticipate and prevent inference in response to congruency proportion manipulation. The results challenge earlier views that older adults have selective deficits in proactive control but are spared in reactive control.

  16. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood

    NARCIS (Netherlands)

    Steenbergen, L.; Sellaro, R.; van Hemert, S.; Bosch, J.A.; Colzato, L.S.

    2015-01-01

    Background: Recent insights into the role of the human microbiota in cognitive and affective functioning have led to the hypothesis that probiotic supplementation may act as an adjuvant strategy to ameliorate or prevent depression. Objective: Heightened cognitive reactivity to normal, transient

  17. Reactive Oxygen Species-Mediated Mechanisms of Action of Targeted Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Hanna-Riikka Teppo

    2017-01-01

    Full Text Available Targeted cancer therapies, involving tyrosine kinase inhibitors and monoclonal antibodies, for example, have recently led to substantial prolongation of survival in many metastatic cancers. Compared with traditional chemotherapy and radiotherapy, where reactive oxygen species (ROS have been directly linked to the mediation of cytotoxic effects and adverse events, the field of oxidative stress regulation is still emerging in targeted cancer therapies. Here, we provide a comprehensive review regarding the current evidence of ROS-mediated effects of antibodies and tyrosine kinase inhibitors, use of which has been indicated in the treatment of solid malignancies and lymphomas. It can be concluded that there is rapidly emerging evidence of ROS-mediated effects of some of these compounds, which is also relevant in the context of drug resistance and how to overcome it.

  18. Insight, Cognitive Insight and Sociodemographic Features in Obsessive Compulsive Disorder Presenting with Reactive and Autogeneus Features

    Directory of Open Access Journals (Sweden)

    Katre ÇAMLI

    2012-03-01

    Full Text Available Objective: The aim of the present study was to test hypothesis that obsessive compulsive disorder (OCD patients who have autogenous obsessions and reactive obsessions show different sociodemographic and clinical characteristics with different insight and cognitive insight levels. Method: Sixty-one patients diagnosed as OCD according to the Structured Clinical Interview for DSM-III-R (SCID-I are recruited. 31 patients had reactive obsessions and 30 had autogenous obsessions. The sociodemographic characteristics of patients and the symptomatology were evaluated using psychiatric scales including SCID-I, Yale Brown Obsessive- Compulsive Scale (YBOCS, Yale Brown Obsessive-Compulsive Scale-Symptom Checklist (YBOCS-SC and Beck Insight Scale. Results: The percentage of women in reactive obsessive group was higher and also this group had significantly less antipsychotic medication prescribed than the autogenous obsessive group. No significant difference was found for the other demographic variables. No significant difference was identified for the Beck Insight Self-Reflectiveness subscale but for the Self-Certainty subscale, reactive obsessives had higher scores. Although there was no significant difference for the composit index points, which is the subtraction of the two subscales, the p value was close to the limit. On the other hand YBOCS item- 11 scores which evaluates insight were higher in autogenous obsessives meaning low levels of insight. Conclusion: For the sociodemographic and clinical characteristics; there was no significant difference between the groups except gender distribution and antipsychotic medication. Our data about insight seems inconsistent but insight and cognitive insight can be different entities which show different levels of insight. Further investigation with different obsession types is needed.

  19. Reactive Transport Modeling of Microbe-mediated Fe (II) Oxidation for Enhanced Oil Recovery

    Science.gov (United States)

    Surasani, V.; Li, L.

    2011-12-01

    Microbially Enhanced Oil Recovery (MEOR) aims to improve the recovery of entrapped heavy oil in depleted reservoirs using microbe-based technology. Reservoir ecosystems often contain diverse microbial communities those can interact with subsurface fluids and minerals through a network of nutrients and energy fluxes. Microbe-mediated reactions products include gases, biosurfactants, biopolymers those can alter the properties of oil and interfacial interactions between oil, brine, and rocks. In addition, the produced biomass and mineral precipitates can change the reservoir permeability profile and increase sweeping efficiency. Under subsurface conditions, the injection of nitrate and Fe (II) as the electron acceptor and donor allows bacteria to grow. The reaction products include minerals such as Fe(OH)3 and nitrogen containing gases. These reaction products can have large impact on oil and reservoir properties and can enhance the recovery of trapped oil. This work aims to understand the Fe(II) oxidation by nitrate under conditions relevant to MEOR. Reactive transport modeling is used to simulate the fluid flow, transport, and reactions involved in this process. Here we developed a complex reactive network for microbial mediated nitrate-dependent Fe (II) oxidation that involves both thermodynamic controlled aqueous reactions and kinetic controlled Fe (II) mineral reaction. Reactive transport modeling is used to understand and quantify the coupling between flow, transport, and reaction processes. Our results identify key parameter controls those are important for the alteration of permeability profile under field conditions.

  20. A re-view of cognitive mediators in learned helplessness.

    Science.gov (United States)

    Tennen, H

    1982-12-01

    The findings of Oakes and Curtis (1982), Tennen, Drum, Gillen, and Stanton (1982), and Tennen, Gillen, and Drum (1982) provide a challenge to learned helplessness theory's focus on cognitive mediators of the helplessness phenomenon. In response to these findings, Alloy (1982) argues that these studies do not challenge helplessness theory because they do not measure expected control and because they confuse necessary and sufficient causes of learned helplessness. Silver, Wortman, and Klos (1982) contend that these studies provide an inadequate test of the model because subjects are confronted with experiences which are unlike those in their natural environment. The present article argues that by Alloy's (1982) criteria, an adequate test of the learned helplessness model has not yet been conducted. Previous studies which measured expected control have not supported the model's predictions. Moreover, if perceived response-outcome independence is a sufficient, but not a necessary cause of learned helplessness, the model loses much of its heuristic value. In response to the argument that these studies lack ecological validity, this article clarifies the distinction between experimental realism and mundane realism. While real-world studies have discovered intriguing relations between perceptions of control, attributions, and coping with illness or victimization, they have not tested predictions of the learned helplessness model.

  1. Cognitive Deficits as a Mediator of Poor Occupational Function in Remitted Major Depressive Disorder Patients

    Science.gov (United States)

    Woo, Young Sup; Rosenblat, Joshua D.; Kakar, Ron; Bahk, Won-Myong; McIntyre, Roger S.

    2016-01-01

    Cognitive deficits in major depressive disorder (MDD) patients have been described in numerous studies. However, few reports have aimed to describe cognitive deficits in the remitted state of MDD and the mediational effect of cognitive deficits on occupational outcome. The aim of the current review is to synthesize the literature on the mediating and moderating effects of specific domains of cognition on occupational impairment among people with remitted MDD. In addition, predictors of cognitive deficits found to be vocationally important will be examined. Upon examination of the extant literature, attention, executive function and verbal memory are areas of consistent impairment in remitted MDD patients. Cognitive domains shown to have considerable impact on vocational functioning include deficits in memory, attention, learning and executive function. Factors that adversely affect cognitive function related to occupational accommodation include higher age, late age at onset, residual depressive symptoms, history of melancholic/psychotic depression, and physical/psychiatric comorbidity, whereas higher levels of education showed a protective effect against cognitive deficit. Cognitive deficits are a principal mediator of occupational impairment in remitted MDD patients. Therapeutic interventions specifically targeting cognitive deficits in MDD are needed, even in the remitted state, to improve functional recovery, especially in patients who have a higher risk of cognitive deficit. PMID:26792035

  2. Facing urban complexity : towards cognitive modelling. Part 1. Modelling as a cognitive mediator

    Directory of Open Access Journals (Sweden)

    Sylvie Occelli

    2002-03-01

    Full Text Available Over the last twenty years, complexity issues have been a central theme of enquiry for the modelling field. Whereas contributing to both a critical revisiting of the existing methods and opening new ways of reasoning, the effectiveness (and sense of modelling activity was rarely questioned. Acknowledgment of complexity however has been a fruitful spur new and more sophisticated methods in order to improve understanding and advance geographical sciences. However its contribution to tackle urban problems in everyday life has been rather poor and mainly limited to rhetorical claims about the potentialities of the new approach. We argue that although complexity has put the classical modelling activity in serious distress, it is disclosing new potentialities, which are still largely unnoticed. These are primarily related to what the authors has called the structural cognitive shift, which involves both the contents and role of modelling activity. This paper is a first part of a work aimed to illustrate the main features of this shift and discuss its main consequences on the modelling activity. We contend that a most relevant aspect of novelty lies in the new role of modelling as a cognitive mediator, i.e. as a kind of interface between the various components of a modelling process and the external environment to which a model application belongs.

  3. Parent-child mediated learning interactions as determinants of cognitive modifiability: recent research and future directions.

    Science.gov (United States)

    Tzuriel, D

    1999-05-01

    The main objectives of this article are to describe the effects of mediated learning experience (MLE) strategies in mother-child interactions on the child's cognitive modifiability, the effects of distal factors (e.g., socioeconomic status, mother's intelligence, child's personality) on MLE interactions, and the effects of situational variables on MLE processes. Methodological aspects of measurement of MLE interactions and of cognitive modifiability, using a dynamic assessment approach, are discussed. Studies with infants showed that the quality of mother-infant MLE interactions predict later cognitive functioning and that MLE patterns and children's cognitive performance change as a result of intervention programs. Studies with preschool and school-aged children showed that MLE interactions predict cognitive modifiability and that distal factors predict MLE interactions but not the child's cognitive modifiability. The child's cognitive modifiability was predicted by MLE interactions in a structured but not in a free-play situation. Mediation for transcendence (e.g., teaching rules and generalizations) appeared to be the strongest predictor of children's cognitive modifiability. Discussion of future research includes the consideration of a holistic transactional approach, which refers to MLE processes, personality, and motivational-affective factors, the cultural context of mediation, perception of the whole family as a mediational unit, and the "mediational normative scripts."

  4. Information processing speed as a mediator between psychosocial stress and global cognition in older adults.

    Science.gov (United States)

    Foong, Hui F; Hamid, Tengku A; Ibrahim, Rahimah; Haron, Sharifah A

    2018-01-01

    The link between psychosocial stress and cognitive function is complex, and previous studies have indicated that it may be mediated by processing speed. Therefore, the main aim of this study was to examine whether processing speed mediates the association between psychosocial stress and global cognition in older adults. Moreover, the moderating role of gender in this model is examined as well. The study included 2322 community-dwelling older adults in Malaysia who were randomly selected through a multistage proportional cluster random sampling technique. Global cognition construct was measured by the Mini-Mental State Examination and Montreal Cognitive Assessment; psychosocial stress construct was measured by perceived stress, depression, loneliness, and neuroticism; and processing speed was assessed by the Digit Symbol Substitution Test. Structural equation modelling was used to analyze the mediation and moderation tests. Processing speed was found to partially mediate the relationship between psychosocial stress and global cognition (β in the direct model = -0.15, P cognition was found to be significant in men only, whereas the association between processing speed and global cognition was significant in men and women. Psychosocial stress may increase the likelihood that older adults will experience poor processing capacity, which could reduce their higher level cognition. Results indicate that there is a need to develop processing capacity intervention programmes for psychologically distressed older adults to prevent them from suffering cognitive decline. © 2018 Japanese Psychogeriatric Society.

  5. Sympathetic arousal, but not disturbed executive functioning, mediates the impairment of cognitive flexibility under stress.

    Science.gov (United States)

    Marko, Martin; Riečanský, Igor

    2018-05-01

    Cognitive flexibility emerges from an interplay of multiple cognitive systems, of which lexical-semantic and executive are thought to be the most important. Yet this has not been addressed by previous studies demonstrating that such forms of flexible thought deteriorate under stress. Motivated by these shortcomings, the present study evaluated several candidate mechanisms implied to mediate the impairing effects of stress on flexible thinking. Fifty-seven healthy adults were randomly assigned to psychosocial stress or control condition while assessed for performance on cognitive flexibility, working memory capacity, semantic fluency, and self-reported cognitive interference. Stress response was indicated by changes in skin conductance, hearth rate, and state anxiety. Our analyses showed that acute stress impaired cognitive flexibility via a concomitant increase in sympathetic arousal, while this mediator was positively associated with semantic fluency. Stress also decreased working memory capacity, which was partially mediated by elevated cognitive interference, but neither of these two measures were associated with cognitive flexibility or sympathetic arousal. Following these findings, we conclude that acute stress impairs cognitive flexibility via sympathetic arousal that modulates lexical-semantic and associative processes. In particular, the results indicate that stress-level of sympathetic activation may restrict the accessibility and integration of remote associates and bias the response competition towards prepotent and dominant ideas. Importantly, our results indicate that stress-induced impairments of cognitive flexibility and executive functions are mediated by distinct neurocognitive mechanisms. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Emotional reactivity across the adult life span: the cognitive pragmatics make a difference.

    Science.gov (United States)

    Kunzmann, Ute; Richter, David

    2009-12-01

    Previously, we found that during films about age-typical losses, older adults experienced greater sadness than young adults, whereas their physiological responses were just as large. In the present study, our goal was to replicate this finding and extend past work by examining the role of cognitive functioning in age differences in emotional reactivity. We measured the autonomic and subjective responses of 240 adults (age range=20 to 70) while they viewed films about age-typical losses from our previous work. Findings were fully supportive of our past work: The magnitude of subjective reactions to our films increased linearly over the adult years, whereas there were no age differences on the level of physiological reactivity. We also found that the subjective reactions of adults with high pragmatic intelligence were of moderate size independent of their own age or the age relevance of the emotion elicitor. In contrast, the subjective reactions of adults low on pragmatic intelligence were more variable. Together, this evidence suggests that research on age differences in emotional reactivity may benefit from a perspective that considers individual difference variables as well as contextual variations. PsycINFO Database Record Copyright (c) 2009 APA, all rights reserved

  7. C-reactive protein, APOE genotype and longitudinal cognitive change in an older population

    Science.gov (United States)

    Lima, Thomas A. S.; Adler, Amanda L.; Minett, Thais; Matthews, Fiona E.; Brayne, Carol; Marioni, Riccardo E.

    2014-01-01

    Background: circulating measures of inflammatory markers, such as C-reactive protein (CRP) have been associated with an increased risk of future cognitive decline. However, the nature of the relationship among the very old (>75 years) is unclear. Cross-sectional evidence suggests that elevated CRP may even be protective in this age group. This study examines these associations longitudinally. Methods: logistic regression was used to investigate the association between CRP and drop in cognitive performance (≥3 point change on the Mini-Mental State Examination) over a 4-year period in a population of 266 people, mean age 77 years. Results: increased levels of CRP were associated with a decreased risk of a drop in cognitive performance; however, this association was only seen in those without an APOE e4 allele [odds ratio of decline per unit increase in ln(CRP) 0.57, P = 0.04]. The magnitude of the finding remained consistent after adjustment for cardiovascular confounders (smoking, drinking, MI, stroke, diabetes, education, medication and blood pressure). For those with an e4 allele, the relationship with longitudinal cognitive decline was neither statistically significant nor in a consistent direction after controlling for acute inflammation. Conclusions: this study strengthens previous cross-sectional findings and shows elevated levels of CRP to be linked to a decreased risk of longitudinal cognitive decline in the very old. However, as with prior analyses, this was only observed in those not carrying an APOE e4 allele. Future work on larger APOE e4 allele carrying samples is required to determine the nature of the association in this population. PMID:24305621

  8. The Association Between Obesity and Cognitive Function in Older Persons: How Much Is Mediated by Inflammation, Fasting Plasma Glucose, and Hypertriglyceridemia?

    Science.gov (United States)

    Gunathilake, Roshan; Oldmeadow, Christopher; McEvoy, Mark; Inder, Kerry J; Schofield, Peter W; Nair, Balakrishnan R; Attia, John

    2016-12-01

    The aim of the study was to determine how much of the association between obesity, measured by body mass index (BMI), and cognition in older persons is mediated through inflammation, fasting plasma glucose, and hypertriglyceridemia. Anthropometrics, high-sensitivity C-reactive protein (CRP), fasting plasma glucose, and serum triglycerides were measured in 3,256 community-dwelling individuals aged 55-85 years residing in Newcastle, New South Wales, Australia. Audio recorded cognitive screen (ARCS) was used to assess multiple cognitive domains. Mediation analyses showed very modest but significant direct mediation effects, whereby obesity was associated with better cognitive function after adjusting for potential confounders (controlled direct effect ≈ 1/500 point increase in the total ARCS score per 1.0-kg/m 2 increase in BMI). There were significant indirect negative mediation effects from BMI to cognition mediated through CRP, that is, increased BMI was associated with increased CRP which was associated with decreased cognition (natural indirect effect -0.20 unit; 95% confidence interval [CI] -0.39, -0.02), and through fasting plasma glucose, that is, increased BMI was associated with increased fasting plasma glucose which was associated with decreased cognition (natural indirect effect -0.12 unit; 95% CI -0.24, -0.01], but not through serum triglycerides. There is a weak positive association between obesity and cognitive performance in older persons, which is partially antagonized by inflammation and elevated fasting plasma glucose, but not hypertriglyceridemia. Further studies are needed to elucidate whether this is due to selection bias, or truly reflects biologically complex and counter balancing pathways involved in obesity. © The Author 2016. 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.

  9. Changes in illness perceptions mediated the effect of cognitive behavioural therapy in severe functional somatic syndromes

    DEFF Research Database (Denmark)

    Christensen, Sara Sletten; Frostholm, Lisbeth; Ørnbøl, Eva

    2014-01-01

    Objective Although there is substantial evidence that cognitive behavioural therapy alleviates symptoms in functional somatic syndromes, the mechanisms of change are less investigated. This study examined whether changes in illness perceptions mediated the effect of cognitive behavioural therapy....... Methods We analysed additional data from a randomised controlled trial comparing completers of cognitive behavioural group therapy (46 patients) to an enhanced usual care group (66 patients). Proposed mediators (illness perceptions) and primary (physical health) and secondary (somatic symptoms and illness...... worry) outcomes were assessed by means of questionnaires at referral, baseline, end of treatment, and 10 and 16 months after randomisation. Multiple mediation analysis determined whether (1) changes in specific illness perceptions during treatment mediated the effect of cognitive behavioural therapy...

  10. Lower C-reactive protein and IL-6 associated with vegetarian diets are mediated by BMI.

    Science.gov (United States)

    Jaceldo-Siegl, K; Haddad, E; Knutsen, S; Fan, J; Lloren, J; Bellinger, D; Fraser, G E

    2018-03-13

    The mechanism by which vegetarian diets are associated with less inflammation is not clear. We investigated the role of BMI as a mediator in the relationship between vegetarian diet and concentrations of C-reactive protein (CRP), and the cytokines IL-6, IL-10 and TNF-α. We used data from participants of the Adventist Health Study 2 (AHS-2) Calibration (n = 893) and Biological Manifestations of Religion (n = 478) sub-studies. Vegetarian diet variations were determined based on reported intake of animal products assessed by FFQ. Combining all participants, the proportion of non-vegetarians (NVs), partial vegetarians (PVs), lacto-ovo vegetarians (LOVs), and strict vegetarians (SVs) was 44%, 16%, 31%, and 9%, respectively. NV and PV participants were older than other dietary groups, and non-vegetarians had the highest BMI. Mediation analyses supported the mediating effect of BMI in associations of vegetarian diet with CRP (p vegetarian diet and the biomarkers IL-10 and TNF-α. A direct pathway was significant only in the association between strict vegetarians and CRP (p = 0.017). The lower CRP and IL-6 concentrations among vegetarians may be mediated by BMI. Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  11. Specificity of Cognitive Vulnerability in Fear and Sad Affect: Anxiety Sensitivity, Looming Cognitive Style and Hopelessness in Emotion Reactivity and Recovery

    DEFF Research Database (Denmark)

    del Palacio Gonzalez, Adriana; Clark, David A.

    2015-01-01

    Cognitive models of the pathogenesis of anxiety and depressive disorders identify looming cognitive style (LCS) and anxiety sensitivity (AS) as vulnerability factors specifically related to anxiety disorders, whereas hopelessness (HS) is considered more applicable to depression. Given...... their dimensional perspective most cognitive models of psychopathology may also be extended to explain normal emotional responses. To investigate the effect of cognitive vulnerability on the reactivity and regulation of negative emotion, 183 undergraduates were assigned to watch a sad or fearful movie clip. Then......, all participants retrieved positive memories in an expressive writing task. Hierarchical regression analyses revealed that LCS was uniquely associated with greater fear reactivity. AS and HS were significant predictors of greater fear and sadness after a down-regulation task, respectively...

  12. Fitness, Sleep-Disordered Breathing, Symptoms of Depression, and Cognition in Inactive Overweight Children: Mediation Models.

    Science.gov (United States)

    Stojek, Monika M K; Montoya, Amanda K; Drescher, Christopher F; Newberry, Andrew; Sultan, Zain; Williams, Celestine F; Pollock, Norman K; Davis, Catherine L

    We used mediation models to examine the mechanisms underlying the relationships among physical fitness, sleep-disordered breathing (SDB), symptoms of depression, and cognitive functioning. We conducted a cross-sectional secondary analysis of the cohorts involved in the 2003-2006 project PLAY (a trial of the effects of aerobic exercise on health and cognition) and the 2008-2011 SMART study (a trial of the effects of exercise on cognition). A total of 397 inactive overweight children aged 7-11 received a fitness test, standardized cognitive test (Cognitive Assessment System, yielding Planning, Attention, Simultaneous, Successive, and Full Scale scores), and depression questionnaire. Parents completed a Pediatric Sleep Questionnaire. We used bootstrapped mediation analyses to test whether SDB mediated the relationship between fitness and depression and whether SDB and depression mediated the relationship between fitness and cognition. Fitness was negatively associated with depression ( B = -0.041; 95% CI, -0.06 to -0.02) and SDB ( B = -0.005; 95% CI, -0.01 to -0.001). SDB was positively associated with depression ( B = 0.99; 95% CI, 0.32 to 1.67) after controlling for fitness. The relationship between fitness and depression was mediated by SDB (indirect effect = -0.005; 95% CI, -0.01 to -0.0004). The relationship between fitness and the attention component of cognition was independently mediated by SDB (indirect effect = 0.058; 95% CI, 0.004 to 0.13) and depression (indirect effect = -0.071; 95% CI, -0.01 to -0.17). SDB mediates the relationship between fitness and depression, and SDB and depression separately mediate the relationship between fitness and the attention component of cognition.

  13. Cortisol response mediates the effect of post-reactivation stress exposure on contextualization of emotional memories.

    Science.gov (United States)

    Bos, Marieke G N; Jacobs van Goethem, Tessa H; Beckers, Tom; Kindt, Merel

    2014-12-01

    Retrieval of traumatic experiences is often accompanied by strong feelings of distress. Here, we examined in healthy participants whether post-reactivation stress experience affects the context-dependency of emotional memory. First, participants studied words from two distinctive emotional categories (i.e., war and disease) presented against a category-related background picture. One day later, participants returned to the lab and received a reminder of the words of one emotional category followed by exposure to a stress task (Stress group, n=22) or a control task (Control group, n=24). Six days later, memory contextualization was tested using a word stem completion task. Half of the word stems were presented against the encoding context (i.e., congruent context) and the other half of the word stems were presented against the other context (i.e., incongruent context). The results showed that participants recalled more words in the congruent context than in the incongruent context. Interestingly, cortisol mediated the effect of stress exposure on memory contextualization. The stronger the post-reactivation cortisol response, the more memory performance relied on the contextual embedding of the words. Taken together, the current findings suggest that a moderate cortisol response after memory reactivation might serve an adaptive function in preventing generalization of emotional memories over contexts. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Mother-Child Attachment and Cognitive Performance in Middle Childhood: An Examination of Mediating Mechanisms

    Science.gov (United States)

    West, Katara K.; Mathews, Brittany L.; Kerns, Kathryn A.

    2013-01-01

    Although mother-child attachment has been shown to predict cognitive performance, there has been a lack of attention to the mediating mechanisms that explain these associations. In the present study, we investigated relations of early mother-child attachment and cognitive performance in middle childhood (the latter in terms of both academic…

  15. The Mediating Roles of Generative Cognition and Organizational Culture between Personality Traits and Student Imagination

    Science.gov (United States)

    Liu, Yi-Lin; Liang, Chaoyun

    2014-01-01

    Using science majors as an example, we analyzed how generative cognition, organizational culture, and personality traits affect student imagination, and examined the mediating effects of generative cognition and organizational culture. A total of 473 undergraduates enrolled in physical, chemical, mathematical, and biological science programs…

  16. Harsh Parenting and Adolescent Depression: Mediation by Negative Self-Cognition and Moderation by Peer Acceptance

    Science.gov (United States)

    Tang, Ai-Min; Deng, Xue-Li; Du, Xiu-Xiu; Wang, Ming-Zhong

    2018-01-01

    Guided by Beck's cognitive model of depression, this study examined the mediating role of negative self-cognition in the association between harsh parenting and adolescent depression and whether peer acceptance moderated this indirect relationship. Eight hundred and fifty-nine seventh to ninth graders (379 girls and 480 boys, mean age = 13.58…

  17. Potential Mediators of Cognitive-Behavioral Therapy for Adolescents With Comorbid Major Depression and Conduct Disorder

    Science.gov (United States)

    Kaufman, Noah K.; Rohde, Paul; Seeley, John R.; Clarke, Gregory N.; Stice, Eric

    2005-01-01

    Several possible mediators of a group cognitive-behavioral therapy (CBT) for depressed adolescents were examined. Six measures specific to CBT (e.g., negative cognitions, engagement in pleasurable activities) and 2 nonspecific measures (therapeutic alliance, group cohesion) were examined in 93 adolescents with comorbid major depressive disorder…

  18. Mediated Moderation in Combined Cognitive Behavioral Therapy versus Component Treatments for Generalized Anxiety Disorder

    Science.gov (United States)

    Newman, Michelle G.; Fisher, Aaron J.

    2013-01-01

    Objective: This study examined (a) duration of generalized anxiety disorder (GAD) as a moderator of cognitive behavioral therapy (CBT) versus its components (cognitive therapy and self-control desensitization) and (b) increases in dynamic flexibility of anxious symptoms during the course of psychotherapy as a mediator of this moderation. Degree of…

  19. Effects of prenatal stress and emotional reactivity of the mother on emotional and cognitive abilities in lambs.

    Science.gov (United States)

    Coulon, Marjorie; Nowak, Raymond; Andanson, Stephane; Petit, Bérengère; Lévy, Frédéric; Boissy, Alain

    2015-07-01

    Consequences of prenatal stress on emotional reactivity and cognitive abilities in offspring are under-documented in precocial mammals. Here, we investigated to what extent emotional reactivity, judgment bias and spatial learning abilities of lambs are affected by chronic stress during late pregnancy and by their dams' emotional reactivity. The 20 highest-responsive (HR) and 20 lowest-responsive (LR) ewes from a population of 120 Romane ewes were selected according to their pre-mating reactivity to social isolation in a new environment. Over the final third of pregnancy, 10 HR ewes and 10 LR ewes were exposed daily to various unpredictable aversive events such as restraint, mixing groups and transport while the other 20 selected ewes were not. In a human and an object test, prenatally-stressed lambs were more fearful than control lambs, but the prenatal stress effect was moderated by the reactivity of the mothers: prenatally-stressed lambs from ewes with high emotional reactivity were more affected. Prenatally-stressed lambs did not perform as well as control lambs in a maze test and showed pessimistic-like judgment in a cognitive bias test. Prenatally-stressed lambs were thus characterized by a negative affective state with increased fear reactions and impaired cognitive evaluation. The development of negative moods could have long-lasting consequences on the coping strategies of the lambs in response to their rearing conditions. © 2015 Wiley Periodicals, Inc.

  20. Within-subject mediation analysis for experimental data in cognitive psychology and neuroscience.

    Science.gov (United States)

    Vuorre, Matti; Bolger, Niall

    2017-12-15

    Statistical mediation allows researchers to investigate potential causal effects of experimental manipulations through intervening variables. It is a powerful tool for assessing the presence and strength of postulated causal mechanisms. Although mediation is used in certain areas of psychology, it is rarely applied in cognitive psychology and neuroscience. One reason for the scarcity of applications is that these areas of psychology commonly employ within-subjects designs, and mediation models for within-subjects data are considerably more complicated than for between-subjects data. Here, we draw attention to the importance and ubiquity of mediational hypotheses in within-subjects designs, and we present a general and flexible software package for conducting Bayesian within-subjects mediation analyses in the R programming environment. We use experimental data from cognitive psychology to illustrate the benefits of within-subject mediation for theory testing and comparison.

  1. Mindfulness mediates the relation between disordered eating-related cognitions and psychological distress.

    Science.gov (United States)

    Masuda, Akihiko; Wendell, Johanna W

    2010-12-01

    The present study investigated whether mindfulness mediates the relation between disordered eating-related cognitions and negative psychological outcomes within a non-clinical college sample. Disordered eating-related cognitions were positively associated with general psychological ill-health and emotional distress in interpersonal contexts and inversely related to mindfulness. Mindfulness, which was also inversely related to general psychological ill-health and emotional distress, was found to partially mediate the relations between disordered eating-related cognitions and the two predicted variables. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

    NARCIS (Netherlands)

    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).

  3. Socioeconomic position, health behaviors, and C-reactive protein: A moderated-mediation analysis

    Science.gov (United States)

    Kershaw, Kiarri N.; Mezuk, Briana; Abdou, Cleopatra M.; Rafferty, Jane A.; Jackson, James S.

    2010-01-01

    Objective We sought to understand the link between low SEP and cardiovascular disease (CVD) by examining the association between SEP, health-related coping behaviors, and C-reactive protein (CRP), an inflammatory marker and independent risk factor for CVD in a US sample of adults. Design We used a multiple mediation model to evaluate how these behaviors work in concert to influence CRP levels and whether these relationships were moderated by gender and race/ethnicity. Main outcome measures CRP levels were divided into two categories: elevated CRP (3.1–10.0 mg/L) and normal CRP (≤ 3.0 mg/L). Results Both poverty and low educational attainment were associated with elevated CRP, and these associations were primarily explained through higher levels of smoking and lower levels of exercise. In the education model, poor diet also emerged as a significant mediator. These behaviors accounted for 87.9% of the total effect of education on CRP and 55.8% the total effect of poverty on CRP. We also found significant moderation of these mediated effects by gender and race/ethnicity. Conclusion These findings demonstrate the influence of socioeconomically-patterned environmental constraints on individual-level health behaviors. Specifically, reducing socioeconomic inequalities may have positive effects on CVD disparities through reducing cigarette smoking and increasing vigorous exercise. PMID:20496985

  4. Overweight and Cognitive Performance: High Body Mass Index Is Associated with Impairment in Reactive Control during Task Switching

    Directory of Open Access Journals (Sweden)

    Laura Steenbergen

    2017-10-01

    Full Text Available The prevalence of weight problems is increasing worldwide. There is growing evidence that high body mass index (BMI is associated with frontal lobe dysfunction and deficits in cognitive control. The present study aims to clarify the association between weight status and the degree of impairment in cognitive flexibility, i.e., the ability to efficiently switch from one task to another, by disentangling the preparatory and residual domains of task switching. Twenty-six normal weight (BMI < 25, five males and twenty-six overweight (BMI ≥ 25, seven males university students performed a task-switching paradigm that provides a relatively well-established diagnostic measure of proactive vs. reactive control with regard to cognitive flexibility. Compared to individuals with a BMI lower than 25, overweight (i.e., ≥25 was associated with increased switching costs in the reactive switching condition (i.e., when preparation time is short, representing reduced cognitive flexibility in the preparatory domain. In addition, the overweight group reported significantly more depression and binge eating symptoms, although still indicating minimal depression. No between-group differences were found with regard to self-reported autism spectrum symptoms, impulsiveness, state- and trait anxiety, and cognitive reactivity to depression. The present findings are consistent with and extend previous literature showing that elevated BMI in young, otherwise healthy individuals is associated with significantly more switching costs due to inefficiency in the retrieval, implementation, and maintenance of task sets, indicating less efficient cognitive control functioning.

  5. Preliminary Evidence for Cognitive Mediation During Cognitive–Behavioral Therapy of Panic Disorder

    Science.gov (United States)

    Hofmann, Stefan G.; Suvak, Michael K.; Barlow, David H.; Shear, M. Katherine; Meuret, Alicia E.; Rosenfield, David; Gorman, Jack M.; Woods, Scott W.

    2007-01-01

    Cognitive–behavioral therapy (CBT) and pharmacotherapy are similarly effective for treating panic disorder with mild or no agoraphobia, but little is known about the mechanism through which these treatments work. The present study examined some of the criteria for cognitive mediation of treatment change in CBT alone, imipramine alone, CBT plus imipramine, and CBT plus placebo. Ninety-one individuals who received 1 of these interventions were assessed before and after acute treatment, and after a 6-month maintenance period. Multilevel moderated mediation analyses provided preliminary support for the notion that changes in panic-related cognitions mediate changes in panic severity only in treatments that include CBT. PMID:17563154

  6. Effects of early language, speech, and cognition on later reading: A mediation analysis

    Directory of Open Access Journals (Sweden)

    Vanessa N Durand

    2013-09-01

    Full Text Available This longitudinal secondary analysis examined which early language and speech abilities are associated with school-aged reading skills, and whether these associations are mediated by cognitive ability. We analyzed vocabulary, syntax, speech sound maturity, and cognition in a sample of healthy children at age 3 years (N=241 in relation to single word reading (decoding, comprehension, and oral reading fluency in the same children at age 9 to 11 years. All predictor variables and the mediator variable were associated with the three reading outcomes. The predictor variables were all associated with cognitive abilities, the mediator. Cognitive abilities partially mediated the effects of language on reading. After mediation, decoding was associated with speech sound maturity; comprehension was associated with receptive vocabulary; and oral fluency was associated with speech sound maturity, receptive vocabulary, and syntax. In summary, all of the effects of language on reading could not be explained by cognition as a mediator. Specific components of language and speech skills in preschool made independent contributions to reading skills 6 to 8 years later. These early precursors to later reading skill represent potential targets for early intervention to improve reading.

  7. Beliefs About Appearance, Cognitive Distraction and Sexual Functioning in Men and Women: A Mediation Model Based on Cognitive Theory.

    Science.gov (United States)

    Silva, Elizabet; Pascoal, Patrícia M; Nobre, Pedro

    2016-09-01

    Dysfunctional beliefs about body appearance and cognitive distraction from body appearance during sexual activity have been associated with sexual problems, particularly in women. However, there are no studies examining the interplay between these dimensions and the mechanisms by which they affect sexual functioning. To examine the mediating role of cognitive distraction with body appearance on the relation between beliefs about appearance and sexual functioning. The study sample consisted of 426 heterosexual participants (129 men and 297 women) involved in an exclusive dyadic committed relationship who answered an online questionnaire. The Body Appearance Cognitive Distraction Scale, the Beliefs About Appearance Scale, the International Index of Erectile Function, and the Female Sexual Function Index. The findings indicated that cognitive distraction with body appearance fully mediated the relation between beliefs about appearance and sexual functioning in men and women. The results support the role of beliefs about appearance and cognitive distraction based on body appearance in predicting sexual functioning, reaffirming the role of cognitive models in explaining sexual functioning in men and women. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  8. Are Improvements in Cognitive Content and Depressive Symptoms Correlates or Mediators during Acute-Phase Cognitive Therapy for Recurrent Major Depressive Disorder?

    Science.gov (United States)

    Vittengl, Jeffrey R; Clark, Lee Anna; Thase, Michael E; Jarrett, Robin B

    2014-01-09

    The cognitive model of depression posits that cognitive therapy's (CT) effect on depressive symptoms is mediated by changes in cognitive content (e.g., automatic negative thoughts dysfunctional attitudes, failure attributions). We tested improvement and normalization of cognitive content among outpatients ( N = 523) with recurrent major depressive disorder treated with acute-phase CT (Jarrett & Thase, 2010; Jarrett et al., 2013). We also tested whether improvement in cognitive content accounted for subsequent changes in depressive symptoms and vice versa. Five measures of content improved substantively from pre- to post-CT (median d = 0.96), and the proportions of patients scoring in "healthy" ranges increased (median 45% to 82%). Evidence for cognitive mediation of symptom reduction was limited (median r = .06), as was evidence for symptom mediation of cognitive content improvement (median r = .07). We discuss measurement and design issues relevant to detection of mediators and consider alternative theories of change.

  9. Reactive relay selection in underlay cognitive networks with fixed gain relays

    KAUST Repository

    Hussain, Syed Imtiaz

    2012-06-01

    Best relay selection is a bandwidth efficient technique for multiple relay environments without compromising the system performance. The problem of relay selection is more challenging in underlay cognitive networks due to strict interference constraints to the primary users. Generally, relay selection is done on the basis of maximum end-to-end signal to noise ratio (SNR). However, it requires large amounts of channel state information (CSI) at different network nodes. In this paper, we present and analyze a reactive relay selection scheme in underlay cognitive networks where the relays are operating with fixed gains near a primary user. The system model minimizes the amount of CSI required at different nodes and the destination selects the best relay on the basis of maximum relay to destination SNR. We derive close form expressions for the received SNR statistics, outage probability, bit error probability and average channel capacity of the system. Simulation results are also presented to confirm the validity of the derived expressions. © 2012 IEEE.

  10. Psychological Vulnerability and Problem Gambling: The Mediational Role of Cognitive Distortions.

    Science.gov (United States)

    Lévesque, David; Sévigny, Serge; Giroux, Isabelle; Jacques, Christian

    2018-01-03

    Despite numerous studies demonstrating the influence of cognitive distortions on gambling problem severity, empirical data regarding the role of psychological vulnerability on the latter is limited. Hence, this study assesses the mediating effect of cognitive distortions between psychological vulnerability (personality and mood), and gambling problem severity. It also verifies whether the relationships between these variables differs according to the preferred gambling activity. The sample is composed of 272 male gamblers [191 poker players; 81 video lottery terminal (VLT) players] aged between 18 and 82 years (M = 35.2). Bootstrap analysis results revealed that cognitive distortions mediate the effect of narcissism on gambling problem severity for both groups. The level of depression for VLT players significantly predicted gambling problem severity, both directly and indirectly via the mediating effect of cognitive distortions. Mediation analyses also indicated that narcissism had an indirect impact on problem gambling through cognitive distortions for both groups. These findings suggest that certain vulnerabilities related to personality and mood may influence cognitive distortion intensity and gambling problem severity. In addition, psychological vulnerabilities could differ based on preferred gambling activity. These results may be useful for prevention policies, identifying high risk gamblers and planning psychological interventions.

  11. The association between personality traits, cognitive reactivity and body mass index is dependent on depressive and/or anxiety status.

    Science.gov (United States)

    Paans, Nadine P G; Bot, Mariska; Gibson-Smith, Deborah; Van der Does, Willem; Spinhoven, Philip; Brouwer, Ingeborg; Visser, Marjolein; Penninx, Brenda W J H

    2016-10-01

    A range of biological, social and psychological factors, including depression and anxiety disorders, is thought to be associated with higher body mass index (BMI). Depression and anxiety disorders are associated with specific psychological vulnerabilities, like personality traits and cognitive reactivity, that may also be associated with BMI. The relationship between those psychological vulnerabilities and BMI is possibly different in people with and without depression and anxiety disorders. Therefore, we examined the relationship between personality traits, cognitive reactivity and severity of affective symptoms with BMI in people with and without depression and anxiety disorders. Data from 1249 patients with current major depressive and/or anxiety disorder and 631 healthy controls were sourced from the Netherlands Study of Depression and Anxiety. Linear and logistic regression analyses were used to determine the associations between personality traits (neuroticism, extraversion, conscientiousness), cognitive reactivity (hopelessness, aggression, rumination, anxiety sensitivity), depression and anxiety symptoms with BMI classes (normal: 18.5-24.9, overweight: 25-29.9, and obese: ≥30kg/m(2)) and continuous BMI. Due to significant statistical interaction, analyses were stratified for healthy individuals and depressed/anxious patients. Personality traits were not consistently related to BMI. In patients, higher hopelessness and aggression reactivity and higher depression and anxiety symptoms were associated with higher BMI. In contrast, in healthy individuals lower scores on hopelessness, rumination, aggression reactivity and anxiety sensitivity were associated with higher BMI. These results suggest that, particularly in people with psychopathology, cognitive reactivity may contribute to obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Chinese Beliefs in Luck are Linked to Gambling Problems via Strengthened Cognitive Biases: A Mediation Test.

    Science.gov (United States)

    Lim, Matthew S M; Rogers, Robert D

    2017-12-01

    Problematic patterns of gambling and their harms are known to have culturally specific expressions. For ethnic Chinese people, patterns of superstitious belief in this community appear to be linked to the elevated rates of gambling-related harms; however, little is known about the mediating psychological mechanisms. To address this issue, we surveyed 333 Chinese gamblers residing internationally and used a mediation analysis to explore how gambling-related cognitive biases, gambling frequency and variety of gambling forms ('scope') mediate the association between beliefs in luck and gambling problems. We found that cognitive biases and scope were significant mediators of this link but that the former is a stronger mediator than the latter. The mediating erroneous beliefs were not specific to any particular type of cognitive bias. These results suggest that Chinese beliefs in luck are expressed as gambling cognitive biases that increase the likelihood of gambling problems, and that biases that promote gambling (and its harms) are best understood within their socio-cultural context.

  13. Mediation, moderation, and context: Understanding complex relations among cognition, affect, and health behaviour.

    Science.gov (United States)

    Kiviniemi, Marc T; Ellis, Erin M; Hall, Marissa G; Moss, Jennifer L; Lillie, Sarah E; Brewer, Noel T; Klein, William M P

    2018-01-01

    Researchers have historically treated cognition and affect as separate constructs in motivating health behaviour. We present a framework and empirical evidence for complex relations between cognition and affect in predicting health behaviour. Main Outcome, Design and Results: First, affect and cognition can mediate each other's relation to health behaviour. Second, affect and cognition can moderate the other's impact. Third, context can change the interplay of affect and cognition. Fourth, affect and cognition may be indelibly fused in some psychological constructs (e.g. worry, anticipated regret and reactance). These four propositions in our framework are not mutually exclusive. Examination of the types of complex relations described here can benefit theory development, empirical testing of theories and intervention design. Doing so will advance the understanding of mechanisms involved in regulation of health behaviours and the effectiveness of interventions to change health behaviours.

  14. The Role of Brain-Reactive Autoantibodies in Brain Pathology and Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Simone Mader

    2017-09-01

    Full Text Available Antibodies to different brain proteins have been recently found to be associated with an increasing number of different autoimmune diseases. They need to penetrate the blood–brain barrier (BBB in order to bind antigens within the central nervous system (CNS. They can target either neuronal or non-neuronal antigen and result in damage either by themselves or in synergy with other inflammatory mediators. Antibodies can lead to acute brain pathology, which may be reversible; alternatively, they may trigger irreversible damage that persists even though the antibodies are no longer present. In this review, we will describe two different autoimmune conditions and the role of their antibodies in causing brain pathology. In systemic lupus erythematosus (SLE, patients can have double stranded DNA antibodies that cross react with the neuronal N-methyl-d-aspartate receptor (NMDAR, which have been recently linked to neurocognitive dysfunction. In neuromyelitis optica (NMO, antibodies to astrocytic aquaporin-4 (AQP4 are diagnostic of disease. There is emerging evidence that pathogenic T cells also play an important role for the disease pathogenesis in NMO since they infiltrate in the CNS. In order to enable appropriate and less invasive treatment for antibody-mediated diseases, we need to understand the mechanisms of antibody-mediated pathology, the acute and chronic effects of antibody exposure, if the antibodies are produced intrathecally or systemically, their target antigen, and what triggers their production. Emerging data also show that in utero exposure to some brain-reactive antibodies, such as those found in SLE, can cause neurodevelopmental impairment since they can penetrate the embryonic BBB. If the antibody exposure occurs at a critical time of development, this can result in irreversible damage of the offspring that persists throughout adulthood.

  15. Induction of apoptosis by plumbagin through reactive oxygen species-mediated inhibition of topoisomerase II

    International Nuclear Information System (INIS)

    Kawiak, Anna; Piosik, Jacek; Stasilojc, Grzegorz; Gwizdek-Wisniewska, Anna; Marczak, Lukasz; Stobiecki, Maciej; Bigda, Jacek; Lojkowska, Ewa

    2007-01-01

    Reactive oxygen species (ROS) have been recognized as key molecules, which can selectively modify proteins and therefore regulate cellular signalling including apoptosis. Plumbagin, a naphthoquinone exhibiting antitumor activity, is known to generate ROS and has been found to inhibit the activity of topoisomerase II (Topo II) through the stabilization of the Topo II-DNA cleavable complex. The objective of this research was to clarify the role of ROS and Topo II inhibition in the induction of apoptosis mediated by plumbagin. As determined by the comet assay, plumbagin induced DNA cleavage in HL-60 cells, whereas in a cell line with reduced Topo II activity-HL-60/MX2, the level of DNA damage was significantly decreased. The onset of DNA strand break formation in HL-60 cells was delayed in comparison with the generation of intracellular ROS. In HL-60/MX2 cells, ROS were generated at a similar rate, whereas a significant reduction in the level of DNA damage was detected. The pretreatment of cells with N-acetylcysteine (NAC) attenuated plumbagin-induced DNA damage, pointing out to the involvement of ROS generation in cleavable complex formation. These results suggest that plumbagin-induced ROS does not directly damage DNA but requires the involvement of Topo II. Furthermore, experiments carried out using light spectroscopy indicated no direct interactions between plumbagin and DNA. The induction of apoptosis was significantly delayed in HL-60/MX2 cells indicating the involvement of Topo II inhibition in plumbagin-mediated apoptosis. Thus, these findings strongly suggest ROS-mediated inhibition of Topo II as an important mechanism contributing to the apoptosis-inducing properties of plumbagin

  16. Threat Reappraisal as a Mediator of Symptom Change in Cognitive-Behavioral Treatment of Anxiety Disorders: A Systematic Review

    NARCIS (Netherlands)

    Smits, J.A.J.; Julian, K.; Rosenfield, D.; Powers, M.B.

    2012-01-01

    Objective: Identifying mediators of therapeutic change is important to the development of interventions and augmentation strategies. Threat reappraisal is considered a key mediator underlying the effects of cognitive-behavioral therapy (CBT) for anxiety disorders. The present study systematically

  17. Engagement with the auditory processing system during targeted auditory cognitive training mediates changes in cognitive outcomes in individuals with schizophrenia.

    Science.gov (United States)

    Biagianti, Bruno; Fisher, Melissa; Neilands, Torsten B; Loewy, Rachel; Vinogradov, Sophia

    2016-11-01

    Individuals with schizophrenia who engage in targeted cognitive training (TCT) of the auditory system show generalized cognitive improvements. The high degree of variability in cognitive gains maybe due to individual differences in the level of engagement of the underlying neural system target. 131 individuals with schizophrenia underwent 40 hours of TCT. We identified target engagement of auditory system processing efficiency by modeling subject-specific trajectories of auditory processing speed (APS) over time. Lowess analysis, mixed models repeated measures analysis, and latent growth curve modeling were used to examine whether APS trajectories were moderated by age and illness duration, and mediated improvements in cognitive outcome measures. We observed significant improvements in APS from baseline to 20 hours of training (initial change), followed by a flat APS trajectory (plateau) at subsequent time-points. Participants showed interindividual variability in the steepness of the initial APS change and in the APS plateau achieved and sustained between 20 and 40 hours. We found that participants who achieved the fastest APS plateau, showed the greatest transfer effects to untrained cognitive domains. There is a significant association between an individual's ability to generate and sustain auditory processing efficiency and their degree of cognitive improvement after TCT, independent of baseline neurocognition. APS plateau may therefore represent a behavioral measure of target engagement mediating treatment response. Future studies should examine the optimal plateau of auditory processing efficiency required to induce significant cognitive improvements, in the context of interindividual differences in neural plasticity and sensory system efficiency that characterize schizophrenia. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  18. ERP Correlates of Proactive and Reactive Cognitive Control in Treatment-Naïve Adult ADHD.

    Directory of Open Access Journals (Sweden)

    Venke Arntsberg Grane

    Full Text Available This study investigated whether treatment naïve adults with Attention Deficit Hyperactivity Disorder (ADHD; n = 33; 19 female differed from healthy controls (n = 31; 17 female in behavioral performance, event-related potential (ERP indices of preparatory attention (CueP3 and late CNV, and reactive response control (Go P3, NoGo N2, and NoGo P3 derived from a visual cued Go/NoGo task. On several critical measures, Cue P3, late CNV, and NoGo N2, there were no significant differences between the groups. This indicated normal preparatory processes and conflict monitoring in ADHD patients. However, the patients had attenuated Go P3 and NoGoP3 amplitudes relative to controls, suggesting reduced allocation of attentional resources to processes involved in response control. The patients also had a higher rate of Go signal omission errors, but no other performance decrements compared with controls. Reduced Go P3 and NoGo P3 amplitudes were associated with poorer task performance, particularly in the ADHD group. Notably, the ERPs were not associated with self-reported mood or anxiety. The results provide electrophysiological evidence for reduced effortful engagement of attentional resources to both Go and NoGo signals when reactive response control is needed. The absence of group differences in ERP components indexing proactive control points to impairments in specific aspects of cognitive processes in an untreated adult ADHD cohort. The associations between ERPs and task performance provided additional support for the altered electrophysiological responses.

  19. Reactivity to television food commercials in overweight and lean adults: Physiological, cognitive and behavioural responses.

    Science.gov (United States)

    Boyland, Emma J; Burgon, Rachel H; Hardman, Charlotte A

    2017-08-01

    Recent evidence indicates that acute exposure to food advertising increases food intake. However, little research to date has explored the potential mechanisms underpinning this, such as the extent to which food commercials elicit conditioned physiological responses (e.g. increased salivation). The aim of the current study was to examine salivary, cognitive and consumptive responses to televised food commercials in overweight (N=26) and lean (N=29) adult females. Participants attended two laboratory sessions in a counterbalanced order; in one session they viewed a television show with embedded commercials for unhealthy foods, and in the other session they viewed the same show with non-food commercials. In both conditions, following viewing participants were exposed to an in vivo food cue (freshly cooked pizza) which they were then invited to eat ad libitum. Salivation was measured at baseline, during commercial exposure, and during in vivo exposure. Participants also self-reported components of appetite on visual analogue scales and completed a word stem task. Results indicated little evidence of increased salivary reactivity to the food commercials. In both conditions, lean participants showed reliable salivary responses to the in vivo food cue. In contrast, overweight participants only showed increased salivation to the in vivo cue in the food commercials condition. Food commercial exposure did not increase the number of food-related cognitions or amount of food consumed, but did drive a greater increase in desire to eat prior to pizza consumption than exposure to the control commercials. Exposure to food advertising primes eating-related motivations, and while it may not be associated with increased intake or salivation per se, non-food commercials may attenuate subsequent physiological responses to actual food cues in overweight individuals. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Cognitions as mediators in the relationship between self-compassion and affect

    OpenAIRE

    Arimitsu, Kohki; Hofmann, Stefan G.

    2015-01-01

    Previous studies suggest that self-compassion is related to numerous facets of mental health, but the role of cognitions in this relationship remains unknown. To examine the mediating role of cognitions in the relationship between self-compassion and anxiety, depression, and life satisfaction when controlling for self-esteem in Japanese people, we conducted two studies. Study 1 (N = 231) examined the relationship between self-compassion and affect by modeling negative automatic thoughts as a ...

  1. Efficacy of Guided iCBT for Depression and Mediation of Change by Cognitive Skill Acquisition.

    Science.gov (United States)

    Forand, Nicholas R; Barnett, Jeffrey G; Strunk, Daniel R; Hindiyeh, Mohammed U; Feinberg, Jason E; Keefe, John R

    2018-03-01

    Guided internet CBT (iCBT) is a promising treatment for depression; however, it is less well known through what mechanisms iCBT works. Two possible mediators of change are the acquisition of cognitive skills and increases in behavioral activation. We report results of an 8-week waitlist controlled trial of guided iCBT, and test whether early change in cognitive skills or behavioral activation mediated subsequent change in depression. The sample was 89 individuals randomized to guided iCBT (n = 59) or waitlist (n = 30). Participants were 75% female, 72% Caucasian, and 33 years old on average. The PHQ9 was the primary outcome measure. Mediators were the Competencies of Cognitive Therapy Scale-Self Report and the Behavioral Activation Scale for Depression-Short Form. Treatment was Beating the Blues plus manualized coaching. Outcomes were analyzed using linear mixed models, and mediation with a bootstrap resampling approach. The iCBT group was superior to waitlist, with large effect sizes at posttreatment (Hedges' g = 1.45). Dropout of iCBT was 29% versus 10% for waitlist. In the mediation analyses, the acquisition of cognitive skills mediated subsequent depression change (indirect effect = -.61, 95% bootstrapped biased corrected CI: -1.47, -0.09), but increases in behavioral activation did not. iCBT is an effective treatment for depression, but dropout rates remain high. Change in iCBT appears to be mediated by improvements in the use of cognitive skills, such as critically evaluating and restructuring negative thoughts. Copyright © 2017. Published by Elsevier Ltd.

  2. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood.

    Science.gov (United States)

    Steenbergen, Laura; Sellaro, Roberta; van Hemert, Saskia; Bosch, Jos A; Colzato, Lorenza S

    2015-08-01

    Recent insights into the role of the human microbiota in cognitive and affective functioning have led to the hypothesis that probiotic supplementation may act as an adjuvant strategy to ameliorate or prevent depression. Heightened cognitive reactivity to normal, transient changes in sad mood is an established marker of vulnerability to depression and is considered an important target for interventions. The present study aimed to test if a multispecies probiotic containing Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, and Lactococcus lactis (W19 and W58) may reduce cognitive reactivity in non-depressed individuals. In a triple-blind, placebo-controlled, randomized, pre- and post-intervention assessment design, 20 healthy participants without current mood disorder received a 4-week probiotic food-supplement intervention with the multispecies probiotics, while 20 control participants received an inert placebo for the same period. In the pre- and post-intervention assessment, cognitive reactivity to sad mood was assessed using the revised Leiden index of depression sensitivity scale. Compared to participants who received the placebo intervention, participants who received the 4-week multispecies probiotics intervention showed a significantly reduced overall cognitive reactivity to sad mood, which was largely accounted for by reduced rumination and aggressive thoughts. These results provide the first evidence that the intake of probiotics may help reduce negative thoughts associated with sad mood. Probiotics supplementation warrants further research as a potential preventive strategy for depression. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Cognitive neuroscience of cognitive retraining for addiction medicine : From mediating mechanisms to questions of efficacy

    NARCIS (Netherlands)

    Gladwin, T.E.; Wiers, C.E.; Wiers, R.W.

    2016-01-01

    Cognitive retraining or cognitive bias modification (CBM) involves having subjects repeatedly perform a computerized task designed to reduce the impact of automatic processes that lead to harmful behavior. We first discuss the theory underlying CBM and provide a brief overview of important research

  4. Activities, self-referent memory beliefs, and cognitive performance: evidence for direct and mediated relations.

    Science.gov (United States)

    Jopp, Daniela; Hertzog, Christopher

    2007-12-01

    In this study, the authors investigated the role of activities and self-referent memory beliefs for cognitive performance in a life-span sample. A factor analysis identified 8 activity factors, including Developmental Activities, Experiential Activities, Social Activities, Physical Activities, Technology Use, Watching Television, Games, and Crafts. A second-order general activity factor was significantly related to a general factor of cognitive function as defined by ability tests. Structural regression models suggested that prediction of cognition by activity level was partially mediated by memory beliefs, controlling for age, education, health, and depressive affect. Models adding paths from general and specific activities to aspects of crystallized intelligence suggested additional unique predictive effects for some activities. In alternative models, nonsignificant effects of beliefs on activities were detected when cognition predicted both variables, consistent with the hypothesis that beliefs derive from monitoring cognition and have no influence on activity patterns. PsycINFO Database Record (c) 2008 APA, all rights reserved.

  5. Cognitive capitalism: the effect of cognitive ability on wealth, as mediated through scientific achievement and economic freedom.

    Science.gov (United States)

    Rindermann, Heiner; Thompson, James

    2011-06-01

    Traditional economic theories stress the relevance of political, institutional, geographic, and historical factors for economic growth. In contrast, human-capital theories suggest that peoples' competences, mediated by technological progress, are the deciding factor in a nation's wealth. Using three large-scale assessments, we calculated cognitive-competence sums for the mean and for upper- and lower-level groups for 90 countries and compared the influence of each group's intellectual ability on gross domestic product. In our cross-national analyses, we applied different statistical methods (path analyses, bootstrapping) and measures developed by different research groups to various country samples and historical periods. Our results underscore the decisive relevance of cognitive ability--particularly of an intellectual class with high cognitive ability and accomplishments in science, technology, engineering, and math--for national wealth. Furthermore, this group's cognitive ability predicts the quality of economic and political institutions, which further determines the economic affluence of the nation. Cognitive resources enable the evolution of capitalism and the rise of wealth.

  6. Mediating role of stress reactivity in the effects of prenatal tobacco exposure on childhood mental health outcomes.

    Science.gov (United States)

    Park, Aesoon; O'Malley, Stephanie S; King, Sarah L; Picciotto, Marina R

    2014-02-01

    Prenatal tobacco exposure, through maternal smoking during pregnancy, has been associated with adverse mental health outcomes in childhood. However, the mechanisms by which prenatal tobacco exposure compromises mental health later in life are unclear. We hypothesized that sensitized reactivity to stressful life events in early childhood mediates the effect of prenatal tobacco exposure on mental health outcomes in middle childhood, after accounting for earlier mental health outcomes. Data were from 12,308 mothers and their children drawn from the Avon Longitudinal Study of Parents and Children, a large prospective population-based study. Mothers' self-reports of smoking during pregnancy, mothers' ratings of their child's reactivity to stressful life events, and teachers' and mothers' ratings of the Strengths and Difficulties Questionnaire assessing 5 domains of mental health outcomes were measured. A positive association was found between prenatal tobacco exposure and stress reactivity between the ages of 2 and 6. In turn, stress reactivity was positively associated with peer (isolation), hyperactivity, conduct, and emotional problems (but not prosocial behaviors) between the ages of 7 and 11, after accounting for the mental health outcome at age 4 and other confounders. Heightened stress reactivity in preschool ages mediated the effect of prenatal tobacco exposure on adverse mental health outcomes between the ages of 7 and 11. Interventions to assist children exposed to tobacco smoke during gestation in coping with stressful life events may help mitigate psychiatric symptoms in this population.

  7. Epstein-Barr virus reactivation associated with diminished cell-mediated immunity in antarctic expeditioners

    Science.gov (United States)

    Mehta, S. K.; Pierson, D. L.; Cooley, H.; Dubow, R.; Lugg, D.

    2000-01-01

    Epstein-Barr virus (EBV) reactivation and cell-mediated immune (CMI) responses were followed in 16 Antarctic expeditioners during winter-over isolation at 2 Australian National Antarctic Research Expedition stations. Delayed-type hypersensitivity (DTH) skin testing was used as an indicator of the CMI response, that was evaluated 2 times before winter isolation and 3 times during isolation. At all 5 evaluation times, 8 or more of the 16 subjects had a diminished CMI response. Diminished DTH was observed on every test occasion in 4/16 subjects; only 2/16 subjects exhibited normal DTH responses for all 5 tests. A polymerase chain reaction (PCR) assay was used to detect EBV DNA in saliva specimens collected before, during, and after the winter isolation. EBV DNA was present in 17% (111/642) of the saliva specimens; all 16 subjects shed EBV in their saliva on at least 1 occasion. The probability of EBV shedding increased (P = 0.013) from 6% before or after winter isolation to 13% during the winter period. EBV appeared in saliva during the winter isolation more frequently (P viruses.

  8. Free radicals and related reactive species as mediators of tissue injury and disease: implications for Health.

    Science.gov (United States)

    Kehrer, James P; Klotz, Lars-Oliver

    2015-01-01

    A radical is any molecule that contains one or more unpaired electrons. Radicals are normal products of many metabolic pathways. Some exist in a controlled (caged) form as they perform essential functions. Others exist in a free form and interact with various tissue components. Such interactions can cause both acute and chronic dysfunction, but can also provide essential control of redox regulated signaling pathways. The potential roles of endogenous or xenobiotic-derived free radicals in several human pathologies have stimulated extensive research linking the toxicity of numerous xenobiotics and disease processes to a free radical mechanism. In recent years, improvements in analytical methodologies, as well as the realization that subtle effects induced by free radicals and oxidants are important in modulating cellular signaling, have greatly improved our understanding of the roles of these reactive species in toxic mechanisms and disease processes. However, because free radical-mediated changes are pervasive, and a consequence as well as a cause of injury, whether such species are a major cause of tissue injury and human disease remains unclear. This concern is supported by the fact that the bulk of antioxidant defenses are enzymatic and the findings of numerous studies showing that exogenously administered small molecule antioxidants are unable to affect the course of most toxicities and diseases purported to have a free radical mechanism. This review discusses cellular sources of various radical species and their reactions with vital cellular constituents, and provides examples of selected disease processes that may have a free radical component.

  9. Reactive oxygen species mediates homocysteine-induced mitochondrial biogenesis in human endothelial cells: Modulation by antioxidants

    International Nuclear Information System (INIS)

    Perez-de-Arce, Karen; Foncea, Rocio; Leighton, Federico

    2005-01-01

    It has been proposed that homocysteine (Hcy)-induces endothelial dysfunction and atherosclerosis by generation of reactive oxygen species (ROS). A previous report has shown that Hcy promotes mitochondrial damage. Considering that oxidative stress can affect mitochondrial biogenesis, we hypothesized that Hcy-induced ROS in endothelial cells may lead to increased mitochondrial biogenesis. We found that Hcy-induced ROS (1.85-fold), leading to a NF-κB activation and increase the formation of 3-nitrotyrosine. Furthermore, expression of the mitochondrial biogenesis factors, nuclear respiratory factor-1 and mitochondrial transcription factor A, was significantly elevated in Hcy-treated cells. These changes were accompanied by increase in mitochondrial mass and higher mRNA and protein expression of the subunit III of cytochrome c oxidase. These effects were significantly prevented by pretreatment with the antioxidants, catechin and trolox. Taken together, our results suggest that ROS is an important mediator of mitochondrial biogenesis induced by Hcy, and that modulation of oxidative stress by antioxidants may protect against the adverse vascular effects of Hcy

  10. Affective and Cognitive Empathy as Mediators of Gender Differences in Cyber and Traditional Bullying

    Science.gov (United States)

    Topcu, Cigdem; Erdur-Baker, Ozgur

    2012-01-01

    Gender differences in bullying behavior among adolescents have been observed, but the reasons for the discrepancy in males' and females' bullying experiences has been the focus of few studies. This study examined the role of the cognitive and affective empathy in explaining gender differences in bullying through multiple mediation analysis. The…

  11. Myelin Breakdown Mediates Age-Related Slowing in Cognitive Processing Speed in Healthy Elderly Men

    Science.gov (United States)

    Lu, Po H.; Lee, Grace J.; Tishler, Todd A.; Meghpara, Michael; Thompson, Paul M.; Bartzokis, George

    2013-01-01

    Background: To assess the hypothesis that in a sample of very healthy elderly men selected to minimize risk for Alzheimer's disease (AD) and cerebrovascular disease, myelin breakdown in late-myelinating regions mediates age-related slowing in cognitive processing speed (CPS). Materials and methods: The prefrontal lobe white matter and the genu of…

  12. Information Processing Versus Social Cognitive Mediators of Weight Loss in a Podcast-Delivered Health Intervention

    Science.gov (United States)

    Ko, Linda K.; Turner-McGrievy, Gabrielle M.; Campbell, Marci K.

    2014-01-01

    Podcasting is an emerging technology, and previous interventions have shown promising results using theory-based podcast for weight loss among overweight and obese individuals. This study investigated whether constructs of social cognitive theory and information processing theories (IPTs) mediate the effect of a podcast intervention on weight loss…

  13. The Role of Social Factors in Shaping Students' Test Emotions: A Mediation Analysis of Cognitive Appraisals

    Science.gov (United States)

    Buric, Irena

    2015-01-01

    The aim of this study was to examine the relationships between test emotions and their proximal and distal antecedents in the math domain as proposed by the control-value theory of achievement emotions, using structural equation modeling. More specifically, it investigates the mediating role of cognitive appraisals of control and value in the…

  14. Age Differences in Perseveration: Cognitive and Neuroanatomical Mediators of Performance on the Wisconsin Card Sorting Test

    Science.gov (United States)

    Head, Denise; Kennedy, Kristen M.; Rodrigue, Karen M.; Raz, Naftali

    2009-01-01

    Aging effects on the Wisconsin Card Sorting Test (WCST) are fairly well established but the mechanisms of the decline are not clearly understood. In this study, we examined the cognitive and neural mechanisms mediating age-related increases in perseveration on the WCST. MRI-based volumetry and measures of selected executive functions in…

  15. Cognitive-emotional reactivation during deep transcranial magnetic stimulation over the prefrontal cortex of depressive patients affects antidepressant outcome.

    Science.gov (United States)

    Isserles, Moshe; Rosenberg, Oded; Dannon, Pinchas; Levkovitz, Yechiel; Kotler, Moshe; Deutsch, Frederic; Lerer, Bernard; Zangen, Abraham

    2011-02-01

    Transcranial magnetic stimulation (TMS) enables non-surgical activation of specific brain areas. TMS over the prefrontal cortex (PFC) is emerging as a significant tool that can augment or replace non/partially effective antidepressant medications. Deep TMS (DTMS) utilizes newly developed coils that enable effective stimulation of deeper cortical layers involved in the pathophysiology of depression. We aimed to assess the H1-DTMS coil as an add-on to antidepressants in treating patients with major depression. We also intended to evaluate whether the antidepressant outcome of DTMS treatment is affected by a cognitive-emotional procedure performed during stimulation. 57 patients were enrolled in the study that included 4 weeks of daily 20 Hz stimulation sessions and additional 4 weekly sessions as a short maintenance phase. Two subgroups of patients received either positive or negative cognitive-emotional reactivation along with the stimulation sessions. 21 of 46 patients (46%) who received at least 10 stimulation sessions achieved response (improvement of ≥ 50% in the Hamilton Depression Rating Scale (HDRS)) and 13 of them (28%) achieved remission (HDRS-24 ≤ 10) by the end of the daily treatment phase. Improvements were smaller in the negatively reactivated group and Beck Depression Inventory scores were not significantly improved in this group. DTMS over the PFC proved to be safe and effective in augmenting antidepressant medications. Negative cognitive-emotional reactivation can disrupt the therapeutic effect of DTMS. A large sham controlled study is required to further establish the effectiveness of DTMS as an augmentation treatment and the role of cognitive reactivation during stimulation. © 2010 Elsevier B.V. All rights reserved.

  16. How does MBCT for depression work? studying cognitive and affective mediation pathways.

    Directory of Open Access Journals (Sweden)

    Tim Batink

    Full Text Available Mindfulness based cognitive therapy (MBCT is a non-pharmacological intervention to reduce current symptoms and to prevent recurrence of major depressive disorder. At present, it is not well understood which underlying mechanisms during MBCT are associated with its efficacy. The current study (n = 130 was designed to examine the roles of mindfulness skills, rumination, worry and affect, and the interplay between those factors, in the mechanisms of change in MBCT for residual depressive symptoms. An exploratory but systematic approach was chosen using Sobel-Goodman mediation analyses to identify mediators on the pathway from MBCT to reduction in depressive symptoms. We replicated earlier findings that therapeutic effects of MBCT are mediated by changes in mindfulness skills and worry. Second, results showed that changes in momentary positive and negative affect significantly mediated the efficacy of MBCT, and also mediated the effect of worry on depressive symptoms. Third, within the group of patients with a prior history of ≤ 2 episodes of MDD, predominantly changes in cognitive and to a lesser extent affective processes mediated the effect of MBCT. However, within the group of patients with a prior history of ≥ 3 episodes of MDD, only changes in affect were significant mediators for the effect of MBCT.[corrected] Nederlands Trial Register NTR1084.

  17. Cognitive reactivity, self-depressed associations, and the recurrence of depression.

    Science.gov (United States)

    Elgersma, Hermien J; de Jong, Peter J; van Rijsbergen, Gerard D; Kok, Gemma D; Burger, Huibert; van der Does, Willem; Penninx, Brenda W J H; Bockting, Claudi L H

    2015-09-01

    Mixed evidence exists regarding the role of cognitive reactivity (CR; cognitive responsivity to a negative mood) as a risk factor for recurrences of depression. One explanation for the mixed evidence may lie in the number of previous depressive episodes. Heightened CR may be especially relevant as a risk factor for the development of multiple depressive episodes and less so for a single depressive episode. In addition, it is theoretically plausible but not yet tested that the relationship between CR and number of episodes is moderated by the strength of automatic depression-related self-associations. To investigate (i) the strength of CR in remitted depressed individuals with a history of a single vs. multiple episodes, and (ii) the potentially moderating role of automatic negative self-associations in the relationship between the number of episodes and CR. Cross-sectional analysis of data obtained in a cohort study (Study 1) and during baseline assessments in two clinical trials (Study 2). Study 1 used data from the Netherlands Study of Depression and Anxiety (NESDA) and compared never-depressed participants (n=901) with remitted participants with either a single (n=336) or at least 2 previous episodes (n=273). Study 2 included only remitted participants with at least two previous episodes (n=273). The Leiden Index of Depression Sensitivity Revised (LEIDS-R) was used to index CR and an Implicit Association Test (IAT) to measure implicit self-associations. In Study 1, remitted depressed participants with multiple episodes had significantly higher CR than those with a single or no previous episode. The remitted individuals with multiple episodes of Study 2 had even higher CR scores than those of Study 1. Within the group of individuals with multiple episodes, CR was not heightened as a function of the number of episodes, even if individual differences in automatic negative self-associations were taken into account. The study employed a cross-sectional design, which

  18. The mediating role of pain acceptance during mindfulness-based cognitive therapy for headache.

    Science.gov (United States)

    Day, Melissa A; Thorn, Beverly E

    2016-04-01

    This study aimed to determine if mindfulness-based cognitive therapy (MBCT) engenders improvement in headache outcomes via the mechanisms specified by theory: (1) change in psychological process, (i.e., pain acceptance); and concurrently (2) change in cognitive content, (i.e., pain catastrophizing; headache management self-efficacy). A secondary analysis of a randomized controlled trial comparing MBCT to a medical treatment as usual, delayed treatment (DT) control was conducted. Participants were individuals with headache pain who completed MBCT or DT (N=24) at the Kilgo Headache Clinic or psychology clinic. Standardized measures of the primary outcome (pain interference) and proposed mediators were administered at pre- and post-treatment; change scores were calculated. Bootstrap mediation models were conducted. Pain acceptance emerged as a significant mediator of the group-interference relation (pMediation models examining acceptance subscales showed nuances in this effect, with activity engagement emerging as a significant mediator (pmediation due to a non-significant pathway from the mediator to outcome. Criteria for mediation was also not met for the catastrophizing or self-efficacy models as neither of these variables significantly predicted pain interference. Pain acceptance, and specifically engagement in valued activities despite pain, may be a key mechanism underlying improvement in pain outcome during a MBCT for headache pain intervention. The theorized mediating role of cognitive content factors was not supported in this preliminary study. A large, definitive trial is warranted to replicate and extend the findings in order to streamline and optimize MBCT for headache. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Association between stress-related sleep reactivity and cognitive processes in insomnia disorder and insomnia subgroups: preliminary results.

    Science.gov (United States)

    Palagini, Laura; Faraguna, Ugo; Mauri, Mauro; Gronchi, Alessia; Morin, Charles M; Riemann, Dieter

    2016-03-01

    Stress-related sleep reactivity, sleep-related cognitions, and psychological factors play an important role in insomnia. The aim was to investigate their possible association in Insomnia Disorder, insomnia subgroups, and healthy subjects. The cross-sectional study consisted of 93 subjects who met diagnostic criteria for Insomnia Disorder according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) and of 30 healthy subjects. Survey instruments included the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Ford Insomnia Response to Stress Test (FIRST), Dysfunctional Beliefs about Sleep scale (DBAS), Beck Depression Inventory (BDI), and Zung Self-Rating Anxiety Scale (SAS). Descriptive statistics, Pearson correlations, χ(2)-test, and multiple linear regression were performed. FIRST and SAS best determined the insomnia subjects vs good sleepers (FIRST χ(2) = 109.6, p insomnia, stress-related sleep reactivity, and psychological factors, such as anxiety symptoms, may distinguish insomnia subjects from good sleepers; (2) sleep reactivity and sleep-related cognitions seem interrelated, unhelpful beliefs may affect the stress reactivity; (3) psychological factors may influence sleep quality and the severity of insomnia; (4) these important sleep-related variables may have similar associations in insomnia subgroups; they may constitute the core factors for insomnia development and maintenance. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Mediating pathways and gender differences between shift work and subjective cognitive function.

    Science.gov (United States)

    Wong, Imelda S; Smith, Peter M; Ibrahim, Selahadin; Mustard, Cameron A; Gignac, Monique A M

    2016-11-01

    Increased injury risk among shift workers is often attributed to cognitive function deficits that come about as a result of sleep disruptions. However, little is known about the intermediate influences of other factors (eg, work stress, health) which may affect this relationship. In addition, gender differences in these the complex relationships have not been fully explored. The purpose of this study is to (1) identify the extent to which work and non-work factors mediate the relationship between shift work, sleep and subsequent subjective cognitive function; and (2) determine if the mediating pathways differ for men and women. Data from the 2010 National Population Health Survey was used to create a cross-sectional sample of 4255 employed Canadians. Using path modelling, we examined the direct and indirect relationships between shift work, sleep duration, sleep quality and subjective cognitive function. Multigroup analyses tested for significantly different pathways between men and women. Potential confounding effects of age and self-reported health and potential mediating effects of work stress were simultaneously examined. Work stress and sleep quality significantly mediated the effects of shift work on cognition. Age and health confounded the relationship between sleep quality and subjective cognition. No differences were found between men and women. Occupational health and safety programmes are needed to address stress and health factors, in addition to sleep hygiene, to effectively address cognitive function among shift workers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  1. Moderators and Mediators of the Relationship Between Stress and Insomnia: Stressor Chronicity, Cognitive Intrusion, and Coping

    Science.gov (United States)

    Pillai, Vivek; Roth, Thomas; Mullins, Heather M.; Drake, Christopher L.

    2014-01-01

    Study Objectives: To assess moderators, such as stressor chronicity, and mediators, including stress response in the form of cognitive intrusion and coping behavior, of the prospective association between naturalistic stress and incident insomnia. Design: Longitudinal. Setting: Epidemiological. Participants: A community-based sample of good sleepers (n = 2,892) with no lifetime history of insomnia. Interventions: None. Measurements and Results: Participants reported the number of stressful events they had encountered at baseline, as well as the perceived severity and chronicity of each event. Similarly, volitional stress responses such as coping, as well as more involuntary responses such as cognitive intrusion were assayed for each stressor. Follow-up assessment 1 y hence revealed an insomnia incidence rate of 9.1%. Stress exposure was a significant predictor of insomnia onset, such that the odds of developing insomnia increased by 19% for every additional stressor. Chronicity significantly moderated this relationship, such that the likelihood of developing insomnia as a result of stress exposure increased as a function of chronicity. Cognitive intrusion significantly mediated the association between stress exposure and insomnia. Finally, three specific coping behaviors also acted as mediators: behavioral disengagement, distraction, and substance use. Conclusions: Most studies characterize the relationship between stress exposure and insomnia as a simple dose-response phenomenon. However, our data suggest that certain stressor characteristics significantly moderate this association. Stress response in the form of cognitive intrusion and specific maladaptive coping behaviors mediate the effects of stress exposure. These findings highlight the need for a multidimensional approach to stress assessment in future research and clinical practice. Citation: Pillai V, Roth T, Mullins HM, Drake CL. Moderators and mediators of the relationship between stress and insomnia

  2. Immunoglobulin E (IgE)-mediated cross-reactivity between mesquite pollen proteins and lima bean, an edible legume.

    Science.gov (United States)

    Dhyani, A; Arora, N; Jain, V K; Sridhara, S; Singh, B P

    2007-09-01

    Immunoglobulin E (IgE)-mediated food allergy often develops as a consequence of allergic sensitization to pollen proteins. Mesquite (Prosopis juliflora) tree pollen is reported to be cross-reactive with other pollen species, but little has been reported on its cross-reactivity with plant-derived foods belonging to the same/different families. The present study investigates the in vitro cross-reactivity of mesquite pollen and lima bean (Phaseolus lunatus), an edible seed belonging to the Leguminosae family. Of 110 patients (asthma, rhinitis or both) tested intradermally, 20 showed marked positive reactions with Prosopis pollen extract. Of these, 12 patients showed elevated specific IgE to Prosopis pollen extract alone and four to both Phaseolus and pollen extract. In vitro cross-reactivity was investigated using inhibition assays [enzyme-linked immunosorbent assay (ELISA) inhibition, immunoblot inhibition], histamine release and lymphoproliferation. P. lunatus extract could inhibit IgE binding to P. juliflora in a dose-dependent manner, requiring 400 ng of protein for 50% inhibition in ELISA assay. Immunoblot and immunoblot inhibition demonstrated the presence of 20, 26, 35, 66 and 72 kDa as shared IgE binding components between the two extracts. Histamine release, peripheral blood mononuclear cells proliferation and interleukin (IL)-4 levels also suggested allergenic cross-reactivity. In conclusion, there is humoral and cellular cross-reactivity between Prosopis pollen and Phaseolus seed allergens.

  3. Variability in proactive and reactive cognitive control processes across the adult lifespan

    Directory of Open Access Journals (Sweden)

    Frini eKarayanidis

    2011-11-01

    Full Text Available Task-switching paradigms produce a highly consistent age-related increase in mixing cost (longer RT on repeat trials in mixed-task than single task blocks but a less consistent age effect on switch cost (longer RT on switch than repeat trials in mixed-task blocks. We use two approaches to examine the adult lifespan trajectory of control processes contributing to mixing cost and switch cost: latent variables derived from an evidence accumulation model of choice, and event-related potentials (ERP that temporally differentiate proactive (cue-driven and reactive (target-driven control processes. Under highly practiced and prepared task conditions, ageing was associated with increasing RT mixing cost but reducing RT switch cost. Both effects were largely due to the same cause: an age effect for mixed-repeat trials. In terms of latent variables, increasing age was associated with slower non-decision processes, slower rate of evidence accumulation about the target, and higher response criterion. Age effects on mixing costs were evident only on response criterion, the amount of evidence required to trigger a decision, whereas age effects on switch cost were present for all three latent variables. ERPs showed age-related increases in preparation for mixed-repeat trials, anticipatory attention, and post-target interference. Cue-locked ERPs that are linked to proactive control were associated with early emergence of age differences in response criterion. These results are consistent with age effects on strategic processes controlling decision caution. Consistent with an age-related decline in cognitive flexibility, younger adults flexibly adjusted response criterion from trial-to-trial on mixed-task blocks, whereas older adults maintained a high criterion for all trials.

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

    Science.gov (United States)

    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.

  5. Better cognitive control of emotional information is associated with reduced pro-inflammatory cytokine reactivity to emotional stress.

    Science.gov (United States)

    Shields, Grant S; Kuchenbecker, Shari Young; Pressman, Sarah D; Sumida, Ken D; Slavich, George M

    2016-01-01

    Stress is strongly associated with several mental and physical health problems that involve inflammation, including asthma, cardiovascular disease, certain types of cancer, and depression. It has been hypothesized that better cognitive control of emotional information may lead to reduced inflammatory reactivity to stress and thus better health, but to date no studies have examined whether differences in cognitive control predict pro-inflammatory cytokine responses to stress. To address this issue, we conducted a laboratory-based experimental study in which we randomly assigned healthy young-adult females to either an acute emotional stress (emotionally evocative video) or no-stress (control video) condition. Salivary levels of the key pro-inflammatory cytokines IL-1β, IL-6, and IL-8 were measured before and after the experimental manipulation, and following the last cytokine sample, we assessed participants' cognitive control of emotional information using an emotional Stroop task. We also assessed participants' cortisol levels before and after the manipulation to verify that documented effects were specific to cytokines and not simply due to increased nonwater salivary output. As hypothesized, the emotional stressor triggered significant increases in IL-1β, IL-6, and IL-8. Moreover, even in fully adjusted models, better cognitive control following the emotional (but not control) video predicted less pronounced cytokine responses to that stressor. In contrast, no effects were observed for cortisol. These data thus indicate that better cognitive control specifically following an emotional stressor is uniquely associated with less pronounced pro-inflammatory cytokine reactivity to such stress. These findings may therefore help explain why superior cognitive control portends better health over the lifespan.

  6. Acupuncture elicits neuroprotective effect by inhibiting NAPDH oxidase-mediated reactive oxygen species production in cerebral ischaemia.

    Science.gov (United States)

    Shi, Guang-Xia; Wang, Xue-Rui; Yan, Chao-Qun; He, Tian; Yang, Jing-Wen; Zeng, Xiang-Hong; Xu, Qian; Zhu, Wen; Du, Si-Qi; Liu, Cun-Zhi

    2015-12-10

    In the current study, we aimed to investigate whether NADPH oxidase, a major ROS-producing enzyme, was involved in the antioxidant effect of acupuncture on cognitive impairment after cerebral ischaemia. The cognitive function, infract size, neuron cell loss, level of superoxide anion and expression of NADPH oxidase subunit in hippocampus of two-vessel occlusion (2VO) rats were determined after 2-week acupuncture. Furthermore, the cognitive function and production of O2(-) were determined in the presence and absence of NADPH oxidase agonist (TBCA) and antagonist (Apocynin). The effect of acupuncture on cognitive function after cerebral ischaemia in gp91phox-KO mice was evaluated by Morris water maze. Acupuncture reduced infarct size, attenuated overproduction of O2(-), and reversed consequential cognitive impairment and neuron cell loss in 2VO rats. The elevations of gp91phox and p47phox after 2VO were significantly decreased after acupuncture treatment. However, no differences of gp91phox mRNA were found among any experimental groups. Furthermore, these beneficial effects were reversed by TBCA, whereas apocynin mimicked the effect of acupuncture by improving cognitive function and decreasing O2(-) generation. Acupuncture failed to improve the memory impairment in gp91phox KO mice. Full function of the NADPH oxidase enzyme plays an important role in neuroprotective effects against cognitive impairment via inhibition of NAPDH oxidase-mediated oxidative stress.

  7. Reactive oxygen species regulated mitochondria-mediated apoptosis in PC12 cells exposed to chlorpyrifos

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Eun [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Park, Jae Hyeon [Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); Shin, In Chul [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Koh, Hyun Chul, E-mail: hckoh@hanyang.ac.kr [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of)

    2012-09-01

    Reactive oxidative species (ROS) generated by environmental toxicants including pesticides could be one of the factors underlying the neuronal cell damage in neurodegenerative diseases. In this study we found that chlorpyrifos (CPF) induced apoptosis in dopaminergic neuronal components of PC12 cells as demonstrated by the activation of caspases and nuclear condensation. Furthermore, CPF also reduced the tyrosine hydroxylase-positive immunoreactivity in substantia nigra of the rat. In addition, CPF induced inhibition of mitochondrial complex I activity. Importantly, N-acetyl cysteine (NAC) treatment effectively blocked apoptosis via the caspase-9 and caspase-3 pathways while NAC attenuated the inhibition of mitochondrial complex I activity as well as the oxidative metabolism of dopamine (DA). These results demonstrated that CPF-induced apoptosis was involved in mitochondrial dysfunction through the production of ROS. In the response of cellular antioxidant systems to CPF, we found that CPF treatment increased HO-1 expression while the expression of CuZnSOD and MnSOD was reduced. In addition, we found that CPF treatment activated MAPK pathways, including ERK 1/2, the JNK, and the p38 MAP kinase in a time-dependent manner. NAC treatment abolished MAPK phosphorylation caused by CPF, indicating that ROS are upstream signals of MAPK. Interestingly, MAPK inhibitors abolished cytotoxicity and reduced ROS generation by CPF treatment. Our results demonstrate that CPF induced neuronal cell death in part through MAPK activation via ROS generation, suggesting its potential to generate oxidative stress via mitochondrial damage and its involvement in oxidative stress-related neurodegenerative disease. -- Highlights: ► Chlorpyrifos induces apoptosis. ► Chlorpyrifos inhibits mitochondrial complex I activity. ► ROS is involved in chlorpyrifos-induced apoptosis. ► Chlorpyrifos affects cellular antioxidant systems. ► Chlorpyrifos-induced apoptosis mediates activation of MAPK.

  8. Reactive oxygen species regulated mitochondria-mediated apoptosis in PC12 cells exposed to chlorpyrifos

    International Nuclear Information System (INIS)

    Lee, Jeong Eun; Park, Jae Hyeon; Shin, In Chul; Koh, Hyun Chul

    2012-01-01

    Reactive oxidative species (ROS) generated by environmental toxicants including pesticides could be one of the factors underlying the neuronal cell damage in neurodegenerative diseases. In this study we found that chlorpyrifos (CPF) induced apoptosis in dopaminergic neuronal components of PC12 cells as demonstrated by the activation of caspases and nuclear condensation. Furthermore, CPF also reduced the tyrosine hydroxylase-positive immunoreactivity in substantia nigra of the rat. In addition, CPF induced inhibition of mitochondrial complex I activity. Importantly, N-acetyl cysteine (NAC) treatment effectively blocked apoptosis via the caspase-9 and caspase-3 pathways while NAC attenuated the inhibition of mitochondrial complex I activity as well as the oxidative metabolism of dopamine (DA). These results demonstrated that CPF-induced apoptosis was involved in mitochondrial dysfunction through the production of ROS. In the response of cellular antioxidant systems to CPF, we found that CPF treatment increased HO-1 expression while the expression of CuZnSOD and MnSOD was reduced. In addition, we found that CPF treatment activated MAPK pathways, including ERK 1/2, the JNK, and the p38 MAP kinase in a time-dependent manner. NAC treatment abolished MAPK phosphorylation caused by CPF, indicating that ROS are upstream signals of MAPK. Interestingly, MAPK inhibitors abolished cytotoxicity and reduced ROS generation by CPF treatment. Our results demonstrate that CPF induced neuronal cell death in part through MAPK activation via ROS generation, suggesting its potential to generate oxidative stress via mitochondrial damage and its involvement in oxidative stress-related neurodegenerative disease. -- Highlights: ► Chlorpyrifos induces apoptosis. ► Chlorpyrifos inhibits mitochondrial complex I activity. ► ROS is involved in chlorpyrifos-induced apoptosis. ► Chlorpyrifos affects cellular antioxidant systems. ► Chlorpyrifos-induced apoptosis mediates activation of MAPK.

  9. Cognitive mediational deficits and the role of coping styles in pedophile and ephebophile Roman Catholic clergy.

    Science.gov (United States)

    Ryan, Gregory P; Baerwald, Jeffrey P; McGlone, Gerard

    2008-01-01

    This study was designed to examine hypothesized differences between sex offending and nonoffending Roman Catholic clergy on cognitive mediation abilities as measured by the Rorschach Inkblot Test (H. Rorschach, 1921/1942). This study compared 78 priest pedophiles and 77 priest ephebophiles with 80 nonoffending priest controls on the Inkblot test using J. E. Exner's (2003) Comprehensive System. The three groups were compared on seven variables that constitute Exner's Cognitive Mediation cluster. Additionally, the groups' coping styles were compared to examine the interaction of coping style and cognitive mediational abilities. We found interactions between coping style and offending status across most of the cognitive variables indicating impairment in the mild to pathological ranges. Moreover, significantly higher unusual thinking styles (Xu%) and significantly lower conventional thinking styles (X+%) in offenders compared to nonoffenders. Those with an Extratensive style (n=31) showed significantly higher distorted thinking when compared to the Introversive (n=81), Ambitent (n=73), and Avoidant (n=50) coping styles. This study suggests that offenders display significantly higher distorted thinking styles than do nonoffenders. Possible reasons for these discrepancies and the role of coping styles in abusive behaviors were discussed. (c) 2007 Wiley Periodicals, Inc.

  10. Cognitive Engagement Mediates the Relationship between Positive Life Events and Positive Emotionality

    Directory of Open Access Journals (Sweden)

    Alexander Strobel

    2017-10-01

    Full Text Available Need for Cognition (NFC is conceptualized as an individuals’ tendency to engage in and enjoy effortful cognitive activity and, thus, captures one’s cognitive engagement. It plays a well-established role in information processing in experimental or academic contexts. However, so far comparably little is known about its consequences for other than purely cognitive or academic outcomes. Indeed, NFC is positively associated with personality traits pertaining to Positive Emotionality (PE and negatively to traits related to Negative Emotionality (NE. Moreover, evidence suggests NFC to be related to an active, problem-focused coping style. We therefore hypothesized NFC to mediate between life events and individual differences in PE and NE. In a sample of N = 202 volunteers from the general population, we observed that the number of past positive and negative life events had direct effects on PE, and NE, respectively, and that for positive life events, a mediating effect on PE via NFC was observed, with a higher number of past positive life events being related to higher NFC that in turn was related to increased PE. Thus, the present results lend support to the notion of NFC as an important factor supporting personal well-being by way of its mediating role between the number of past positive life events and positive affect.

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

    NARCIS (Netherlands)

    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

  12. Technology Mediated Instruction and its Effect on Cognitive Scaffolding, motivation and Academic Performance in EFL Context

    Directory of Open Access Journals (Sweden)

    Sepideh Berenji

    2017-11-01

    Full Text Available Technology mediated learning brings together the users with shared interests. This method makes learners informally engaged in language learning. This study intended to investigate the effect of technology mediated instruction on cognitive scaffolding, academic performance and motivation. Employing a quasi-experimental research, 80 learners from two intact classes at Islamic Azad University, Osku Branch were selected as the experimental and control groups. Telegram as a tool was used in the experimental group, while the control group received traditional way of instruction. Critical ethnography approach was implemented to consider the amount of cognitive scaffolding. To measure the students’ motivational level in both groups, Course Interest Survey (CIS was administered at the end of the semester. The total average score for each group was calculated. To compare students’ academic achievement, their average scores in the final academic test were considered. An Independent samples t-test in was used to compare the mean scores. The results indicated that technology mediated learning brought about cognitive scaffolding and the students in the experimental group outperformed the control group in terms of motivation and academic achievement. The results of the study suggest that to bring about academically successful students, practitioners should use technology mediated instruction.

  13. The association between aerobic fitness and cognitive function in older men mediated by frontal lateralization.

    Science.gov (United States)

    Hyodo, Kazuki; Dan, Ippeita; Kyutoku, Yasushi; Suwabe, Kazuya; Byun, Kyeongho; Ochi, Genta; Kato, Morimasa; Soya, Hideaki

    2016-01-15

    Previous studies have shown that higher aerobic fitness is related to higher cognitive function and higher task-related prefrontal activation in older adults. However, a holistic picture of these factors has yet to be presented. As a typical age-related change of brain activation, less lateralized activity in the prefrontal cortex during cognitive tasks has been observed in various neuroimaging studies. Thus, this study aimed to reveal the relationship between aerobic fitness, cognitive function, and frontal lateralization. Sixty male older adults each performed a submaximal incremental exercise test to determine their oxygen intake (V·O2) at ventilatory threshold (VT) in order to index their aerobic fitness. They performed a color-word Stroop task while prefrontal activation was monitored using functional near infrared spectroscopy. As an index of cognitive function, Stroop interference time was analyzed. Partial correlation analyses revealed significant correlations among higher VT, shorter Stroop interference time and greater left-lateralized dorsolateral prefrontal cortex (DLPFC) activation when adjusting for education. Moreover, mediation analyses showed that left-lateralized DLPFC activation significantly mediated the association between VT and Stroop interference time. These results suggest that higher aerobic fitness is associated with cognitive function via lateralized frontal activation in older adults. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Day-to-day relations between stress and sleep and the mediating role of perseverative cognition.

    Science.gov (United States)

    Van Laethem, Michelle; Beckers, Debby G J; van Hooff, Madelon L M; Dijksterhuis, Ap; Geurts, Sabine A E

    2016-08-01

    The goals of this longitudinal diary-based study were to shed light on the day-level relationship between stress and subsequent sleep, and to examine whether perseverative cognition is a mediating factor in this relation. A total of 44 Dutch PhD students were followed during a two-month period, from one month before their public thesis defense (ie, a stressful life event), until one month thereafter. Participants completed short evening and morning questionnaires on eight occasions (in anticipation of and following the defense), including questions about day-level stress, sleep quality, and perseverative cognition. Objective sleep parameters were collected with the SenseWear Pro Armband. Multilevel analysis was used to analyze daily observations nested within individuals. Analyses revealed that day-level stress was not directly related to subsequent subjective sleep indicators or to subsequent objective sleep indicators. Day-level stress was significantly associated with day-level perseverative cognition, and daily variations in perseverative cognition were significantly related to several day-level objective sleep parameters (sleep efficiency, marginally to number of awakenings, and wake after sleep onset), and to several day-level subjective sleep parameters (sleep quality, number of awakenings, wake after sleep onset). Finally, mediation analyses using path analysis suggested that, on the day level, perseverative cognition functions as a mediator between stress and several sleep parameters, namely, subjective sleep quality, objective sleep efficiency, and subjective wake after sleep onset. Perseverative cognition is a promising explanatory mechanism linking day-level stress to subjective and objective measures of sleep. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Social Cognitive Antecedents of Fruit and Vegetable Consumption in Truck Drivers: A Sequential Mediation Analysis.

    Science.gov (United States)

    Hamilton, Kyra; Vayro, Caitlin; Schwarzer, Ralf

    2015-01-01

    To examine a mechanism by which social cognitive factors may predict fruit and vegetable consumption in long-haul truck drivers. Dietary self-efficacy, positive outcome expectancies, and intentions were assessed in 148 Australian truck drivers, and 1 week later they reported their fruit and vegetable consumption. A theory-guided sequential mediation model was specified that postulated self-efficacy and intention as mediators between outcome expectancies and behavior. The hypothesized model was confirmed. A direct effect of outcome expectancies was no longer present when mediators were included, and all indirect effects were significant, including the 2-mediator chain (β = .15; P role of outcome expectancies and self-efficacy are important to consider for understanding and predicting healthy eating intentions in truck drivers. Copyright © 2015 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

  16. Social cues-customer behavior relationship : the mediating role of emotions and cognition

    OpenAIRE

    Nusairat, NM; Akhorshaideh, AHO; Rashid, T; Sahadev, S; Rembielak, G

    2017-01-01

    This paper investigates the effect of social cues in a mall’s shopping environment on customer behavior. Two competing mediation scenarios are assessed: emotion-cognition and cognition-emotion in a stimulus-organism-response (SOR)-based framework. Although the role of social cues in driving customer behavior in shopping contexts is largely addressed in the extant literature, the mechanism of the effect is still under-researched area and this study is an attempt to fill this gap.\\ud The concep...

  17. Individual differences in emotion-cognition interactions: Emotional valence interacts with serotonin transporter genotype to influence brain systems involved in emotional reactivity and cognitive control

    Directory of Open Access Journals (Sweden)

    Melanie eStollstorff

    2013-07-01

    Full Text Available The serotonin transporter gene (5-HTTLPR influences emotional reactivity and attentional bias towards or away from emotional stimuli and has been implicated in psychopathological states, such as depression and anxiety disorder. The short allele is associated with increased reactivity and attention towards negatively-valenced emotional information, whereas the long allele is associated with that towards positively-valenced emotional information. The neural basis for individual differences in the ability to exert cognitive control over these bottom-up biases in emotional reactivity and attention is unknown, an issue investigated in the present study. Two groups, homozygous 5-HTTLPR long allele carriers or homozygous short allele carriers, underwent functional magnetic resonance imaging (fMRI while completing an Emotional Stroop-like task that varied with regards to the congruency of task-relevant and task-irrelevant information and the emotional valence of the task-irrelevant information. Behaviorally, participants demonstrated the classic Stroop effect (slower responses for incongruent than congruent trials, which did not differ by 5-HTTLPR genotype. However, fMRI results revealed that genotype influenced the degree to which neural systems were engaged depending on the valence of the conflicting task-irrelevant information. While the Long group recruited prefrontal control regions and superior temporal sulcus during conflict when task-irrelevant information was positively-valenced, the "Short" group recruited these regions when task-irrelevant information was negatively-valenced. Thus, participants successfully engaged cognitive control to overcome conflict in an emotional context using similar neural circuitry, but the engagement of this circuitry depended on emotional valence and 5-HTTLPR status. These results suggest that the interplay between emotion and cognition is modulated, in part, by a genetic polymorphism that influences serotonin

  18. Social Cognitive Mediators of Sociodemographic Differences in Colorectal Cancer Screening Uptake

    Directory of Open Access Journals (Sweden)

    Siu Hing Lo

    2015-01-01

    Full Text Available Background. This study examined if and how sociodemographic differences in colorectal cancer (CRC screening uptake can be explained by social cognitive factors. Methods. Face-to-face interviews were conducted with individuals aged 60–70 years (n=1309 living in England as part of a population-based omnibus survey. Results. There were differences in screening uptake by SES, marital status, ethnicity, and age but not by gender. Perceived barriers (stand. b=-0.40, p<0.001, social norms (stand. b=0.33, p<0.001, and screening knowledge (stand. b=0.17, p<0.001 had independent associations with uptake. SES differences in uptake were mediated through knowledge, social norms, and perceived barriers. Ethnic differences were mediated through knowledge. Differences in uptake by marital status were primarily mediated through social norms and to a lesser extent through knowledge. Age differences were largely unmediated, except for a small mediated effect via social norms. Conclusions. Sociodemographic differences in CRC screening uptake were largely mediated through social cognitive factors. Impact. Our findings suggest that multifaceted interventions might be needed to reduce socioeconomic inequalities. Ethnic differences might be reduced through improved screening knowledge. Normative interventions could emphasise screening as an activity endorsed by important others outside the immediate family to appeal to a wider audience.

  19. Adolescent Depression and Negative Life Events, the Mediating Role of Cognitive Emotion Regulation

    Science.gov (United States)

    Stikkelbroek, Yvonne; Bodden, Denise H. M.; Kleinjan, Marloes; Reijnders, Mirjam; van Baar, Anneloes L.

    2016-01-01

    Background Depression during adolescence is a serious mental health problem. Difficulties in regulating evoked emotions after stressful life events are considered to lead to depression. This study examined if depressive symptoms were mediated by various cognitive emotion regulation strategies after stressful life events, more specifically, the loss of a loved one, health threats or relational challenges. Methods We used a sample of 398 adolescents (Mage = 16.94, SD = 2.90), including 52 depressed outpatients, who all reported stressful life event(s). Path analyses in Mplus were used to test mediation, for the whole sample as well as separately for participants scoring high versus low on depression, using multigroup analyses. Results Health threats and relational challenging stressful life events were associated with depressive symptoms, while loss was not. More frequent use of maladaptive strategies was related to more depressive symptoms. More frequent use of adaptive strategies was related to less depressive symptoms. Specific life events were associated with specific emotion regulation strategies. The relationship between challenging, stressful life events and depressive symptoms in the whole group was mediated by maladaptive strategies (self-blame, catastrophizing and rumination). No mediation effect was found for adaptive strategies. Conclusion The association between relational challenging, stressful life events and depressive symptoms was mediated by maladaptive, cognitive emotion regulation strategies. PMID:27571274

  20. Self-reflection and set-shifting mediate awareness in cognitively preserved schizophrenia patients.

    Science.gov (United States)

    Gilleen, James; David, Anthony; Greenwood, Kathryn

    2016-05-01

    Poor insight in schizophrenia has been linked to poor cognitive functioning, psychological processes such as denial, or more recently with impaired metacognitive capacity. Few studies, however, have investigated the potential co-dependency of multiple factors in determining level of insight, but such a model is necessary in order to account for patients with good cognitive functioning who have very poor awareness. As evidence suggests that set-shifting and cognitive insight (self-reflection (SR) and self-certainty) are strong predictors of awareness we proposed that these factors are key mediators in the relationship between cognition and awareness. We hypothesised that deficits specifically in SR and set-shifting determine level of awareness in the context of good cognition. Thirty schizophrenia patients were stratified by high and low awareness of illness and executive functioning scores. Cognitive insight, cognition, mood and symptom measures were compared between sub-groups. A low insight/high executive functioning (LI-HE) group, a high insight/high executive functioning (HI-HE) group and a low insight/low executive functioning (LI-LE) group were revealed. As anticipated, the LI-HE patients showed significantly lower capacity for SR and set-shifting than the HI-HE patients. This study indicates that good cognitive functioning is necessary but not sufficient for good awareness; good awareness specifically demands preserved capacity to self-reflect and shift-set. Results support Nelson and Narens' [1990. Metamemory: A theoretical framework and new findings. The Psychology of Learning and Motivation, 26, 125-173] model of metacognition by which awareness is founded on control (set-shifting) and monitoring (SR) processes. These specific factors could be targeted to improve insight in patients with otherwise unimpaired cognitive function.

  1. Procrastination and suicide proneness: A moderated-mediation model for cognitive schemas and gender.

    Science.gov (United States)

    Klibert, Jeffrey; LeLeux-LaBarge, Kayla; Tarantino, Nicholas; Yancey, Thresa; Lamis, Dorian A

    2016-07-01

    This study examined the direct and indirect paths between procrastination and suicide proneness while considering gender differences. Participants included 547 undergraduates from a southeastern university. Procrastination was positively related to suicide proneness for both genders, although this relation was stronger for women. Moderated-mediation analyses with bootstrapping highlighted insufficient self-control schemas as a mediator in the relation between procrastination and suicide proneness. However, indirect pathways did not vary by gender. Results represent an extension of the Procrastination-Health Model by highlighting the contribution of cognitive factors in explaining the relation between procrastination and suicide proneness.

  2. Neural Reactivity to Emotional Faces May Mediate the Relationship between Childhood Empathy and Adolescent Prosocial Behavior

    Science.gov (United States)

    Flournoy, John C.; Pfeifer, Jennifer H.; Moore, William E.; Tackman, Allison M.; Masten, Carrie L.; Mazziotta, John C.; Iacoboni, Marco; Dapretto, Mirella

    2016-01-01

    Reactivity to others' emotions not only can result in empathic concern (EC), an important motivator of prosocial behavior, but can also result in personal distress (PD), which may hinder prosocial behavior. Examining neural substrates of emotional reactivity may elucidate how EC and PD differentially influence prosocial behavior. Participants…

  3. Neuroanatomical and cognitive mediators of age-related differences in perceptual priming and learning

    OpenAIRE

    Kennedy, Kristen M.; Rodrigue, Karen M.; Head, Denise; Gunning-Dixon, Faith; Raz, Naftali

    2009-01-01

    Our objectives were to assess age differences in perceptual repetition priming and perceptual skill learning, and to determine whether they are mediated by cognitive resources and regional cerebral volume differences. Fragmented picture identification paradigm allows the study of both priming and learning within the same task. We presented this task to 169 adults (ages 18–80), assessed working memory and fluid intelligence, and measured brain volumes of regions that were deemed relevant to th...

  4. Cognitive appraisal as a mediator in the relationship between stress and burnout

    OpenAIRE

    Gomes, António Rui; Faria, Susana; Gonçalves, A. Manuela

    2013-01-01

    The relation between job stressors and burnout is well established in the literature. However, the mechanisms behind this relationship are still not clear. Thus, this study has the main goal of analysing the mediating role of cognitive appraisal on the relation between occupational stress and burnout. To test this relation, structural equation modelling was used in a sample of teachers (N=333) working at a public university in the north of Portugal. The participants answered a protocol with m...

  5. The Principle of Transparency of the Sign and the Problem of Cognitive Mediation and Epistemological Immediatism

    Directory of Open Access Journals (Sweden)

    Józef Dębowski

    2011-12-01

    Full Text Available The article consists of two parts. In the first part (I three different formulations of the principle of the transparency of the sign are described. In the first description (E. Husserl it is said that the sign in a proper sense (both an iconic and conventional one is transparent for its denotations. In the second description (A. Schaff only the transparence of its meaning is admitted. As far as the third description is concerned (L. Koj conviction, that every sign is transparent both for a signed object and its meaning, is typical. In the second part of the article (II we consider relationship between the principle of the transparency of the sign and traditional distinction between “transparent” and “opaque” cognitive mediator – distinction between medium quo and medium quod . The main conclusion of this article is included in a thesis that linguistic cognition and significative cognition – because it isn’t a direct cognition in the sense of primary directness (perceptive – isn’t able to guarantee a source of access to a cognized object, so it is not a direct cognition in a proper sense. It means that the transparency of the sign, when it appears in the face of its denotations (E. Husserl’s interpretations a sign or a system of signs are not able to function as a transparent mediator, i e medium quo . It is like that because – as E. Husserl noticed – the sign (due to its transparency indeed shows us its denotations, but always through the mediation of its meaning and some significative intention. 

  6. Cognitive behavioural therapy for MS-related fatigue explained: A longitudinal mediation analysis.

    Science.gov (United States)

    van den Akker, L E; Beckerman, H; Collette, E H; Knoop, H; Bleijenberg, G; Twisk, J W; Dekker, J; de Groot, V

    2018-03-01

    Cognitive behavioural therapy (CBT) effectively reduces fatigue directly following treatment in patients with Multiple Sclerosis (MS), but little is known about the process of change during and after CBT. Additional analysis of a randomized clinical trial. To investigate which psychological factors mediate change in fatigue during and after CBT. TREFAMS-CBT studied the effectiveness of a 16-week CBT treatment for MS-related fatigue. Ninety-one patients were randomized (44 to CBT, 47 to the MS-nurse consultations). Mediation during CBT treatment was studied using assessments at baseline, 8 and 16weeks. Mediation of the change in fatigue from post-treatment to follow-up was studied separately using assessments at 16, 26 and 52weeks. Proposed mediators were: changes in illness cognitions, general self-efficacy, coping styles, daytime sleepiness, concentration and physical activity, fear of disease progression, fatigue perceptions, depression and physical functioning. Mediators were separately analysed according to the product-of-coefficients approach. Confidence intervals were calculated with a bootstrap procedure. During treatment the decrease in fatigue brought on by CBT was mediated by improved fatigue perceptions, increased physical activity, less sleepiness, less helplessness, and improved physical functioning. Post-treatment increases in fatigue levels were mediated by reduced physical activity, reduced concentration, and increased sleepiness. These results suggests that focusing on improving fatigue perceptions, perceived physical activity, daytime sleepiness, helplessness, and physical functioning may further improve the effectiveness of CBT for fatigue in patients with MS. Maintenance of treatment effects may be obtained by focusing on improving physical activity, concentration and sleepiness. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. The Williams syndrome prosociality gene GTF2I mediates oxytocin reactivity and social anxiety in a healthy population.

    Science.gov (United States)

    Procyshyn, Tanya L; Spence, Jason; Read, Silven; Watson, Neil V; Crespi, Bernard J

    2017-04-01

    The neurohormone oxytocin plays a central role in human social behaviour and cognition, and oxytocin dysregulation may contribute to psychiatric disorders. However, genetic factors influencing individual variation in the oxytocinergic system remain poorly understood. We genotyped 169 healthy adults for a functional polymorphism in GTF2I ( general transcription factor II-I ), a gene associated with high prosociality and reduced social anxiety in Williams syndrome, a condition reported to involve high oxytocin levels and reactivity. Participants' salivary oxytocin levels were measured before and after watching a validated empathy-inducing video. Oxytocin reactivity, defined as pre- to post-video percentage change in salivary oxytocin, varied substantially and significantly between individuals with different GTF2I genotypes, with, additionally, a trend towards an interaction between genotype and sex. Individuals with more oxytocin-reactive genotypes also reported significantly lower social anxiety. These findings suggest a model whereby GTF2I has a continuum of effects on human sociality, from the extreme social phenotypes and oxytocin dysregulation associated with gene deletion in Williams syndrome, to individual differences in oxytocin reactivity and sociality associated with common polymorphisms in healthy populations. © 2017 The Author(s).

  8. Deliberate play and preparation jointly benefit motor and cognitive development: mediated and moderated effects

    Directory of Open Access Journals (Sweden)

    Caterina ePesce

    2016-03-01

    Full Text Available In light of the interrelation between motor and cognitive development and the predictive value of the former for the latter, the secular decline observed in motor coordination ability as early as preschool urges identification of interventions that may jointly impact motor and cognitive efficiency.The aim of this study was twofold. It (1 explored the outcomes of enriched physical education, centered on deliberate play and cognitively challenging variability of practice, on motor coordination and cognitive processing; (2 examined whether motor coordination outcomes mediate intervention effects on children’s cognition, while controlling for moderation by lifestyle factors as outdoor play habits and weight status. Four hundred and sixty children aged 5-10 years participated in a 6-month group randomized intervention in physical education, with or without playful coordinative and cognitive enrichment. The weight status and spontaneous outdoor play habits of children (parental report of outdoor play were evaluated at baseline. Before and after the intervention, motor developmental level (Movement Assessment Battery for Children was evaluated in all children, who were then assessed either with a test of working memory (Random Number Generation task, or with a test of attention (from the Cognitive Assessment System, CAS.Children assigned to the ‘enriched’ intervention showed more pronounced improvements in all motor coordination assessments (manual dexterity, ball skills, static/dynamic balance. The beneficial effect on ball skills was amplified by the level of spontaneous outdoor play and weight status. Among indices of executive function and attention, only that of inhibition showed a differential effect of intervention type. Moderated mediation showed that the better outcome of the enriched physical education on ball skills mediated the better inhibition outcome, but only when the enrichment intervention was paralleled by a medium

  9. Mediated moderation in combined cognitive behavioral therapy versus component treatments for generalized anxiety disorder.

    Science.gov (United States)

    Newman, Michelle G; Fisher, Aaron J

    2013-06-01

    This study examined (a) duration of generalized anxiety disorder (GAD) as a moderator of cognitive behavioral therapy (CBT) versus its components (cognitive therapy and self-control desensitization) and (b) increases in dynamic flexibility of anxious symptoms during the course of psychotherapy as a mediator of this moderation. Degree of dynamic flexibility in daily symptoms was quantified as the inverse of spectral power due to daily to intradaily oscillations in four-times-daily diary data (Fisher, Newman, & Molenaar, 2011). This was a secondary analysis of the data of Borkovec, Newman, Pincus, and Lytle (2002). Seventy-six participants with a principle diagnosis of GAD were assigned randomly to combined CBT (n = 24), cognitive therapy (n = 25), or self-control desensitization (n = 27). Duration of GAD moderated outcome such that those with longer duration showed greater reliable change from component treatments than they showed from CBT, whereas those with shorter duration fared better in response to CBT. Decreasing predictability in daily and intradaily oscillations of anxiety symptoms during therapy reflected less rigidity and more flexible responding. Increases in flexibility over the course of therapy fully mediated the moderating effect of GAD duration on condition, indicating a mediated moderation process. Individuals with longer duration of GAD may respond better to more focused treatments, whereas those with shorter duration of GAD may respond better to a treatment that offers more coping strategies. Importantly, the mechanism by which this moderation occurs appears to be the establishment of flexible responding during treatment.

  10. How does emotion influence different creative performances? The mediating role of cognitive flexibility.

    Science.gov (United States)

    Lin, Wei-Lun; Tsai, Ping-Hsun; Lin, Hung-Yu; Chen, Hsueh-Chih

    2014-01-01

    Cognitive flexibility is proposed to be one of the factors underlying how positive emotions can improve creativity. However, previous works have seldom set up or empirically measured an independent index to demonstrate its mediating effect, nor have they investigated its mediating role on different types of creative performances, which involve distinct processes. In this study, 120 participants were randomly assigned to positive, neutral or negative affect conditions. Their levels of cognitive flexibility were then measured by a switch task. Finally, their creative performances were calibrated by either an open-ended divergent thinking test or a closed-ended insight problem-solving task. The results showed that positive emotional states could reduce switch costs and enhance both types of creative performances. However, cognitive flexibility exhibited a full mediating effect only on the relationship between positive emotion and insight problem solving, but not between positive emotion and divergent thinking. Divergent thinking was instead more associated with arousal level. These results suggest that emotions might influence different creative performances through distinct mechanisms.

  11. Parental Cognitive Errors Mediate Parental Psychopathology and Ratings of Child Inattention.

    Science.gov (United States)

    Haack, Lauren M; Jiang, Yuan; Delucchi, Kevin; Kaiser, Nina; McBurnett, Keith; Hinshaw, Stephen; Pfiffner, Linda

    2017-09-01

    We investigate the Depression-Distortion Hypothesis in a sample of 199 school-aged children with ADHD-Predominantly Inattentive presentation (ADHD-I) by examining relations and cross-sectional mediational pathways between parental characteristics (i.e., levels of parental depressive and ADHD symptoms) and parental ratings of child problem behavior (inattention, sluggish cognitive tempo, and functional impairment) via parental cognitive errors. Results demonstrated a positive association between parental factors and parental ratings of inattention, as well as a mediational pathway between parental depressive and ADHD symptoms and parental ratings of inattention via parental cognitive errors. Specifically, higher levels of parental depressive and ADHD symptoms predicted higher levels of cognitive errors, which in turn predicted higher parental ratings of inattention. Findings provide evidence for core tenets of the Depression-Distortion Hypothesis, which state that parents with high rates of psychopathology hold negative schemas for their child's behavior and subsequently, report their child's behavior as more severe. © 2016 Family Process Institute.

  12. Repetitive Hyperbaric Oxygenation Attenuates Reactive Astrogliosis and Suppresses Expression of Inflammatory Mediators in the Rat Model of Brain Injury

    Directory of Open Access Journals (Sweden)

    Irena Lavrnja

    2015-01-01

    Full Text Available The exact mechanisms by which treatment with hyperbaric oxygen (HBOT exerts its beneficial effects on recovery after brain injury are still unrevealed. Therefore, in this study we investigated the influence of repetitive HBOT on the reactive astrogliosis and expression of mediators of inflammation after cortical stab injury (CSI. CSI was performed on male Wistar rats, divided into control, sham, and lesioned groups with appropriate HBO. The HBOT protocol was as follows: 10 minutes of slow compression, 2.5 atmospheres absolute (ATA for 60 minutes, and 10 minutes of slow decompression, once a day for 10 consecutive days. Data obtained using real-time polymerase chain reaction, Western blot, and immunohistochemical and immunofluorescence analyses revealed that repetitive HBOT applied after the CSI attenuates reactive astrogliosis and glial scarring, and reduces expression of GFAP (glial fibrillary acidic protein, vimentin, and ICAM-1 (intercellular adhesion molecule-1 both at gene and tissue levels. In addition, HBOT prevents expression of CD40 and its ligand CD40L on microglia, neutrophils, cortical neurons, and reactive astrocytes. Accordingly, repetitive HBOT, by prevention of glial scarring and limiting of expression of inflammatory mediators, supports formation of more permissive environment for repair and regeneration.

  13. Relationship between cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers: Exploring multiple mediation model.

    Science.gov (United States)

    Cai, Wen-Peng; Pan, Yu; Zhang, Shui-Miao; Wei, Cun; Dong, Wei; Deng, Guang-Hui

    2017-10-01

    The current study aimed to explore the association of cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers and to understand the multiple mediation effects of social support and resilience on the relationship between cognitive emotion regulation and acute stress responses. A total of 1477 male soldiers completed mental scales, including the cognitive emotion regulation questionnaire-Chinese version, the perceived social support scale, the Chinese version of the Connor-Davidson resilience scale, and the military acute stress scale. As hypothesized, physiological responses, psychological responses, and acute stress were associated with negative-focused cognitive emotion regulation, and negatively associated with positive-focused cognitive emotion regulation, social supports and resilience. Besides, positive-focused cognitive emotion regulation, social support, and resilience were significantly associated with one another, and negative-focused cognitive emotion regulation was negatively associated with social support. Regression analysis and bootstrap analysis showed that social support and resilience had partly mediating effects on negative strategies and acute stress, and fully mediating effects on positive strategies and acute stress. These results thus indicate that military acute stress is significantly associated with cognitive emotion regulation, social support, and resilience, and that social support and resilience have multiple mediation effects on the relationship between cognitive emotion regulation and acute stress responses. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Blood Pressure Reactivity to Psychological Stress in Young Adults and Cognition in Midlife: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

    Science.gov (United States)

    Yano, Yuichiro; Ning, Hongyan; Reis, Jared P; Lewis, Cora E; Launer, Lenore J; Bryan, R Nick; Yaffe, Kristine; Sidney, Stephen; Albanese, Emiliano; Greenland, Philip; Lloyd-Jones, Donald; Liu, Kiang

    2016-01-13

    The classic view of blood pressure (BP) reactivity to psychological stress in relation to cardiovascular risks assumes that excess reactivity is worse and lower reactivity is better. Evidence addressing how stress-induced BP reactivity in young adults is associated with midlife cognitive function is sparse. We assessed BP reactivity during a star tracing task and a video game in adults aged 20 to 32 years. Twenty-three years later, cognitive function was assessed with use of the Digit Symbol Substitution Test (a psychomotor speed test), the Rey Auditory Verbal Learning Test (a verbal memory test), and the modified Stroop test (an executive function test). At the time of follow-up, participants (n=3021) had a mean age of 50.2 years; 56% were women, and 44% were black. In linear regression models adjusted for demographic and clinical characteristics including baseline and follow-up resting BP, lower systolic BP (SBP) reactivity during the star tracing and video game was associated with worse Digit Symbol Substitution Test scores (β [SE]: 0.11 [0.02] and 0.05 [0.02], respectively) and worse performance on the Stroop test (β [SE]: -0.06 [0.02] and -0.05 [0.02]; all Pstress-induced SBP reactivity in younger adults was associated with lower cognitive function in midlife. BP reactivity to psychological stressors may have different associations with target organs in hypertension. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  15. Cognitions as mediators in the relationship between self-compassion and affect

    Science.gov (United States)

    Arimitsu, Kohki; Hofmann, Stefan G.

    2014-01-01

    Previous studies suggest that self-compassion is related to numerous facets of mental health, but the role of cognitions in this relationship remains unknown. To examine the mediating role of cognitions in the relationship between self-compassion and anxiety, depression, and life satisfaction when controlling for self-esteem in Japanese people, we conducted two studies. Study 1 (N = 231) examined the relationship between self-compassion and affect by modeling negative automatic thoughts as a mediator; Study 2 (N = 233) tested whether positive and negative automatic thoughts meditate this relationship. Results suggested that both self-compassion and self-esteem increased positive automatic thoughts and decreased trait anxiety, whereas only self-esteem increased life satisfaction and decreased depression directly. Positive automatic thoughts increased life satisfaction and decreased depression and trait anxiety, and positive automatic thoughts mediated the relationship between self-compassion and negative affect. These findings suggest that both positive and negative automatic thoughts mediate the relationship between self-compassion and affect in Japanese people. PMID:25395717

  16. Cortisol response mediates the effect of post-reactivation stress exposure on contextualization of emotional memories

    NARCIS (Netherlands)

    Bos, M.G.N.; Jacobs van Goethem, T.H.; Beckers, T.; Kindt, M.

    2014-01-01

    Retrieval of traumatic experiences is often accompanied by strong feelings of distress. Here, we examined in healthy participants whether post-reactivation stress experience affects the context-dependency of emotional memory. First, participants studied words from two distinctive emotional

  17. An Examination of Mediators of the Transfer of Cognitive Speed of Processing Training to Everyday Functional Performance

    OpenAIRE

    Edwards, Jerri D.; Ruva, Christine L.; O’Brien, Jennifer L.; Haley, Christine B.; Lister, Jennifer J.

    2012-01-01

    The purpose of these analyses was to examine mediators of the transfer of cognitive speed of processing training to improved everyday functional performance (Edwards, Wadley, Vance, Roenker, & Ball, 2005). Cognitive speed of processing and visual attention (as measured by the Useful Field of View Test; UFOV) were examined as mediators of training transfer. Secondary data analyses were conducted from the Staying Keen in Later Life (SKILL) study, a randomized cohort study including 126 communit...

  18. Cognitive Changes during Prolonged Stay at High Altitude and Its Correlation with C-Reactive Protein.

    Directory of Open Access Journals (Sweden)

    Sheng Li Hu

    Full Text Available Hypersensitive C-reaction protein (hsCRP may be a risk factor for cognitive impairment resulting from Alzheimer's disease (AD, stroke, and vascular dementia. This study explored the correlation of peripheral blood hsCRP level with cognitive decline due to high altitude exposure. The study was conducted on 100 male military participants who had never been to high altitude. Cerebral oxygen saturation monitoring, event related potentials (P300, N200 detection, and neurocognitive assessment was performed and total hsCRP, interleukin-6 (IL-6, and homocysteine was estimated at 500 m altitude, 3650 m altitude, 3 day, 1, and 3 month post arriving at the base camp (4400 m, and 1 month after coming back to the 500 m altitude. High altitude increased brain oxygen saturation, prolonged P300 and N200 latencies, injured cognitive functions, and raised plasma hsCRP levels. But they all recovered in varying degrees at 1 and 3 month post arriving at the base camp (4400 m. P300 latencies and hsCRP levels were strongly correlated to cognitive performances. These results suggested that cognitive deterioration occurred during the acute period of exposure to high altitude and may recover probably owning to acclimatization after extended stay at high altitude. Plasma hsCRP is inversely correlated to neurological cognition and it may be a potential biomarker for the prediction of high altitude induced cognitive dysfunction.

  19. Induction of Tca8113 tumor cell apoptosis by icotinib is associated with reactive oxygen species mediated p38-MAPK activation.

    Science.gov (United States)

    Yang, Cailing; Yan, Jianguo; Yuan, Guoyan; Zhang, Yinghua; Lu, Derong; Ren, Mingxin; Cui, Weigang

    2014-08-01

    Icotinib, a selective EGFR tyrosine kinase inhibitor (EGFR-TKI), has been shown to exhibit anti-tumor activity against several tumor cell lines. However, the exact molecular mechanism of icotinib's anti-tumor effect remains unknown. This study aims to examine the zytotoxic effect of icotinib on Tca8113 cells and its potential molecular mechanism. Icotinib significantly resulted in dose-dependent cell death as determined by MTT assay, accompanied by increased levels of Bax and DNA fragmentation. Icotinib could also induce Reactive Oxygen Species (ROS) generation. Further studies confirmed that scavenging of reactive oxygen species by N-acetyl-L-cysteine (NAC), and pharmacological inhibition of MAPK reversed icotinib-induced apoptosis in Tca8113 cells. Our data provide evidence that icotinib induces apoptosis, possibly via ROS-mediated MAPK pathway in Tca8113 cells.

  20. BMP signaling mediates effects of exercise on hippocampal neurogenesis and cognition in mice.

    Directory of Open Access Journals (Sweden)

    Kevin T Gobeske

    2009-10-01

    Full Text Available Exposure to exercise or to environmental enrichment increases the generation of new neurons in the adult hippocampus and promotes certain kinds of learning and memory. While the precise role of neurogenesis in cognition has been debated intensely, comparatively few studies have addressed the mechanisms linking environmental exposures to cellular and behavioral outcomes. Here we show that bone morphogenetic protein (BMP signaling mediates the effects of exercise on neurogenesis and cognition in the adult hippocampus. Elective exercise reduces levels of hippocampal BMP signaling before and during its promotion of neurogenesis and learning. Transgenic mice with decreased BMP signaling or wild type mice infused with a BMP inhibitor both exhibit remarkable gains in hippocampal cognitive performance and neurogenesis, mirroring the effects of exercise. Conversely, transgenic mice with increased BMP signaling have diminished hippocampal neurogenesis and impaired cognition. Exercise exposure does not rescue these deficits, suggesting that reduced BMP signaling is required for environmental effects on neurogenesis and learning. Together, these observations show that BMP signaling is a fundamental mechanism linking environmental exposure with changes in cognitive function and cellular properties in the hippocampus.

  1. Reactive Oxygen Species-Mediated Loss of Synaptic Akt1 Signaling Leads to Deficient Activity-Dependent Protein Translation Early in Alzheimer's Disease.

    Science.gov (United States)

    Ahmad, Faraz; Singh, Kunal; Das, Debajyoti; Gowaikar, Ruturaj; Shaw, Eisha; Ramachandran, Arathy; Rupanagudi, Khader Valli; Kommaddi, Reddy Peera; Bennett, David A; Ravindranath, Vijayalakshmi

    2017-12-01

    Synaptic deficits are known to underlie the cognitive dysfunction seen in Alzheimer's disease (AD). Generation of reactive oxygen species (ROS) by β-amyloid has also been implicated in AD pathogenesis. However, it is unclear whether ROS contributes to synaptic dysfunction seen in AD pathogenesis and, therefore, we examined whether altered redox signaling could contribute to synaptic deficits in AD. Activity dependent but not basal translation was impaired in synaptoneurosomes from 1-month old presymptomatic APP Swe /PS1ΔE9 (APP/PS1) mice, and this deficit was sustained till middle age (MA, 9-10 months). ROS generation leads to oxidative modification of Akt1 in the synapse and consequent reduction in Akt1-mechanistic target of rapamycin (mTOR) signaling, leading to deficiency in activity-dependent protein translation. Moreover, we found a similar loss of activity-dependent protein translation in synaptoneurosomes from postmortem AD brains. Loss of activity-dependent protein translation occurs presymptomatically early in the pathogenesis of AD. This is caused by ROS-mediated loss of pAkt1, leading to reduced synaptic Akt1-mTOR signaling and is rescued by overexpression of Akt1. ROS-mediated damage is restricted to the synaptosomes, indicating selectivity. We demonstrate that ROS-mediated oxidative modification of Akt1 contributes to synaptic dysfunction in AD, seen as loss of activity-dependent protein translation that is essential for synaptic plasticity and maintenance. Therapeutic strategies promoting Akt1-mTOR signaling at synapses may provide novel target(s) for disease-modifying therapy in AD. Antioxid. Redox Signal. 27, 1269-1280.

  2. Direct and Mediated Effects of Language and Cognitive Skills on Comprehension or Oral Narrative Texts (Listening Comprehension) for Children

    Science.gov (United States)

    Kim, Young-Suk Grace

    2016-01-01

    We investigated component language and cognitive skills of oral language comprehension of narrative texts (i.e., listening comprehension). Using the construction--integration model of text comprehension as an overarching theoretical framework, we examined direct and mediated relations of foundational cognitive skills (working memory and…

  3. The Applicability of Cognitive Mediational and Moderational Models to Explain Children's Depression Inventory Factor Scores in Urban Youth

    Science.gov (United States)

    Reinemann, Dawn H. S.; Teeter Ellison, Phyllis A.

    2004-01-01

    This investigation examined whether cognition serves as a direct factor, mediates, or moderates the relationship between stressful life events and Children's Depression Inventory (CDI; Kovacs, 1992) factor scores in urban, ethnic minority youth. Ninety-eight middle school students completed measures of stressful life events, cognition (cognitive…

  4. Reactive relay selection in underlay cognitive networks with fixed gain relays

    KAUST Repository

    Hussain, Syed Imtiaz; Alouini, Mohamed-Slim; Qaraqe, Khalid A.; Hasna, Mazen Omar

    2012-01-01

    Best relay selection is a bandwidth efficient technique for multiple relay environments without compromising the system performance. The problem of relay selection is more challenging in underlay cognitive networks due to strict interference

  5. Menadione induces the formation of reactive oxygen species and depletion of GSH-mediated apoptosis and inhibits the FAK-mediated cell invasion.

    Science.gov (United States)

    Kim, Yun Jeong; Shin, Yong Kyoo; Sohn, Dong Suep; Lee, Chung Soo

    2014-09-01

    Menadione induces apoptosis in tumor cells. However, the mechanism of apoptosis in ovarian cancer cells exposed to menadione is not clear. In addition, it is unclear whether menadione-induced apoptosis is mediated by the depletion of glutathione (GSH) contents that is associated with the formation of reactive oxygen species. Furthermore, the effect of menadione on the invasion and migration of human epithelial ovarian cancer cells has not been studied. Therefore, we investigated the effects of menadione exposure on apoptosis, cell adhesion, and cell migration using the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3. The results suggest that menadione may induce apoptotic cell death in ovarian carcinoma cell lines by activating the mitochondrial pathway and the caspase-8- and Bid-dependent pathways. The apoptotic effect of menadione appears to be mediated by the formation of reactive oxygen species and the depletion of GSH. Menadione inhibited fetal-bovine-serum-induced cell adhesion and migration of OVCAR-3 cells, possibly through the suppression the focal adhesion kinase (FAK)-dependent activation of cytoskeletal-associated components. Therefore, menadione might be beneficial in the treatment of epithelial ovarian adenocarcinoma and combination therapy.

  6. Social cognitive mediators of the effect of the MobileMums intervention on physical activity.

    Science.gov (United States)

    Fjeldsoe, Brianna S; Miller, Yvette D; Marshall, Alison L

    2013-07-01

    To explore whether improvements in physical activity following the MobileMums intervention were mediated by changes in Social Cognitive Theory (SCT) constructs targeted in the intervention (barrier self efficacy, goal setting skills, outcome expectancy, social support, and perceived environmental opportunity for exercise). This paper also examined if the mediating constructs differed between initial (baseline to 6 weeks) and overall (baseline to 13 weeks) changes in physical activity. Secondary analysis of data from a randomized controlled trial involving 88 postnatal women (Exercise frequency was assessed using the Australian Women's Activity Survey and frequency of moderate-to-vigorous physical activity (MVPA) was assessed using a single-item question. Initial improvements in goal-setting skills mediated the relationship between experimental condition and initial changes in MVPA, αβ (95% CI) = 0.23(0.01, 0.59), and Walking for Exercise, αβ (95% CI) = 0.34(0.06, 0.73). Initial improvements in barrier self efficacy mediated the relationship between experimental condition and initial change in MVPA, αβ (95% CI) = 0.36(0.12, 0.65), but not Walking for Exercise. None of the SCT outcomes significantly mediated the relationship between experimental condition and overall (baseline to 13 weeks) change in frequency of MVPA or Walking for Exercise. Future interventions with postnatal women using SCT should target barrier self-efficacy and goal setting skills in order to increase physical activity. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  7. Beyond cognitive framing processes: anger mediates the effects of responsibility framing on the preference for punitive measures

    NARCIS (Netherlands)

    Kühne, R.J.; Weber, P.; Sommer, K.

    2015-01-01

    A new stream of research indicates that framing effects are based on emotional as well as cognitive processes. However, it is not entirely clear whether emotions mediate framing effects and what the moderators of emotional mediation processes are. To address these questions, we conducted an

  8. Embodiment in tests of cognitive functioning: A study of an interpreter-mediated dementia evaluation.

    Science.gov (United States)

    Majlesi, Ali Reza; Plejert, Charlotta

    2018-02-01

    This study explores how manners of mediation, and the use of embodiment in interpreter-mediated conversation have an impact on tests of cognitive functioning in a dementia evaluation. By a detailed analysis of video recordings, we show how participants-an occupational therapist, an interpreter, and a patient-use embodied practices to make the tasks of a test of cognitive functioning intelligible, and how participants collaboratively put the instructions of the tasks into practice. We demonstrate that both instructions and instructed actions-and the whole procedure of accomplishing the tasks-are shaped co-operatively by embodied practices of all three participants involved in the test situation. Consequently, the accomplishment of the tasks should be viewed as the outcome of a collaborative achievement of instructed actions, rather than an individual product. The result of the study calls attention to issues concerning interpretations of, and the reliability of interpreter-mediated tests and their bearings for diagnostic procedures in dementia evaluations.

  9. Reactivity to Stress and the Cognitive Components of Math Disability in Grade 1 Children

    Science.gov (United States)

    MacKinnon McQuarrie, Maureen A.; Siegel, Linda S.; Perry, Nancy E.; Weinberg, Joanne

    2014-01-01

    This study investigated the relationship among working memory, processing speed, math performance, and reactivity to stress in 83 Grade 1 children. Specifically, 39 children with math disability (MD) were compared to 44 children who are typically achieving (TA) in mathematics. It is the first study to use a physiological index of stress (salivary…

  10. Cr(VI) induces mitochondrial-mediated and caspase-dependent apoptosis through reactive oxygen species-mediated p53 activation in JB6 Cl41 cells

    International Nuclear Information System (INIS)

    Son, Young-Ok; Hitron, J. Andrew; Wang Xin; Chang Qingshan; Pan Jingju; Zhang Zhuo; Liu Jiankang; Wang Shuxia; Lee, Jeong-Chae; Shi Xianglin

    2010-01-01

    Cr(VI) compounds are known to cause serious toxic and carcinogenic effects. Cr(VI) exposure can lead to a severe damage to the skin, but the mechanisms involved in the Cr(VI)-mediated toxicity in the skin are unclear. The present study examined whether Cr(VI) induces cell death by apoptosis or necrosis using mouse skin epidermal cell line, JB6 Cl41 cells. We also investigated the cellular mechanisms of Cr(VI)-induced cell death. This study showed that Cr(VI) induced apoptotic cell death in a dose-dependent manner, as demonstrated by the appearance of cell shrinkage, the migration of cells into the sub-G1 phase, the increase of Annexin V positively stained cells, and the formation of nuclear DNA ladders. Cr(VI) treatment resulted in the increases of mitochondrial membrane depolarization and caspases activation. Electron spin resonance (ESR) and fluorescence analysis revealed that Cr(VI) increased intracellular levels of reactive oxygen species (ROS) such as hydrogen peroxide and superoxide anion radical in dose-dependent manner. Blockage of p53 by si-RNA transfection suppressed mitochondrial changes of Bcl-2 family composition, mitochondrial membrane depolarization, caspase activation and PARP cleavage, leading to the inhibition of Cr(VI)-induced apoptosis. Further, catalase treatment prevented p53 phosphorylation stimulated by Cr(VI) with the concomitant inhibition of caspase activation. These results suggest that Cr(VI) induced a mitochondrial-mediated and caspase-dependent apoptosis in skin epidermal cells through activation of p53, which are mainly mediated by reactive oxidants generated by the chemical.

  11. Burden and Cognitive Appraisal of Stroke Survivors' Informal Caregivers: An Assessment of Depression Model With Mediating and Moderating Effects.

    Science.gov (United States)

    Tsai, Yi-Chen; Pai, Hsiang-Chu

    2016-04-01

    This study proposes and evaluates a model of depression that concerns the role of burden and cognitive appraisal as mediators or moderators of outcomes among stroke survivor caregivers. A total of 105 informal caregivers of stroke survivor completed the self-report measures of Caregiver Burden Inventory, Center for Epidemiologic Studies Depression Scale, and Cognitive Impact of Appraisal Scale. The Glasgow Coma Scale and Barthel Index were used by the researcher to examine the physical functional status of the survivor. Partial least squares (PLS) path modeling was used to estimate the parameters of a depression model that included mediating or moderating effects. The model shows that burden and impact of cognitive appraisal have a significant direct and indirect impact on depression, while survivor physical functional status does not have a direct impact. The model also demonstrates that burden and impact of cognitive appraisal separately play a mediating role between survivor physical functional status and caregiver depression. In addition, cognitive appraisal has a moderating influence on the relationship between burden and depression. Overall, survivor physical functional status, burden, and cognitive appraisal were the predictors of caregiver depression, explaining 47.1% of the variance. This study has shown that burden and cognitive appraisal are mediators that more fully explain the relationship between patient severity and caregiver depression. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Do Executive and Reactive Disinhibition Mediate the Effects of Familial Substance Use Disorders on Adolescent Externalizing Outcomes?

    Science.gov (United States)

    Handley, Elizabeth D.; Chassin, Laurie; Haller, Moira M.; Bountress, Kaitlin E.; Dandreaux, Danielle; Beltran, Iris

    2011-01-01

    The present study examined the potential mediating roles of executive and reactive disinhibition in predicting conduct problems, ADHD symptoms, and substance use among adolescents with and without a family history of substance use disorders. Using data from 247 high-risk adolescents, parents, and grandparents, structural equation modeling indicated that reactive disinhibition, as measured by sensation seeking, mediated the effect of familial drug use disorders on all facets of the adolescent externalizing spectrum. Executive disinhibition, as measured by response disinhibition, spatial short term memory, and “trait” impulsivity, was associated with ADHD symptoms. Moreover, although executive functioning weakness were unrelated to familial substance use disorders, adolescents with familial alcohol use disorders were at risk for “trait” impulsivity marked by a lack of planning. These results illustrate the importance of “unpacking” the broad temperament style of disinhibition and of studying the processes that underlie the commonality among facets of the externalizing spectrum and processes that that predict specific externalizing outcomes. PMID:21668077

  13. Listening to music and physiological and psychological functioning: the mediating role of emotion regulation and stress reactivity.

    Science.gov (United States)

    Thoma, M V; Scholz, U; Ehlert, U; Nater, U M

    2012-01-01

    Music listening has been suggested to have short-term beneficial effects. The aim of this study was to investigate the association and potential mediating mechanisms between various aspects of habitual music-listening behaviour and physiological and psychological functioning. An internet-based survey was conducted in university students, measuring habitual music-listening behaviour, emotion regulation, stress reactivity, as well as physiological and psychological functioning. A total of 1230 individuals (mean = 24.89 ± 5.34 years, 55.3% women) completed the questionnaire. Quantitative aspects of habitual music-listening behaviour, i.e. average duration of music listening and subjective relevance of music, were not associated with physiological and psychological functioning. In contrast, qualitative aspects, i.e. reasons for listening (especially 'reducing loneliness and aggression', and 'arousing or intensifying specific emotions') were significantly related to physiological and psychological functioning (all p = 0.001). These direct effects were mediated by distress-augmenting emotion regulation and individual stress reactivity. The habitual music-listening behaviour appears to be a multifaceted behaviour that is further influenced by dispositions that are usually not related to music listening. Consequently, habitual music-listening behaviour is not obviously linked to physiological and psychological functioning.

  14. Combined MEK and ERK inhibition overcomes therapy-mediated pathway reactivation in RAS mutant tumors.

    Directory of Open Access Journals (Sweden)

    Mark Merchant

    Full Text Available Mitogen-activated protein kinase (MAPK pathway dysregulation is implicated in >30% of all cancers, rationalizing the development of RAF, MEK and ERK inhibitors. While BRAF and MEK inhibitors improve BRAF mutant melanoma patient outcomes, these inhibitors had limited success in other MAPK dysregulated tumors, with insufficient pathway suppression and likely pathway reactivation. In this study we show that inhibition of either MEK or ERK alone only transiently inhibits the MAPK pathway due to feedback reactivation. Simultaneous targeting of both MEK and ERK nodes results in deeper and more durable suppression of MAPK signaling that is not achievable with any dose of single agent, in tumors where feedback reactivation occurs. Strikingly, combined MEK and ERK inhibition is synergistic in RAS mutant models but only additive in BRAF mutant models where the RAF complex is dissociated from RAS and thus feedback productivity is disabled. We discovered that pathway reactivation in RAS mutant models occurs at the level of CRAF with combination treatment resulting in a markedly more active pool of CRAF. However, distinct from single node targeting, combining MEK and ERK inhibitor treatment effectively blocks the downstream signaling as assessed by transcriptional signatures and phospho-p90RSK. Importantly, these data reveal that MAPK pathway inhibitors whose activity is attenuated due to feedback reactivation can be rescued with sufficient inhibition by using a combination of MEK and ERK inhibitors. The MEK and ERK combination significantly suppresses MAPK pathway output and tumor growth in vivo to a greater extent than the maximum tolerated doses of single agents, and results in improved anti-tumor activity in multiple xenografts as well as in two Kras mutant genetically engineered mouse (GEM models. Collectively, these data demonstrate that combined MEK and ERK inhibition is functionally unique, yielding greater than additive anti-tumor effects and

  15. 5-Azacytidine mediated reactivation of silenced transgenes in potato (Solanum tuberosum) at the whole plant level.

    Science.gov (United States)

    Tyč, Dimitrij; Nocarová, Eva; Sikorová, Lenka; Fischer, Lukáš

    2017-08-01

    Transient 5-azacytidine treatment of leaf explants from potato plants with transcriptionally silenced transgenes allows de novo regeneration of plants with restored transgene expression at the whole plant level. Transgenes introduced into plant genomes frequently become silenced either at the transcriptional or the posttranscriptional level. Transcriptional silencing is usually associated with DNA methylation in the promoter region. Treatments with inhibitors of maintenance DNA methylation were previously shown to allow reactivation of transcriptionally silenced transgenes in single cells or tissues, but not at the whole plant level. Here we analyzed the effect of DNA methylation inhibitor 5-azacytidine (AzaC) on the expression of two silenced reporter genes encoding green fluorescent protein (GFP) and neomycin phosphotransferase (NPTII) in potato plants. Whereas no obvious reactivation was observed in AzaC-treated stem cuttings, transient treatment of leaf segments with 10 μM AzaC and subsequent de novo regeneration of shoots on the selective medium with kanamycin resulted in the production of whole plants with clearly reactivated expression of previously silenced transgenes. Reactivation of nptII expression was accompanied by a decrease in cytosine methylation in the promoter region of the gene. Using the plants with reactivated GFP expression, we found that re-silencing of this transgene can be accidentally triggered by de novo regeneration. Thus, testing the incidence of transgene silencing during de novo regeneration could be a suitable procedure for negative selection of transgenic lines (insertion events) which have an inclination to be silenced. Based on our analysis of non-specific inhibitory effects of AzaC on growth of potato shoots in vitro, we estimated that AzaC half-life in the culture media is approximately 2 days.

  16. Community Violence and Reactive and Proactive Aggression: The Mediating Role of Cognitive and Emotional Variables

    Directory of Open Access Journals (Sweden)

    Enrique Chaux

    2012-01-01

    Full Text Available Los niños y niñas expuestos a elevados niveles de violencia tienden a ser más agresivos que los demás, pero los mecanismos específicos que explican esta relación todavía se están descubriendo. Este estudio buscó identificar la relación entre la exposición a la violencia comunitaria y la agresión reactiva y proactiva, así como las variables cognitivas y emocionales que median dicha relación. Con la participación de 1,235 estudiantes (de quinto a noveno grado de diferentes localidades de Bogotá, Colombia, y de diversos niveles de violencia comunitaria, los análisis de las medidas de autoreporte confirmaron la existencia de asociaciones significativas entre la exposición a la violencia comunitaria y la agresión tanto reactiva como proactiva. Las creencias que legitiman la agresión, la atribución hostil de intenciones, las expectativas positivas sobre la agresión, y la falta de culpa al agredir, mediaron parcialmente estas relaciones, sugiriendo estrategias de prevención.

  17. Age differences in conservatism: evidence on the mediating effects of personality and cognitive style.

    Science.gov (United States)

    Cornelis, Ilse; Van Hiel, Alain; Roets, Arne; Kossowska, Malgorzata

    2009-02-01

    The present study investigates the commonly found age-conservatism relationship by combining insights from studies on the development of personality and motivated social cognition with findings on the relationships between these factors and conservative beliefs. Based on data collected in Belgium (N=2,373) and Poland (N=939), we found the expected linear effect of age on indicators of social-cultural conservatism in Belgium and Poland and the absence of such effects for indicators of economic-hierarchical conservatism. We further demonstrated that these effects of age on indicators of cultural conservatism in both countries were (in part) mediated through the personality factor Openness to Experience and the motivated cognition variable Need for Closure. The consistency of these findings in two countries with a very dissimilar sociopolitical history attests to the importance of the developmental perspective for the study of the relationship between age and conservatism.

  18. Mapping the minds of the mediators: The cognitive frames of climate journalists from five countries.

    Science.gov (United States)

    Engesser, Sven; Brüggemann, Michael

    2016-10-01

    This article is based on the premise that journalists play an important role as mediators of scientific information and their interpretations of climate change influence media debates and public opinion. The study maps the minds of climate journalists from five different countries (Germany, India, Switzerland, the United Kingdom, and the United States) and different types of leading media outlets. It identifies five cognitive frames that vary between attributing the responsibility for climate change to lobbying and national interests, blaming consumerist culture and the capitalist system, and expressing technological optimism. The study provides evidence for the emergence of a sustainability frame, indicates a "blame game" between industrialized countries and emerging economies, and shows the demand for a global ecological discourse. Finally, it explores how individual factors such as specialization, professional aims, and political alignment correlate with the cognitive frames of journalists. © The Author(s) 2015.

  19. Moms in motion: a group-mediated cognitive-behavioral physical activity intervention

    Directory of Open Access Journals (Sweden)

    Brawley Lawrence R

    2006-08-01

    Full Text Available Abstract Background When examining the prevalence of physical inactivity by gender and age, women over the age of 25 are at an increased risk for sedentary behavior. Childbearing and motherhood have been explored as one possible explanation for this increased risk. Post natal exercise studies to date demonstrate promising physical and psychological outcomes, however few physical activity interventions have been theory-driven and tailored to post natal exercise initiates. The purpose of this study was to compare the effects of a group-mediated cognitive behavioral intervention based upon social-cognitive theory and group dynamics (GMCB to a standard care postnatal exercise program (SE. Method A randomized, two-arm intervention design was used. Fifty-seven post natal women were randomized to one of two conditions: (1 a standard exercise treatment (SE and (2 a standard exercise treatment plus group-mediated cognitive behavioral intervention (GMCB. Participants in both conditions participated in a four-week intensive phase where participants received standard exercise training. In addition, GMCB participants received self-regulatory behavioral skills training via six group-mediated counseling sessions. Following the intensive phase, participants engaged in a four-week home-based phase of self-structured exercise. Measures of physical activity, barrier efficacy, and proximal outcome expectations were administered and data were analyzed using ANCOVA procedures. Results and discussion ANCOVA of change scores for frequency, minutes, and volume of physical activity revealed significant treatment effects over the intensive and home-based phases (p's Conclusion While both exercise programs resulted in improvements to exercise participation, the GMCB intervention produced greater improvement in overall physical activity, barrier efficacy and proximal outcome expectations.

  20. Enhanced visual memory during hypnosis as mediated by hypnotic responsiveness and cognitive strategies.

    Science.gov (United States)

    Crawford, H J; Allen, S N

    1983-12-01

    To investigate the hypothesis that hypnosis has an enhancing effect on imagery processing, as mediated by hypnotic responsiveness and cognitive strategies, four experiments compared performance of low and high, or low, medium, and high, hypnotically responsive subjects in waking and hypnosis conditions on a successive visual memory discrimination task that required detecting differences between successively presented picture pairs in which one member of the pair was slightly altered. Consistently, hypnotically responsive individuals showed enhanced performance during hypnosis, whereas nonresponsive ones did not. Hypnotic responsiveness correlated .52 (p less than .001) with enhanced performance during hypnosis, but it was uncorrelated with waking performance (Experiment 3). Reaction time was not affected by hypnosis, although high hypnotizables were faster than lows in their responses (Experiments 1 and 2). Subjects reported enhanced imagery vividness on the self-report Vividness of Visual Imagery Questionnaire during hypnosis. The differential effect between lows and highs was in the anticipated direction but not significant (Experiments 1 and 2). As anticipated, hypnosis had no significant effect on a discrimination task that required determining whether there were differences between pairs of simultaneously presented pictures. Two cognitive strategies that appeared to mediate visual memory performance were reported: (a) detail strategy, which involved the memorization and rehearsal of individual details for memory, and (b) holistic strategy, which involved looking at and remembering the whole picture with accompanying imagery. Both lows and highs reported similar predominantly detail-oriented strategies during waking; only highs shifted to a significantly more holistic strategy during hypnosis. These findings suggest that high hypnotizables have a greater capacity for cognitive flexibility (Batting, 1979) than do lows. Results are discussed in terms of several

  1. Orexins Mediate Sex Differences in the Stress Response and in Cognitive Flexibility.

    Science.gov (United States)

    Grafe, Laura A; Cornfeld, Amanda; Luz, Sandra; Valentino, Rita; Bhatnagar, Seema

    2017-04-15

    Women are twice as likely as men to experience stress-related psychiatric disorders. The biological basis of these sex differences is poorly understood. Orexins are altered in anxious and depressed patients. Using a rat model of repeated stress, we examined whether orexins contribute to sex differences in outcomes relevant to stress-related psychiatric diseases. Behavioral, neural, and endocrine habituation to repeated restraint stress and subsequent cognitive flexibility was examined in adult male and female rats. In parallel, orexin expression and activation were determined in both sexes, and chromatin immunoprecipitation was used to determine transcription factors acting at the orexin promoter. Designer receptors exclusively activated by designer drugs were used to inhibit orexin activation throughout repeated restraint to determine if the stress-related impairments in female rats could be reduced. Female rats exhibited impaired habituation to repeated restraint with subsequent deficits in cognitive flexibility compared with male rats. Increased orexin expression and activation were observed in female rats compared with male rats. The higher expression of orexin messenger RNA in female rats was due to actions of glucocorticoid receptors on the orexin promoter, as determined by chromatin immunoprecipitation. Inhibition of orexins using designer receptors exclusively activated by designer drugs in female rats throughout repeated restraint abolished their heightened hypothalamic-pituitary-adrenal responsivity and reduced stress-induced cognitive impairments. Orexins mediate the impairments in adaptations to repeated stress and in subsequent cognitive flexibility exhibited by female rats and provide evidence for a broader role for orexins in mediating functions relevant to stress-related psychiatric diseases. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. A translational investigation targeting stress-reactivity and prefrontal cognitive control with guanfacine for smoking cessation.

    Science.gov (United States)

    McKee, Sherry A; Potenza, Marc N; Kober, Hedy; Sofuoglu, Mehmet; Arnsten, Amy F T; Picciotto, Marina R; Weinberger, Andrea H; Ashare, Rebecca; Sinha, Rajita

    2015-03-01

    Stress and prefrontal cognitive dysfunction have key roles in driving smoking; however, there are no therapeutics for smoking cessation that attenuate the effects of stress on smoking and enhance cognition. Central noradrenergic pathways are involved in stress-induced reinstatement to nicotine and in the prefrontal executive control of adaptive behaviors. We used a novel translational approach employing a validated laboratory analogue of stress-precipitated smoking, functional magnetic resonance imaging (fMRI), and a proof-of-concept treatment period to evaluate whether the noradrenergic α2a agonist guanfacine (3 mg/day) versus placebo (0 mg/day) reduced stress-precipitated smoking in the laboratory, altered cortico-striatal activation during the Stroop cognitive-control task, and reduced smoking following a quit attempt. In nicotine-deprived smokers (n=33), stress versus a neutral condition significantly decreased the latency to smoke, and increased tobacco craving, ad-libitum smoking, and systolic blood pressure in placebo-treated subjects, and these effects were absent or reduced in guanfacine-treated subjects. Following stress, placebo-treated subjects demonstrated decreased cortisol levels whereas guanfacine-treated subjects demonstrated increased levels. Guanfacine, compared with placebo, altered prefrontal activity during a cognitive-control task, and reduced cigarette use but did not increase complete abstinence during treatment. These preliminary laboratory, neuroimaging, and clinical outcome data were consistent and complementary and support further development of guanfacine for smoking cessation. © The Author(s) 2014.

  3. Epstein-Barr virus (EBV Rta-mediated EBV and Kaposi's sarcoma-associated herpesvirus lytic reactivations in 293 cells.

    Directory of Open Access Journals (Sweden)

    Yen-Ju Chen

    Full Text Available Epstein-Barr virus (EBV Rta belongs to a lytic switch gene family that is evolutionarily conserved in all gamma-herpesviruses. Emerging evidence indicates that cell cycle arrest is a common means by which herpesviral immediate-early protein hijacks the host cell to advance the virus's lytic cycle progression. To examine the role of Rta in cell cycle regulation, we recently established a doxycycline (Dox-inducible Rta system in 293 cells. In this cell background, inducible Rta modulated the levels of signature G1 arrest proteins, followed by induction of the cellular senescence marker, SA-β-Gal. To delineate the relationship between Rta-induced cell growth arrest and EBV reactivation, recombinant viral genomes were transferred into Rta-inducible 293 cells. Somewhat unexpectedly, we found that Dox-inducible Rta reactivated both EBV and Kaposi's sarcoma-associated herpesvirus (KSHV, to similar efficacy. As a consequence, the Rta-mediated EBV and KSHV lytic replication systems, designated as EREV8 and ERKV, respectively, were homogenous, robust, and concurrent with cell death likely due to permissive lytic replication. In addition, the expression kinetics of EBV lytic genes in Dox-treated EREV8 cells was similar to that of their KSHV counterparts in Dox-induced ERKV cells, suggesting that a common pathway is used to disrupt viral latency in both cell systems. When the time course was compared, cell cycle arrest was achieved between 6 and 48 h, EBV or KSHV reactivation was initiated abruptly at 48 h, and the cellular senescence marker was not detected until 120 h after Dox treatment. These results lead us to hypothesize that in 293 cells, Rta-induced G1 cell cycle arrest could provide (1 an ideal environment for virus reactivation if EBV or KSHV coexists and (2 a preparatory milieu for cell senescence if no viral genome is available. The latter is hypothetical in a transient-lytic situation.

  4. Childhood adversity and social functioning in psychosis: Exploring clinical and cognitive mediators.

    Science.gov (United States)

    Palmier-Claus, Jasper; Berry, Katherine; Darrell-Berry, Hannah; Emsley, Richard; Parker, Sophie; Drake, Richard; Bucci, Sandra

    2016-04-30

    Childhood adversity may increase risk of impaired social functioning across the continuum of psychosis. However, the pathways by which adversity dictates functional outcome remain underexplored. This study investigated the association between childhood adversity and social functioning, and the clinical and cognitive mediators of this relationship. Fifty-four clinical (20 chronic, 20 first episode, 14 at ultra-high risk) and 120 non-clinical participants completed standardised questionnaires, semi-structured interviews and tests of theory of mind ability. The authors used multiple group structural equation modelling to fit mediation models allowing for differential relationships between the clinical and non-clinical samples. When examining each pathway separately, depression, paranoia and anxious attachment mediated the effect of childhood adversity on social functioning. In a combined model, depression was the only significant mediating variable with greater adversity predicting lower mood across groups. Childhood adversity did not significantly predict theory of mind ability in any of the models. This is the first study to indicate that childhood adversity acts on social functioning by increasing levels of depression, suggesting a common mechanism across the spectrum of psychosis. Clinical interventions should target low mood in order to improve social functioning at all stages of psychotic disorder. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. TET-mediated oxidation of methylcytosine causes TDG or NEIL glycosylase dependent gene reactivation.

    Science.gov (United States)

    Müller, Udo; Bauer, Christina; Siegl, Michael; Rottach, Andrea; Leonhardt, Heinrich

    2014-07-01

    The discovery of hydroxymethyl-, formyl- and carboxylcytosine, generated through oxidation of methylcytosine by TET dioxygenases, raised the question how these modifications contribute to epigenetic regulation. As they are subjected to complex regulation in vivo, we dissected links to gene expression with in vitro modified reporter constructs. We used an Oct4 promoter-driven reporter gene and demonstrated that in vitro methylation causes gene silencing while subsequent oxidation with purified catalytic domain of TET1 leads to gene reactivation. To identify proteins involved in this pathway we screened for TET interacting factors and identified TDG, PARP1, XRCC1 and LIG3 that are involved in base-excision repair. Knockout and rescue experiments demonstrated that gene reactivation depended on the glycosylase TDG, but not MBD4, while NEIL1, 2 and 3 could partially rescue the loss of TDG. These results clearly show that oxidation of methylcytosine by TET dioxygenases and subsequent removal by TDG or NEIL glycosylases and the BER pathway results in reactivation of epigenetically silenced genes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. Immediate and long-term effects of meditation on acute stress reactivity, cognitive functions, and intelligence.

    Science.gov (United States)

    Singh, Yogesh; Sharma, Ratna; Talwar, Anjana

    2012-01-01

    With the current globalization of the world's economy and demands for enhanced performance, stress is present universally. Life's stressful events and daily stresses cause both deleterious and cumulative effects on the human body. The practice of meditation might offer a way to relieve that stress. The research team intended to study the effects of meditation on stress-induced changes in physiological parameters, cognitive functions, intelligence, and emotional quotients. The research team conducted the study in two phases, with a month between them. Each participant served as his own control, and the first phase served as the control for the second phase. In phase 1, the research team studied the effects of a stressor (10 minutes playing a computer game) on participants' stress levels. In phase 2, the research team examined the effects of meditation on stress levels. The research team conducted the study in a lab setting at the All India Institute of Medical Sciences (AIIMS), New Delhi, India. The participants were 34 healthy, male volunteers who were students. To study the effects of long-term meditation on stress levels, intelligence, emotional quotients, and cognitive functions participants meditated daily for 1 month, between phases 1 and 2. To study the immediate effects of meditation on stress levels, participants meditated for 15 minutes after playing a computer game to induce stress. The research team measured galvanic skin response (GSR), heart rate (HR), and salivary cortisol and administered tests for the intelligence and emotional quotients (IQ and EQ), acute and perceived stress (AS and PS), and cognitive functions (ie, the Sternberg memory test [short-term memory] and the Stroop test [cognitive flexibility]). Using a pre-post study design, the team performed this testing (1) prior to the start of the study (baseline); (2) in phase 1, after induced stress; (3) in part 1 of phase 2, after 1 month of daily meditation, and (4) in part 2 of phase 2, after

  7. Different perspectives of cultural mediation: implications for the research design on studies examining its effect on students' cognition

    Science.gov (United States)

    Teo, Tang Wee

    2013-06-01

    In this forum, I extend Tao, Oliver, and Venville's paper Chinese and Australian children's understanding of the earth: a cross cultural study of conceptual development to discuss the different views on culture and cultural mediation. I tease out nuances in the viewpoints to suggest three ways to theoretically frame studies examining cultural mediation of students' cognition. Specifically, cultural mediation may be attributed to innate psychological attributes, an accretion of cultural elements, or the social interaction process. Each of these ideas represents a theoretical lens and has implications for the research design of studies relating cultural mediation to cognition. In the final section of this forum paper, I show how a study conducted from the symbolic interactionist viewpoint underscoring cultural mediation as a social interaction process might unfold.

  8. Autonomic reactivity and romantic relational aggression among female emerging adults: moderating roles of social and cognitive risk.

    Science.gov (United States)

    Murray-Close, Dianna

    2011-04-01

    This study investigates the association between autonomic arousal in response to a relational stressor and the perpetration of relational aggression against romantic partners. In addition, the moderating role of social risk (relational victimization by a romantic partner) and cognitive risk (hostile attribution biases) was explored. Skin conductance, heart rate, and respiratory sinus arrhythmia during an experience of exclusion were assessed in a sample of female emerging adults (N=131). Participants provided self-reports of romantic relational aggression, romantic relational victimization, and hostile attribution biases. Results indicated that both heightened and blunted reactivity served as risk factors for the perpetration of romantic relational aggression depending on women's social and contextual risks. Implications for understanding the development of intimate aggression are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Role of protein disulfide isomerase and other thiol-reactive proteins in HIV-1 envelope protein-mediated fusion

    International Nuclear Information System (INIS)

    Ou Wu; Silver, Jonathan

    2006-01-01

    Cell-surface protein disulfide isomerase (PDI) has been proposed to promote disulfide bond rearrangements in HIV-1 envelope protein (Env) that accompany Env-mediated fusion. We evaluated the role of PDI in ways that have not been previously tested by downregulating PDI with siRNA and by overexpressing wild-type or variant forms of PDI in transiently and stably transfected cells. These manipulations, as well as treatment with anti-PDI antibodies, had only small effects on infection or cell fusion mediated by NL4-3 or AD8 strains of HIV-1. However, the cell-surface thiol-reactive reagent 5, 5'-dithiobis(2-nitrobenzoic acid) (DTNB) had a much stronger inhibitory effect in our system, suggesting that cell-surface thiol-containing molecules other than PDI, acting alone or in concert, have a greater effect than PDI on HIV-1 Env-mediated fusion. We evaluated one such candidate, thioredoxin, a PDI family member reported to reduce a labile disulfide bond in CD4. We found that the ability of thioredoxin to reduce the disulfide bond in CD4 is enhanced in the presence of HIV-1 Env gp120 and that thioredoxin also reduces disulfide bonds in gp120 directly in the absence of CD4. We discuss the implications of these observations for identification of molecules involved in disulfide rearrangements in Env during fusion

  10. C-reactive protein enhances IgG-mediated phagocyte responses and thrombocytopenia

    NARCIS (Netherlands)

    Kapur, Rick; Heitink-Polle, Katja M. J.; Porcelijn, Leendert; Bentlage, Arthur E. H.; Bruin, MCA; Visser, Remco; Roos, Dirk; Schasfoort, Richard B. M.; de Haas, Masja; van der Schoot, C. Ellen; Vidarsson, Gestur

    2015-01-01

    Immune-mediated platelet destruction is most frequently caused by allo-or autoantibodies via Fc gamma receptor-dependent phagocytosis. Disease severity can be predicted neither by antibody isotype nor by titer, indicating that other factors play a role. Here we show that the acute phase protein

  11. Neural mechanisms of proactive and reactive cognitive control in social anxiety.

    Science.gov (United States)

    Schmid, Petra C; Kleiman, Tali; Amodio, David M

    2015-09-01

    Social anxiety--the fear of social embarrassment and negative evaluation by others--ranks among people's worst fears, and it is often thought to impair task performance. We investigated the neurocognitive processes through which trait social anxiety relates to task performance, proposing a model of the joint contributions of reactive control, theoretically associated with conflict monitoring and activity of the dorsal anterior cingulate cortex (dACC), and proactive control, theoretically associated with top-down regulation and activity of the dorsolateral prefrontal cortex (dlPFC). Participants varying in their degree of trait social anxiety completed the Eriksen flanker task while electroencephalography (EEG) was recorded. Task-related left dlPFC activity was indexed by relative left prefrontal EEG (inverse alpha), and conflict-related dACC activity was indexed by the N2r component of the event-related potential. Stronger activity in both regions predicted better response control, and greater social anxiety was associated with worse response control. Furthermore, for all participants, greater left prefrontal EEG activity predicted better behavioral control, but for high social anxiety participants only, greater N2r responses also predicted behavioral control. This pattern suggests that low social anxiety individuals engaged a proactive control process, driven by dlPFC activity, whereas high social anxiety individuals relied additionally on a reactive control process, driven by conflict-related dACC activity. These findings support a model of control that involves different patterns of interplay between proactive and reactive strategies and may help to explain self-regulatory impairments in social anxiety. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Social Marketing in Malaysia: Cognitive, Affective, and Normative Mediators of the TAK NAK Antismoking Advertising Campaign.

    Science.gov (United States)

    Lee, Wonkyong Beth; Fong, Geoffrey T; Dewhirst, Timothy; Kennedy, Ryan D; Yong, Hua-Hie; Borland, Ron; Awang, Rahmat; Omar, Maizurah

    2015-01-01

    Antismoking mass media campaigns are known to be effective as part of comprehensive tobacco control programs in high-income countries, but such campaigns are relatively new in low- and middle-income countries and there is a need for strong evaluation studies from these regions. This study examines Malaysia's first national antismoking campaign, TAK NAK. The data are from the International Tobacco Control Malaysia Survey, which is an ongoing cohort survey of a nationally representative sample of adult smokers (18 years and older; N = 2,006). The outcome variable was quit intentions of adult smokers, and the authors assessed the extent to which quit intentions may have been strengthened by exposure to the antismoking campaign. The authors also tested whether the impact of the campaign on quit intentions was related to cognitive mechanisms (increasing thoughts about the harm of smoking), affective mechanisms (increasing fear from the campaign), and perceived social norms (increasing perceived social disapproval about smoking). Mediational regression analyses revealed that thoughts about the harm of smoking, fear arousal, and social norms against smoking mediated the relation between TAK NAK impact and quit intentions. Effective campaigns should prompt smokers to engage in both cognitive and affective processes and encourage consideration of social norms about smoking in their society.

  13. Endoplasmic Reticulum Stress-Mediated Hippocampal Neuron Apoptosis Involved in Diabetic Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Xiaoming Zhang

    2013-01-01

    Full Text Available Poor management of DM causes cognitive impairment while the mechanism is still unconfirmed. The aim of the present study was to investigate the activation of C/EBP Homology Protein (CHOP, the prominent mediator of the endoplasmic reticulum (ER stress-induced apoptosis under hyperglycemia. We employed streptozotocin- (STZ- induced diabetic rats to explore the ability of learning and memory by the Morris water maze test. The ultrastructure of hippocampus in diabetic rats and cultured neurons in high glucose medium were observed by transmission electron microscopy and scanning electron microscopy. TUNEL staining was also performed to assess apoptotic cells while the expression of CHOP was assayed by immunohistochemistry and Western blot assay in these hippocampal neurons. Six weeks after diabetes induction, the escape latency increased and the average frequency in finding the platform decreased in diabetic rats (P<0.05. The morphology of neuron and synaptic structure was impaired; the number of TUNEL-positive cells and the expression of CHOP in hippocampus of diabetic rats and high glucose medium cultured neurons were markedly altered (P<0.05. The present results suggested that the CHOP-dependent endoplasmic reticulum (ER stress-mediated apoptosis may be involved in hyperglycemia-induced hippocampal synapses and neurons impairment and promote the diabetic cognitive impairment.

  14. State of the art on targeted memory reactivation: Sleep your way to enhanced cognition.

    Science.gov (United States)

    Schouten, Daphne I; Pereira, Sofia I R; Tops, Mattie; Louzada, Fernando M

    2017-04-01

    Targeted memory reactivation is a fairly simple technique that has the potential to influence the course of memory formation through application of cues during sleep. Studies have shown that cueing memory during sleep can lead to either an enhanced or decreased representation of the information encoded in the targeted networks, depending on experimental variations. The effects have been associated with sleep parameters and accompanied by activation of memory related brain areas. The findings suggest a causal role of neuronal replay in memory consolidation and provide evidence for the active system consolidation hypothesis. However, the observed inconsistencies across studies suggest that further research is warranted regarding the underlying neural mechanisms and optimal conditions for the application of targeted memory reactivation. The goal of the present review is to integrate the currently available experimental data and to provide an overview of this technique's limitations and pitfalls, as well as its potential applications in everyday use and clinical treatment. Exploring the open questions herein identified should lead to insight into safer and more effective ways of adjusting memory representations to better suit individual needs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Cardiovascular reactivity of younger and older adults to positive-, negative-, and mixed-emotion cognitive challenge.

    Science.gov (United States)

    Hogan, Michael J; James, Jack E; McCabe, Tadhg R; Kilmartin, Liam; Howard, Siobhán; Noone, Chris

    2012-03-01

    Although aging is associated with progressive increases in blood pressure level, previous research has been inconsistent as to whether older adults show greater or lesser cardiovascular reactivity (CVR) to emotion than do younger adults. There is reason to believe that these inconsistencies could be clarified by examining age-related differences in hemodynamic profile revealed by measuring the pattern of cardiac output and total peripheral resistance associated with changes in blood pressure reactivity. Accordingly, the present study examined the performance, CVR, and hemodynamic profile of younger and older adults during encoding and recognition of word pairs involving four valence types: positive, negative, mixed (positive/negative), and neutral word pairs. Results revealed higher baseline blood pressure, increased CVR characterized by a vascular hemodynamic profile, and more rapid recovery (especially during encoding) for older than for younger participants. Results are discussed in light of research and theory on the relationship between aging and cardiovascular health. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Participation Structures as a Mediational Means: Learning Balinese Gamelan in the United States through Intent Participation, Mediated Discourse, and Distributed Cognition

    Science.gov (United States)

    Jocuns, Andrew

    2009-01-01

    Participation has presented a complex unit of analysis for interactional sociolinguistics. In this study I add another dimension to participation by considering recent theories related to sociocultural activity theory--mediated discourse analysis and distributed cognition. Drawing on examples from "maguru panggul", the traditional…

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

    Science.gov (United States)

    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. Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure

    International Nuclear Information System (INIS)

    Wang, Cheng; Nie, Xiaoke; Zhang, Yan; Li, Ting; Mao, Jiamin; Liu, Xinhang; Gu, Yiyang; Shi, Jiyun; Xiao, Jing; Wan, Chunhua; Wu, Qiyun

    2015-01-01

    Perfluorooctane sulfonate (PFOS), an emerging persistent contaminant that is commonly encountered during daily life, has been shown to exert toxic effects on the central nervous system (CNS). However, the molecular mechanisms underlying the neurotoxicity of PFOS remain largely unknown. It has been widely acknowledged that the inflammatory mediators released by hyper-activated microglia play vital roles in the pathogenesis of various neurological diseases. In the present study, we examined the impact of PFOS exposure on microglial activation and the release of proinflammatory mediators, including nitric oxide (NO) and reactive oxidative species (ROS). We found that PFOS exposure led to concentration-dependent NO and ROS production by rat HAPI microglia. We also discovered that there was rapid activation of the ERK/JNK MAPK signaling pathway in the HAPI microglia following PFOS treatment. Moreover, the PFOS-induced iNOS expression and NO production were attenuated after the inhibition of ERK or JNK MAPK by their corresponding inhibitors, PD98059 and SP600125. Interestingly, NAC, a ROS inhibitor, blocked iNOS expression, NO production, and activation of ERK and JNK MAPKs, which suggested that PFOS-mediated microglial NO production occurs via a ROS/ERK/JNK MAPK signaling pathway. Finally, by exposing SH-SY5Y cells to PFOS-treated microglia-conditioned medium, we demonstrated that NO was responsible for PFOS-mediated neuronal apoptosis. - Highlights: • PFOS exposure induced expression of iNOS and production of NO in HAPI microglia. • PFOS induced the production of ROS in HAPI microglia. • ERK/JNK MAPK pathways were activated following PFOS exposure in HAPI microglia. • NO released by HAPI microglia participated in the apoptosis of SH-SY5Y cells.

  19. Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Cheng; Nie, Xiaoke; Zhang, Yan [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Li, Ting; Mao, Jiamin [Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Liu, Xinhang [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Gu, Yiyang; Shi, Jiyun [Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Xiao, Jing [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Wan, Chunhua [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Wu, Qiyun, E-mail: wqy@ntu.edu.cn [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China)

    2015-10-15

    Perfluorooctane sulfonate (PFOS), an emerging persistent contaminant that is commonly encountered during daily life, has been shown to exert toxic effects on the central nervous system (CNS). However, the molecular mechanisms underlying the neurotoxicity of PFOS remain largely unknown. It has been widely acknowledged that the inflammatory mediators released by hyper-activated microglia play vital roles in the pathogenesis of various neurological diseases. In the present study, we examined the impact of PFOS exposure on microglial activation and the release of proinflammatory mediators, including nitric oxide (NO) and reactive oxidative species (ROS). We found that PFOS exposure led to concentration-dependent NO and ROS production by rat HAPI microglia. We also discovered that there was rapid activation of the ERK/JNK MAPK signaling pathway in the HAPI microglia following PFOS treatment. Moreover, the PFOS-induced iNOS expression and NO production were attenuated after the inhibition of ERK or JNK MAPK by their corresponding inhibitors, PD98059 and SP600125. Interestingly, NAC, a ROS inhibitor, blocked iNOS expression, NO production, and activation of ERK and JNK MAPKs, which suggested that PFOS-mediated microglial NO production occurs via a ROS/ERK/JNK MAPK signaling pathway. Finally, by exposing SH-SY5Y cells to PFOS-treated microglia-conditioned medium, we demonstrated that NO was responsible for PFOS-mediated neuronal apoptosis. - Highlights: • PFOS exposure induced expression of iNOS and production of NO in HAPI microglia. • PFOS induced the production of ROS in HAPI microglia. • ERK/JNK MAPK pathways were activated following PFOS exposure in HAPI microglia. • NO released by HAPI microglia participated in the apoptosis of SH-SY5Y cells.

  20. FOXO3a reactivation mediates the synergistic cytotoxic effects of rapamycin and cisplatin in oral squamous cell carcinoma cells

    International Nuclear Information System (INIS)

    Fang Liang; Wang Huiming; Zhou Lin; Yu Da

    2011-01-01

    FOXO3a, a well-known transcriptional regulator, controls a wide spectrum of biological processes. The Phosphoinositide-3-kinase (PI3K)/Akt signaling pathway inactivates FOXO3a via phosphorylation-induced nuclear exclusion and degradation. A loss or gain of FOXO3a activity has been correlated with efficiency of chemotherapies in various cancers including oral squamous cell carcinoma (OSCC). Therefore, in the current study, we have investigated the FOXO3a activity modulating and antitumor effects of rapamycin and cisplatin in OSCC cells. Cisplatin inhibited proliferation and induced apoptosis in a dose-dependent way in OSCC Tca8113 cells. Rapamycin alone had no effect on cell proliferation and apoptosis. Rapamycin downregulated the expression of S-phase kinase associated protein-2 (Skp2) and increased the FOXO3a protein stability but induced the upregulation of feedback Akt activation-mediated FOXO3a phosphorylation. Cisplatin decreased the phosphorylation of FOXO3a via Akt inhibition. Rapamycin combined with cisplatin as its feedback Akt activation inhibitor revealed the most dramatic FOXO3a nuclear localization and reactivation with the prevention of its feedback loop and exposed significant synergistic effects of decreased cell proliferation and increased apoptosis in vitro and decreased tumor size in vivo. Furthermore, the downstream effects of FOXO3a reactivation were found to be accumulation of p27 and Bim. In conclusion, rapamycin/cisplatin combination therapy boosts synergistic antitumor effects through the significant FOXO3a reactivation in OSCC cells. These results may represent a novel mechanism by which rapamycin/cisplatin combination therapy proves to be a potent molecular-targeted strategy for OSCC.

  1. Considering a Threshold Energy in Reactive Transport Modeling of Microbially Mediated Redox Reactions in an Arsenic-Affected Aquifer

    Directory of Open Access Journals (Sweden)

    Marco Rotiroti

    2018-01-01

    Full Text Available The reductive dissolution of Fe-oxide driven by organic matter oxidation is the primary mechanism accepted for As mobilization in several alluvial aquifers. These processes are often mediated by microorganisms that require a minimum Gibbs energy available to conduct the reaction in order to sustain their life functions. Implementing this threshold energy in reactive transport modeling is rarely used in the existing literature. This work presents a 1D reactive transport modeling of As mobilization by the reductive dissolution of Fe-oxide and subsequent immobilization by co-precipitation in iron sulfides considering a threshold energy for the following terminal electron accepting processes: (a Fe-oxide reduction, (b sulfate reduction, and (c methanogenesis. The model is then extended by implementing a threshold energy on both reaction directions for the redox reaction pairs Fe(III reduction/Fe(II oxidation and methanogenesis/methane oxidation. The optimal threshold energy fitted in 4.50, 3.76, and 1.60 kJ/mol e− for sulfate reduction, Fe(III reduction/Fe(II oxidation, and methanogenesis/methane oxidation, respectively. The use of models implementing bidirectional threshold energy is needed when a redox reaction pair can be transported between domains with different redox potentials. This may often occur in 2D or 3D simulations.

  2. Exposure of Bacterial Biofilms to Electrical Current Leads to Cell Death Mediated in Part by Reactive Oxygen Species.

    Science.gov (United States)

    Brinkman, Cassandra L; Schmidt-Malan, Suzannah M; Karau, Melissa J; Greenwood-Quaintance, Kerryl; Hassett, Daniel J; Mandrekar, Jayawant N; Patel, Robin

    2016-01-01

    Bacterial biofilms may form on indwelling medical devices such as prosthetic joints, heart valves and catheters, causing challenging-to-treat infections. We have previously described the 'electricidal effect', in which bacterial biofilms are decreased following exposure to direct electrical current. Herein, we sought to determine if the decreased bacterial quantities are due to detachment of biofilms or cell death and to investigate the role that reactive oxygen species (ROS) play in the observed effect. Using confocal and electron microscopy and flow cytometry, we found that direct current (DC) leads to cell death and changes in the architecture of biofilms formed by Gram-positive and Gram-negative bacteria. Reactive oxygen species (ROS) appear to play a role in DC-associated cell death, as there was an increase in ROS-production by Staphylococcus aureus and Staphylococcus epidermidis biofilms following exposure to DC. An increase in the production of ROS response enzymes catalase and superoxide dismutase (SOD) was observed for S. aureus, S. epidermidis and Pseudomonas aeruginosa biofilms following exposure to DC. Additionally, biofilms were protected from cell death when supplemented with antioxidants and oxidant scavengers, including catalase, mannitol and Tempol. Knocking out SOD (sodAB) in P. aeruginosa led to an enhanced DC effect. Microarray analysis of P. aeruginosa PAO1 showed transcriptional changes in genes related to the stress response and cell death. In conclusion, the electricidal effect results in death of bacteria in biofilms, mediated, at least in part, by production of ROS.

  3. Pharmacologically-mediated reactivation and reconsolidation blockade of the psychostimulant-abuse circuit: A novel treatment strategy

    Science.gov (United States)

    Lee, Tong H.; Szabo, Steven T.; Fowler, J. Corey; Mannelli, Paolo; Mangum, O. Barry; Beyer, Wayne F.; Patkar, Ashwin; Wetsel, William C.

    2012-01-01

    Psychostimulant abuse continues to present legal, socioeconomic and medical challenges as a primary psychiatric disorder, and represents a significant comorbid factor in major psychiatric and medical illnesses. To date, monotherapeutic drug treatments have not proven effective in promoting long-term abstinence in psychostimulant abusers. In contrast to clinical trials utilizing monotherapies, combinations of dopamine (DA) agonists and selective 5-HT3, 5HT2A/2C, or NK1 antagonists have shown robust efficacy in reversing behavioral and neurobiological alterations in animal models of psychostimulant abuse. One important temporal requirement for these treatments is that the 5-HT or NK1 receptor antagonist be given at a critical time window after DA agonist administration. This requirement may reflect a necessary dosing regimen towards normalizing underlying dysfunctional neural circuits and “addiction memory” states. Indeed, chronic psychostimulant abuse can be conceptualized as a consolidated form of dysfunctional memory maintained by repeated drug- or cue-induced reactivation of neural circuit and subsequent reconsolidation. According to this concept, the DA agonist given first may reactivate this memory circuit, thereby rendering it transiently labile. The subsequent antagonist is hypothesized to disrupt reconsolidation necessary for restabilization, thus leading progressively to a therapeutically-mediated abolishment of dysfunctional synaptic plasticity. We propose that long-term abstinence in psychostimulant abusers may be achieved not only by targeting putative mechanistic pathways, but also by optimizing drug treatment regimens designed to disrupt the neural processes underlying the addicted state. PMID:22356892

  4. Structural Insights into 2,2′-Azino-Bis(3-Ethylbenzothiazoline-6-Sulfonic Acid) (ABTS)-Mediated Degradation of Reactive Blue 21 by Engineered Cyathus bulleri Laccase and Characterization of Degradation Products

    OpenAIRE

    Kenzom, T.; Srivastava, P.; Mishra, S.

    2014-01-01

    Advanced oxidation processes are currently used for the treatment of different reactive dyes which involve use of toxic catalysts. Peroxidases are reported to be effective on such dyes and require hydrogen peroxide and/or metal ions. Cyathus bulleri laccase, expressed in Pichia pastoris, catalyzes efficient degradation (78 to 85%) of reactive azo dyes (reactive black 5, reactive orange 16, and reactive red 198) in the presence of synthetic mediator ABTS [2,2′-azino-bis(3-ethylbenzothiazoline-...

  5. Cell-mediated reduction of protein and peptide hydroperoxides to reactive free radicals

    DEFF Research Database (Denmark)

    Headlam, Henrietta A; Davies, Michael Jonathan

    2003-01-01

    Radical attack on proteins in the presence of O(2) gives protein hydroperoxides in high yields. These peroxides are decomposed by transition metal ions, reducing agents, UV light and heat, with the formation of a range of reactive radicals that are capable of initiating further damage. Evidence has...... been presented for the formation of alcohols as stable products of peroxide decomposition, and these have been employed as markers of oxidative damage in vivo. The mechanism of formation of these alcohols is unclear, with both radical and nonradical pathways capable of generating these products....... In this study we have investigated the reduction of peptide and protein hydroperoxides by THP-1 (human monocyte-like) cells and it is shown that this process is accompanied by radical formation as detected by EPR spin trapping. The radicals detected, which are similar to those detected from metal-ion catalyzed...

  6. Mitochondrial reactive oxygen species regulate the strength of inhibitory GABA-mediated synaptic transmission

    Science.gov (United States)

    Accardi, Michael V.; Daniels, Bryan A.; Brown, Patricia M. G. E.; Fritschy, Jean-Marc; Tyagarajan, Shiva K.; Bowie, Derek

    2014-01-01

    Neuronal communication imposes a heavy metabolic burden in maintaining ionic gradients essential for action potential firing and synaptic signalling. Although cellular metabolism is known to regulate excitatory neurotransmission, it is still unclear whether the brain’s energy supply affects inhibitory signalling. Here we show that mitochondrial-derived reactive oxygen species (mROS) regulate the strength of postsynaptic GABAA receptors at inhibitory synapses of cerebellar stellate cells. Inhibition is strengthened through a mechanism that selectively recruits α3-containing GABAA receptors into synapses with no discernible effect on resident α1-containing receptors. Since mROS promotes the emergence of postsynaptic events with unique kinetic properties, we conclude that newly recruited α3-containing GABAA receptors are activated by neurotransmitter released onto discrete postsynaptic sites. Although traditionally associated with oxidative stress in neurodegenerative disease, our data identify mROS as a putative homeostatic signalling molecule coupling cellular metabolism to the strength of inhibitory transmission.

  7. An examination of mediators of the transfer of cognitive speed of processing training to everyday functional performance.

    Science.gov (United States)

    Edwards, Jerri D; Ruva, Christine L; O'Brien, Jennifer L; Haley, Christine B; Lister, Jennifer J

    2013-06-01

    The purpose of these analyses was to examine mediators of the transfer of cognitive speed of processing training to improved everyday functional performance (J. D. Edwards, V. G. Wadley,, D. E. Vance, D. L. Roenker, & K. K. Ball, 2005, The impact of speed of processing training on cognitive and everyday performance. Aging & Mental Health, 9, 262-271). Cognitive speed of processing and visual attention (as measured by the Useful Field of View Test; UFOV) were examined as mediators of training transfer. Secondary data analyses were conducted from the Staying Keen in Later Life (SKILL) study, a randomized cohort study including 126 community dwelling adults 63 to 87 years of age. In the SKILL study, participants were randomized to an active control group or cognitive speed of processing training (SOPT), a nonverbal, computerized intervention involving perceptual practice of visual tasks. Prior analyses found significant effects of training as measured by the UFOV and Timed Instrumental Activities of Daily Living (TIADL) Tests. Results from the present analyses indicate that speed of processing for a divided attention task significantly mediated the effect of SOPT on everyday performance (e.g., TIADL) in a multiple mediation model accounting for 91% of the variance. These findings suggest that everyday functional improvements found from SOPT are directly attributable to improved UFOV performance, speed of processing for divided attention in particular. Targeting divided attention in cognitive interventions may be important to positively affect everyday functioning among older adults. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  8. Response expectancies, treatment credibility, and hypnotic suggestibility: mediator and moderator effects in hypnotic and cognitive-behavioral pain interventions.

    Science.gov (United States)

    Milling, Leonard S; Shores, Jessica S; Coursen, Elizabeth L; Menario, Deanna J; Farris, Catherine D

    2007-04-01

    Several studies have shown that response expectancies are an important mechanism of popular psychological interventions for pain. However, there has been no research on whether response expectancies and treatment credibility independently mediate hypnotic and cognitive-behavioral pain interventions and whether the pattern of mediation is affected by experience with the interventions. Also, past research has indicated that hypnotic pain interventions may be moderated by hypnotic suggestibility. However, these studies have typically failed to measure the full range of suggestibility and have assessed pain reduction and suggestibility in the same experimental context, possibly inflating the association between these variables. To clarify the mediator role of response expectancies and treatment credibility, and the moderator role of hypnotic suggestibility in the hypnotic and cognitive-behavioral reduction of pain. Approximately 300 participants were assessed for suggestibility. Then, as part of an apparently unrelated experiment, 124 of these individuals received analogue cognitive-behavioral, hypnotic, or placebo control pain interventions. Response expectancies and credibility independently mediated treatment. The extent of mediation increased as participants gained more experience with the interventions. Suggestibility moderated treatment and was associated with relief only from the hypnotic intervention. Response expectancies and treatment credibility are unique mechanisms of hypnotic and cognitive-behavioral pain interventions. Hypnotic suggestibility predicts relief from hypnotic pain interventions and this association is not simply an artifact of measuring suggestibility and pain reduction in the same experimental context. The relationship between suggestibility and hypnotic pain reduction appears to be linear in nature.

  9. Right Frontotemporal Cortex Mediates the Relationship between Cognitive Insight and Subjective Quality of Life in Patients with Schizophrenia.

    Science.gov (United States)

    Pu, Shenghong; Nakagome, Kazuyuki; Itakura, Masashi; Ohtachi, Hiroaki; Iwata, Masaaki; Nagata, Izumi; Kaneko, Koichi

    2018-01-01

    Although prior studies identified a relationship between cognitive insight and subjective quality of life (QOL) in patients with schizophrenia, the brain regions mediating this relationship remain unknown. Recent studies have shown that the ventrolateral prefrontal cortex may be particularly important for cognitive insight in individuals with schizophrenia. Here, we examined whether frontotemporal function mediates the relationship between cognitive insight and QOL in 64 participants, including 32 patients with schizophrenia and 32 healthy controls. Cognitive insight was measured using the Beck Cognitive Insight Scale (BCIS), while participants' subjective QOL was assessed using the Medical Outcomes Study 36-item Short-form Health Survey. Frontotemporal function was evaluated during a verbal fluency task using multichannel near-infrared spectroscopy. Consistent with previous findings, we found that frontotemporal function was impaired in patients with schizophrenia. Interestingly, our data also revealed that the right ventrolateral PFC and the right anterior part of the temporal cortex significantly mediated the relationship between the self-reflectiveness (SR) subscale of the BCIS and subjective QOL. These findings suggest that cognitive insight, particularly SR, is associated with subjective QOL in patients with schizophrenia via right frontotemporal function. The findings of this study provide important insight into a QOL model of schizophrenia, which may guide the development of cost-effective interventions that target frontotemporal function in patients with schizophrenia.

  10. Mobilization of Intracellular Copper by Gossypol and Apogossypolone Leads to Reactive Oxygen Species-Mediated Cell Death: Putative Anticancer Mechanism

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    Haseeb Zubair

    2016-06-01

    Full Text Available There is compelling evidence that serum, tissue and intracellular levels of copper are elevated in all types of cancer. Copper has been suggested as an important co-factor for angiogenesis. It is also a major metal ion present inside the nucleus, bound to DNA bases, particularly guanine. We have earlier proposed that the interaction of phenolic-antioxidants with intracellular copper leads to the generation of reactive oxygen species (ROS that ultimately serve as DNA cleaving agents. To further validate our hypothesis we show here that the antioxidant gossypol and its semi-synthetic derivative apogossypolone induce copper-mediated apoptosis in breast MDA-MB-231, prostate PC3 and pancreatic BxPC-3 cancer cells, through the generation of ROS. MCF10A breast epithelial cells refractory to the cytotoxic property of these compounds become sensitized to treatment against gossypol, as well as apogossypolone, when pre-incubated with copper. Our present results confirm our earlier findings and strengthen our hypothesis that plant-derived antioxidants mobilize intracellular copper instigating ROS-mediated cellular DNA breakage. As cancer cells exist under significant oxidative stress, this increase in ROS-stress to cytotoxic levels could be a successful anticancer approach.

  11. Getting the Message? Native Reactive Electrophiles Pass Two Out of Three Thresholds to be Bona Fide Signaling Mediators.

    Science.gov (United States)

    Poganik, Jesse R; Long, Marcus J C; Aye, Yimon

    2018-05-01

    Precision cell signaling activities of reactive electrophilic species (RES) are arguably among the most poorly-understood means to transmit biological messages. Latest research implicates native RES to be a chemically-distinct subset of endogenous redox signals that influence cell decision making through non-enzyme-assisted modifications of specific proteins. Yet, fundamental questions remain regarding the role of RES as bona fide second messengers. Here, we lay out three sets of criteria we feel need to be met for RES to be considered as true cellular signals that directly mediate information transfer by modifying "first-responding" sensor proteins. We critically assess the available evidence and define the extent to which each criterion has been fulfilled. Finally, we offer some ideas on the future trajectories of the electrophile signaling field taking inspiration from work that has been done to understand canonical signaling mediators. Also see the video abstract here: https://youtu.be/rG7o0clVP0c. © 2018 WILEY Periodicals, Inc.

  12. Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation

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    Yoon TH

    2012-03-01

    Full Text Available Ki-Chun Yoo1, Chang-Hwan Yoon1, Dongwook Kwon2, Kyung-Hwan Hyun1, Soo Jung Woo1, Rae-Kwon Kim1, Eun-Jung Lim1, Yongjoon Suh1, Min-Jung Kim1, Tae Hyun Yoon2, Su-Jae Lee11Laboratory of Molecular Biochemistry, 2Laboratory of Nanoscale Characterization and Environmental Chemistry, Department of Chemistry, Hanyang University, Seoul, Republic of KoreaBackground: Titanium dioxide (TiO2 has been widely used in many areas, including biomedicine, cosmetics, and environmental engineering. Recently, it has become evident that some TiO2 particles have a considerable cytotoxic effect in normal human cells. However, the molecular basis for the cytotoxicity of TiO2 has yet to be defined.Methods and results: In this study, we demonstrated that combined treatment with TiO2 nanoparticles sized less than 100 nm and ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-dependent upregulation of Fas and conformational activation of Bax in normal human cells. Treatment with P25 TiO2 nanoparticles with a hydrodynamic size distribution centered around 70 nm (TiO2P25–70 together with ultraviolet A irradiation-induced caspase-dependent apoptotic cell death, accompanied by transcriptional upregulation of the death receptor, Fas, and conformational activation of Bax. In line with these results, knockdown of either Fas or Bax with specific siRNA significantly inhibited TiO2-induced apoptotic cell death. Moreover, inhibition of reactive oxygen species with an antioxidant, N-acetyl-L-cysteine, clearly suppressed upregulation of Fas, conformational activation of Bax, and subsequent apoptotic cell death in response to combination treatment using TiO2P25–70 and ultraviolet A irradiation.Conclusion: These results indicate that sub-100 nm sized TiO2 treatment under ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-mediated upregulation of the death receptor, Fas, and activation of the preapoptotic protein

  13. Reactive Oxygen Species-Induced TXNIP Drives Fructose-Mediated Hepatic Inflammation and Lipid Accumulation Through NLRP3 Inflammasome Activation

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    Zhang, Xian; Zhang, Jian-Hua; Chen, Xu-Yang; Hu, Qing-Hua; Wang, Ming-Xing; Jin, Rui; Zhang, Qing-Yu; Wang, Wei; Wang, Rong; Kang, Lin-Lin; Li, Jin-Sheng; Li, Meng

    2015-01-01

    Abstract Aims: Increased fructose consumption predisposes the liver to nonalcoholic fatty liver disease (NAFLD), but the mechanisms are elusive. Thioredoxin-interacting protein (TXNIP) links oxidative stress to NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and this signaling axis may be involved in fructose-induced NAFLD. Here, we explore the role of reactive oxygen species (ROS)-induced TXNIP overexpression in fructose-mediated hepatic NLRP3 inflammasome activation, inflammation, and lipid accumulation. Results: Rats were fed a 10% fructose diet for 8 weeks and treated with allopurinol and quercetin during the last 4 weeks. Five millimolars of fructose-exposed hepatocytes (primary rat hepatocytes, rat hepatic parenchymal cells [RHPCs], HLO2, HepG2) were co-incubated with antioxidants or caspase-1 inhibitor or subjected to TXNIP or NLRP3 siRNA interference. Fructose induced NLRP3 inflammasome activation and pro-inflammatory cytokine secretion, janus-activated kinase 2/signal transducers and activators of transcription 3-mediated inflammatory signaling, and expression alteration of lipid metabolism-related genes in cultured hepatocytes and rat livers. NLRP3 silencing and caspase-1 suppression blocked these effects in primary rat hepatocytes and RHPCs, confirming that inflammasome activation alters hepatocyte lipid metabolism. Hepatocellular ROS and TXNIP were increased in animal and cell models. TXNIP silencing blocked NLRP3 inflammasome activation, inflammation, and lipid metabolism perturbations but not ROS induction in fructose-exposed hepatocytes, whereas antioxidants addition abrogated TXNIP induction and diminished the detrimental effects in fructose-exposed hepatocytes and rat livers. Innovation and Conclusions: This study provides a novel mechanism for fructose-induced NAFLD pathogenesis by which the ROS-TXNIP pathway mediates hepatocellular NLRP3 inflammasome activation, inflammation and lipid accumulation. Antioxidant

  14. Mediation of the Physical Activity and Healthy Nutrition Behaviors of Preschool Children by Maternal Cognition in China.

    Science.gov (United States)

    Xu, Xianglong; Sharma, Manoj; Liu, Lingli; Hu, Ping; Zhao, Yong

    2016-09-13

    (1) OBJECTIVE: We aimed to explore the role of social cognitive theory (SCT) of mothers in the physical activity and healthy nutrition behaviors of preschool children; (2) METHODS: We used a self-administered five-point Likert common physical activity and nutrition behaviors scale in Chinese based on a social cognitive theory scale in English with established validity and reliability in the USA. The current study adopted the proportional sampling method to survey mothers of preschool children in four areas-namely, Chongqing, Chengdu, Taiyuan, and Shijiazhuang-of China; (3) RESULTS: We included 1208 mothers (80.0% mothers of normal weight children, age 31.87 ± 4.19 years). Positive correlations were found between maternal social cognition and preschool children's physical activity (PA) behavior (p mediation of maternal social cognition on preschool children's ST behavior and the correlations between maternal social cognition and children's ST behavior.

  15. Depression in Adults with Attention-Deficit/Hyperactivity Disorder (ADHD): The Mediating Role of Cognitive-Behavioral Factors

    Science.gov (United States)

    Zvorsky, Ivori; Safren, Steven A.

    2015-01-01

    Adults with Attention-Deficit/Hyperactivity Disorder (ADHD) are at increased risk for depressive disorders but little is known about the potential cognitive and behavioral mechanisms of risk that could shape treatment. This study evaluated the degree to which cognitive-behavioral constructs associated with depression and its treatment—dysfunctional attitudes and cognitive-behavioral avoidance—accounted for variance in depressive symptoms and disorder in adults with ADHD. 77 adults clinically diagnosed with ADHD completed self-report questionnaires, diagnostic interviews, and clinician-administered symptom rating scales. Statistical mediation analysis was employed and indirect effects assessed using bootstrap analysis and bias-corrected confidence intervals. Controlling for recent negative life events, dysfunctional attitudes and cognitive-behavioral avoidance fully accounted for the variance between ADHD symptoms and depressive symptoms. Each independent variable partially mediated the other in accounting for depression symptoms suggesting overlapping and unique variance. Cognitive-behavioral avoidance, however, was more strongly related to meeting diagnostic criteria for a depressive disorder than were dysfunctional attitudes. Processes that are targeted in cognitive behavior therapy (CBT) for depression were associated with symptoms in adults with ADHD. Current CBT approaches for ADHD incorporate active coping skills and cognitive restructuring and such approaches could be further tailored to address the ADHD-depression comorbidity. PMID:26089578

  16. The relation of close friends to cognitive performance in old age: the mediating role of leisure activities.

    Science.gov (United States)

    Ihle, Andreas; Oris, Michel; Baeriswyl, Marie; Kliegel, Matthias

    2018-06-01

    ABSTRACTBackground:From a conceptual point of view, close friends are an important resource for promoting activity engagement in old age. Leisure activity engagement in turn is a key predictor of cognitive performance. Empirically, it remains unclear so far whether leisure activity engagement mediates between having close friends on the one hand and cognitive performance on the other, which we investigated in a large sample of older adults. We assessed cognitive performance (Mill Hill vocabulary scale and Trail Making Test (TMT) parts A and B) in 2,812 older adults. Participants reported information on leisure activity engagement and close friends. A larger number of leisure activities and a larger number of close friends were significantly related to better cognitive performance in the Mill Hill vocabulary scale and TMT parts A and B. A larger number of close friends were significantly related to a larger number of leisure activities. The number of leisure activities mediated more than half of the relation of the number of close friends to performance in all three cognitive measures. Having close friends may be helpful to stimulate and promote activity participation in old age. By enhancing individuals' cognitive reserve, this may finally preserve their cognitive performance level in old age.

  17. Reactive oxygen species are key mediators of the nitric oxide apoptotic pathway in anterior pituitary cells.

    Science.gov (United States)

    Machiavelli, Leticia I; Poliandri, Ariel H; Quinteros, Fernanda A; Cabilla, Jimena P; Duvilanski, Beatriz H

    2007-03-01

    We previously showed that long-term exposure of anterior pituitary cells to nitric oxide (NO) induces apoptosis. The intracellular signals underlying this effect remained unclear. In this study, we searched for possible mechanisms involved in the early stages of the NO apoptotic cascade. Caspase 3 was activated by NO with no apparent disruption of mitochondrial membrane potential. NO caused a rapid increase of reactive oxygen species (ROS), and this increase seems to be dependent of mitochondrial electron transport chain. The antioxidant N-acetyl-cysteine avoided ROS increase, prevented the NO-induced caspase 3 activation, and reduced the NO apoptotic effect. Catalase was inactivated by NO, while glutathione peroxidase (GPx) activity and reduced glutathione (GSH) were not modified at first, but increased at later times of NO exposure. The increase of GSH level is important for the scavenging of the NO-induced ROS overproduction. Our results indicate that ROS have an essential role as a trigger of the NO apoptotic cascade in anterior pituitary cells. The permanent inhibition of catalase may strengthen the oxidative damage induced by NO. GPx activity and GSH level augment in response to the oxidative damage, though this increase seems not to be enough to rescue the cells from the NO effect.

  18. Multiple sclerosis severity and concern about falling: Physical, cognitive and psychological mediating factors.

    Science.gov (United States)

    van Vliet, Rob; Hoang, Phu; Lord, Stephen; Gandevia, Simon; Delbaere, Kim

    2015-01-01

    Concern about falling can have devastating physical and psychological consequences in people with multiple sclerosis (MS). However, little is known about physical and cognitive determinants for increased concern about falling inthis group. To investigate direct and indirect relationships between MS severity and concern about falling using structural equation modelling (SEM). Two hundred and ten community-dwelling people (21-73 years) with MS Disease Steps 0-5 completed several physical, cognitive and psychological assessments. Concern about falling was assessed using the Falls Efficacy Scale-International. Concern about falling was significantly associated with MS Disease Step and also balance, muscle strength, disability, previous falls, and executive functioning. SEM revealed a strong direct path between MS Disease Step and concern about falling (r = 0.31, p concern about falling in people with MS and had an excellent goodness-of-fit. The relationship between MS severity and increased concern about falling was primarily mediated by reduced physical ability (especially if this resulted in disability and falls) and less so by executive functioning. This suggests people with MS have a realistic appraisal of their concern about falling.

  19. The Influence of Proactive Green Innovation and Reactive Green Innovation on Green Product Development Performance: The Mediation Role of Green Creativity

    Directory of Open Access Journals (Sweden)

    Yu-Shan Chen

    2016-09-01

    Full Text Available This study fills the research gap in the exploration of the relationships between both proactive and reactive green innovations and green product development performance, and examines the mediating effect of green creativity. Structural equation modeling (SEM is utilized to test the hypotheses. From the sample of 146 valid respondents, the results show that proactive green innovation positively affects green creativity and green product development performance, and green creativity positively affects green product development performance. In addition, our findings also indicate that the relationship between proactive green innovation and green product development performance is partially mediated by green creativity. Accordingly, green creativity plays a critical role for companies to achieve a great green product development performance. However, reactive green innovation does not significantly influence green creativity and green product development performance. Companies should develop proactive green innovation rather than reactive green innovation in order to enhance their green creativity and increase their product development performance.

  20. Reactive oxygen species promote heat shock protein 90-mediated HBV capsid assembly

    International Nuclear Information System (INIS)

    Kim, Yoon Sik; Seo, Hyun Wook; Jung, Guhung

    2015-01-01

    Hepatitis B virus (HBV) infection induces reactive oxygen species (ROS) production and has been associated with the development of hepatocellular carcinoma (HCC). ROS are also an important factor in HCC because the accumulated ROS leads to abnormal cell proliferation and chromosome mutation. In oxidative stress, heat shock protein 90 (Hsp90) and glutathione (GSH) function as part of the defense mechanism. Hsp90 prevents cellular component from oxidative stress, and GSH acts as antioxidants scavenging ROS in the cell. However, it is not known whether molecules regulated by oxidative stress are involved in HBV capsid assembly. Based on the previous study that Hsp90 facilitates HBV capsid assembly, which is an important step for the packing of viral particles, here, we show that ROS enrich Hsp90-driven HBV capsid formation. In cell-free system, HBV capsid assembly was facilitated by ROS with Hsp90, whereas it was decreased without Hsp90. In addition, GSH inhibited the function of Hsp90 to decrease HBV capsid assembly. Consistent with the result of cell-free system, ROS and buthionine sulfoximine (BS), an inhibitor of GSH synthesis, increased HBV capsid formation in HepG2.2.15 cells. Thus, our study uncovers the interplay between ROS and Hsp90 during HBV capsid assembly. - Highlights: • We examined H 2 O 2 and GSH modulate HBV capsid assembly. • H 2 O 2 facilitates HBV capsid assembly in the presence of Hsp90. • GSH inhibits function of Hsp90 in facilitating HBV capsid assembly. • H 2 O 2 and GSH induce conformation change of Hsp90

  1. Green synthesized silver nanoparticles destroy multidrug resistant bacteria via reactive oxygen species mediated membrane damage

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    Balaram Das

    2017-09-01

    Full Text Available The growing need of antimicrobial agent for novel therapies against multi-drug resistant bacteria has drawn researchers to green nanotechnology. Especially, eco-friendly biosynthesis of silver nanoparticles (Ag NPs has shown its interesting impact against bacterial infection in laboratory research. In this study, a simple method was developed to form Ag NPs at room temperature, bio-reduction of silver ions from silver nitrate salt by leaf extract from Ocimum gratissimum. The Ag NPs appear to be capped with plant proteins, but are otherwise highly crystalline and pure. The Ag NPs have a zeta potential of −15 mV, a hydrodynamic diameter of 31 nm with polydispersity index of 0.65, and dry sizes of 18 ± 3 nm and 16 ± 2 nm, based on scanning and transmission electron microscopy respectively. The minimum inhibitory concentration (MIC of the Ag NPs against a multi-drug resistant Escherichia coli was 4 μg/mL and the minimum bactericidal concentration (MBC was 8 μg/mL, while the MIC and MBC against a resistant strain of Staphylococcus aureus were slightly higher at 8 μg/mL and 16 μg/mL respectively. Further, the Ag NPs inhibited biofilm formation by both Escherichia coli and S. aureus at concentrations similar to the MIC for each strain. Treatment of E. coli and S. aureus with Ag NPs resulted in damage to the surface of the cells and the production of reactive oxygen species. Both mechanisms likely contribute to bacterial cell death. In summary, this new method appears promising for green biosynthesis of pure Ag NPs with potent antimicrobial activity.

  2. Reactive oxygen species mediate TNFR1 increase after TRPV1 activation in mouse DRG neurons

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    Westlund Karin N

    2009-06-01

    Full Text Available Abstract Background Transient receptor potential vanilloid subtype 1 (TRPV1 is activated by low pH/protons and is well known to be involved in hyperalgesia during inflammation. Tumor necrosis factor α (TNF-α, a proinflammatory cytokine, is involved in nociceptive responses causing hyperalgesia through TNF receptor type 1 (TNFR1 activation. Reactive oxygen species (ROS production is also prominently increased in inflamed tissue. The present study investigated TNFR1 receptors in primary cultured mouse dorsal root ganglion (DRG neurons after TRPV1 activation and the involvement of ROS. C57BL/6 mice, both TRPV1 knockout and wild type, were used for immunofluorescent and live cell imaging. The L4 and L5 DRGs were dissected bilaterally and cultured overnight. TRPV1 was stimulated with capsaicin or its potent analog, resiniferatoxin. ROS production was measured with live cell imaging and TNFR1 was detected with immunofluorescence in DRG primary cultures. The TRPV1 knockout mice, TRPV1 antagonist, capsazepine, and ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN, were employed to explore the functional relationship among TRPV1, ROS and TNFR1 in these studies. Results The results demonstrate that TRPV1 activation increases TNFR1 receptors and ROS generation in primary cultures of mouse DRG neurons. Activated increases in TNFR1 receptors and ROS production are absent in TRPV1 deficient mice. The PBN blocks increases in TNFR1 and ROS production induced by capsaicin/resiniferatoxin. Conclusion TRPV1 activation increases TNFR1 in cultured mouse DRG neurons through a ROS signaling pathway, a novel sensitization mechanism in DRG neurons.

  3. Reactive oxygen species promote heat shock protein 90-mediated HBV capsid assembly

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoon Sik, E-mail: yumshak@naver.com; Seo, Hyun Wook, E-mail: suruk@naver.com; Jung, Guhung, E-mail: drjung@snu.ac.kr

    2015-02-13

    Hepatitis B virus (HBV) infection induces reactive oxygen species (ROS) production and has been associated with the development of hepatocellular carcinoma (HCC). ROS are also an important factor in HCC because the accumulated ROS leads to abnormal cell proliferation and chromosome mutation. In oxidative stress, heat shock protein 90 (Hsp90) and glutathione (GSH) function as part of the defense mechanism. Hsp90 prevents cellular component from oxidative stress, and GSH acts as antioxidants scavenging ROS in the cell. However, it is not known whether molecules regulated by oxidative stress are involved in HBV capsid assembly. Based on the previous study that Hsp90 facilitates HBV capsid assembly, which is an important step for the packing of viral particles, here, we show that ROS enrich Hsp90-driven HBV capsid formation. In cell-free system, HBV capsid assembly was facilitated by ROS with Hsp90, whereas it was decreased without Hsp90. In addition, GSH inhibited the function of Hsp90 to decrease HBV capsid assembly. Consistent with the result of cell-free system, ROS and buthionine sulfoximine (BS), an inhibitor of GSH synthesis, increased HBV capsid formation in HepG2.2.15 cells. Thus, our study uncovers the interplay between ROS and Hsp90 during HBV capsid assembly. - Highlights: • We examined H{sub 2}O{sub 2} and GSH modulate HBV capsid assembly. • H{sub 2}O{sub 2} facilitates HBV capsid assembly in the presence of Hsp90. • GSH inhibits function of Hsp90 in facilitating HBV capsid assembly. • H{sub 2}O{sub 2} and GSH induce conformation change of Hsp90.

  4. Nickel nanowires induced and reactive oxygen species mediated apoptosis in human pancreatic adenocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Kleve MG

    2011-07-01

    Full Text Available Md. Zakir Hossain1, Maurice G Kleve21Applied Biosciences (Bionanotechnology Research, Department of Applied Science, 2Molecular Biotechnology and Microscopy Laboratory, Department of Biology, University of Arkansas at Little Rock, Little Rock, Arkansas, USABackground: The ability to evade apoptosis is one of the key properties of cancer. The apoptogenic effect of nickel nanowires (Ni NWs on cancer cell lines has never been adequately addressed. Due to the unique physicochemical characteristics of Ni NWs, we envision the development of a novel anticancer therapeutics specifically for pancreatic cancer. Thus, we investigated whether Ni NWs induce ROS-mediated apoptosis in human pancreatic adenocarcinoma (Panc-1 cells. Methods: In this study Ni NWs were fabricated using the electrodeposition method. Synthesized Ni NWs were physically characterized by energy dispersive X-ray analysis, UV-Vis spectroscopy of NanoDrop 2000 (UV-Vis, magnetization study, scanning electron microscopy, and transmission electron microscopy. Assessment of morphological apoptotic characteristics by phase contrast microscopy (PCM, Ni-NWs-induced apoptosis staining with ethidium bromide (EB and acridine orange (AO followed by fluorescence microscopy (FM was performed. For molecular biological and biochemical characterization, Panc-1 cell culture and cytotoxic effect of Ni NWs were determined by using 3-(4, 5-dimethylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide (MTT assay. Quantitative apoptosis was analyzed by flow cytometry staining with propidium iodide through cell cycle arrest and generation of ROS using 2', 7'-dichlorofluorescein diacetate fluorescence intensity. In all experiments, Panc-1 cancer cells without any treatment were used as the negative controls.Results: The intracellular uptake of Ni NWs through endocytosis by Panc-1 cells was observed by PCM. EB and AO staining of FM and MTT assay qualitatively and quantitatively confirmed the extent of apoptosis. Flow

  5. Does Emotion Dysregulation Mediate the Association Between Sluggish Cognitive Tempo and College Students' Social Impairment?

    Science.gov (United States)

    Flannery, Andrew J; Becker, Stephen P; Luebbe, Aaron M

    2016-09-01

    Studies demonstrate an association between sluggish cognitive tempo (SCT) and social impairment, although no studies have tested possible mechanisms of this association. This study aimed to (a) examine SCT in relation to college students' social functioning; (b) test if SCT is significantly associated with emotion dysregulation beyond depressive, anxious, and ADHD symptoms; and (c) test if emotion dysregulation mediates the association between SCT symptoms and social impairment. College students (N = 158) completed measures of psychopathology symptoms, emotion dysregulation, and social functioning. Participants with elevated SCT (12%) had higher ADHD, depressive, and anxious symptoms in addition to poorer emotion regulation and social adjustment than participants without elevated SCT. Above and beyond other psychopathologies, SCT was significantly associated with social impairment but not general interpersonal functioning. SCT was also associated with emotion dysregulation, even after accounting for the expectedly strong association between depression and emotion dysregulation. Further analyses supported emotion dysregulation as a mediator of the association between SCT and social impairment. These findings are important for theoretical models of SCT and underscore the need for additional, longitudinal research. © The Author(s) 2014.

  6. Cognition-Based and Affect-Based Trust as Mediators of Leader Behavior Influences on Team Performance

    Science.gov (United States)

    Schaubroeck, John; Lam, Simon S. K.; Peng, Ann Chunyan

    2011-01-01

    We develop a model in which cognitive and affective trust in the leader mediate the relationship between leader behavior and team psychological states that, in turn, drive team performance. The model is tested on a sample of 191 financial services teams in Hong Kong and the U.S. Servant leadership influenced team performance through affect-based…

  7. Genetic variants associated with altered plasma levels of C-reactive protein are not associated with late-life cognitive ability in four Scottish samples.

    Science.gov (United States)

    Marioni, Riccardo E; Deary, Ian J; Murray, Gordon D; Lowe, Gordon D O; Rafnsson, Snorri B; Strachan, Mark W J; Luciano, Michelle; Houlihan, Lorna M; Gow, Alan J; Harris, Sarah E; Stewart, Marlene C; Rumley, Ann; Fowkes, F Gerry R; Price, Jackie F

    2010-01-01

    It is unknown whether the relationship between raised inflammatory biomarker levels and late-life cognitive ability is causal. We explored this issue by testing the association between genetic regulators of plasma C-reactive protein (CRP) and cognition. Data were analysed from four cohorts based in central Scotland (Total N = 4,782). Associations were tested between variants in the CRP gene and both plasma CRP levels and a battery of neuropsychological tests, including a vocabulary-based estimate of peak prior cognitive ability and a general (summary) cognitive factor score, or 'g'. CRP levels were associated with a number of variants in the CRP gene (SNPs), including rs1205, rs1130864, rs1800947, and rs1417938 (P range 4.2e-06 to 0.041). Higher CRP levels were also associated with vocabulary-adjusted cognitive ability, used here to estimate lifetime cognitive change (P range 1.7e-04 to 0.038). After correction for multiple testing and adjustment for age and sex, no statistically significant associations were found between the SNPs and cognition. CRP is unlikely to be a causal determinant of late-life cognitive ability.

  8. Changes in negative cognitions mediate PTSD symptom reductions during client-centered therapy and prolonged exposure for adolescents.

    Science.gov (United States)

    McLean, Carmen P; Yeh, Rebecca; Rosenfield, David; Foa, Edna B

    2015-05-01

    To assess whether changes in negative trauma-related cognitions play an important role in reducing symptoms of posttraumatic stress disorder (PTSD) and depression during prolonged exposure therapy for adolescents (PE-A). Secondary analysis of data from a randomized controlled trial comparing PE-A with client-centered therapy (CCT) for PTSD. Participants were 61 adolescent female sexual assault survivors ages 13-18 who received 8-14 weekly sessions of PE-A or CCT at a community rape crisis center. PTSD severity was assessed at baseline, mid-treatment, post-treatment, and 3-months post-treatment. Participants also completed self-report measures of negative posttraumatic cognitions and depressive symptoms at the same assessment points. Cross lag panel mediation analyses showed that change in negative trauma-related cognitions mediated change in PTSD symptoms and depressive symptoms whereas change in PTSD and depressive symptoms did not mediate change in negative cognitions. Our findings support EPT and suggest that change in negative trauma-related cognitions is a mechanism of both PE-A and CCT. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Low dose gamma irradiation enhances defined signaling components of intercellular reactive oxygen-mediated apoptosis induction

    International Nuclear Information System (INIS)

    Bauer, G

    2011-01-01

    Transformed cells are selectively removed by intercellular ROS-mediated induction of apoptosis. Signaling is based on the HOCl and the NO/peroxynitrite pathway (major pathways) and the nitryl chloride and the metal-catalyzed Haber-Weiss pathway (minor pathways). During tumor progression, resistance against intercellular induction of apoptosis is acquired through expression of membrane-associated catalase. Low dose radiation of nontransformed cells has been shown to enhance intercellular induction of apoptosis. The present study was performed to define the signaling components which are modulated by low dose gamma irradiation. Low dose radiation induced the release of peroxidase from nontransformed, transformed and tumor cells. Extracellular superoxide anion generation was strongly enhanced in the case of transformed cells and tumor cells, but not in nontransformed cells. Enhancement of peroxidase release and superoxide anion generation either increased intercellular induction of apoptosis of transformed cells, or caused a partial protection under specific signaling conditions. In tumor cells, low dose radiation enhanced the production of major signaling components, but this had no effect on apoptosis induction, due to the strong resistance mechanism of tumor cells. Our data specify the nature of low dose radiation-induced effects on specific signaling components of intercellular induction of apoptosis at defined stages of multistep carcinogenesis.

  10. Human Galectin-9 Is a Potent Mediator of HIV Transcription and Reactivation.

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    Mohamed Abdel-Mohsen

    2016-06-01

    Full Text Available Identifying host immune determinants governing HIV transcription, latency and infectivity in vivo is critical to developing an HIV cure. Based on our recent finding that the host factor p21 regulates HIV transcription during antiretroviral therapy (ART, and published data demonstrating that the human carbohydrate-binding immunomodulatory protein galectin-9 regulates p21, we hypothesized that galectin-9 modulates HIV transcription. We report that the administration of a recombinant, stable form of galectin-9 (rGal-9 potently reverses HIV latency in vitro in the J-Lat HIV latency model. Furthermore, rGal-9 reverses HIV latency ex vivo in primary CD4+ T cells from HIV-infected, ART-suppressed individuals (p = 0.002, more potently than vorinostat (p = 0.02. rGal-9 co-administration with the latency reversal agent "JQ1", a bromodomain inhibitor, exhibits synergistic activity (p<0.05. rGal-9 signals through N-linked oligosaccharides and O-linked hexasaccharides on the T cell surface, modulating the gene expression levels of key transcription initiation, promoter proximal-pausing, and chromatin remodeling factors that regulate HIV latency. Beyond latent viral reactivation, rGal-9 induces robust expression of the host antiviral deaminase APOBEC3G in vitro and ex vivo (FDR<0.006 and significantly reduces infectivity of progeny virus, decreasing the probability that the HIV reservoir will be replenished when latency is reversed therapeutically. Lastly, endogenous levels of soluble galectin-9 in the plasma of 72 HIV-infected ART-suppressed individuals were associated with levels of HIV RNA in CD4+ T cells (p<0.02 and with the quantity and binding avidity of circulating anti-HIV antibodies (p<0.009, suggesting a role of galectin-9 in regulating HIV transcription and viral production in vivo during therapy. Our data suggest that galectin-9 and the host glycosylation machinery should be explored as foundations for novel HIV cure strategies.

  11. Potential Mediators between Fibromyalgia and C-Reactive protein: Results from a Large U.S. Community Survey.

    Science.gov (United States)

    Feinberg, Termeh; Sambamoorthi, Usha; Lilly, Christa; Innes, Kim Karen

    2017-07-07

    Fibromyalgia, a potentially debilitating chronic pain syndrome of unknown etiology, may be characterized by inflammation. In this study, we investigated the relation of FMS to serum C-reactive protein (CRP) in a large population of adults (18+) and investigated the influence of other factors on this relationship, including BMI, comorbidities, as well as mood and sleep disturbance. Participants were 52,535 Ohio Valley residents (Fibromyalgia n = 1125). All participants completed a comprehensive health survey (2005-2006) part of the C8 Health Project; serum levels of CRP were obtained, as was history of Fibromyalgia physician diagnosis. Logistic and linear regressions were used for this cross-sectional analysis. Mean CRP was higher among participants reporting Fibromyalgia than those without (5.54 ± 9.8 vs.3.75 ± 7.2 mg/L, p BMI) and comorbidities to the model markedly weakened this relationship (AORs, respectively, for highest vs lowest CRP quartile = 1.2 (CI 1.0,1.4) and 1.1 (CI 0.9,1.3). In contrast, inclusion of mood and sleep impairment only modestly reduced the adjusted risk estimate (AORs for highest vs. lowest quartile = 1.3 (CI 1.1,1.5) for each)). Findings from this large cross-sectional study indicate a significant positive cross-sectional association of Fibromyalgia to serum C-reactive protein may be explained, in part, by BMI and comorbidity. Prospective research is needed to confirm this, and clarify the potential mediating influence of obesity and comorbid conditions on this relationship.

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

    Science.gov (United States)

    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.

  13. Interleukin-6 and C-Reactive Protein Levels and 9-Year Cognitive Decline in Community-Dwelling Older Women: The Women's Health and Aging Study II.

    Science.gov (United States)

    Palta, Priya; Xue, Qian-Li; Deal, Jennifer A; Fried, Linda P; Walston, Jeremy D; Carlson, Michelle C

    2015-07-01

    Elevated inflammation is a proposed mechanism relating chronic diseases to cognitive dysfunction. The objective of this study was to test the hypothesis that greater levels of inflammation, as measured by the proinflammatory cytokine interleukin-6 (IL-6) and C-reactive protein, are associated with faster rates of cognitive decline among cognitively intact community-dwelling older women. We analyzed 336 women from the Women's Health and Aging Study II. Cognitive assessments were performed at baseline and every 18-36 months, and included the following domains: immediate and delayed memory (Hopkins Verbal Learning Test), psychomotor speed (Trail Making Test, Part A), and executive function (Trail Making Test, Part B). Aggregate measures of IL-6 and C-reactive protein, based on the average from visits one and two, were analyzed categorically. Random effects models were employed to test the relationship between tertiles of each inflammatory marker and changes in cognitive domain scores over 9 years. Moderate and high levels of IL-6 predicted early declines in psychomotor speed by 1.0 connection/min per year. There were no differences in baseline scores or rates of change across tertiles of IL-6 in memory or executive function. No differences were observed across tertiles of C-reactive protein for all cognitive domains. Higher levels of serum IL-6 were associated with greater declines in psychomotor speed over 9 years. This finding could suggest that elevated IL-6 may result in microvascular changes that may lead to damage of myelin sheaths that line neuronal axons, leading to decreased neuron propagation and impaired processing speed; however, mechanistic studies are needed to evaluate these hypotheses. © The Author 2014. 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.

  14. Resveratrol induces acute endothelium-dependent renal vasodilation mediated through nitric oxide and reactive oxygen species scavenging

    Science.gov (United States)

    Gordish, Kevin L.

    2014-01-01

    Resveratrol is suggested to have beneficial cardiovascular and renoprotective effects. Resveratrol increases endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis. We hypothesized resveratrol acts as an acute renal vasodilator, mediated through increased NO production and scavenging of reactive oxygen species (ROS). In anesthetized rats, we found 5.0 mg/kg body weight (bw) of resveratrol increased renal blood flow (RBF) by 8% [from 6.98 ± 0.42 to 7.54 ± 0.17 ml·min−1·gram of kidney weight−1 (gkw); n = 8; P resveratrol before and after 10 mg/kg bw of the NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME). l-NAME reduced the increase in RBF to resveratrol by 54% (from 0.59 ± 0.05 to 0.27 ± 0.06 ml·min−1·gkw−1; n = 10; P resveratrol before and after 1 mg/kg bw tempol, a superoxide dismutase mimetic. Resveratrol increased RBF 7.6% (from 5.91 ± 0.32 to 6.36 ± 0.12 ml·min−1·gkw−1; n = 7; P resveratrol-induced increase in RBF (from 0.45 ± 0.12 to 0.10 ± 0.05 ml·min−1·gkw−1; n = 7; P Resveratrol-induced vasodilation remained unaffected. We conclude intravenous resveratrol acts as an acute renal vasodilator, partially mediated by increased NO production/NO bioavailability and superoxide scavenging but not by inducing vasodilatory cyclooxygenase products. PMID:24431202

  15. Reactive Oxygen Species and Mitochondrial KATP Channels Mediate Helium-Induced Preconditioning Against Myocardial Infarction In Vivo

    Science.gov (United States)

    Pagel, Paul S.; Krolikowski, John G.; Pratt, Phillip F.; Shim, Yon Hee; Amour, Julien; Warltier, David C.; Weihrauch, Dorothee

    2008-01-01

    Objectives Helium produces preconditioning by activating prosurvival kinases, but the roles of reactive oxygen species (ROS) or mitochondrial KATP channels in this process are unknown. We tested the hypothesis that ROS and mitochondrial KATP channels mediate helium-induced preconditioning in vivo. Design Randomized, prospective study. Setting University research laboratory. Participants Male New Zealand white rabbits. Interventions Rabbits (n=64) were instrumented for measurement of systemic hemodynamics and subjected to a 30 min left anterior descending coronary artery (LAD) occlusion and 3 h reperfusion. In separate experimental groups, rabbits (n=7 or 8 per group) were randomly assigned to receive 0.9% saline (control) or three cycles of 70% helium-30% oxygen administered for 5 min interspersed with 5 min of an air-oxygen mixture before LAD occlusion with or without the ROS scavengers N-acetylcysteine (NAC; 150 mg/kg) or N-2-mercaptoproprionyl glycine (2-MPG; 75 mg/kg), or the mitochondrial KATP antagonist 5-hydroxydecanoate (5-HD; 5 mg/kg). Statistical analysis of data was performed with analysis of variance for repeated measures followed by Bonferroni's modification of Student's t test. Measurements and Main Results Myocardial infarct size was determined using triphenyltetrazolium chloride staining and presented as a percentage of the left ventricular area at risk. Helium significantly (P<0.05) reduced infarct size (23±4% of the area at risk; mean±SD) compared with control (46±3%). NAC, 2-MPG, and 5-HD did not affect irreversible ischemic injury when administered alone (49±5, 45±6, and 45±3%), but these drugs blocked reductions in infarct size produced by helium (45±4, 45±2, and 44±3%). Conclusions The results suggest that ROS and mitochondrial KATP channels mediate helium-induced preconditioning in vivo. PMID:18662630

  16. Cognitive cooperation groups mediated by computers and internet present significant improvement of cognitive status in older adults with memory complaints: a controlled prospective study

    Directory of Open Access Journals (Sweden)

    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.

  17. Computer-Mediated Communication Preferences and Individual Differences in Neurocognitive Measures of Emotional Attention Capture, Reactivity and Regulation

    Science.gov (United States)

    Babkirk, Sarah; Luehring-Jones, Peter; Dennis, Tracy A.

    2016-01-01

    The use of computer-mediated communication (CMC) to engage socially has become increasingly prevalent, yet few studies examined individual differences that may shed light on implications of CMC for adjustment. The current study examined neurocognitive individual differences associated with preferences to use technology in relation to social-emotional outcomes. In Study 1 (N =91), a self-report measure, the Social Media Communication Questionnaire (SMCQ), was evaluated as an assessment of preferences for communicating positive and negative emotions on a scale ranging from purely via CMC to purely face-to-face. In Study 2, SMCQ preferences were examined in relation to event-related potentials (ERPs) associated with early emotional attention capture and reactivity (the frontal N1) and later sustained emotional processing and regulation [the late positive potential (LPP)]. Electroencephalography (EEG) was recorded while 22 participants passively viewed emotional and neutral pictures and completed an emotion regulation task with instructions to increase, decrease or maintain their emotional responses. A greater preference for CMC was associated with reduced size of and satisfaction with social support, greater early (N1) attention capture by emotional stimuli, and reduced LPP amplitudes to unpleasant stimuli in the increase emotion regulatory task. These findings are discussed in the context of possible emotion- and social-regulatory functions of CMC. PMID:26613269

  18. Serum C-reactive protein concentrations in Nova Scotia Duck Tolling Retrievers with immune-mediated rheumatic disease.

    Science.gov (United States)

    Bremer, Hanna Dorotea; Hillström, Anna; Kånåhols, Malin; Hagman, Ragnvi; Hansson-Hamlin, Helene

    2017-04-17

    Nova Scotia Duck Tolling Retrievers (NSDTRs) are a dog breed often affected by immune-mediated rheumatic disease (IMRD), a disorder characterised by chronic stiffness and joint pain. Most, but not all, dogs with IMRD, have antinuclear antibodies (ANA), which are also commonly present in the autoimmune disease systemic lupus erythematosus (SLE). The clinical and diagnostic findings of IMRD indicate that it is an SLE-related disorder. C-reactive protein (CRP), an acute phase protein, is a quantitative marker of inflammation for many diseases and is used for diagnosing and monitoring systemic inflammation in both humans and dogs. However, in human SLE, CRP concentrations are often elevated but correlate poorly with disease activity; they can be low in individual patients with active disease. The aim of the study was to investigate CRP in a group of NSDTRs with the SLE-related disorder IMRD. The hypothesis was that CRP concentrations would be increased in dogs with IMRD compared to healthy dogs, but that the increase would be mild. Serum CRP concentrations were measured in 18 IMRD-affected NSDTRs and 19 healthy control NSDTRs using two different canine-specific CRP assays. Dogs with IMRD and ANA had higher CRP concentrations than the control dogs, but the concentrations were below the clinical decision limit for systemic inflammation for most of the IMRD dogs. These results indicate that CRP concentrations were increased in dogs with IMRD and ANA, but the increase was mild, similar to what has been observed in human SLE.

  19. Cytotoxicity of pyrrolizidine alkaloid in human hepatic parenchymal and sinusoidal endothelial cells: Firm evidence for the reactive metabolites mediated pyrrolizidine alkaloid-induced hepatotoxicity.

    Science.gov (United States)

    Yang, Mengbi; Ruan, Jianqing; Fu, Peter P; Lin, Ge

    2016-01-05

    Pyrrolizidine alkaloids (PAs) widely distribute in plants and can cause hepatic sinusoidal obstruction syndrome (HSOS), which typically presents as a primary sinusoidal endothelial cell damage. It is well-recognized that after ingestion, PAs undergo hepatic cytochromes P450 (CYPs)-mediated metabolic activation to generate dehydropyrrolizidine alkaloids (DHPAs), which are hydrolyzed to dehydroretronecine (DHR). DHPAs and DHR are reactive metabolites having same core pyrrole moiety, and can bind proteins to form pyrrole-protein adducts, which are believed as the primary cause for PA-induced HSOS. However, to date, the direct evidences supporting the toxicity of DHPAs and DHR in the liver, in particular in the sinusoidal endothelial cells, are lacking. Using human hepatic sinusoidal endothelial cells (HSEC) and HepG2 (representing hepatic parenchymal cells), cells that lack CYPs activity, this study determined the direct cytotoxicity of dehydromonocrotaline, a representative DHPA, and DHR, but no cytotoxicity of the intact PA (monocrotaline) in both cell lines, confirming that reactive metabolites mediate PA intoxication. Comparing with HepG2, HSEC had significantly lower basal glutathione (GSH) level, and was significantly more susceptible to the reactive metabolites with severer GSH depletion and pyrrole-protein adducts formation. The toxic potency of two reactive metabolites was also compared. DHPA was more reactive than DHR, leading to severer toxicity. In conclusion, our results unambiguously provided the first direct evidence for the critical role of DHPA and DHR in the reactive metabolites-mediated PA-induced hepatotoxicity, which occurs predominantly in HSEC due to severe GSH depletion and the significant formation of pyrrole-protein adducts in HSEC. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Ornithine Decarboxylase-Mediated Production of Putrescine Influences Ganoderic Acid Biosynthesis by Regulating Reactive Oxygen Species in Ganoderma lucidum.

    Science.gov (United States)

    Wu, Chen-Gao; Tian, Jia-Long; Liu, Rui; Cao, Peng-Fei; Zhang, Tian-Jun; Ren, Ang; Shi, Liang; Zhao, Ming-Wen

    2017-10-15

    Putrescine is an important polyamine that participates in a variety of stress responses. Ornithine decarboxylase (ODC) is a key enzyme that catalyzes the biosynthesis of putrescine. A homolog of the gene encoding ODC was cloned from Ganoderma lucidum In the ODC -silenced strains, the transcript levels of the ODC gene and the putrescine content were significantly decreased. The ODC -silenced strains were more sensitive to oxidative stress. The content of ganoderic acid was increased by approximately 43 to 46% in the ODC -silenced strains. The content of ganoderic acid could be recovered after the addition of exogenous putrescine. Additionally, the content of reactive oxygen species (ROS) was significantly increased by approximately 1.3-fold in the ODC -silenced strains. The ROS content was significantly reduced after the addition of exogenous putrescine. The gene transcript levels and the activities of four major antioxidant enzymes were measured to further explore the effect of putrescine on the intracellular ROS levels. Further studies showed that the effect of the ODC-mediated production of putrescine on ROS might be a factor influencing the biosynthesis of ganoderic acid. Our study reports the role of putrescine in large basidiomycetes, providing a basis for future studies of the physiological functions of putrescine in microbes. IMPORTANCE It is well known that ODC and the ODC-mediated production of putrescine play an important role in resisting various environmental stresses, but there are few reports regarding the mechanisms underlying the effect of putrescine on secondary metabolism in microorganisms, particularly in fungi. G. lucidum is gradually becoming a model organism for studying environmental regulation and metabolism. In this study, a homolog of the gene encoding ODC was cloned in Ganoderma lucidum We found that the transcript level of the ODC gene and the content of putrescine were significantly decreased in the ODC -silenced strains. The content of

  1. Increased stress reactivity is associated with cognitive deficits and decreased hippocampal brain-derived neurotrophic factor in a mouse model of affective disorders.

    Science.gov (United States)

    Knapman, A; Heinzmann, J-M; Hellweg, R; Holsboer, F; Landgraf, R; Touma, C

    2010-07-01

    Cognitive deficits are a common feature of major depression (MD), with largely unknown biological underpinnings. In addition to the affective and cognitive symptoms of MD, a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is commonly observed in these patients. Increased plasma glucocorticoid levels are known to render the hippocampus susceptible to neuronal damage. This structure is important for learning and memory, creating a potential link between HPA axis dysregulation and cognitive deficits in depression. In order to further elucidate how altered stress responsiveness may contribute to the etiology of MD, three mouse lines with high (HR), intermediate (IR), or low (LR) stress reactivity were generated by selective breeding. The aim of the present study was to investigate whether increased stress reactivity is associated with deficits in hippocampus-dependent memory tests. To this end, we subjected mice from the HR, IR, and LR breeding lines to tests of recognition memory, spatial memory, and depression-like behavior. In addition, measurements of brain-derived neurotrophic factor (BDNF) in the hippocampus and plasma of these animals were conducted. Our results demonstrate that HR mice exhibit hippocampus-dependent memory deficits along with decreased hippocampal, but not plasma, BDNF levels. Thus, the stress reactivity mouse lines are a promising animal model of the cognitive deficits in MD with the unique feature of a genetic predisposition for an altered HPA axis reactivity, which provides the opportunity to explore the progression of the symptoms of MD, predisposing genetic factors as well as new treatment strategies. Copyright 2009 Elsevier Ltd. All rights reserved.

  2. Mediation of social cognitive theory variables in the relationship of exercise and improved eating in sedentary adults with severe obesity.

    Science.gov (United States)

    Annesi, James J; Tennant, Gisèle A

    2013-01-01

    Results from behavioral treatments for obesity have been disappointing due to an inability to sustain healthy eating. The concurrent use of theory, research, and practical application has the potential of reducing overeating through innovative treatments. When overweight individuals begin an exercise program their eating tends to improve, however, the basis of this relationship is not determined. If the psychosocial mediators of the relationship between exercise and improved eating are better understood, supported exercise may be a key component for improving the efficacy of behavioral weight management treatments. In Phase 1 of this research, psychosocial variables derived from social cognitive theory were tested as possible mediators of the relationship of exercise participation with increased fruit and vegetable intake in severely obese adults initiating a 26-week treatment of supported exercise and standard nutrition education (n = 161). Change in self-regulation for healthy eating and self-regulation at treatment end was a strong mediator; with the addition of mood and self-efficacy for healthy eating being additional mediators that notably increased effect ratios. In Phase 2, participants in a cognitive-behavioral nutrition treatment tailored to improve the identified mediators (n = 163) were contrasted with the original group. The cognitive-behavioral nutrition treatment was associated with significantly greater increases than standard nutrition education in self-regulation, p = 0.023, CIs [4.69, 6.48], and [3.19, 5.02], respectively; self-efficacy, p = 0.013, CIs [19.72, 29.41], and [11.70, 20.71], respectively; and a marginally significant decrease in negative mood, p = 0.062, CIs [-14.26, -9.36], and [-10.90, -6.45], respectively. Findings served to inform treatment designs concerning the use of supported exercise and cognitive-behavioral means to derive better outcomes related to nutrition and weight loss in individuals with severe

  3. Purple sweet potato color attenuates domoic acid-induced cognitive deficits by promoting estrogen receptor-α-mediated mitochondrial biogenesis signaling in mice.

    Science.gov (United States)

    Lu, Jun; Wu, Dong-Mei; Zheng, Yuan-Lin; Hu, Bin; Cheng, Wei; Zhang, Zi-Feng

    2012-02-01

    Recent findings suggest that endoplasmic reticulum stress may be involved in the pathogenesis of domoic acid-induced neurodegeneration. Purple sweet potato color, a class of naturally occurring anthocyanins, has beneficial health and biological effects. Recent studies have also shown that anthocyanins have estrogenic activity and can enhance estrogen receptor-α expression. In this study, we evaluated the effect of purple sweet potato color on cognitive deficits induced by hippocampal mitochondrial dysfunction in domoic acid-treated mice and explored the potential mechanisms underlying this effect. Our results showed that the oral administration of purple sweet potato color to domoic acid-treated mice significantly improved their behavioral performance in a step-through passive avoidance task and a Morris water maze task. These improvements were mediated, at least in part, by a stimulation of estrogen receptor-α-mediated mitochondrial biogenesis signaling and by decreases in the expression of p47phox and gp91phox. Decreases in reactive oxygen species and protein carbonylation were also observed, along with a blockade of the endoplasmic reticulum stress pathway. Furthermore, purple sweet potato color significantly suppressed endoplasmic reticulum stress-induced apoptosis, which prevented neuron loss and restored the expression of memory-related proteins. However, knockdown of estrogen receptor-α using short hairpin RNA only partially blocked the neuroprotective effects of purple sweet potato color in the hippocampus of mice cotreated with purple sweet potato color and domoic acid, indicating that purple sweet potato color acts through multiple pathways. These results suggest that purple sweet potato color could be a possible candidate for the prevention and treatment of cognitive deficits in excitotoxic and other brain disorders. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  4. The effects of mother-child mediated learning strategies on psychological resilience and cognitive modifiability of boys with learning disability.

    Science.gov (United States)

    Tzuriel, David; Shomron, Vered

    2018-06-01

    The theoretical framework of the current study is based on mediated learning experience (MLE) theory, which is similar to the scaffolding concept. The main question of the current study was to what extent mother-child MLE strategies affect psychological resilience and cognitive modifiability of boys with learning disability (LD). Secondary questions were to what extent the home environment, severity of boy's LD, and mother's attitude towards her child's LD affect her MLE strategies and consequently the child's psychological resilience and cognitive modifiability. The main objectives of this study were the following: (a) to investigate the effects of mother-child MLE strategies on psychological resilience and cognitive modifiability among 7- to 10-year-old boys with LD, (b) to study the causal effects of distal factors (i.e., socio-economic status [SES], home environment, severity of child's LD, mother's attitude towards LD) and proximal factors (i.e., MLE strategies) on psychological resilience and cognitive modifiability. A sample of mother-child dyads (n = 100) were videotaped during a short teaching interaction. All children were boys diagnosed as children with LD. The interaction was analysed for MLE strategies by the Observation of Mediation Interaction scale. Children were administered psychological resilience tests and their cognitive modifiability was measured by dynamic assessment using the Analogies subtest from the Cognitive Modifiability Battery. Home environment was rated by the Home Observation for Measurement of the Environment (HOME), and mothers answered a questionnaire of attitudes towards child's LD. The findings showed that mother-child MLE strategies, HOME, and socio-economic level contributed significantly to prediction of psychological resilience (78%) and cognitive modifiability (51%). Psychological resilience was positively correlated with cognitive modifiability (Rc = 0.67). Structural equation modelling analysis supported, in general

  5. Trauma and Depression among North Korean Refugees: The Mediating Effect of Negative Cognition

    Directory of Open Access Journals (Sweden)

    Subin Park

    2018-03-01

    Full Text Available North Korean refugees experience adaptation difficulties, along with a wide range of psychological problems. Accordingly, this study examined the associations between early traumatic experiences, negative automatic thoughts, and depression among young North Korean refugees living in South Korea. Specifically, we examined how different factors of negative automatic thoughts would mediate the relationship between early trauma and depressive symptoms. A total of 109 North Korean refugees aged 13–29 years were recruited from two alternative schools. Our path analysis indicated that early trauma was positively linked with thoughts of personal failure, physical threat, and hostility, but not with thoughts of social threat. The link with depressive symptoms was only significant for thoughts of personal failure. After removing all non-significant pathways, the model revealed that early traumatic experiences were positively associated with depressive symptoms (ß = 0.61, 95% CI = 0.48–0.73 via thoughts of personal failure (ß = 0.17, 95% CI = 0.08–0.28, as well as directly (ß = 0.44, 95% CI = 0.27–0.59. Interventions that target negative cognitions of personal failure may be helpful for North Korean refugees at risk of depression.

  6. A test of cognitive mediation in a 12-month physical activity workplace intervention: does it explain behaviour change in women?

    Science.gov (United States)

    Plotnikoff, Ronald C; Pickering, Michael A; Rhodes, Ryan E; Courneya, Kerry S; Spence, John C

    2010-05-03

    Attempts to demonstrate the efficacy of interventions aimed at increasing physical activity (PA) have been mixed. Further, studies are seldom designed in a manner that facilitates the understanding of how or why a treatment is effective or ineffective and PA intervention designs should be guided by a heavier reliance upon behavioral theory. The use of a mediating variable framework offers a systematic methodological approach to testing the role of theory, and could also identify the effectiveness of specific intervention components. The primary purpose of this paper was to test the mediating role that cognitive constructs may have played in regards to the positive effect that a workplace behavioral intervention had on leisure-time PA for women. A subsidiary purpose was to examine the cross-sectional relationships of these cognitive constructs with PA behavior. The Physical Activity Workplace Study was a randomized controlled trial which compared the effects of stage-matched and standard print materials upon self-reported leisure-time PA, within a workplace sample at 6 and 12-months. In this secondary analysis we examined the mediation effects of 14 psychosocial constructs across 3 major social-cognitive theories which were operationalized for the intervention materials and measured at baseline, 6 and 12-months. We examined change in PA and change in the psychological constructs employing a mediation strategy proposed by Baron and Kenny for: (1) the first 6-months (i.e., initial change), (2) the second 6-months (i.e., delayed change), and (3) the entire 12-months (overall change) of the study on 323 women (n = 213 control/standard materials group; n = 110 stage-matched materials group). Of the 14 constructs and 42 tests (including initial, delayed and overall change) two positive results were identified (i.e., overall change in pros, initial change in experiential powerful intervention approaches processes), with very small effect sizes. However, these mediating

  7. A test of cognitive mediation in a 12-month physical activity workplace intervention: does it explain behaviour change in women?

    Directory of Open Access Journals (Sweden)

    Pickering Michael A

    2010-05-01

    Full Text Available Abstract Background Attempts to demonstrate the efficacy of interventions aimed at increasing physical activity (PA have been mixed. Further, studies are seldom designed in a manner that facilitates the understanding of how or why a treatment is effective or ineffective and PA intervention designs should be guided by a heavier reliance upon behavioral theory. The use of a mediating variable framework offers a systematic methodological approach to testing the role of theory, and could also identify the effectiveness of specific intervention components. The primary purpose of this paper was to test the mediating role that cognitive constructs may have played in regards to the positive effect that a workplace behavioral intervention had on leisure-time PA for women. A subsidiary purpose was to examine the cross-sectional relationships of these cognitive constructs with PA behavior. Methods The Physical Activity Workplace Study was a randomized controlled trial which compared the effects of stage-matched and standard print materials upon self-reported leisure-time PA, within a workplace sample at 6 and 12-months. In this secondary analysis we examined the mediation effects of 14 psychosocial constructs across 3 major social-cognitive theories which were operationalized for the intervention materials and measured at baseline, 6 and 12-months. We examined change in PA and change in the psychological constructs employing a mediation strategy proposed by Baron and Kenny for: (1 the first 6-months (i.e., initial change, (2 the second 6-months (i.e., delayed change, and (3 the entire 12-months (overall change of the study on 323 women (n = 213 control/standard materials group; n = 110 stage-matched materials group. Results Of the 14 constructs and 42 tests (including initial, delayed and overall change two positive results were identified (i.e., overall change in pros, initial change in experiential powerful intervention approaches processes, with very

  8. The Influence of Proactive Green Innovation and Reactive Green Innovation on Green Product Development Performance: The Mediation Role of Green Creativity

    OpenAIRE

    Yu-Shan Chen; Tai-Wei Chang; Chun-Yu Lin; Pi-Yu Lai; Kuan-Hung Wang

    2016-01-01

    This study fills the research gap in the exploration of the relationships between both proactive and reactive green innovations and green product development performance, and examines the mediating effect of green creativity. Structural equation modeling (SEM) is utilized to test the hypotheses. From the sample of 146 valid respondents, the results show that proactive green innovation positively affects green creativity and green product development performance, and green creativity positivel...

  9. Motivations for Social Media Use and Impact on Political Participation in China: A Cognitive and Communication Mediation Approach.

    Science.gov (United States)

    Chen, Zhuo; Chan, Michael

    2017-02-01

    Integrating uses and gratifications theory and the cognitive/communication mediation model: this study examines Chinese students' use of social media and subsequent impact on political participation. An integrative framework is proposed where media use, political expression, and political cognitions (efficacy and knowledge) play important mediating roles between audience motivations and participation. Structural equation analyses showed support for the integrated model. Guidance and social utility motivations exhibited different indirect effects on online and offline participation through social media news, discussion, and political efficacy. Entertainment motivations exhibited no direct or indirect effects. Contrary to expectations and previous literature, surveillance motivations exhibited negative direct and indirect effects on offline participation, which may be attributed to the particular Chinese social and political context. Implications of the findings are discussed.

  10. Distinct and shared cognitive functions mediate event- and time-based prospective memory impairment in normal ageing

    Science.gov (United States)

    Gonneaud, Julie; Kalpouzos, Grégoria; Bon, Laetitia; Viader, Fausto; Eustache, Francis; Desgranges, Béatrice

    2011-01-01

    Prospective memory (PM) is the ability to remember to perform an action at a specific point in the future. Regarded as multidimensional, PM involves several cognitive functions that are known to be impaired in normal aging. In the present study, we set out to investigate the cognitive correlates of PM impairment in normal aging. Manipulating cognitive load, we assessed event- and time-based PM, as well as several cognitive functions, including executive functions, working memory and retrospective episodic memory, in healthy subjects covering the entire adulthood. We found that normal aging was characterized by PM decline in all conditions and that event-based PM was more sensitive to the effects of aging than time-based PM. Whatever the conditions, PM was linked to inhibition and processing speed. However, while event-based PM was mainly mediated by binding and retrospective memory processes, time-based PM was mainly related to inhibition. The only distinction between high- and low-load PM cognitive correlates lays in an additional, but marginal, correlation between updating and the high-load PM condition. The association of distinct cognitive functions, as well as shared mechanisms with event- and time-based PM confirms that each type of PM relies on a different set of processes. PMID:21678154

  11. Anticancer Effect of Ginger Extract against Pancreatic Cancer Cells Mainly through Reactive Oxygen Species-Mediated Autotic Cell Death

    Science.gov (United States)

    Akimoto, Miho; Iizuka, Mari; Kanematsu, Rie; Yoshida, Masato; Takenaga, Keizo

    2015-01-01

    The extract of ginger (Zingiber officinale Roscoe) and its major pungent components, [6]-shogaol and [6]-gingerol, have been shown to have an anti-proliferative effect on several tumor cell lines. However, the anticancer activity of the ginger extract in pancreatic cancer is poorly understood. Here, we demonstrate that the ethanol-extracted materials of ginger suppressed cell cycle progression and consequently induced the death of human pancreatic cancer cell lines, including Panc-1 cells. The underlying mechanism entailed autosis, a recently characterized form of cell death, but not apoptosis or necroptosis. The extract markedly increased the LC3-II/LC3-I ratio, decreased SQSTM1/p62 protein, and enhanced vacuolization of the cytoplasm in Panc-1 cells. It activated AMPK, a positive regulator of autophagy, and inhibited mTOR, a negative autophagic regulator. The autophagy inhibitors 3-methyladenine and chloroquine partially prevented cell death. Morphologically, however, focal membrane rupture, nuclear shrinkage, focal swelling of the perinuclear space and electron dense mitochondria, which are unique morphological features of autosis, were observed. The extract enhanced reactive oxygen species (ROS) generation, and the antioxidant N-acetylcystein attenuated cell death. Our study revealed that daily intraperitoneal administration of the extract significantly prolonged survival (P = 0.0069) in a peritoneal dissemination model and suppressed tumor growth in an orthotopic model of pancreatic cancer (P < 0.01) without serious adverse effects. Although [6]-shogaol but not [6]-gingerol showed similar effects, chromatographic analyses suggested the presence of other constituent(s) as active substances. Together, these results show that ginger extract has potent anticancer activity against pancreatic cancer cells by inducing ROS-mediated autosis and warrants further investigation in order to develop an efficacious candidate drug. PMID:25961833

  12. Epitope diversification driven by non-tumor epitope-specific Th1 and Th17 mediates potent antitumor reactivity.

    Science.gov (United States)

    Ichikawa, Kosuke; Kagamu, Hiroshi; Koyama, Kenichi; Miyabayashi, Takao; Koshio, Jun; Miura, Satoru; Watanabe, Satoshi; Yoshizawa, Hirohisa; Narita, Ichiei

    2012-09-21

    MHC class I-restricted peptide-based vaccination therapies have been conducted to treat cancer patients, because CD8⁺ CTL can efficiently induce apoptosis of tumor cells in an MHC class I-restricted epitope-specific manner. Interestingly, clinical responders are known to demonstrate reactivity to epitopes other than those used for vaccination; however, the mechanism underlying how antitumor T cells with diverse specificity are induced is unclear. In this study, we demonstrated that dendritic cells (DCs) that engulfed apoptotic tumor cells in the presence of non-tumor MHC class II-restricted epitope peptides, OVA(323-339), efficiently presented tumor-associated antigens upon effector-dominant CD4⁺ T cell balance against regulatory T cells (Treg) for the OVA(323-339) epitope. Th1 and Th17 induced tumor-associated antigens presentation of DC, while Th2 ameliorated tumor-antigen presentation for CD8⁺ T cells. Blocking experiments with anti-IL-23p19 antibody and anti-IL-23 receptor indicated that an autocrine mechanism of IL-23 likely mediated the diverted tumor-associated antigens presentation of DC. Tumor-associated antigens presentation of DC induced by OVA(323-339) epitope-specific CD4⁺ T cells resulted in facilitated antitumor immunity in both priming and effector phase in vivo. Notably, this immunotherapy did not require pretreatment to reduce Treg induced by tumor. This strategy may have clinical implications for designing effective antitumor immunotherapies. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Generation of reactive oxygen species by a novel berberine–bile acid analog mediates apoptosis in hepatocarcinoma SMMC-7721 cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qingyong, E-mail: li_qingyong@126.com [Key Laboratory of Forest Plant Ecology (Northeast Forestry University), Ministry of Education (China); Zhang, Li; Zu, Yuangang; Liu, Tianyu; Zhang, Baoyou; He, Wuna [Key Laboratory of Forest Plant Ecology (Northeast Forestry University), Ministry of Education (China)

    2013-04-19

    Graphical abstract: - Highlights: • Anticancer effects of B4, a novel berberine–bile acid analog, were tested. • B4 inhibited cell proliferation in hepatocellular carcinoma cells. • It also stimulated mitochondrial ROS production and membrane depolarization. • Effects of B4 were inhibited by a non-specific ROS scavenger. • Regulation of ROS generation may be a strategy for treating hepatic carcinoma. - Abstract: 2,3-Methenedioxy-9-O-(3′α,7′α-dihydroxy-5′β-cholan-24′-propy-lester) berberine (B4) is a novel berberine–bile acid analog synthesized in our laboratory. Previously, we showed that B4 exerted greater cytotoxicity than berberine in several human cancer cell lines. Therefore, we further evaluated the mechanism governing its anticancer actions in hepatocellular carcinoma SMMC-7721 cells. B4 inhibited the proliferation of SMMC-7721 cells, and stimulated reactive oxygen species (ROS) production and mitochondrial membrane depolarization; anti-oxidant capacity was reduced. B4 also induced the release of cytochrome c from the mitochondria to the cytosol and an increase in poly ADP-ribose polymerase (PARP) cleavage products, reflective of caspase-3 activation. Moreover, B4 induced the nuclear translocation of apoptosis-inducing factor (AIF) and a rise in DNA fragmentation. Pretreatment with the anti-oxidant N-acetylcysteine (NAC) inhibited B4-mediated effects, including cytotoxicity, ROS production, mitochondrial membrane depolarization increase in intracellular Ca{sup 2+}, cytochrome c release, PARP cleavage, and AIF translocation. Our data suggest that B4 induces ROS-triggered caspase-dependent and caspase-independent apoptosis pathways in SMMC-7721 cells and that ROS production may be a specific potential strategy for treating hepatic carcinoma.

  14. In vitro bacterial cytotoxicity of CNTs: reactive oxygen species mediate cell damage edges over direct physical puncturing.

    Science.gov (United States)

    Rajavel, Krishnamoorthy; Gomathi, Rajkumar; Manian, Sellamuthu; Rajendra Kumar, Ramasamy Thangavelu

    2014-01-21

    Understanding the bacterial cytotoxicity of CNTs is important for a wide variety of applications in the biomedical, environmental, and health sectors. A majority of the earlier reports attributed the bactericidal cytotoxicity of CNTs to bacterial cell membrane damage by direct physical puncturing. Our results reveal that bacterial cell death via bacterial cell membrane damage is induced by reactive oxygen species (ROS) produced from CNTs and is not due to direct physical puncturing by CNTs. To understand the actual mechanism of bacterial killing, we elucidated the bacterial cytotoxicity of SWCNTs and MWCNTs against Gram-negative human pathogenic bacterial species Escherichia coli, Shigella sonnei, Klebsiella pneumoniae, and Pseudomonas aeruginosa and its amelioration upon functionalizing the CNTs with antioxidant tannic acid (TA). Interestingly, the bacterial cells treated with CNTs exhibited severe cell damage under laboratory (ambient) and sunlight irradiation conditions. However, CNTs showed no cytotoxicity to the bacterial cells when incubated in the dark. The quantitative assessments carried out by us made it explicit that CNTs are effective generators of ROS such as (1)O2, O2(•-), and (•)OH in an aqueous medium under both ambient and sunlight-irradiated conditions. Both naked and TA-functionalized CNTs showed negligible ROS production in the dark. Furthermore, strong correlations were obtained between ROS produced by CNTs and the bacterial cell mortality (with the correlation coefficient varying between 0.7618 and 0.9891) for all four tested pathogens. The absence of bactericidal cytotoxicity in both naked and functionalized CNTs in the dark reveals that the presence of ROS is the major factor responsible for the bactericidal action compared to direct physical puncturing. This understanding of the bactericidal activity of the irradiated CNTs, mediated through the generation of ROS, could be interesting for novel applications such as regulated ROS delivery

  15. Anticancer Effect of Ginger Extract against Pancreatic Cancer Cells Mainly through Reactive Oxygen Species-Mediated Autotic Cell Death.

    Directory of Open Access Journals (Sweden)

    Miho Akimoto

    Full Text Available The extract of ginger (Zingiber officinale Roscoe and its major pungent components, [6]-shogaol and [6]-gingerol, have been shown to have an anti-proliferative effect on several tumor cell lines. However, the anticancer activity of the ginger extract in pancreatic cancer is poorly understood. Here, we demonstrate that the ethanol-extracted materials of ginger suppressed cell cycle progression and consequently induced the death of human pancreatic cancer cell lines, including Panc-1 cells. The underlying mechanism entailed autosis, a recently characterized form of cell death, but not apoptosis or necroptosis. The extract markedly increased the LC3-II/LC3-I ratio, decreased SQSTM1/p62 protein, and enhanced vacuolization of the cytoplasm in Panc-1 cells. It activated AMPK, a positive regulator of autophagy, and inhibited mTOR, a negative autophagic regulator. The autophagy inhibitors 3-methyladenine and chloroquine partially prevented cell death. Morphologically, however, focal membrane rupture, nuclear shrinkage, focal swelling of the perinuclear space and electron dense mitochondria, which are unique morphological features of autosis, were observed. The extract enhanced reactive oxygen species (ROS generation, and the antioxidant N-acetylcystein attenuated cell death. Our study revealed that daily intraperitoneal administration of the extract significantly prolonged survival (P = 0.0069 in a peritoneal dissemination model and suppressed tumor growth in an orthotopic model of pancreatic cancer (P < 0.01 without serious adverse effects. Although [6]-shogaol but not [6]-gingerol showed similar effects, chromatographic analyses suggested the presence of other constituent(s as active substances. Together, these results show that ginger extract has potent anticancer activity against pancreatic cancer cells by inducing ROS-mediated autosis and warrants further investigation in order to develop an efficacious candidate drug.

  16. Mitochondrial Reactive Oxygen Species Mediate Cardiac Structural, Functional, and Mitochondrial Consequences of Diet-Induced Metabolic Heart Disease.

    Science.gov (United States)

    Sverdlov, Aaron L; Elezaby, Aly; Qin, Fuzhong; Behring, Jessica B; Luptak, Ivan; Calamaras, Timothy D; Siwik, Deborah A; Miller, Edward J; Liesa, Marc; Shirihai, Orian S; Pimentel, David R; Cohen, Richard A; Bachschmid, Markus M; Colucci, Wilson S

    2016-01-11

    Mitochondrial reactive oxygen species (ROS) are associated with metabolic heart disease (MHD). However, the mechanism by which ROS cause MHD is unknown. We tested the hypothesis that mitochondrial ROS are a key mediator of MHD. Mice fed a high-fat high-sucrose (HFHS) diet develop MHD with cardiac diastolic and mitochondrial dysfunction that is associated with oxidative posttranslational modifications of cardiac mitochondrial proteins. Transgenic mice that express catalase in mitochondria and wild-type mice were fed an HFHS or control diet for 4 months. Cardiac mitochondria from HFHS-fed wild-type mice had a 3-fold greater rate of H2O2 production (P=0.001 versus control diet fed), a 30% decrease in complex II substrate-driven oxygen consumption (P=0.006), 21% to 23% decreases in complex I and II substrate-driven ATP synthesis (P=0.01), and a 62% decrease in complex II activity (P=0.002). In transgenic mice that express catalase in mitochondria, all HFHS diet-induced mitochondrial abnormalities were ameliorated, as were left ventricular hypertrophy and diastolic dysfunction. In HFHS-fed wild-type mice complex II substrate-driven ATP synthesis and activity were restored ex vivo by dithiothreitol (5 mmol/L), suggesting a role for reversible cysteine oxidative posttranslational modifications. In vitro site-directed mutation of complex II subunit B Cys100 or Cys103 to redox-insensitive serines prevented complex II dysfunction induced by ROS or high glucose/high palmitate in the medium. Mitochondrial ROS are pathogenic in MHD and contribute to mitochondrial dysfunction, at least in part, by causing oxidative posttranslational modifications of complex I and II proteins including reversible oxidative posttranslational modifications of complex II subunit B Cys100 and Cys103. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  17. "Thinking about numbers is not my idea of fun": need for cognition mediates age differences in numeracy performance.

    Science.gov (United States)

    Bruine de Bruin, Wändi; McNair, Simon J; Taylor, Andrea L; Summers, Barbara; Strough, JoNell

    2015-01-01

    Numeracy refers to people's ability to use numbers. Low numeracy has been associated with difficulties in understanding risk-benefit information and making health decisions. Older adults tend to perform worse than younger adults on measures of numeracy, but some theories of aging suggest that older adults may lack motivation for such tasks. We therefore test whether age differences in numeracy performance are mediated by a reduced motivation to think hard about complex problems-as measured by need for cognition. We recruited an age-diverse convenience sample of 306 UK adults. They completed measures of numeracy and need for cognition. They self-reported their educational attainment and other demographics. Older age was related to lower numeracy and lower need for cognition. The negative relationship between age and numeracy was mediated by need for cognition. These findings held after we controlled for educational attainment and other demographic factors. Older adults may show lower numeracy performance due to lack of motivation. We discuss strategies for improving people's motivation to complete numeracy measures and other numerical tasks. © The Author(s) 2014.

  18. Cyclosporin A-Mediated Activation of Endogenous Neural Precursor Cells Promotes Cognitive Recovery in a Mouse Model of Stroke

    Directory of Open Access Journals (Sweden)

    Labeeba Nusrat

    2018-04-01

    Full Text Available Cognitive dysfunction following stroke significantly impacts quality of life and functional independance; yet, despite the prevalence and negative impact of cognitive deficits, post-stroke interventions almost exclusively target motor impairments. As a result, current treatment options are limited in their ability to promote post-stroke cognitive recovery. Cyclosporin A (CsA has been previously shown to improve post-stroke functional recovery of sensorimotor deficits. Interestingly, CsA is a commonly used immunosuppressant and also acts directly on endogenous neural precursor cells (NPCs in the neurogenic regions of the brain (the periventricular region and the dentate gyrus. The immunosuppressive and NPC activation effects are mediated by calcineurin-dependent and calcineurin-independent pathways, respectively. To develop a cognitive stroke model, focal bilateral lesions were induced in the medial prefrontal cortex (mPFC of adult mice using endothelin-1. First, we characterized this stroke model in the acute and chronic phase, using problem-solving and memory-based cognitive tests. mPFC stroke resulted in early and persistent deficits in short-term memory, problem-solving and behavioral flexibility, without affecting anxiety. Second, we investigated the effects of acute and chronic CsA treatment on NPC activation, neuroprotection, and tissue damage. Acute CsA administration post-stroke increased the size of the NPC pool. There was no effect on neurodegeneration or lesion volume. Lastly, we looked at the effects of chronic CsA treatment on cognitive recovery. Long-term CsA administration promoted NPC migration toward the lesion site and rescued cognitive deficits to control levels. This study demonstrates that CsA treatment activates the NPC population, promotes migration of NPCs to the site of injury, and leads to improved cognitive recovery following long-term treatment.

  19. Cingulo-opercular network efficiency mediates the association between psychotic-like experiences and cognitive ability in the general population.

    Science.gov (United States)

    Sheffield, Julia M; Kandala, Sridhar; Burgess, Gregory C; Harms, Michael P; Barch, Deanna M

    2016-11-01

    Psychosis is hypothesized to occur on a spectrum between psychotic disorders and healthy individuals. In the middle of the spectrum are individuals who endorse psychotic-like experiences (PLEs) that may not impact daily functioning or cause distress. Individuals with PLEs show alterations in both cognitive ability and functional connectivity of several brain networks, but the relationship between PLEs, cognition, and functional networks remains poorly understood. We analyzed resting-state fMRI data, a range of neuropsychological tasks, and questions from the Achenbach Adult Self Report (ASR) in 468 individuals from the Human Connectome Project. We aimed to determine whether global efficiency of specific functional brain networks supporting higher-order cognition (the fronto-parietal network (FPN), cingulo-opercular network (CON), and default mode network (DMN)) was associated with PLEs and cognitive ability in a non-psychiatric sample. 21.6% of individuals in our sample endorsed at least one PLE. PLEs were significantly negatively associated with higher-order cognitive ability, CON global efficiency, and DMN global efficiency, but not crystallized knowledge. Higher-order cognition was significantly positively associated with CON and DMN global efficiency. Interestingly, the association between PLEs and cognitive ability was partially mediated by CON global efficiency and, in a subset of individuals who tested negative for drugs (N=405), the participation coefficient of the right anterior insula (a hub within the CON). These findings suggest that CON integrity may represent a shared mechanism that confers risk for psychotic experiences and the cognitive deficits observed across the psychosis spectrum.

  20. Emotional Reactivity and Appraisal of Food in Relation to Eating Disorder Cognitions and Behaviours: Evidence to Support the Motivational Conflict Hypothesis.

    Science.gov (United States)

    Racine, Sarah E; Hebert, Karen R; Benning, Stephen D

    2018-01-01

    Eating disorders are associated with both negative and positive emotional reactions towards food. Individual eating disorder symptoms may relate to distinct emotional responses to food, which could necessitate tailored treatments based on symptom presentation. We examined associations between eating disorder symptoms and psychophysiological responses to food versus neutral images in 87 college students [mean (SD) age = 19.70 (2.09); mean (SD) body mass index = 23.25(2.77)]. Reflexive and facial electromyography measures tapping negative emotional reactivity (startle blink reflex) and appraisal (corrugator muscle response) as well as positive emotional reactivity (postauricular reflex) and appraisal (zygomaticus muscle response) were collected. Eating disorder cognitions correlated with more corrugator activity to food versus neutral images, indicating negative appraisals of food. Binge eating was associated with increased postauricular reflex reactivity to food versus neutral images, suggesting enhanced appetitive motivation to food. The combination of cognitive eating disorder symptoms and binge eating may result in motivational conflict towards food. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

  1. Educational achievement and chronic pain disability: mediating role of pain-related cognitions.

    Science.gov (United States)

    Roth, Randy S; Geisser, Michael E

    2002-01-01

    This study examined the relation between level of educational achievement (LOE) and the clinical morbidity associated with chronic pain. a multidisciplinary pain rehabilitation program located within a university hospital. Two hundred ninety-nine consecutive patients with chronic spinal pain, average age 39.6 years (SD = 10.7) and with an average duration of pain of 41.9 months (SD = 51.6). Age, duration of pain, sex, and compensation and litigation status were controlled for in the statistical analysis because each was found to be significantly associated with LOE. Pain intensity was assessed by the McGill Pain Questionnaire. Affective distress was assessed by the Global Severity Index from the Brief Symptom Inventory. Severity of depressive symptoms was derived from scores from the Center for Epidemiological Studies-Depression Scale. Pain beliefs and pain coping strategies were assessed by the Survey of Pain Attitudes and the Coping Strategies Questionnaire, respectively. Finally, self-report of pain-related disability was assessed by the Pain Disability Index. After controlling for relevant covariates, LOE was unrelated to pain intensity, severity of depressive symptoms, or affective distress, but was inversely related to self-reported disability. Persons with lower LOEs possessed a greater belief that pain is a "signal of harm," unrelated to emotional experience, disabling and uncontrollable. They also endorsed more passive and maladaptive coping strategies, including a tendency to catastrophize about their pain. Path analysis indicated that, after controlling for the influence of both the belief that pain is a "signal of harm" and catastrophizing on the association between LOE and disability, this relation loses statistical significance. These results suggest that pain-related cognitions mediate the relation between LOE and pain disability and that persons with lower LOEs are more likely to develop maladaptive pain beliefs and coping strategies.

  2. When bad stress goes good: increased threat reactivity predicts improved category learning performance.

    Science.gov (United States)

    Ell, Shawn W; Cosley, Brandon; McCoy, Shannon K

    2011-02-01

    The way in which we respond to everyday stressors can have a profound impact on cognitive functioning. Maladaptive stress responses in particular are generally associated with impaired cognitive performance. We argue, however, that the cognitive system mediating task performance is also a critical determinant of the stress-cognition relationship. Consistent with this prediction, we observed that stress reactivity consistent with a maladaptive, threat response differentially predicted performance on two categorization tasks. Increased threat reactivity predicted enhanced performance on an information-integration task (i.e., learning is thought to depend upon a procedural-based memory system), and a (nonsignificant) trend for impaired performance on a rule-based task (i.e., learning is thought to depend upon a hypothesis-testing system). These data suggest that it is critical to consider both variability in the stress response and variability in the cognitive system mediating task performance in order to fully understand the stress-cognition relationship.

  3. Chronic condition as a mediator between metabolic syndrome and cognition among community-dwelling older adults: The moderating role of sex.

    Science.gov (United States)

    Foong, Hui Foh; Hamid, Tengku Aizan; Ibrahim, Rahimah; Haron, Sharifah Azizah; Shahar, Suzana

    2017-11-01

    Metabolic syndrome and chronic conditions are significant predictors of cognition; however, few studies have examined how they work together in predicting cognition in old age. Therefore, the present study examines whether a chronic condition mediates the association between metabolic syndrome and cognition. In addition, it discusses the moderating role of sex in the relationships between metabolic syndrome, chronic conditions and cognition. Secondary analysis was carried out of data from the Malaysian national survey that involved 2322 community residents aged 60 years or older in Peninsular Malaysia. Cognition was measured by the digit symbol substitution test. Metabolic syndrome was assessed by five biomarkers: triglyceride, fasting blood sugar, systolic blood pressure, cholesterol ratio and body mass index. Chronic conditions were assessed by self-reported medical history. The structural equation modeling technique was used to analyze the mediation and moderation tests. The number of chronic conditions partially mediated the association between metabolic syndrome and cognition. Men and women did not differ in the relationship between metabolic syndrome and cognition; however, the number of chronic conditions was found to be negatively associated with cognition in older women, but not in men. Metabolic syndrome might increase the likelihood of older adults to suffer from more chronic conditions; these responses might reduce their cognition. To prevent cognitive decline in old age, specific intervention to minimize the number of chronic conditions by reducing their vascular risk factors is warranted, especially among older women. Geriatr Gerontol Int 2017; 17: 1914-1920. © 2017 Japan Geriatrics Society.

  4. Posttraumatic stress disorder and suicidal ideation, plans, and impulses: The mediating role of anxiety sensitivity cognitive concerns among veterans.

    Science.gov (United States)

    Raines, Amanda M; Capron, Daniel W; Stentz, Lauren A; Walton, Jessica L; Allan, Nicholas P; McManus, Eliza S; Uddo, Madeline; True, Gala; Franklin, C Laurel

    2017-11-01

    Although the relationship between posttraumatic stress disorder (PTSD) and suicide has been firmly established, research on underlying mechanisms has been disproportionately low. The cognitive concerns subscale of anxiety sensitivity (AS), which reflects fears of cognitive dyscontrol, has been linked to both PTSD and suicide and thus may serve as an explanatory mechanism between these constructs. The sample consisted of 60 male veterans presenting to an outpatient Veteran Affairs (VA) clinic for psychological services. Upon intake, veterans completed a diagnostic interview and brief battery of self-report questionnaires to assist with differential diagnosis and treatment planning. Results revealed a significant association between PTSD symptom severity and higher suicidality (i.e., ideation, plans, and impulses), even after accounting for relevant demographic and psychological constructs. Moreover, AS cognitive concerns mediated this association. Limitations include the small sample size and cross-sectional nature of the current study. These findings add considerably to a growing body of literature examining underlying mechanisms that may help to explain the robust associations between PTSD and suicide. Considering the malleable nature of AS cognitive concerns, research is needed to determine the extent to which reductions in this cognitive risk factor are associated with reductions in suicide among at risk samples, such as those included in the present investigation. Published by Elsevier B.V.

  5. BMI-1 Mediates Estrogen-Deficiency-Induced Bone Loss by Inhibiting Reactive Oxygen Species Accumulation and T Cell Activation.

    Science.gov (United States)

    Li, Jinbo; Wang, Qian; Yang, Renlei; Zhang, Jiaqi; Li, Xing; Zhou, Xichao; Miao, Dengshun

    2017-05-01

    Previous studies have shown that estrogen regulates bone homeostasis through regulatory effects on oxidative stress. However, it is unclear how estrogen deficiency triggers reactive oxygen species (ROS) accumulation. Recent studies provide evidence that the B lymphoma Mo-MLV insertion region 1 (BMI-1) plays a critical role in protection against oxidative stress and that this gene is directly regulated by estrogen via estrogen receptor (ER) at the transcriptional level. In this study, ovariectomized mice were given drinking water with/without antioxidant N-acetyl-cysteine (NAC, 1 mg/mL) supplementation, and compared with each other and with sham mice. Results showed that ovariectomy resulted in bone loss with increased osteoclast surface, increased ROS levels, T cell activation, and increased TNF and RANKL levels in serum and in CD4 T cells; NAC supplementation largely prevented these alterations. BMI-1 expression levels were dramatically downregulated in CD4 T cells from ovariectomized mice. We supplemented drinking water to BMI-1-deficient mice with/without NAC and compared them with each other and with wild-type (WT) mice. We found that BMI-1 deficiency mimicked alterations observed in ovariectomy whereas NAC supplementation reversed all alterations induced by BMI-1 deficiency. Because T cells are critical in mediating ovariectomy-induced bone loss, we further assessed whether BMI-1 overexpression in lymphocytes can protect against estrogen deficiency-induced osteoclastogenesis and bone loss by inhibiting oxidative stress, T cell activation, and RANKL production. When WT and Eμ-BMI-1 transgenic mice with BMI-1 specifically overexpressed in lymphocytes were ovariectomized and compared with each other and with WT sham mice, we found that BMI-1 overexpression in lymphocytes clearly reversed all alterations induced by ovariectomy. Results from this study indicate that estrogen deficiency downregulates BMI-1 and subsequently increases ROS, T cell activation, and

  6. Mothers' Early Depressive Symptoms Predict Children's Low Social Competence in First Grade: Mediation by Children's Social Cognition

    Science.gov (United States)

    Wang, Yiji; Dix, Theodore

    2015-01-01

    Background: This study examined whether social-cognitive processes in children mediate relations between mothers' depressive symptoms across the first 3 years and children's first-grade social competence. Three maladaptive cognitions were examined: self-perceived social inadequacy, hostile attribution, and aggressive response generation.…

  7. The Mediator Roles of Life Satisfaction and Self-Esteem between the Affective Components of Psychological Well-Being and the Cognitive Symptoms of Problematic Internet Use

    Science.gov (United States)

    Senol-Durak, Emre; Durak, Mithat

    2011-01-01

    The factors associated with cognitions about problematic Internet use have been empirically tested in various studies. The aim of the present study was to examine the mediator roles of both life satisfaction and self-esteem between affective components of subjective well-being and cognitions about problematic Internet use. For this purpose, the…

  8. Do cognitive schema mediate the association between childhood trauma and being at ultra-high risk for psychosis?

    Science.gov (United States)

    Appiah-Kusi, E; Fisher, H L; Petros, N; Wilson, R; Mondelli, V; Garety, P A; Mcguire, P; Bhattacharyya, S

    2017-05-01

    Exposure to childhood trauma has been associated with psychotic symptoms, being at ultra-high risk for psychosis (UHR), and psychotic disorders such as schizophrenia. Negative self-beliefs have been shown to partially mediate the relationship between childhood trauma and paranoia and have been shown to be characteristic of patients with psychosis. However, whether the association between childhood trauma and being at high risk of developing psychosis (e.g., UHR) and paranoia symptoms is mediated by altered cognitive schema is unknown and warrants investigation to inform preventive interventions. Data was collected on 30 UHR patients from Outreach and Support in South London about exposure to childhood trauma, cognitive schema, paranoia and cannabis use. Relative to healthy controls (n = 38), UHR patients were significantly more likely to report exposure to various types of childhood trauma (emotional and sexual abuse, and emotional and physical neglect), had more negative schema and less positive schema about themselves and others, and were more likely to use cannabis more than once a month. Emotional neglect was found to be significantly associated with UHR status even after controlling for the effects of previous exposure to cannabis use (b = 0.262, 95% CI: 0.115-0.408), and this association was partially mediated by negative self-schema (b = 0.045, 95% CI: 0.004-0.159). Similarly, emotional neglect was significantly associated with paranoia (b = 1.354, 95% CI: 0.246-2.462), and this association was partially mediated by negative self-schema (b = 0.988, 95% CI: 0.323-1.895). These findings provide preliminary evidence about the cognitive mechanisms that may underlie the association between childhood trauma and later risk for psychosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Resveratrol Prevents High Fluence Red Light-Emitting Diode Reactive Oxygen Species-Mediated Photoinhibition of Human Skin Fibroblast Migration.

    Directory of Open Access Journals (Sweden)

    Andrew Mamalis

    Full Text Available Skin fibrosis is a significant medical problem that leads to a functional, aesthetic, and psychosocial impact on quality-of-life. Light-emitting diode-generated 633-nm red light (LED-RL is part of the visible light spectrum that is not known to cause DNA damage and is considered a safe, non-invasive, inexpensive, and portable potential alternative to ultraviolet phototherapy that may change the treatment paradigm of fibrotic skin disease.The goal of our study was to investigate the how reactive oxygen species (ROS free radicals generated by high fluence LED-RL inhibit the migration of skin fibroblasts, the main cell type involved in skin fibrosis. Fibroblast migration speed is increased in skin fibrosis, and we studied cellular migration speed of cultured human skin fibroblasts as a surrogate measure of high fluence LED-RL effect on fibroblast function. To ascertain the inhibitory role of LED-RL generated ROS on migration speed, we hypothesized that resveratrol, a potent antioxidant, could prevent the photoinhibitory effects of high fluence LED-RL on fibroblast migration speed.High fluence LED-RL generated ROS were measured by flow cytometry analysis using dihydrorhodamine (DHR. For purposes of comparison, we assessed the effects of ROS generated by hydrogen peroxide (H2O2 on fibroblast migration speed and the ability of resveratrol, a well known antioxidant, to prevent LED-RL and H2O2 generated ROS-associated changes in fibroblast migration speed. To determine whether resveratrol could prevent the high fluence LED-RL ROS-mediated photoinhibition of human skin fibroblast migration, treated cells were incubated with resveratrol at concentrations of 0.0001% and 0.001% for 24 hours, irradiated with high fluences LED-RL of 480, 640, and 800 J/cm2.High fluence LED-RL increases intracellular fibroblast ROS and decreases fibroblast migration speed. LED-RL at 480, 640 and 800 J/cm2 increased ROS levels to 132.8%, 151.0%, and 158.4% relative to matched

  10. Meta-cognitive beliefs as a mediator for the relationship between Cloninger's temperament and character dimensions and depressive and anxiety symptoms among healthy subjects.

    Science.gov (United States)

    Gawęda, Łukasz; Kokoszka, Andrzej

    2014-05-01

    Previous studies suggest that temperament and character may impact depression and anxiety through dysfunctional cognition. This study targets the mediating role of meta-cognitive beliefs in the relationship between Cloninger's temperament and character dimensions and symptoms of depression and anxiety. One hundred and sixty-one healthy subjects filled out Cloninger's Temperament Character Inventory (TCI), a Metacognitions Questionnaire (MCQ), the Beck Depression Inventory (BDI) and the State and Trait Anxiety Inventory (STAI). Correlation and mediation analyses according to Baron and Kenny's method were performed. Harm avoidance (HA) and self-directedness (SD) were related to depression and anxiety. HA was related to negative beliefs about uncontrollability of thoughts and to beliefs about cognitive confidence. SD was associated with the same types of meta-cognitive beliefs and with general negative beliefs. Cooperativeness (CO) was related to positive beliefs about worry, beliefs about cognitive confidence and to general negative beliefs. Self-transcendence (ST) was related to all types of meta-cognitive beliefs. Mediation analysis revealed that the relationship between HA and depression and anxiety is partially mediated by certain types of meta-cognitive beliefs. The same results were obtained for the relationship between SD and depression and anxiety. General negative beliefs fully mediated the relationship between CO and depression and the relationship between ST and anxiety. Meta-cognitive beliefs mediate the relationship between temperament and character dimension and depressive and anxiety symptoms, thus providing further evidence for the meta-cognitive theory of emotional disorders as presented by Wells and Matthews (Behav Res Ther 1996;32:867-870). Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Parent-Reported Behavioral and Psychiatric Problems Mediate the Relationship between Sleep-Disordered Breathing and Cognitive Deficits in School-Aged Children

    Directory of Open Access Journals (Sweden)

    Dale L. Smith

    2017-08-01

    Full Text Available BackgroundNumerous studies over the past several decades have illustrated that children who suffer from sleep-disordered breathing (SDB are at greater risk for cognitive, behavioral, and psychiatric problems. Although behavioral problems have been proposed as a potential mediator between SDB and cognitive functioning, these relationships have not been critically examined.MethodsThis analysis is based on a community-based cohort of 1,115 children who underwent overnight polysomnography, and cognitive and behavioral phenotyping. Structural model of the relationships between SDB, behavior, and cognition, and two recently developed mediation approaches based on propensity score weighting and resampling were used to assess the mediational role of parent-reported behavior and psychiatric problems in the relationship between SDB and cognitive functioning. Multiple models utilizing two different SDB definitions further explored direct effects of SDB on cognition as well as indirect effects through behavioral pathology. All models were adjusted for age, sex, race, BMI z-score, and asthma status.ResultsIndirect effects of SDB through behavior problems were significant in all mediation models, while direct effects of SDB on cognition were not. The findings were consistent across different mediation procedures and remained essentially unaltered when different criteria for SDB, behavior, and cognition were used.ConclusionPotential effects of SDB on cognitive functioning appear to occur through behavioral problems that are detectable in this pediatric population. Thus, early attentional or behavioral pathology may be implicated in the cognitive functioning deficits associated with SDB, and may present an early morbidity-related susceptibility biomarker.

  12. Stereotype threat and lift effects in motor task performance: the mediating role of somatic and cognitive anxiety.

    Science.gov (United States)

    Laurin, Raphael

    2013-01-01

    The aim of this investigation was to replicate the stereotype threat and lift effects in a motor task in a neutral sex-typed activity, using somatic and cognitive anxiety as key mediators of these phenomena. It was hypothesized that an ingroup/outgroup social categorization based on gender would have distinctive effects for female and male participants. A total of 161 French physical education students were randomly assigned to three threat conditions--no threat, female threat, and male threat--thus leading to a 3 x 2 (threat by gender) design. The analyses revealed a stereotype lift effect on the performances for both male and female participants, as well as a stereotype threat effect only for female participants. They also indicated that somatic anxiety had a mediating effect on the performance of female participants targeted by a negative stereotype, but that it had a facilitating effect on their performance. The stereotype threat and lift effects on motor tasks were replicated in a neutral sex-typed activity and somatic anxiety seems to have a facilitating mediating effect of the relationships between the gender-conditions (control or female threat) interaction and free-throw performance. The model used to distinguish somatic and cognitive anxiety appeared to be a relevant means of explaining the stereotype threat and lift mechanisms.

  13. The relationship among self-efficacy, negative self-referent cognitions, and social anxiety in children: a multiple mediator model.

    Science.gov (United States)

    Rudy, Brittany M; Davis, Thompson E; Matthews, Russell A

    2012-09-01

    Evidence suggests that general self-efficacy, an individual's beliefs about his global abilities, and social self-efficacy, an individual's beliefs in his ability to navigate social situations, are strongly connected to levels of social anxiety. Negative self-statements, also known as negative self-referent cognitions, have also been linked with levels of social anxiety. Although self-efficacy and negative self-statements have been shown to be important variables in the phenomenology and maintenance of social anxiety in children, they have yet to be examined in conjunction with one another. The purpose of this study was to examine the relationship between negative self-referent cognitions and self-efficacy and to examine both general self-efficacy and social self-efficacy as mediator variables in the relationship between negative self-statements and social anxiety. Results were based on a sample of 126 children ages 11 to 14 years. A significant association between negative self-statements and both general self-efficacy and social self-efficacy was established. Results also indicated that general self-efficacy fully mediated the relationship between negative self-statements and social anxiety; however, contrary to hypotheses, social self-efficacy did not mediate the relationship between negative self-statements and social anxiety. Implications and future recommendations are discussed. Copyright © 2011. Published by Elsevier Ltd.

  14. RNA sequencing supports distinct reactive oxygen species-mediated pathways of apoptosis by high and low size mass fractions of Bay leaf (Lauris nobilis) in HT-29 cells.

    Science.gov (United States)

    Rodd, Annabelle L; Ververis, Katherine; Sayakkarage, Dheeshana; Khan, Abdul W; Rafehi, Haloom; Ziemann, Mark; Loveridge, Shanon J; Lazarus, Ross; Kerr, Caroline; Lockett, Trevor; El-Osta, Assam; Karagiannis, Tom C; Bennett, Louise E

    2015-08-01

    Anti-proliferative and pro-apoptotic effects of Bay leaf (Laurus nobilis) in mammalian cancer and HT-29 adenocarcinoma cells have been previously attributed to effects of polyphenolic and essential oil chemical species. Recently, we demonstrated differentiated growth-regulating effects of high (HFBL) versus low molecular mass (LFBL) aqueous fractions of bay leaf and now confirm by comparative effects on gene expression, that HFBL and LFBL suppress HT-29 growth by distinct mechanisms. Induction of intra-cellular lesions including DNA strand breakage by extra-cellular HFBL, invoked the hypothesis that iron-mediated reactive oxygen species with capacity to penetrate cell membrane, were responsible for HFBL-mediated effects, supported by equivalent effects of HFBL in combination with γ radiation. Activities of HFBL and LFBL were interpreted to reflect differentiated responses to iron-mediated reactive oxygen species (ROS), occurring either outside or inside cells. In the presence of LFBL, apoptotic death was relatively delayed compared with HFBL. ROS production by LFBL mediated p53-dependent apoptosis and recovery was suppressed by promoting G1/S phase arrest and failure of cellular tight junctions. In comparison, intra-cellular anti-oxidant protection exerted by LFBL was absent for extra-cellular HFBL (likely polysaccharide-rich), which potentiated more rapid apoptosis by producing DNA double strand breaks. Differentiated effects on expression of genes regulating ROS defense and chromatic condensation by LFBL versus HFBL, were observed. The results support ferrous iron in cell culture systems and potentially in vivo, can invoke different extra-cellular versus intra-cellular ROS-mediated chemistries, that may be regulated by exogenous, including dietary species.

  15. Social Information Processing as a Mediator between Cognitive Schemas and Aggressive Behavior in Adolescents

    Science.gov (United States)

    Calvete, Esther; Orue, Izaskun

    2012-01-01

    This longitudinal investigation assessed whether cognitive schemas of justification of violence, mistrust, and narcissism predicted social information processing (SIP), and SIP in turn predicted aggressive behavior in adolescents. A total of 650 adolescents completed measures of cognitive schemas at Time 1, SIP in ambiguous social scenarios at…

  16. A Collaboration-Mediated Exploration of Nonnative L2 Teachers' Cognition of Language Teaching Methodology

    Science.gov (United States)

    Tajeddin, Zia; Aryaeian, Nafeeseh

    2017-01-01

    The present study sought to investigate nonnative L2 teachers' cognition of teaching methodology based on their collaborative talks. Participants were 12 nonnative EFL teachers categorized into three collaborative discussion groups by their teaching experience. Collaborative discussions were aimed at exploring the participants' cognition of…

  17. How Does Parental Reading Influence Children's Reading? A Study of Cognitive Mediation

    Science.gov (United States)

    van Bergen, Elsje; Bishop, Dorothy; van Zuijen, Titia; de Jong, Peter F.

    2015-01-01

    Cognitive processes underlying a behavioural outcome (like reading ability) and the impact of familial risk (e.g., for dyslexia) have been studied in isolation. We present a novel design, linking the two avenues. How do familial influences impact on children's cognitive skills, which subsequently underlie reading development? Participants from the…

  18. NADPH oxidase-mediated generation of reactive oxygen species: A new mechanism for X-ray-induced HeLa cell death

    International Nuclear Information System (INIS)

    Liu Qing; He Xiaoqing; Liu Yongsheng; Du Bingbing; Wang Xiaoyan; Zhang Weisheng; Jia Pengfei; Dong Jingmei; Ma Jianxiu; Wang Xiaohu; Li Sha; Zhang Hong

    2008-01-01

    Oxidative damage is an important mechanism in X-ray-induced cell death. Radiolysis of water molecules is a source of reactive oxygen species (ROS) that contribute to X-ray-induced cell death. In this study, we showed by ROS detection and a cell survival assay that NADPH oxidase has a very important role in X-ray-induced cell death. Under X-ray irradiation, the upregulation of the expression of NADPH oxidase membrane subunit gp91 phox was dose-dependent. Meanwhile, the cytoplasmic subunit p47 phox was translocated to the cell membrane and localized with p22 phox and gp91 phox to form reactive NADPH oxidase. Our data suggest, for the first time, that NADPH oxidase-mediated generation of ROS is an important contributor to X-ray-induced cell death. This suggests a new target for combined gene transfer and radiotherapy.

  19. Direct and mediated effects of language and cognitive skills on comprehension of oral narrative texts (listening comprehension) for children.

    Science.gov (United States)

    Kim, Young-Suk Grace

    2016-01-01

    We investigated component language and cognitive skills of oral language comprehension of narrative texts (i.e., listening comprehension). Using the construction-integration model of text comprehension as an overarching theoretical framework, we examined direct and mediated relations of foundational cognitive skills (working memory and attention), foundational language skills (vocabulary and grammatical knowledge), and higher-order cognitive skills (inference, theory of mind, and comprehension monitoring) to listening comprehension. A total of 201 first grade children in South Korea participated in the study. Structural equation modeling results showed that listening comprehension is directly predicted by working memory, grammatical knowledge, inference, and theory of mind and is indirectly predicted by attention, vocabulary, and comprehension monitoring. The total effects were .46 for working memory, .07 for attention, .30 for vocabulary, .49 for grammatical knowledge, .31 for inference, .52 for theory of mind, and .18 for comprehension monitoring. These results suggest that multiple language and cognitive skills make contributions to listening comprehension, and their contributions are both direct and indirect. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. The influence of aging on outgroup stereotypes: the mediating role of cognitive and motivational facets of deficient flexibility.

    Science.gov (United States)

    Czarnek, Gabriela; Kossowska, Malgorzata; Sedek, Grzegorz

    2015-01-01

    BACKGROUND/STUDY CONTEXT: The current study was designed to examine previously reported findings about age-related changes in drawing stereotypic inferences; specifically, that older adults are more likely than younger adults to stereotype outgroup members. The study replicates previous research and extends it by exploring the cognitive and motivational facets of deficient flexibility underlying this effect and comparing stereotypes towards ingroup and outgroup members. In the experiment, younger and older adults read stories that allowed for stereotypic inferences. They also completed the Trail Making Test (TMT) and Need for Closure Scale (NFC) as cognitive and motivational measures of deficient flexibility. The results of the experiment revealed that, compared to younger participants, older adults were more likely to rely upon stereotypic inferences when they read a story about outgroup members; however, there were no age-group differences in using stereotypes when they read a story about ingroup members. In addition, the findings showed that making more stereotypical inferences by older versus younger adults in relation to outgroup members was mediated by cognitive (TMT) and motivational (NFC) facets of deficient flexibility. A major implication of these findings is that both cognitive and motivational facets of deficient flexibility contribute to the reliance of older adults on stereotypes compared with younger adults. However, this is only true when older adults process information about outgroup members, but not about ingroup members. Thus, the current research goes beyond previous results by providing direct evidence that ingroup-outgroup perception contributes to stereotyping among older participants.

  1. Cognitive development in 7- to 24-month-old extremely/very-to-moderately/late preterm and full-term born infants: The mediating role of focused attention.

    Science.gov (United States)

    Reuner, Gitta; Weinschenk, Andrea; Pauen, Sabina; Pietz, Joachim

    2015-01-01

    The present study analyzed the links between prematurity, attention, and global cognitive performance in infancy and early childhood. At 7 months, focused attention (FA) was examined with an object examination task in 93 preterm infants (39 of them born extremely/very preterm, 54 born moderately/late preterm, and 38 infants born full-term). Global cognition was assessed at 7 and 24 months with the Bayley-II cognitive scale. Groups did not differ with respect to global cognitive performance but FA of infants born extremely/very preterm was significantly lower than in infants born moderately/late preterm. FA correlated significantly with both prematurity and cognitive performance at 7 months of age but not with global cognition in childhood. Findings point to a subtle adverse effect of prematurity on early attention and reveal evidence for the mediating role of FA on the effect of prematurity on cognition.

  2. Mediatization

    DEFF Research Database (Denmark)

    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...

  3. Cognitive behavioural therapy for MS-related fatigue explained: A longitudinal mediation analysis

    NARCIS (Netherlands)

    Akker, L.E. van den; Beckerman, H.; Collette, E.H.; Knoop, H.; Bleijenberg, G.; Twisk, J.W.; Dekker, J.; Groot, V. de

    2018-01-01

    BACKGROUND: Cognitive behavioural therapy (CBT) effectively reduces fatigue directly following treatment in patients with Multiple Sclerosis (MS), but little is known about the process of change during and after CBT. DESIGN: Additional analysis of a randomized clinical trial. OBJECTIVE: To

  4. Role of reactive oxygen intermediates in the interferon-mediated depression of hepatic drug metabolism and protective effect of N-acetylcysteine in mice.

    Science.gov (United States)

    Ghezzi, P; Bianchi, M; Gianera, L; Landolfo, S; Salmona, M

    1985-08-01

    Interferon (IFN) and IFN inducers are known to depress hepatic microsomal cytochrome P-450 levels, and the liver toxicity of IFN was reported to be lethal in newborn mice. We have observed that administration to mice of IFN and IFN inducers caused a marked increase in liver xanthine oxidase activity. Because this enzyme is well known to produce reactive oxygen intermediates and cytochrome P-450 was reported to be sensitive to the oxidative damage, we have tested the hypothesis that a free radical mechanism could mediate the depression of cytochrome P-450 levels by IFN. Administration to mice of the IFN inducer polyinosinic-polycytidylic acid (2 mg/kg i.p.) caused a 29 to 52% decrease in liver cytochrome P-450. Concomitant p.o. administration of the free radical scavenger, N-acetylcysteine (as a 2.5% solution in drinking water), or the xanthine oxidase inhibitor, allopurinol (100 mg/kg), protected against the IFN-mediated depression of P-450 kg), protected against the IFN-mediated depression of P-450 levels. The results suggest that an increased endogenous generation of free radicals, possibly due to the induction of xanthine oxidase, is implicated in the IFN-mediated depression of liver drug metabolism. The relevance of these data also extends to cases in which this side effect is observed in pathological situations (e.g., viral diseases and administration of vaccines) associated with an induction of IFN.

  5. Differentiating Motivational from Affective Influence of Performance-contingent Reward on Cognitive Control: The Wanting Component Enhances Both Proactive and Reactive Control.

    Science.gov (United States)

    Chaillou, Anne-Clémence; Giersch, Anne; Hoonakker, Marc; Capa, Rémi L; Bonnefond, Anne

    2017-04-01

    Positive affect strongly modulates goal-directed behaviors and cognitive control mechanisms. It often results from the presence of a pleasant stimulus in the environment, whether that stimulus appears unpredictably or as a consequence of a particular behavior. The influence of positive affect linked to a random pleasant stimulus differs from the influence of positive affect resulting from performance-contingent pleasant stimuli. However, the mechanisms by which the performance contingency of pleasant stimuli modulates the influence of positive affect on cognitive control mechanisms have not been elucidated. Here, we tested the hypothesis that these differentiated effects are the consequence of the activation of the motivational "wanting" component specifically under performance contingency conditions. To that end, we directly compared the effects on cognitive control of pleasant stimuli (a monetary reward) attributed in a performance contingent manner, and of random pleasant stimuli (positive picture) not related to performance, during an AX-CPT task. Both proactive and reactive modes of control were increased specifically by performance contingency, as reflected by faster reaction times and larger amplitude of the CNV and P3a components. Our findings advance our understanding of the respective effects of affect and motivation, which is of special interest regarding alterations of emotion-motivation interaction found in several psychopathological disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Self-care confidence may be more important than cognition to influence self-care behaviors in adults with heart failure: Testing a mediation model.

    Science.gov (United States)

    Vellone, Ercole; Pancani, Luca; Greco, Andrea; Steca, Patrizia; Riegel, Barbara

    2016-08-01

    Cognitive impairment can reduce the self-care abilities of heart failure patients. Theory and preliminary evidence suggest that self-care confidence may mediate the relationship between cognition and self-care, but further study is needed to validate this finding. The aim of this study was to test the mediating role of self-care confidence between specific cognitive domains and heart failure self-care. Secondary analysis of data from a descriptive study. Three out-patient sites in Pennsylvania and Delaware, USA. A sample of 280 adults with chronic heart failure, 62 years old on average and mostly male (64.3%). Data on heart failure self-care and self-care confidence were collected with the Self-Care of Heart Failure Index 6.2. Data on cognition were collected by trained research assistants using a neuropsychological test battery measuring simple and complex attention, processing speed, working memory, and short-term memory. Sociodemographic data were collected by self-report. Clinical information was abstracted from the medical record. Mediation analysis was performed with structural equation modeling and indirect effects were evaluated with bootstrapping. Most participants had at least 1 impaired cognitive domain. In mediation models, self-care confidence consistently influenced self-care and totally mediated the relationship between simple attention and self-care and between working memory and self-care (comparative fit index range: .929-.968; root mean squared error of approximation range: .032-.052). Except for short-term memory, which had a direct effect on self-care maintenance, the other cognitive domains were unrelated to self-care. Self-care confidence appears to be an important factor influencing heart failure self-care even in patients with impaired cognition. As few studies have successfully improved cognition, interventions addressing confidence should be considered as a way to improve self-care in this population. Copyright © 2016 Elsevier Ltd. All

  7. Growth parameters at birth mediate the relationship between prenatal manganese exposure and cognitive test scores among a cohort of 2- to 3-year-old Bangladeshi children.

    Science.gov (United States)

    Lee, Jane J; Valeri, Linda; Kapur, Kush; Ibne Hasan, Md Omar Sharif; Quamruzzaman, Quazi; Wright, Robert O; Bellinger, David C; Christiani, David C; Mazumdar, Maitreyi

    2018-05-03

    Our previous study demonstrated that prenatal manganese exposure is associated with cognitive test scores among a cohort of 2- to 3-year-old Bangladeshi children. This study tested the hypothesis that the adverse effects of manganese are mediated through poor prenatal growth. Pregnant mothers were enrolled in a birth cohort in Bangladesh between 2008 and 2011, and children were followed at birth and age 20-40 months. Manganese concentration was measured in umbilical cord blood. Anthropometric measurements (weight, length, head circumference) were assessed at delivery. Children's cognitive development was assessed at age 20-40 months using the Bayley Scales of Infant and Toddler Development-Third Edition. Using recently developed statistical approaches that estimate mediation and interaction effects simultaneously, we evaluated whether the association between cord blood manganese and cognitive score was mediated through anthropometric measures at birth. This analysis included 764 mother-child pairs. Higher manganese concentration was associated with lower cognitive score [β=-0.61, standard error (SE)=0.23, p = 0.009]. Among the birth measures, we found a significant indirect effect only through birth length (β =-0.10, SE = 0.03, p = 0.001). We also found evidence of mediated interaction (both mediation and interaction, β =-0.03, SE = 0.01, p = 0.01) with birth length in the association between cord blood manganese and cognitive score. The overall proportion mediated by birth length was 33% (p = 0.02) and the proportion attributed to interaction was 11% (p = 0.04). We did not find evidence of a mediating effect through birth weight or head circumference. Our findings confirm that prenatal growth, particularly birth length, contributes to the overall effect of environmental manganese exposure on a child's cognitive development.

  8. Reorganization of functional brain networks mediates the improvement of cognitive performance following real-time neurofeedback training of working memory.

    Science.gov (United States)

    Zhang, Gaoyan; Yao, Li; Shen, Jiahui; Yang, Yihong; Zhao, Xiaojie

    2015-05-01

    Working memory (WM) is essential for individuals' cognitive functions. Neuroimaging studies indicated that WM fundamentally relied on a frontoparietal working memory network (WMN) and a cinguloparietal default mode network (DMN). Behavioral training studies demonstrated that the two networks can be modulated by WM training. Different from the behavioral training, our recent study used a real-time functional MRI (rtfMRI)-based neurofeedback method to conduct WM training, demonstrating that WM performance can be significantly improved after successfully upregulating the activity of the target region of interest (ROI) in the left dorsolateral prefrontal cortex (Zhang et al., [2013]: PloS One 8:e73735); however, the neural substrate of rtfMRI-based WM training remains unclear. In this work, we assessed the intranetwork and internetwork connectivity changes of WMN and DMN during the training, and their correlations with the change of brain activity in the target ROI as well as with the improvement of post-training behavior. Our analysis revealed an "ROI-network-behavior" correlation relationship underlying the rtfMRI training. Further mediation analysis indicated that the reorganization of functional brain networks mediated the effect of self-regulation of the target brain activity on the improvement of cognitive performance following the neurofeedback training. The results of this study enhance our understanding of the neural basis of real-time neurofeedback and suggest a new direction to improve WM performance by regulating the functional connectivity in the WM related networks. © 2014 Wiley Periodicals, Inc.

  9. Brain-derived neurotrophic factor mediates cognitive improvements following acute exercise.

    Science.gov (United States)

    Borror, Andrew

    2017-09-01

    The mechanisms causing improved cognition following acute exercise are poorly understood. This article proposes that brain-derived neurotrophic factor (BDNF) is the main factor contributing to improved cognition following exercise. Additionally, it argues that cerebral blood flow (CBF) and oxidative stress explain the release of BDNF from cerebral endothelial cells. One way to test these hypotheses is to block endothelial function and measure the effect on BDNF levels and cognitive performance. The CBF and oxidative stress can also be examined in relationship to BDNF using a multiple linear regression. If these hypotheses are true, there would be a linear relationship between CBF+oxidative stress and BDNF levels as well as between BDNF levels and cognitive performance. The novelty of these hypotheses comes from the emphasis on the cerebral endothelium and the interplay between BDNF, CBF, and oxidative stress. If found to be valid, these hypotheses would draw attention to the cerebral endothelium and provide direction for future research regarding methods to optimize BDNF release and enhance cognition. Elucidating these mechanisms would provide direction for expediting recovery in clinical populations, such as stroke, and maintaining quality of life in the elderly. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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

  11. Right frontal pole cortical thickness and social competence in children with chronic traumatic brain injury: cognitive proficiency as a mediator.

    Science.gov (United States)

    Levan, Ashley; Baxter, Leslie; Kirwan, C Brock; Black, Garrett; Gale, Shawn D

    2015-01-01

    To examine the association between right frontal pole cortical thickness, social competence, and cognitive proficiency in children participants with a history of chronic traumatic brain injury (TBI). Twenty-three children (65% male; M age = 12.8 years, SD = 2.3 years) at least 1 year post-injury (M = 3.3 years, SD = 1.7 years) were evaluated with the Cognitive Proficiency Index (CPI) from the Wechsler Intelligence Scale for Children, 4th Edition, and their caregiver completed the Child Behavior Checklist. Social competence was evaluated with the Social Competence and Social Problems subscales from the Child Behavior Checklist. Right frontal pole cortical thickness was calculated via FreeSurfer from high-resolution 3-dimensional T1 magnetic resonance imaging scans. Direct effect of right frontal pole cortical thickness on social competence was significant (β = 14.09, SE = 4.6, P Right frontal pole cortical thickness significantly predicted CPI (β = 18.44, SE = 4.9, P right frontal lobe cortical integrity and social competence in pediatric participants with chronic TBI may be mediated through cognitive proficiency.

  12. Cognitive deficits are a matter of emotional context: inflexible strategy use mediates context-specific learning impairments in OCD.

    Science.gov (United States)

    Zetsche, Ulrike; Rief, Winfried; Westermann, Stefan; Exner, Cornelia

    2015-01-01

    The present study examines the interplay between cognitive deficits and emotional context in obsessive-compulsive disorder (OCD) and social phobia (SP). Specifically, this study examines whether the inflexible use of efficient learning strategies in an emotional context underlies impairments in probabilistic classification learning (PCL) in OCD, and whether PCL impairments are specific to OCD. Twenty-three participants with OCD, 30 participants with SP and 30 healthy controls completed a neutral and an OCD-specific PCL task. OCD participants failed to adopt efficient learning strategies and showed fewer beneficial strategy switches than controls only in an OCD-specific context, but not in a neutral context. Additionally, OCD participants did not show any explicit memory impairments. Number of beneficial strategy switches in the OCD-specific task mediated the difference in PCL performance between OCD and control participants. Individuals with SP were impaired in both PCL tasks. In contrast to neuropsychological models postulating general cognitive impairments in OCD, the present findings suggest that it is the interaction between cognition and emotion that is impaired in OCD. Specifically, activated disorder-specific fears may impair the flexible adoption of efficient learning strategies and compromise otherwise unimpaired PCL. Impairments in PCL are not specific to OCD.

  13. Amyloid β-mediated Zn2+ influx into dentate granule cells transiently induces a short-term cognitive deficit.

    Directory of Open Access Journals (Sweden)

    Atsushi Takeda

    Full Text Available We examined an idea that short-term cognition is transiently affected by a state of confusion in Zn2+ transport system due to a local increase in amyloid-β (Aβ concentration. A single injection of Aβ (25 pmol into the dentate gyrus affected dentate gyrus long-term potentiation (LTP 1 h after the injection, but not 4 h after the injection. Simultaneously, 1-h memory of object recognition was affected when the training was performed 1 h after the injection, but not 4 h after the injection. Aβ-mediated impairments of LTP and memory were rescued in the presence of zinc chelators, suggesting that Zn2+ is involved in Aβ action. When Aβ was injected into the dentate gyrus, intracellular Zn2+ levels were increased only in the injected area in the dentate gyrus, suggesting that Aβ induces the influx of Zn2+ into cells in the injected area. When Aβ was added to hippocampal slices, Aβ did not increase intracellular Zn2+ levels in the dentate granule cell layer in ACSF without Zn2+, but in ACSF containing Zn2+. The increase in intracellular Zn2+ levels was inhibited in the presence of CaEDTA, an extracellular zinc chelator, but not in the presence of CNQX, an AMPA receptor antagonist. The present study indicates that Aβ-mediated Zn2+ influx into dentate granule cells, which may occur without AMPA receptor activation, transiently induces a short-term cognitive deficit. Extracellular Zn2+ may play a key role for transiently Aβ-induced cognition deficits.

  14. Amyloid β-mediated Zn2+ influx into dentate granule cells transiently induces a short-term cognitive deficit.

    Science.gov (United States)

    Takeda, Atsushi; Nakamura, Masatoshi; Fujii, Hiroaki; Uematsu, Chihiro; Minamino, Tatsuya; Adlard, Paul A; Bush, Ashley I; Tamano, Haruna

    2014-01-01

    We examined an idea that short-term cognition is transiently affected by a state of confusion in Zn2+ transport system due to a local increase in amyloid-β (Aβ) concentration. A single injection of Aβ (25 pmol) into the dentate gyrus affected dentate gyrus long-term potentiation (LTP) 1 h after the injection, but not 4 h after the injection. Simultaneously, 1-h memory of object recognition was affected when the training was performed 1 h after the injection, but not 4 h after the injection. Aβ-mediated impairments of LTP and memory were rescued in the presence of zinc chelators, suggesting that Zn2+ is involved in Aβ action. When Aβ was injected into the dentate gyrus, intracellular Zn2+ levels were increased only in the injected area in the dentate gyrus, suggesting that Aβ induces the influx of Zn2+ into cells in the injected area. When Aβ was added to hippocampal slices, Aβ did not increase intracellular Zn2+ levels in the dentate granule cell layer in ACSF without Zn2+, but in ACSF containing Zn2+. The increase in intracellular Zn2+ levels was inhibited in the presence of CaEDTA, an extracellular zinc chelator, but not in the presence of CNQX, an AMPA receptor antagonist. The present study indicates that Aβ-mediated Zn2+ influx into dentate granule cells, which may occur without AMPA receptor activation, transiently induces a short-term cognitive deficit. Extracellular Zn2+ may play a key role for transiently Aβ-induced cognition deficits.

  15. Why expressive suppression does not pay? Cognitive costs of negative emotion suppression: The mediating role of subjective tense-arousal

    Directory of Open Access Journals (Sweden)

    Szczygieł Dorota

    2015-09-01

    Full Text Available The aim of this paper was to contribute to a broader understanding of the cognitive consequences of expressive suppression. Specifically, we examined whether the deteriorating effect of expressive suppression on cognitive functioning is caused by tense arousal enhanced by suppression. Two experiments were performed in order to test this prediction. In both studies we tested the effect of expressive suppression on working memory, as measured with a backwards digit-span task (Study 1, N = 43 and anagram problem-solving task (Study 2, N = 60. In addition, in Study 2 we tested whether expressive suppression degrades memory of the events that emerged during the period of expressive suppression. Both studies were conducted in a similar design: Participants watched a film clip which evoked negative emotions (i.e. disgust in Study 1 and a combination of sadness and anxiety in Study 2 under the instruction to suppress those negative emotions or (in the control condition to simply watch the film. The results of these experiments lead to three conclusions. First, the results reveal that expressive suppression degrades memory of the events that emerged during the period of expressive suppression and leads to poorer performance on working memory tasks, as measured with a backwards digit-span task and anagram problem-solving task. Second, the results indicate that expressive suppression leads to a significant increase in subjective tense arousal. Third, the results support our prediction that expressive suppression decreases cognitive performance through its effects on subjective tense arousal. The results of the Study 1 show that tense arousal activated during expressive suppression of disgust fully mediates the negative effect of suppression on working memory as measured with a backwards digit-span task. The results of Study 2 reveal that subjective tense arousal elicited while suppressing sadness and anxiety mediates both the effect of suppression on

  16. High-level cognition in phobics: Abstract anticipatory memory is associated with the attenuation of physiological reactivity to threat.

    NARCIS (Netherlands)

    Kindt, M.; Brosschot, J.F.; Boiten, F.

    1999-01-01

    Investigated whether the cognitive processing of threat in anxious individuals is dominated by abstract anticipatory memory, and whether this abstract memory mode is related to the incomplete activation of the fear network. Activation of the fear network was assessed during phobic exposure, as

  17. A TRANSLATIONAL INVESTIGATION TARGETING STRESS-REACTIVITY AND PRE-FRONTAL COGNITIVE CONTROL WITH GUANFACINE FOR SMOKING CESSATION

    Science.gov (United States)

    McKee, Sherry A.; Potenza, Marc N.; Kober, Hedy; Sofuoglu, Mehmet; Arnsten, Amy F. T.; Picciotto, Marina R.; Weinberger, Andrea H.; Ashare, Rebecca; Sinha, Rajita

    2015-01-01

    Stress and pre-frontal cognitive dysfunction have key roles in driving smoking, however, there are no therapeutics for smoking cessation which attenuate the effects of stress on smoking and enhance cognition. Central noradrenergic pathways are involved in stress-induced reinstatement to nicotine and in the prefrontal executive control of adaptive behaviors. We used a novel translational approach employing a validated laboratory analogue of stress-precipitated smoking, fMRI, and a proof-of-concept treatment period to evaluate whether the noradrenergic α2a agonist, guanfacine (3mg/day) versus placebo (0mg/day) reduced stress-precipitated smoking in the laboratory, altered cortico-striatal activation during the Stroop cognitive-control task, and reduced smoking following a quit attempt. In nicotine-deprived smokers (n=33), stress versus a neutral condition significantly decreased the latency to smoke, and increased tobacco craving, ad-libitum smoking, and systolic blood pressure in placebo-treated subjects, and these effects were absent or reduced in guanfacine-treated subjects. Following stress, placebo-treated subjects demonstrated decreased cortisol levels whereas guanfacine-treated subjects demonstrated increased levels. Guanfacine, compared to placebo, altered prefrontal activity during a cognitive control task, and reduced cigarette use but did not increase complete abstinence during treatment. These preliminary laboratory, neuroimaging and clinical outcome data were consistent and complementary and support further development of guanfacine for smoking cessation. PMID:25516371

  18. Neuro-cognitive effects of acute tyrosine administration on reactive and proactive response inhibition in healthy older adults

    NARCIS (Netherlands)

    Bloemendaal, Mirjam; Froböse, Monja Isabel; Wegman, Joost; Zandbelt, Bram Bastiaan; Rest, van de Ondine; Cools, Roshan; Aarts, Esther

    2018-01-01

    The aging brain is characterized by altered dopamine signaling. The amino acid tyrosine, a catecholamine precursor, is known to improve cognitive performance in young adults, especially during high environmental demands. Tyrosine administration might also affect catecholamine transmission in the

  19. The Relationship Between Posttraumatic Cognitive Change, Posttraumatic Stress Disorder, and Posttraumatic Growth Among Chinese Adolescents After the Yancheng Tornado: The Mediating Effect of Rumination

    Science.gov (United States)

    Zhang, Yi; Xu, Wei; Yuan, Guangzhe; An, Yuanyuan

    2018-01-01

    The aim of this study was to explore the different cognitive processes involved in the development of posttraumatic stress disorders (PTSDs) and posttraumatic growth (PTG). One year after the Yancheng tornado, 455 middle school students were assessed to study how posttraumatic cognitive change (PCC) influenced PTSD and PTG among traumatized Chinese adolescents through the role of rumination. The results indicated that intrusive rumination partly mediated the relationship between PCC and PTSD, and deliberate rumination partly mediated the relationship between PCC and PTSD and completely mediated the relationship between PCC and PTG. These results suggest that the cognitive processes of PTSD and PTG are different. Furthermore, the study also suggests that PTSD and PTG can coexist in individuals. This study may offer some suggestions for clinical practice after traumatic events. PMID:29686638

  20. The Relationship Between Posttraumatic Cognitive Change, Posttraumatic Stress Disorder, and Posttraumatic Growth Among Chinese Adolescents After the Yancheng Tornado: The Mediating Effect of Rumination.

    Science.gov (United States)

    Zhang, Yi; Xu, Wei; Yuan, Guangzhe; An, Yuanyuan

    2018-01-01

    The aim of this study was to explore the different cognitive processes involved in the development of posttraumatic stress disorders (PTSDs) and posttraumatic growth (PTG). One year after the Yancheng tornado, 455 middle school students were assessed to study how posttraumatic cognitive change (PCC) influenced PTSD and PTG among traumatized Chinese adolescents through the role of rumination. The results indicated that intrusive rumination partly mediated the relationship between PCC and PTSD, and deliberate rumination partly mediated the relationship between PCC and PTSD and completely mediated the relationship between PCC and PTG. These results suggest that the cognitive processes of PTSD and PTG are different. Furthermore, the study also suggests that PTSD and PTG can coexist in individuals. This study may offer some suggestions for clinical practice after traumatic events.

  1. The mediational role of panic self-efficacy in cognitive behavioral therapy for panic disorder: A systematic review and meta-analysis

    DEFF Research Database (Denmark)

    Fentz, Hanne Nørr; Arendt, Mikkel; OToole, Mia Skytte

    2014-01-01

    Cognitive models of panic disorder (PD) with and without agoraphobia have stressed the role of catastrophic beliefs of bodily symptoms as a central mediating variable of the efficacy of cognitive behavioral therapy (CBT). Perceived ability to cope with or control panic attacks, panic self......-efficacy, has also been proposed to play a key role in therapeutic change; however, this cognitive factor has received much less attention in research. The aim of the present review is to evaluate panic self-efficacy as a mediator of outcome in CBT for PD using descriptive and meta-analytic procedures. We...... an association between change in panic self-efficacy and change in outcome during therapy (criterion 2); three tested, and one established formal statistical mediation of panic self-efficacy (criterion 3); while four tested and three found change in panic self-efficacy occurring before the reduction of panic...

  2. Divergent pathways to influence: Cognition and behavior differentially mediate the effects of optimism on physical and mental quality of life in Chinese university students.

    Science.gov (United States)

    Ramsay, Jonathan E; Yang, Fang; Pang, Joyce S; Lai, Ching-Man; Ho, Roger Cm; Mak, Kwok-Kei

    2015-07-01

    Previous research has indicated that both cognitive and behavioral variables mediate the positive effect of optimism on quality of life; yet few attempts have been made to accommodate these constructs into a single explanatory framework. Adopting Fredrickson's broaden-and-build perspective, we examined the relationships between optimism, self-rated health, resilience, exercise, and quality of life in 365 Chinese university students using path analysis. For physical quality of life, a two-stage model, in which the effects of optimism were sequentially mediated by cognitive and behavioral variables, provided the best fit. A one-stage model, with full mediation by cognitive variables, provided the best fit for mental quality of life. This suggests that optimism influences physical and mental quality of life via different pathways. © The Author(s) 2013.

  3. The Relationship Between Posttraumatic Cognitive Change, Posttraumatic Stress Disorder, and Posttraumatic Growth Among Chinese Adolescents After the Yancheng Tornado: The Mediating Effect of Rumination

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    2018-04-01

    Full Text Available The aim of this study was to explore the different cognitive processes involved in the development of posttraumatic stress disorders (PTSDs and posttraumatic growth (PTG. One year after the Yancheng tornado, 455 middle school students were assessed to study how posttraumatic cognitive change (PCC influenced PTSD and PTG among traumatized Chinese adolescents through the role of rumination. The results indicated that intrusive rumination partly mediated the relationship between PCC and PTSD, and deliberate rumination partly mediated the relationship between PCC and PTSD and completely mediated the relationship between PCC and PTG. These results suggest that the cognitive processes of PTSD and PTG are different. Furthermore, the study also suggests that PTSD and PTG can coexist in individuals. This study may offer some suggestions for clinical practice after traumatic events.

  4. Reexcision Perineural Invasion and Epithelial Sheath Neuroma Possibly on a Spectrum of Postinjury Reactive Hyperplasia Mediated by IL-6.

    Science.gov (United States)

    Wang, James Y; Nuovo, Gerard; Kline, Mitchell; Magro, Cynthia M

    2017-01-01

    Epithelial sheath neuroma is a rarely recognized but established entity in the medical literature. First described in 2000 by Requena et al, there have only been 7 published cases to date, mostly in female patients and presenting as symptomatic solitary lesions on the back without a known history of trauma. In 2006, Beer et al described and reviewed a dozen cases in which epithelial sheath neuroma-like features were seen in the advent of a surgical procedure, which was termed "re-excision perineural invasion" and attributed to possible eccrine duct implantation during surgery. Our case is a 66-year-old male patient who underwent an excision of a melanocytic neoplasm in which a reactive epithelial sheath neuroma was incidentally discovered in the excision specimen, adjacent to the biopsy site cicatrix. Histologically, there was benign cutaneous nerve hyperplasia with a proliferation of squamous epithelium in intimate apposition to the nerve bundles in the superficial dermis. We postulate that the process active in the formation of re-excision perineural invasion is the same as in epithelial sheath neuroma and that minor trauma not appreciable on histologic examination is responsible in the latter entity. We performed IL-6 staining and documented that IL-6 was upregulated at the interface of the nerve and reactive epithelium, but was absent in nerves distant from the site of surgery, suggesting that IL-6 may be essential to the lesion's development. The recognition of reactive epithelial sheath neuroma including the subcategory of re-excision perineural invasion is crucial for the dermatopathologist to prevent mislabeling this reactive entity as a perineural squamous cell carcinoma, which has clinical consequences for the patient such as wider re-excision and radiation treatment. Additionally, we have identified a potential pathophysiologic basis for this lesion.

  5. 6-Thioguanine Reactivates Epigenetically Silenced Genes in Acute Lymphoblastic Leukemia Cells by Facilitating Proteasome-mediated Degradation of DNMT1

    OpenAIRE

    Yuan, Bifeng; Zhang, Jing; Wang, Hongxia; Xiong, Lei; Cai, Qian; Wang, Tina; Jacobsen, Steven; Pradhan, Sriharsa; Wang, Yinsheng

    2011-01-01

    Thiopurines including 6-thioguanine (SG), 6-mercaptopurine and azathioprine are effective anticancer agents with remarkable success in clinical practice, especially in effective treatment of acute lymphoblastic leukemia (ALL). SG is understood to act as a DNA hypomethylating agent in ALL cells, however, the underlying mechanism leading to global cytosine demethylation remains unclear. Here we report that SG treatment results in reactivation of epigenetically silenced genes in T leukemia cells...

  6. Reactive bonding mediated high mass loading of individualized single-walled carbon nanotubes in an elastomeric polymer

    Science.gov (United States)

    Zhao, Liping; Li, Yongjin; Qiu, Jishan; You, Jichun; Dong, Wenyong; Cao, Xiaojun

    2012-09-01

    A reactive chemical bonding strategy was developed for the incorporation of a high mass loading of individual single-wall carbon nanotubes (SWCNTs) into an elastomeric matrix using a reactive ionic liquid as a linker. This method simultaneously prevented the agglomeration of SWCNTs and caused strong interfacial bonding, while the electronic properties of the SWCNTs remained intact. As a result, the high conductivity of the carbon nanotubes (CNTs) and the flexibility of the elastomeric matrix were retained, producing optimum electrical and mechanical properties. A composite material with a loading of 20 wt% SWCNTs was fabricated with excellent mechanical properties and a high conductivity (9500 S m-1). The method could be used to form transparent thin conductive films that could tolerate over 800 bend cycles at a bending angle of 180° while maintaining a constant sheet resistance.A reactive chemical bonding strategy was developed for the incorporation of a high mass loading of individual single-wall carbon nanotubes (SWCNTs) into an elastomeric matrix using a reactive ionic liquid as a linker. This method simultaneously prevented the agglomeration of SWCNTs and caused strong interfacial bonding, while the electronic properties of the SWCNTs remained intact. As a result, the high conductivity of the carbon nanotubes (CNTs) and the flexibility of the elastomeric matrix were retained, producing optimum electrical and mechanical properties. A composite material with a loading of 20 wt% SWCNTs was fabricated with excellent mechanical properties and a high conductivity (9500 S m-1). The method could be used to form transparent thin conductive films that could tolerate over 800 bend cycles at a bending angle of 180° while maintaining a constant sheet resistance. Electronic supplementary information (ESI) available: Conductivity test of the SEBS-SWCNTs film, transmission spectra and sheet resistance for the spin-coated SEBS-SWCNTs thin films on PET slides. See DOI: 10

  7. Potential Mediators between Fibromyalgia and C-Reactive protein: Results from a Large U.S. Community Survey

    OpenAIRE

    Feinberg, Termeh; Sambamoorthi, Usha; Lilly, Christa; Innes, Kim Karen

    2017-01-01

    Background Fibromyalgia, a potentially debilitating chronic pain syndrome of unknown etiology, may be characterized by inflammation. In this study, we investigated the relation of FMS to serum C-reactive protein (CRP) in a large population of adults (18+) and investigated the influence of other factors on this relationship, including BMI, comorbidities, as well as mood and sleep disturbance. Methods Participants were 52,535 Ohio Valley residents (Fibromyalgia n?=?1125). All participants compl...

  8. Do coping skills mediate the relationship between cognitive-behavioral therapy and reductions in gambling in pathological gamblers?

    Science.gov (United States)

    Petry, Nancy M; Litt, Mark D; Kadden, Ronald; Ledgerwood, David M

    2007-08-01

    Cognitive-behavioral therapy (CBT) is useful for treating substance abusers, and recent data suggest it is also efficacious for pathological gamblers. CBT is purported to exert its beneficial effects by altering coping skills, but data supporting coping changes as the mechanism of action are mixed. This study examined whether coping skills acquisition mediated the effects of CBT on decreasing gambling in pathological gamblers. Participants were assigned randomly to CBT plus referral to Gamblers Anonymous (GA) or to GA referral alone. Setting Out-patient clinic. A total of 127 pathological gamblers. Participants completed the Coping Strategies Scale (CSS) before treatment and 2 months later; indices of gambling behavior and problems were administered pretreatment and at months 2 and 12. Overall, CSS scores increased for participants in both conditions, but those receiving CBT evidenced larger increases than those in the GA condition (P < 0.05), and they also reduced gambling more substantially between pretreatment and month 2. Changes in CSS scores mediated the relationship between treatment assignment and gambling outcomes from pretreatment to month 2, but little evidence of mediation occurred for the long-term follow-ups. CBT's beneficial effects in decreasing gambling may be related partly to changes in coping responses, and improvements in coping are associated with long-term changes in gambling. However, relationships between coping skills and gambling behavior are fairly strong, regardless of treatment received.

  9. Crowding and Cognitive Development: The Mediating Role of Maternal Responsiveness among 36-Month-Old Children

    Science.gov (United States)

    Evans, Gary W.; Ricciuti, Henry N.; Hope, Steven; Schoon, Ingrid; Bradley, Robert H.; Corwyn, Robert F.; Hazan, Cindy

    2010-01-01

    Residential crowding in both U.S. and U.K. samples of 36-month-old children is related concurrently to the Bracken scale, a standard index of early cognitive development skills including letter and color identification, shape recognition, and elementary numeric comprehension. In the U.S. sample, these effects also replicate prospectively.…

  10. Cognitive behavioural therapy for MS-related fatigue explained: A longitudinal mediation analysis

    NARCIS (Netherlands)

    van den Akker, L. E.; Beckerman, H.; Collette, E. H.; Knoop, H.; Bleijenberg, G.; Twisk, J. W.; Dekker, J.; de Groot, V.

    2018-01-01

    Cognitive behavioural therapy (CBT) effectively reduces fatigue directly following treatment in patients with Multiple Sclerosis (MS), but little is known about the process of change during and after CBT. Additional analysis of a randomized clinical trial. To investigate which psychological factors

  11. Students' Problem Solving as Mediated by Their Cognitive Tool Use: A Study of Tool Use Patterns

    Science.gov (United States)

    Liu, M.; Horton, L. R.; Corliss, S. B.; Svinicki, M. D.; Bogard, T.; Kim, J.; Chang, M.

    2009-01-01

    The purpose of this study was to use multiple data sources, both objective and subjective, to capture students' thinking processes as they were engaged in problem solving, examine the cognitive tool use patterns, and understand what tools were used and why they were used. The findings of this study confirmed previous research and provided clear…

  12. Bright-light effects on cognitive performance in elderly persons working simulated night shifts: psychological well-being as a mediator?

    Science.gov (United States)

    Kretschmer, Veronika; Schmidt, Klaus-Helmut; Griefahn, Barbara

    2013-11-01

    The present study examined whether the relationship between light exposure and cognitive functioning is mediated by psychological well-being in elderly persons working night shifts. The role of psychological well-being has been neglected so far in the relationship between bright light and cognitive performance. Sleepiness and mood were applied as indicators of psychological well-being. Cognitive functioning was examined in terms of concentration, working memory, and divided attention. A total of thirty-two test persons worked in three consecutive simulated night shifts, 16 under bright light (3,000 lux) and 16 under room light (300 lux). Concentration, working memory, and divided attention were measured by computerised tasks. The hypothesised mediators were recorded by questionnaires. Mediation analyses were conducted for estimating direct, total, and indirect effects in simple mediation models. Results indicate that sleepiness and mood did not function as mediators in the prediction of concentration, working memory, and/or divided attention by light exposure. Sleepiness led to an underestimation of the positive bright-light effect on concentration performance. Mood showed only a random effect due to the positive bright-light effect on working memory. Sleepiness and mood could completely be excluded as mediators in the relationship between light exposure and cognitive functioning. This study underlines that psychological well-being of elderly persons is not a critical component in the treatment of bright light on cognitive performance in the night shift workplace. In summary, it becomes evident that bright light has a strong direct and independent effect on cognitive performance, particularly on working memory and concentration.

  13. MEDIATING COGNITIVE TRANSFORMATION WITH VR 3D SKETCHING DURING CONCEPTUAL ARCHITECTURAL DESIGN PROCESS

    Directory of Open Access Journals (Sweden)

    Farzad Pour Rahimian

    2011-03-01

    Full Text Available Communications for information synchronization during the conceptual design phase require designers to employ more intuitive digital design tools. This paper presents findings of a feasibility study for using VR 3D sketching interface in order to replace current non-intuitive CAD tools. We used a sequential mixed method research methodology including a qualitative case study and a cognitive-based quantitative protocol analysis experiment. Foremost, the case study research was conducted in order to understand how novice designers make intuitive decisions. The case study documented the failure of conventional sketching methods in articulating complicated design ideas and shortcomings of current CAD tools in intuitive ideation. The case study’s findings then became the theoretical foundations for testing the feasibility of using VR 3D sketching interface during design. The latter phase of study evaluated the designers’ spatial cognition and collaboration at six different levels: "physical-actions", "perceptualactions", "functional-actions", "conceptual-actions", "cognitive synchronizations", and "gestures". The results and confirmed hypotheses showed that the utilized tangible 3D sketching interface improved novice designers’ cognitive and collaborative design activities. In summary this paper presents the influences of current external representation tools on designers’ cognition and collaboration as well as providing the necessary theoretical foundations for implementing VR 3D sketching interface. It contributes towards transforming conceptual architectural design phase from analogue to digital by proposing a new VR design interface. The paper proposes this transformation to fill in the existing gap between analogue conceptual architectural design process and remaining digital engineering parts of building design process hence expediting digital design process.

  14. Role of Reactive Oxygen Species and Nitric Oxide in Mediating Chemotherapeutic Drug Induced Bystander Response in Human Cancer Cells Exposed In-Vitro

    Science.gov (United States)

    Chinnadurai, Mani; Rao, Bhavna S; Deepika, Ramasamy; Paul, Solomon F.D.; Venkatachalam, Perumal

    2012-01-01

    Background The intention of cancer chemotherapy is to control the growth of cancer cells using chemical agents. However, the occurrence of second malignancies has raised concerns, leading to re-evaluation of the current strategy in use for chemotherapeutic agents. Although the mechanisms involved in second malignancy remain ambiguous, therapeutic-agent-induced non-DNA targeted effects like bystander response and genomic instability cannot be eliminated completely. Hence, Bleomycin (BLM) and Neocarzinostatin (NCS), chemotherapeutic drugs with a mode of action similar to ionizing radiation, were used to study the mechanism of bystander response in human cancer cells (A549, CCRF-CEM and HL-60) by employing co-culture methodology. Methods Bystander effect was quantified using micronucleus (MN) assay and in-situ immunofluorescence(γH2AX assay).The role of reactive oxygen species (ROS) and nitric oxide (NO) in mediating the bystander response was explored by pre-treating bystander cells with dimethylsulphoxide (DMSO) and C-PTIO respectively. Results Bystander response was observed only in CCRF-CEM and A549 cells (P bystander response on treatment with DMSO, suggests that ROS has a more significant role in mediating the bystander response.Since the possibility of the ROS and NO in mediating these bystander effect was confirmed, mechanistic control of these signaling molecules could either reduce radiation damage and potential carcinogenicity of normal tissues (by reducing bystander signaling) or maximize cell sterilization during chemotherapy (by amplifying bystander responses in tumors). PMID:29147282

  15. Myeloid-derived suppressor cells in murine AIDS inhibit B-cell responses in part via soluble mediators including reactive oxygen and nitrogen species, and TGF-β

    Energy Technology Data Exchange (ETDEWEB)

    Rastad, Jessica L. [Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756 (United States); Green, William R., E-mail: William.R.Green@dartmouth.edu [Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756 (United States); Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756 (United States)

    2016-12-15

    Monocytic myeloid-derived suppressor cells (M-MDSCs) were increased during LP-BM5 retroviral infection, and were capable of suppressing not only T-cell, but also B-cell responses. In addition to previously demonstrating iNOS- and VISTA-dependent M-MDSC mechanisms, in this paper, we detail how M-MDSCs utilized soluble mediators, including the reactive oxygen and nitrogen species superoxide, peroxynitrite, and nitric oxide, and TGF-β, to suppress B cells in a predominantly contact-independent manner. Suppression was independent of cysteine-depletion and hydrogen peroxide production. When two major mechanisms of suppression (iNOS and VISTA) were eliminated in double knockout mice, M-MDSCs from LP-BM5-infected mice were able to compensate using other, soluble mechanisms in order to maintain suppression of B cells. The IL-10 producing regulatory B-cell compartment was among the targets of M-MDSC-mediated suppression. -- Highlights: •LP-BM5-expanded M-MDSCs utilized soluble mediators nitric oxide, superoxide, peroxynitrite, and TGF-β to suppress B cells. •When two major mechanisms of suppression were eliminated through knockouts, M-MDSCs maintained suppression. •M-MDSCs from LP-BM5-infected mice decreased proliferation of IL-10 producing regulatory B cells.

  16. Study on the effect of reactive oxygen species-mediated oxidative stress on the activation of mitochondrial apoptosis and the tenderness of yak meat.

    Science.gov (United States)

    Wang, Lin-Lin; Yu, Qun-Li; Han, Ling; Ma, Xiu-Li; Song, Ren-De; Zhao, Suo-Nan; Zhang, Wen-Hua

    2018-04-01

    This study investigated the effect of reactive oxygen species-mediated oxidative stress on activation of mitochondrial apoptosis and tenderness of yak meat during postmortem ageing. Oxidative stress degree, Ca 2+ levels, membrane permeability transition pore opening, mitochondrial membrane potential, apoptotic factors and the shear force were examined. Results showed that the ROS generated by H 2 O 2 significantly increased mitochondrial oxidative stress by decreasing the activities of superoxide dismutase, catalase and glutathione peroxidase, and increasing lipid peroxidation. Furthermore, oxidative stress enhanced Ca 2+ production and cytochrome c release, changed the levels of Bcl-2 family proteins and activated caspase-9 and -3 activities. Ultimately, oxidative stress increased the apoptosis rate and tenderness of yak meat. These observations confirmed that ROS-mediated oxidative stress participates in the activation of the apoptotic cascade reaction involving Ca 2+ and Bcl-2 family proteins. The results further suggested that ROS-mediated oxidative stress plays a significant role in meat tenderization through the mitochondrial apoptotic pathway. Copyright © 2017. Published by Elsevier Ltd.

  17. Myeloid-derived suppressor cells in murine AIDS inhibit B-cell responses in part via soluble mediators including reactive oxygen and nitrogen species, and TGF-β

    International Nuclear Information System (INIS)

    Rastad, Jessica L.; Green, William R.

    2016-01-01

    Monocytic myeloid-derived suppressor cells (M-MDSCs) were increased during LP-BM5 retroviral infection, and were capable of suppressing not only T-cell, but also B-cell responses. In addition to previously demonstrating iNOS- and VISTA-dependent M-MDSC mechanisms, in this paper, we detail how M-MDSCs utilized soluble mediators, including the reactive oxygen and nitrogen species superoxide, peroxynitrite, and nitric oxide, and TGF-β, to suppress B cells in a predominantly contact-independent manner. Suppression was independent of cysteine-depletion and hydrogen peroxide production. When two major mechanisms of suppression (iNOS and VISTA) were eliminated in double knockout mice, M-MDSCs from LP-BM5-infected mice were able to compensate using other, soluble mechanisms in order to maintain suppression of B cells. The IL-10 producing regulatory B-cell compartment was among the targets of M-MDSC-mediated suppression. -- Highlights: •LP-BM5-expanded M-MDSCs utilized soluble mediators nitric oxide, superoxide, peroxynitrite, and TGF-β to suppress B cells. •When two major mechanisms of suppression were eliminated through knockouts, M-MDSCs maintained suppression. •M-MDSCs from LP-BM5-infected mice decreased proliferation of IL-10 producing regulatory B cells.

  18. Gambling cognition and subjective well-being as mediators between perceived stress and problem gambling: a cross-cultural study on White and Chinese problem gamblers.

    Science.gov (United States)

    Tang, Catherine So-Kum; Oei, Tian Po

    2011-09-01

    This study aimed to delineate various pathways whereby cognitive and emotional vulnerabilities triggered by stress would lead to disruptive gambling. A multiple mediation framework was proposed to specify that gambling cognition and subjective well-being would mediate the influence of perceived stress on problem gambling. The cross-cultural validity of the proposed framework was examined with 132 White gamblers in Australia and 154 Chinese gamblers in China. They completed psychological scales on perceived stress, gambling expectancy bias, gambling refusal efficacy, negative affect, life satisfaction, and problem gambling. Compared to Chinese gamblers, White gamblers reported higher levels of perceived stress, gambling expectancy bias, and problem gambling as well as more pervasive negative affect and lower levels of life satisfaction. Results showed that the proposed multiple mediation framework fit the data better than two alternative plausible models. Life satisfaction and gambling refusal efficacy were two consistent mediators across White and Chinese gamblers. (c) 2011 APA, all rights reserved.

  19. Applying the social cognitive perspective to volunteer intention in China: the mediating roles of self-efficacy and motivation.

    Science.gov (United States)

    Wang, Ji-Wei; Wei, Chang-Nian; Harada, Koichi; Minamoto, Keiko; Ueda, Kimiyo; Cui, Hong-Wei; Zhang, Cheng-Gang; Cui, Zhi-Ting; Ueda, Atsushi

    2011-06-01

    When predicting volunteer intention, much attention is paid to the volunteer organization environment (VOE). Given that self-efficacy and motivation have emerged as important predictors of volunteer intention, we adopted a combination of ideas of Bandura's social cognitive theory and Ajzen's theory of planned behavior integrating VOE, self-efficacy and motivation to examine their effects on volunteer intention and to determine whether self-efficacy and motivation mediate the relationship between VOE and volunteer intention. The subjects of this study consisted of 198 community health volunteers in Shanghai city, China. Exploratory factor analysis was performed to identify the factor structure using standard principal component analysis. Six new factors were revealed, including two VOE factors, relation with organization and support from government; two motivation factors, personal attitude and social recognition; self-efficacy and volunteer intention. The results of a hierarchical regression analysis indicated that relation with organization accounted for 14.8% of the variance in volunteer intention, and support from government failed to add significantly to variance in volunteer intention; self-efficacy and personal attitude motivation partially mediated the effects of relation with organization on volunteer intention; social recognition motivation did not mediate the relationship between relation with organization and volunteer intention; and relation with organization, self-efficacy and personal attitude motivation accounted for 33.7% of the variance in volunteer intention. These results provide support for self-efficacy and personal attitude motivation as mediators and provide preliminary insight into the potential mechanisms for predicting volunteer intention and improving volunteering by integrating VOE, self-efficacy and motivation factors.

  20. Computer-mediated communication: from a cognitive to a discursive model

    NARCIS (Netherlands)

    Lamerichs, J.M.W.J.; Molder, te H.F.M.

    2003-01-01

    In this article, we evaluate the ways in which computer-mediated communication (CMC) has thus far been conceptualized, proposing an alternative approach. It is argued that traditional perspectives ignore participants' everyday understanding of media use and media characteristics by relying on an

  1. Computer-mediated communication: from a cognitive to a discursive model

    NARCIS (Netherlands)

    Lamerichs, J.M.W.J.; Te Molder, Hedwig

    2003-01-01

    In this article, we evaluate the ways in which computer-mediated communication (CMC) has thus far been conceptualized, proposing an alternative approach. It is argued that traditional perspectives ignore participants’ everyday understanding of media use and media characteristics by relying on an

  2. The relationship between parenting factors and trait anxiety: mediating role of cognitive errors and metacognition.

    Science.gov (United States)

    Gallagher, Bridie; Cartwright-Hatton, Sam

    2008-05-01

    Research examining parenting factors in the development of anxiety has focused largely on the concepts of parental warmth and overcontrolling or intrusive parenting, This study investigated the relationship between these factors, and also parental discipline style and anxiety using self-report methodology with a sample of 16-18 year olds. In order to try to explain the relationship between parenting and anxiety, measures of cognition were also included. A multiple regression was conducted including all parenting factors as predictors of trait anxiety. The regression was a modest fit (R(2)=22%) and the model was significant (F(4, 141)=9.90, pdiscipline was significantly associated with increased cognitive distortions (r=0.361 pdiscipline style and trait anxiety. The implications of these findings and areas for future research are discussed.

  3. Anterior paracingulate and cingulate cortex mediates the effects of cognitive load on speech sound discrimination.

    Science.gov (United States)

    Gennari, Silvia P; Millman, Rebecca E; Hymers, Mark; Mattys, Sven L

    2018-06-11

    Perceiving speech while performing another task is a common challenge in everyday life. How the brain controls resource allocation during speech perception remains poorly understood. Using functional magnetic resonance imaging (fMRI), we investigated the effect of cognitive load on speech perception by examining brain responses of participants performing a phoneme discrimination task and a visual working memory task simultaneously. The visual task involved holding either a single meaningless image in working memory (low cognitive load) or four different images (high cognitive load). Performing the speech task under high load, compared to low load, resulted in decreased activity in pSTG/pMTG and increased activity in visual occipital cortex and two regions known to contribute to visual attention regulation-the superior parietal lobule (SPL) and the paracingulate and anterior cingulate gyrus (PaCG, ACG). Critically, activity in PaCG/ACG was correlated with performance in the visual task and with activity in pSTG/pMTG: Increased activity in PaCG/ACG was observed for individuals with poorer visual performance and with decreased activity in pSTG/pMTG. Moreover, activity in a pSTG/pMTG seed region showed psychophysiological interactions with areas of the PaCG/ACG, with stronger interaction in the high-load than the low-load condition. These findings show that the acoustic analysis of speech is affected by the demands of a concurrent visual task and that the PaCG/ACG plays a role in allocating cognitive resources to concurrent auditory and visual information. Copyright © 2018. Published by Elsevier Inc.

  4. DNA methylation mediates the effect of maternal cognitive appraisal of a disaster in pregnancy on the child's C-peptide secretion in adolescence: Project Ice Storm.

    Directory of Open Access Journals (Sweden)

    Lei Cao-Lei

    Full Text Available Animal and human studies suggest that prenatal exposure to stress is associated with adverse health outcomes such as type 2 diabetes. Epigenetic modification, such as DNA methylation, is considered one possible underlying mechanism. The 1998 Quebec ice storm provides a unique opportunity to study an independent prenatal stressor on child outcomes. C-peptide is the best measure of endogenous insulin secretion and is widely used in the clinical management of patients with diabetes. The objectives of this study are to determine 1 the extent to which prenatal exposure to disaster-related stress (maternal objective hardship and maternal cognitive appraisal influences children's C-peptide secretion, and 2 whether DNA methylation of diabetes-related genes mediates the effects of prenatal stress on C-peptide secretion. Children's (n = 30 C-peptide secretion in response to an oral glucose tolerance test were assessed in blood at 13½ years. DNA methylation levels of selected type 1 and 2 diabetes-related genes were chosen based upon the genes associated with prenatal maternal objective hardship and/or cognitive appraisal levels. Bootstrapping analyses were performed to determine the mediation effect of DNA methylation. We found that children whose mothers experienced higher objective hardship exhibited higher C-peptide secretion. Cognitive appraisal was not directly associated with C-peptide secretion. DNA methylation of diabetes-related genes had a positive mediation effect of objective hardship on C-peptide secretion: higher objective hardship predicted higher C-peptide secretion through DNA methylation. Negative mediation effects of cognitive appraisal were observed: negative cognitive appraisal predicted higher C-peptide secretion through DNA methylation. However, only one gene, LTA, remained a significant mediator of cognitive appraisal on C-peptide secretion after the conservative Bonferroni multiple corrections. Our findings suggest that DNA

  5. Relation of Long-term Exposure to Air Pollution to Brachial Artery Flow-Mediated Dilation and Reactive Hyperemia

    Science.gov (United States)

    Wilker, Elissa H.; Ljungman, Petter L.; Rice, Mary B.; Kloog, Itai; Schwartz, Joel; Gold, Diane R.; Koutrakis, Petros; Vita, Joseph A.; Mitchell, Gary F.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Hamburg, Naomi M.; Mittleman, Murray A.

    2014-01-01

    Long-term exposure to ambient air pollution has been associated with cardiovascular morbidity and mortality. Impaired vascular responses may in part explain these findings, but the association of such long-term exposure with measures of both conduit artery and microvascular function have not been widely reported. We evaluated the association between residential proximity to a major roadway (primary or secondary highway) and spatially resolved average fine particulate matter (PM2.5) and baseline brachial artery diameter and mean flow velocity, flow mediated dilation % and hyperemic flow velocity, in the Framingham Offspring and Third Generation Cohorts. We examined 5,112 participants (2,731 (53%) women, mean age 49±14 years). Spatially resolved average PM2.5 was associated with lower flow mediated dilation% and hyperemic flow velocity. An interquartile range difference in PM2.5 (1.99 μg/m3) was associated with −0.16% (95%CI: −0.27%, −0.05%) lower FMD% and −0.72 (95%CI: −1.38, −0.06) cm/s lower hyperemic flow velocity %. Residential proximity to a major roadway was negatively associated with flow mediated dilation %. Compared to living ≥400 m away, living <50 m from a major roadway was associated with 0.32% lower flow mediated dilation (95% confidence interval (CI): −0.58%, −0.06%), but results for hyperemic flow velocity had wide confidence intervals −0.68 cm/s (95%CI: −2.29, 0.93). In conclusion, residential proximity to a major roadway and higher levels of spatially resolved estimates of PM2.5 at participant residences are associated with impaired conduit artery and microvascular function in this large community-based cohort of middle-aged and elderly adults. PMID:24793676

  6. Oscillatory reactivity to effortful cognitive processing in the subthalamic nucleus and internal pallidum: a depth electrode EEG study

    Czech Academy of Sciences Publication Activity Database

    Bočková, M.; Chládek, Jan; Jurák, Pavel; Halámek, Josef; Rapcsak, S.Z.; Baláž, M.; Chrastina, J.; Rektor, I.

    2017-01-01

    Roč. 124, č. 7 (2017), s. 841-852 ISSN 0300-9564 R&D Projects: GA MZd(CZ) NV16-33798A; GA ČR GAP103/11/0933; GA MŠk(CZ) LO1212; GA MŠk ED0017/01/01 Institutional support: RVO:68081731 Keywords : subthalamic nucleus * internal globus pallidum * complex cognitive functions * lateralization * deep brain stimulation * erd/s Subject RIV: FS - Medical Facilities ; Equipment OBOR OECD: Medical engineering Impact factor: 2.392, year: 2016

  7. Mediators and Moderators of a School-Based Cognitive-Behavioral Depression Prevention Program.

    Science.gov (United States)

    Duong, Mylien T; Kelly, Brynn M; Haaland, Wren L; Matsumiya, Brandon; Huey, Stanley J; McCarty, Carolyn A

    2016-10-01

    This study tested potential moderators and mediators of an indicated depression prevention program for middle school students, Positive Thoughts and Actions (PTA). Participants were 120 students randomly assigned to PTA, or a brief, individually administered supportive intervention (Individual Support Program, or ISP). Youths completed measures of depressive symptoms at baseline, post-intervention, and 12-month follow-up. Hierarchical regression was used to test three moderators-ethnic minority status, gender, and baseline depressive symptoms-and three mediators representing functional outcomes targeted by PTA-parent-child communication, attitude towards school, and health behavior. Ethnic minority status did not moderate PTA effects at post-intervention but did moderate PTA effects at 12-month follow-up. At 12 months, PTA appeared to be more effective for White participants than ethnic minority youth. Follow-up analyses suggested this moderation effect was due to the tendency of ethnic minority youth, especially those with fewer symptoms at baseline, to drop out by 12 months. Neither gender nor baseline depressive symptoms moderated the effects of PTA. Although PTA improved health behavior and attitudes toward school, there was no evidence that any of these functional outcomes measured mediated the impact of PTA on depressive symptoms. Future directions are discussed.

  8. Nox-2-mediated phenotype loss of hippocampal parvalbumin interneurons might contribute to postoperative cognitive decline in aging mice

    Directory of Open Access Journals (Sweden)

    lili qiu

    2016-10-01

    Full Text Available Postoperative cognitive decline (POCD is a common complication following anesthesia and surgery, especially in elderly patients; however, the precise mechanisms of POCD remain unclear. Here, we investigated whether nicotinamide adenine dinucleotide phosphate (NADPH oxidase mediated-abnormalities in parvalbumin (PV interneurons play an important role in the pathophysiology of POCD. The animal model was established using isoflurane anesthesia and exploratory laparotomy in sixteen-month-old male C57BL/6 mice. For interventional experiments, mice were chronically treated with the NADPH oxidase inhibitor apocynin (APO. Open field and fear conditioning behavioral tests were performed on day 6 and 7 post-surgery, respectively. In a separate experiment, brain tissue was harvested and subjected to biochemical analysis. Primary hippocampal neurons challenged with lipopolysaccharide in vitro were used to investigate the mechanisms underlying the oxidative stress-induced abnormalities in PV interneurons. Our results showed that anesthesia and surgery induced significant hippocampus-dependent memory impairment, which was accompanied by PV interneuron phenotype loss and increased expression of interleukin-1β, markers of oxidative stress, and NADPH oxidase 2 (Nox2 in the hippocampus. In addition, lipopolysaccharide exposure increased Nox2 level and decreased the expression of PV and the number of excitatory synapses onto PV interneurons in the primary hippocampal neurons. Notably, treatment with APO reversed these abnormalities. Our study suggests that Nox2-derived ROS production triggers, at least in part, anesthesia- and surgery-induced hippocampal PV interneuron phenotype loss and consequent cognitive impairment in aging mice.

  9. Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term Cognitive Impairment in a Model of Experimental Cerebral Malaria.

    Directory of Open Access Journals (Sweden)

    Brandi D Freeman

    2016-03-01

    Full Text Available Plasmodium falciparum infection causes a wide spectrum of diseases, including cerebral malaria, a potentially life-threatening encephalopathy. Vasculopathy is thought to contribute to cerebral malaria pathogenesis. The vasoactive compound endothelin-1, a key participant in many inflammatory processes, likely mediates vascular and cognitive dysfunctions in cerebral malaria. We previously demonstrated that C57BL6 mice infected with P. berghei ANKA, our fatal experimental cerebral malaria model, sustained memory loss. Herein, we demonstrate that an endothelin type A receptor (ETA antagonist prevented experimental cerebral malaria-induced neurocognitive impairments and improved survival. ETA antagonism prevented blood-brain barrier disruption and cerebral vasoconstriction during experimental cerebral malaria, and reduced brain endothelial activation, diminishing brain microvascular congestion. Furthermore, exogenous endothelin-1 administration to P. berghei NK65-infected mice, a model generally regarded as a non-cerebral malaria negative control for P. berghei ANKA infection, led to experimental cerebral malaria-like memory deficits. Our data indicate that endothelin-1 is critical in the development of cerebrovascular and cognitive impairments with experimental cerebral malaria. This vasoactive peptide may thus serve as a potential target for adjunctive therapy in the management of cerebral malaria.

  10. The Role of Emotional Responses and Physiological Reactivity in the Marital Conflict-Child Functioning Link

    Science.gov (United States)

    El-Sheikh, Mona

    2005-01-01

    Background: Children's emotional responses and physiological reactivity to conflict were examined as mediators and moderators in the associations between exposure to parental marital conflict and child adjustment and cognitive problems. Method: One hundred and eighty elementary school children participated. In response to a simulated argument,…

  11. Iodine-mediated coastal particle formation: an overview of the Reactive Halogens in the Marine Boundary Layer (RHaMBLe Roscoff coastal study

    Directory of Open Access Journals (Sweden)

    G. McFiggans

    2010-03-01

    Full Text Available This paper presents a summary of the measurements made during the heavily-instrumented Reactive Halogens in the Marine Boundary Layer (RHaMBLe coastal study in Roscoff on the North West coast of France throughout September 2006. It was clearly demonstrated that iodine-mediated coastal particle formation occurs, driven by daytime low tide emission of molecular iodine, I2, by macroalgal species fully or partially exposed by the receding waterline. Ultrafine particle concentrations strongly correlate with the rapidly recycled reactive iodine species, IO, produced at high concentrations following photolysis of I2. The heterogeneous macroalgal I2 sources lead to variable relative concentrations of iodine species observed by path-integrated and in situ measurement techniques.

    Apparent particle emission fluxes were associated with an enhanced apparent depositional flux of ozone, consistent with both a direct O3 deposition to macroalgae and involvement of O3 in iodine photochemistry and subsequent particle formation below the measurement height. The magnitude of the particle formation events was observed to be greatest at the lowest tides with the highest concentrations of ultrafine particles growing to the largest sizes, probably by the condensation of anthropogenically-formed condensable material. At such sizes the particles should be able to act as cloud condensation nuclei at reasonable atmospheric supersaturations.

  12. Does school mobility place elementary school children at risk for lower math achievement? The mediating role of cognitive dysregulation.

    Science.gov (United States)

    Friedman-Krauss, Allison H; Raver, C Cybele

    2015-12-01

    Children growing up in poverty have a higher likelihood of exposure to multiple forms of adversity that jeopardize their chances of academic success. The current paper identifies school mobility, or changing schools, as 1 such poverty-related risk. Using a sample of low-income, predominantly ethnic-minority children (n = 381) in Chicago, this study tests the hypothesis that repeatedly changing schools during the 5-year period between Head Start (preschool) and third grade is a potent predictor of children's math achievement in fourth grade and that children's cognitive dysregulation serves as a mechanism through which school mobility may negatively affect children's math achievement. Hierarchical linear models controlling for baseline child and family characteristics (including children's early math and dysregulation measured during Head Start) revealed an inverse relation between the number of times low-income children changed schools between preschool and third grade and children's math achievement on state standardized tests in fourth grade. Furthermore, frequently changing schools (3 or 4 school changes over the same time period) was positively associated with teacher-reported cognitive dysregulation in third grade and negatively associated with children's math achievement in fourth grade. Evidence for the role of children's cognitive dysregulation as a partial statistical mediator was found for the relation between frequently changing schools and math achievement, even after accounting for baseline risk. Results are discussed in terms of school policies, practices, and intervention strategies to prevent the disruptive and potentially stressful experiences of school mobility for young, low-income children. (c) 2015 APA, all rights reserved).

  13. Does School Mobility Place Elementary School Children at Risk for Lower Math Achievement? The Mediating Role of Cognitive Dysregulation

    Science.gov (United States)

    Friedman-Krauss, Allison H.; Raver, C. Cybele

    2015-01-01

    Children growing up in poverty have a higher likelihood of exposure to multiple forms of adversity that jeopardize their chances of academic success. The current paper identifies school mobility, or changing schools, as 1 such poverty-related risk. Using a sample of low-income, predominantly ethnic-minority children (n = 381) in Chicago, this study tests the hypothesis that repeatedly changing schools during the 5-year period between Head Start (preschool) and third grade is a potent predictor of children’s math achievement in fourth grade and that children’s cognitive dysregulation serves as a mechanism through which school mobility may negatively affect children’s math achievement. Hierarchical linear models controlling for baseline child and family characteristics (including children’s early math and dysregulation measured during Head Start) revealed an inverse relation between the number of times low-income children changed schools between preschool and third grade and children’s math achievement on state standardized tests in fourth grade. Furthermore, frequently changing schools (3 or 4 school changes over the same time period) was positively associated with teacher-reported cognitive dysregulation in third grade and negatively associated with children’s math achievement in fourth grade. Evidence for the role of children’s cognitive dysregulation as a partial statistical mediator was found for the relation between frequently changing schools and math achievement, even after accounting for baseline risk. Results are discussed in terms of school policies, practices, and intervention strategies to prevent the disruptive and potentially stressful experiences of school mobility for young, low-income children. PMID:26436870

  14. The relative role of cognitive and emotional reactions in mediating the effects of a social comparison sun protection intervention.

    Science.gov (United States)

    Mahler, Heike I M

    2018-02-01

    This experiment examined the cognitive and emotional impact of two social comparison-based sun protection interventions in a sample of Southern California college students (N = 223). One of the interventions employed comparison UV photos of peers who had either much more (downward social comparison) or much less (upward social comparison) skin damage than did participants themselves. The second intervention consisted of descriptive norms information suggesting that a large majority of the participants' peer group regularly protect their skin from the sun. Participants were randomly assigned to one of eight conditions in a 4 (Social Comparison Information: no photo vs. no comparison photos vs. upward comparison photos vs. downward comparison photos) × 2 (Descriptive Norms Information: Received vs. not received) design. Emotional reactions (e.g. worry, embarrassment, relief) and sun-related cognitive reactions (perceived susceptibility, sun protection intentions) were assessed immediately. Sun protection behaviours were assessed in a surprise telephone follow-up five weeks following the intervention. The results demonstrated that the combination of seeing photos of peers who had very little sun damage and learning that a majority of one's peers engage in regular sun protection resulted in reliably greater subsequent sun protection than all other conditions. Further, there was relatively direct evidence that both negative emotional reactions and sun protection intentions mediated this effect. These findings add to the growing literature suggesting the importance of thoroughly examining the role of emotions in health behaviour decisions. Both theory and intervention efficacy would benefit from a better understanding of the relative role of cognitions and emotions in behaviour change.

  15. Internally-directed cognition and mindfulness:An integrative perspective derived from reactive versus predictive control systems theory

    Directory of Open Access Journals (Sweden)

    Mattie eTops

    2014-05-01

    Full Text Available In the present paper we will apply the Predictive And Reactive Control Systems (PARCS theory as a framework that integrates competing theories of neural substrates of awareness by describing the default mode network (DMN and anterior insula (AI as parts of two different behavioral and homeostatic control systems. The DMN, a network that becomes active at rest when there is no external stimulation or task to perform, has been implicated in self-reflective awareness and prospection. By contrast, the AI is associated with awareness and task-related attention. This has led to competing theories stressing the role of the DMN in self-awareness versus the role of interoceptive and emotional information integration in the AI in awareness of the emotional moment. In PARCS, the respective functions of the DMN and AI in a specific control system explains their association with different qualities of awareness, and how mental states can shift from one state (e.g., prospective self-reflection to the other (e.g., awareness of the emotional moment depending on the relative dominance of control systems. These shifts between reactive and predictive control are part of processes that enable the intake of novel information, integration of this novel information within existing knowledge structures, and the creation of a continuous personal context in which novel information can be integrated and understood. As such, PARCS can explain key characteristics of mental states, such as their temporal and spatial focus (e.g., a focus on the here and now vs. the future; a 1st person vs. a 3rd person perspective. PARCS further relates mental states to brain states and functions, such as activation of the DMN or hemispheric asymmetry in frontal cortical functions. Together, PARCS deepens the understanding of a broad range of mental states, including mindfulness, mind wandering, rumination, autobiographical memory, imagery, and the experience of self.

  16. Alterations in neural systems mediating cognitive flexibility and inhibition in mood disorders.

    Science.gov (United States)

    Piguet, Camille; Cojan, Yann; Sterpenich, Virginie; Desseilles, Martin; Bertschy, Gilles; Vuilleumier, Patrik

    2016-04-01

    Impairment in mental flexibility may be a key component contributing to cardinal cognitive symptoms among mood disorders patients, particularly thought control disorders. Impaired ability to switch from one thought to another might reflect difficulties in either generating new mental states, inhibiting previous states, or both. However, the neural underpinnings of impaired cognitive flexibility in mood disorders remain largely unresolved. We compared a group of mood disorders patients (n = 29) and a group of matched healthy subjects (n = 32) on a novel task-switching paradigm involving happy and sad faces, that allowed us to separate generation of a new mental set (Switch Cost) and inhibition of the previous set during switching (Inhibition Cost), using fMRI. Behavioral data showed a larger Switch Cost in patients relative to controls, but the average Inhibition Cost did not differ between groups. At the neural level, a main effect of group was found with stronger activation of the subgenual cingulate cortex in patients. The larger Switch Cost in patients was reflected by a stronger recruitment of brain regions involved in attention and executive control, including the left intraparietal sulcus, precuneus, left inferior fontal gyrus, and right anterior cingulate. Critically, activity in the subgenual cingulate cortex was not downregulated by inhibition in patients relative to controls. In conclusion, mood disorder patients have exaggerated Switch Cost relative to controls, and this deficit in cognitive flexibility is associated with increased activation of the fronto-parietal attention networks, combined with impaired modulation of the subgenual cingulate cortex when inhibition of previous mental states is needed. © 2016 Wiley Periodicals, Inc.

  17. Copper mediated controlled radical copolymerization of styrene and2-ethylhexyl acrylate and determination of their reactivity ratios.

    Directory of Open Access Journals (Sweden)

    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.

  18. Microcystin-LR induced reactive oxygen species mediate cytoskeletal disruption and apoptosis of hepatocytes in Cyprinus carpio L.

    Directory of Open Access Journals (Sweden)

    Jinlin Jiang

    Full Text Available Microcystins (MCs are a group of cyclic hepatotoxic peptides produced by cyanobacteria. Microcystin-LR (MC-LR contains Leucine (L and Arginine (R in the variable positions, and is one of the most common and potently toxic peptides. MC-LR can inhibit protein phosphatase type 1 and type 2A (PP1 and PP2A activities and induce excessive production of reactive oxygen species (ROS. The underlying mechanism of the inhibition of PP1 and PP2A has been extensively studied. The over-production of ROS is considered to be another main mechanism behind MC-LR toxicity; however, the detailed toxicological mechanism involved in over-production of ROS in carp (Cyprinus carpio L. remains largely unclear. In our present study, the hydroxyl radical (•OH was significantly induced in the liver of carp after a relatively short-term exposure to MC-LR. The elevated reactive oxygen species (ROS production may play an important role in the disruption of microtubule structure. Pre-injection of the antioxidant N-acetyl-cysteine (NAC provided significant protection to the cytoskeleton, however buthionine sulfoximine (BSO exacerbated cytoskeletal destruction. In addition, the elevated ROS formation induced the expression of apoptosis-related genes, including p38, JNKa, and bcl-2. A significant increase in apoptotic cells was observed at 12-48 hours. Our study further supports evidence that ROS are involved in MC-LR induced damage to liver cells in carp, and indicates the need for further study of the molecular mechanisms behind MC-LR toxicity.

  19. Microcystin-LR Induced Reactive Oxygen Species Mediate Cytoskeletal Disruption and Apoptosis of Hepatocytes in Cyprinus carpio L.

    Science.gov (United States)

    Jiang, Jinlin; Shan, Zhengjun; Xu, Weili; Wang, Xiaorong; Zhou, Junying; Kong, Deyang; Xu, Jing

    2013-01-01

    Microcystins (MCs) are a group of cyclic hepatotoxic peptides produced by cyanobacteria. Microcystin-LR (MC-LR) contains Leucine (L) and Arginine (R) in the variable positions, and is one of the most common and potently toxic peptides. MC-LR can inhibit protein phosphatase type 1 and type 2A (PP1 and PP2A) activities and induce excessive production of reactive oxygen species (ROS). The underlying mechanism of the inhibition of PP1 and PP2A has been extensively studied. The over-production of ROS is considered to be another main mechanism behind MC-LR toxicity; however, the detailed toxicological mechanism involved in over-production of ROS in carp (Cyprinus carpio L.) remains largely unclear. In our present study, the hydroxyl radical (•OH) was significantly induced in the liver of carp after a relatively short-term exposure to MC-LR. The elevated reactive oxygen species (ROS) production may play an important role in the disruption of microtubule structure. Pre-injection of the antioxidant N-acetyl-cysteine (NAC) provided significant protection to the cytoskeleton, however buthionine sulfoximine (BSO) exacerbated cytoskeletal destruction. In addition, the elevated ROS formation induced the expression of apoptosis-related genes, including p38, JNKa, and bcl-2. A significant increase in apoptotic cells was observed at 12 - 48 hours. Our study further supports evidence that ROS are involved in MC-LR induced damage to liver cells in carp, and indicates the need for further study of the molecular mechanisms behind MC-LR toxicity. PMID:24376844

  20. The cognitive mediation model: factors influencing public knowledge of the H1N1 pandemic and intention to take precautionary behaviors.

    Science.gov (United States)

    Ho, Shirley S; Peh, Xianghong; Soh, Veronica W L

    2013-01-01

    This study uses the cognitive mediation model as the theoretical framework to examine the influence of motivations, communication, and news elaboration on public knowledge of the H1N1 pandemic and the intention to take precautionary behaviors in Singapore. Using a nationally representative random digit dialing telephone survey of 1,055 adult Singaporeans, the authors' results show that the cognitive mediation model can be applied to health contexts, in which motivations (surveillance gratification, guidance, and need for cognition) were positively associated with news attention, elaboration, and interpersonal communication. News attention, elaboration, and interpersonal communication in turn positively influence public knowledge about the H1N1 influenza. In addition, results show that the motivations have significant indirect effects on behavioral intentions, as partially mediated by communication (media attention and interpersonal communication), elaboration, and knowledge. The authors conclude that the cognitive mediation model can be extended to behavioral outcomes, above and beyond knowledge. Implications for theory and practice for health communication were discussed.

  1. Physiological and cognitive mediators for the association between self-reported depressed mood and impaired choice stepping reaction time in older people.

    NARCIS (Netherlands)

    Kvelde, T.; Pijnappels, M.A.G.M.; Delbaere, K.; Close, J.C.; Lord, S.R.

    2010-01-01

    Background. The aim of the study was to use path analysis to test a theoretical model proposing that the relationship between self-reported depressed mood and choice stepping reaction time (CSRT) is mediated by psychoactive medication use, physiological performance, and cognitive ability.A total of

  2. Approaches to assess IgE mediated allergy risks (sensitization and cross-reactivity) from new or modified dietary proteins

    DEFF Research Database (Denmark)

    Remington, B.; Broekman, H. C. H.; Blom, W. M.

    2018-01-01

    for new proteins, and especially to identify and characterise the risk of sensitization for IgE mediated allergy from oral exposure. Existing tools and tests are capable of assessing potential crossreactivity. However, there are few possibilities to assess the hazard due to de novo sensitization. The only...... methods available are in vivo models, but many limitations exist to use them for assessing risk. We conclude that there is a need to understand which criteria adequately define allergenicity for risk assessment purposes, and from these criteria develop a more suitable battery of tests to distinguish...

  3. Exposure to cigarette smoke increases apoptosis in the rat gastric mucosa through a reactive oxygen species-mediated and p53-independent pathway.

    Science.gov (United States)

    Wang, H; Ma, L; Li, Y; Cho, C H

    2000-04-01

    Cigarette smoking is a major risk factor for gastric cancer and peptic ulcer. The aim of our study was to investigate the relationship between exposure to cigarette smoke and apoptosis in the rat gastric mucosa and the mechanism involved. Rats were exposed to different concentrations of cigarette smoke (0, 2, and 4%) once daily for a different number of 1 h periods (1, 3, 6, and 9 d). Apoptosis was identified by the terminal deoxy-transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) method and caspase-3 activity. The mucosal xanthine oxidase (XO) activity and p53 level were also measured. The results showed that exposure to cigarette smoke produced a time- and concentration-dependent increase in apoptosis in the rat gastric mucosa that was accompanied by an increase in XO activity. The increased apoptosis and XO activity could be detected after even a single exposure. In contrast, the level of p53 was elevated only in the later stage of cigarette smoke exposure. The apoptotic effect could be blocked by pretreatment with an XO inhibitor (allopurinol, 20 mg/kg intraperitoneally) or a hydroxyl free radical scavenger (DMSO, 0.2%, 1 ml/kg intravenously). However, neither of these treatments had any effect on the p53 level of the mucosa. In summary, we conclude that exposure to cigarette smoke can increase apoptosis in the rat gastric mucosa through a reactive oxygen species- (ROS) mediated and a p53-independent pathway.

  4. Antagonizing SET augments the effects of radiotherapy in hepatocellular carcinoma through reactivating PP2A-mediated AKT downregulation.

    Science.gov (United States)

    Huang, Chao-Yuan; Hung, Man-Hsin; Shih, Chi-Ting; Hsieh, Feng-Shu; Kuo, Chiung-Wen; Tsai, Ming-Hsien; Chang, Shih-Shin; Hsiao, Yung-Jen; Chen, Li-Ju; Chao, Tzu-I; Chen, Kuen-Feng

    2018-06-18

    Increasing evidence suggests that SET functions as an oncoprotein and promotes cancer survival and therapeutic resistance. However, whether SET affects radiotherapy (RT)-mediated anti-cancer effects has not yet been explored. Here, we investigated the impact of SET on RT sensitivity in hepatocellular carcinoma (HCC). Using colony and hepatosphere formation assay, we found that RT-induced proliferative inhibition was critically associated with SET expression. Next, we tested a novel SET antagonist, EMQA, in combination with RT. We showed that additive use of EMQA significantly enhanced the effects of RT against HCC in vitro and in vivo. Notably, compared to mice receiving either RT or EMQA alone, the growth of PLC5 xenografted tumor in mice receiving RT plus EMQA was significantly reduced without compromising treatment tolerability. Furthermore, we proved that antagonizing SET to restore PP2A-mediated p-AKT downregulation was responsible for the synergism between EMQA and RT. Our data demonstrate a new oncogenic property of SET, and provide preclinical evidence that combining a SET antagonist and RT may be effective for treatment of HCC. Further investigation is warranted to validate the clinical relevance of this approach. The American Society for Pharmacology and Experimental Therapeutics.

  5. Coping mediates the effects of cognitive-behavioral therapy for alcohol use disorder among out-patient clients in Project MATCH when dependence severity is high.

    Science.gov (United States)

    Roos, Corey R; Maisto, Stephen A; Witkiewitz, Katie

    2017-09-01

    There is inconsistent evidence that alcohol-specific coping is a mechanism of change in cognitive-behavioral therapy (CBT) for alcohol use disorder (AUD). Our primary aim was to test whether baseline dependence severity moderates the mediational effect of CBT on drinking outcomes via coping. Secondary data analysis of Project MATCH , a multi-site alcohol treatment trial in which participants, recruited in out-patient and aftercare arms, were randomized to three treatments: CBT, motivational enhancement therapy (MET) and Twelve-Step facilitation (TSF). Nine research sites in the United States. A total of 1063 adults with AUD. The primary outcomes were percentage days abstinent and percentage heavy drinking days at the 1-year follow-up. Coping was assessed with the Processes of Change Questionnaire . Dependence severity was measured with the Alcohol Dependence Scale . Among the full available sample (across treatment arms), there were no significant moderated mediation effects. Double moderated mediation analyses indicated that several moderated mediation effects were moderated by treatment arm (all P cognitive-behavioral therapy for alcohol use disorder was conditional on dependence severity. End-of-treatment coping mediated the positive treatment effects of cognitive-behavioral therapy on 1-year drinking outcomes among out-patient clients when dependence severity was high, but not when dependence severity was low or moderate. © 2017 Society for the Study of Addiction.

  6. [Pain and depression: cognitive and behavioural mediators of a frequent association].

    Science.gov (United States)

    Radat, F; Koleck, M

    2011-06-01

    The comorbidity between chronic pain and depression is high: in the general population setting, the odds ratio for suffering from one of these disorders when suffering from the other is estimated around 2.5. For chronic pain patients consulting in pain clinics, the comorbidity rate reaches one third to half of the patients. For the International Association for the Study of Pain (IASP), pain consists in an emotional as well as a sensory dimension, both of them have to be assessed systematically. Likewise, affective disorders must be systematically depicted in chronic pain patients. The reasons for such comorbidity are complex and result from the conjunction of common risk factors (environmental and genetic vulnerability factors) and of a bidirectional causality. THE TRANSACTIONAL MODEL OF STRESS AND COPING OF LAZARUS ET FOLKMAN: The appraisal stress model (Lazarus and Folkman, 1984) offers an opportunity to understand how chronic pain can cause depression. Pain is conceptualized as a chronic stress. Its appraisal in terms of loss, injustice, incomprehensibility or changes (primary appraisal), and in terms of control (secondary evaluation) determine how the subject will cope with pain. Several personality traits as optimism, hardiness or internal locus of control play a protective role on these evaluations, whereas others (neuroticism, negative affectivity or external locus of control) are risk factors for depression. Low perceived social support is also related to depression. On the contrary, self-efficiency is linked with low levels of depression. Self-management therapies focus on increase of perceived control of pain by the patient in order to improve his/her motivation to change, and to let the patient become active in the management of his/her pain. According to Lazarus and Folkman (1984), coping strategies are the constantly changing cognitive and behavioural efforts to manage specific external and/or internal demands that are appraised as taxing on or

  7. Functional connections between activated and deactivated brain regions mediate emotional interference during externally directed cognition.

    Science.gov (United States)

    Di Plinio, Simone; Ferri, Francesca; Marzetti, Laura; Romani, Gian Luca; Northoff, Georg; Pizzella, Vittorio

    2018-04-24

    Recent evidence shows that task-deactivations are functionally relevant for cognitive performance. Indeed, higher cognitive engagement has been associated with higher suppression of activity in task-deactivated brain regions - usually ascribed to the Default Mode Network (DMN). Moreover, a negative correlation between these regions and areas actively engaged by the task is associated with better performance. DMN regions show positive modulation during autobiographical, social, and emotional tasks. However, it is not clear how processing of emotional stimuli affects the interplay between the DMN and executive brain regions. We studied this interplay in an fMRI experiment using emotional negative stimuli as distractors. Activity modulations induced by the emotional interference of negative stimuli were found in frontal, parietal, and visual areas, and were associated with modulations of functional connectivity between these task-activated areas and DMN regions. A worse performance was predicted both by lower activity in the superior parietal cortex and higher connectivity between visual areas and frontal DMN regions. Connectivity between right inferior frontal gyrus and several DMN regions in the left hemisphere was related to the behavioral performance. This relation was weaker in the negative than in the neutral condition, likely suggesting less functional inhibitions of DMN regions during emotional processing. These results show that both executive and DMN regions are crucial for the emotional interference process and suggest that DMN connections are related to the interplay between externally-directed and internally-focused processes. Among DMN regions, superior frontal gyrus may be a key node in regulating the interference triggered by emotional stimuli. © 2018 Wiley Periodicals, Inc.

  8. Aspergillus fumigatus Copper Export Machinery and Reactive Oxygen Intermediate Defense Counter Host Copper-Mediated Oxidative Antimicrobial Offense

    Directory of Open Access Journals (Sweden)

    Philipp Wiemann

    2017-05-01

    Full Text Available The Fenton-chemistry-generating properties of copper ions are considered a potent phagolysosome defense against pathogenic microbes, yet our understanding of underlying host/microbe dynamics remains unclear. We address this issue in invasive aspergillosis and demonstrate that host and fungal responses inextricably connect copper and reactive oxygen intermediate (ROI mechanisms. Loss of the copper-binding transcription factor AceA yields an Aspergillus fumigatus strain displaying increased sensitivity to copper and ROI in vitro, increased intracellular copper concentrations, decreased survival in challenge with murine alveolar macrophages (AMΦs, and reduced virulence in a non-neutropenic murine model. ΔaceA survival is remediated by dampening of host ROI (chemically or genetically or enhancement of copper-exporting activity (CrpA in A. fumigatus. Our study exposes a complex host/microbe multifactorial interplay that highlights the importance of host immune status and reveals key targetable A. fumigatus counter-defenses.

  9. Reactive oxygen species-mediated DNA damage and apoptosis in human skin epidermal cells after exposure to nickel nanoparticles.

    Science.gov (United States)

    Alarifi, Saud; Ali, Daoud; Alakhtani, Saad; Al Suhaibani, Entissar S; Al-Qahtani, Ahmed A

    2014-01-01

    Nickel nanoparticles (NiNPs) are increasingly used in various applications due to their unique properties. However, there is little information concerning the toxicity of NiNPs in the human skin cell (A431). The present study was designed to investigate the cytotoxicity, apoptosis, and DNA damage due to NiNPs in A431 cells. A cellular proliferative capacity test showed that NiNPs induce significant cytotoxicity in a dose- and time-dependent manner. NiNPs were also found to induce oxidative stress evidenced by the generation of reactive oxygen species (ROS) and depletion of glutathione (GSH). Further, co-treatment with the antioxidant N-acetylcysteine (NAC) mitigated the ROS generation due to NiNPs, suggesting the potential mechanism of oxidative stress. NiNPs also induced significant elevation of lipid peroxidation, catalase, and superoxide dismutase and caspase-3 activity in A431 cells. In addition, NAC suppressed NiNP-induced caspase-3 activity. DNA fragmentation analysis using the comet assay showed that the NiNPs cause genotoxicity in a dose- and time-dependent manner. Therefore, the study points out the capability of the NiNPs to induce oxidative stress resulting in apoptosis and genotoxicity. This study warrants more careful assessment of NiNPs before their industrial applications.

  10. Intravenous immunoglobulin prevents murine antibody-mediated acute lung injury at the level of neutrophil reactive oxygen species (ROS production.

    Directory of Open Access Journals (Sweden)

    John W Semple

    Full Text Available Transfusion-related acute lung injury (TRALI is a leading cause of transfusion-associated mortality that can occur with any type of transfusion and is thought to be primarily due to donor antibodies activating pulmonary neutrophils in recipients. Recently, a large prospective case controlled clinical study of cardiac surgery patients demonstrated that despite implementation of male donors, a high incidence of TRALI still occurred and suggested a need for additional interventions in susceptible patient populations. To examine if intravenous immunoglobulin (IVIg may be effective, a murine model of antibody-mediated acute lung injury that approximates human TRALI was examined. When BALB/c mice were injected with the anti-major histocompatibility complex class I antibody 34-1-2s, mild shock (reduced rectal temperature and respiratory distress (dyspnea were observed and pre-treatment of the mice with 2 g/kg IVIg completely prevented these symptoms. To determine IVIg's usefulness to affect severe lung damage, SCID mice, previously shown to be hypersensitive to 34-1-2s were used. SCID mice treated with 34-1-2s underwent severe shock, lung damage (increased wet/dry ratios and 40% mortality within 2 hours. Treatment with 2 g/kg IVIg 18 hours before 34-1-2s administration completely protected the mice from all adverse events. Treatment with IVIg after symptoms began also reduced lung damage and mortality. While the prophylactic IVIg administration did not affect 34-1-2s-induced pulmonary neutrophil accumulation, bone marrow-derived neutrophils from the IVIg-treated mice displayed no spontaneous ROS production nor could they be stimulated in vitro with fMLP or 34-1-2s. These results suggest that IVIg prevents murine antibody-mediated acute lung injury at the level of neutrophil ROS production and thus, alleviating tissue damage.

  11. Adolescent D-amphetamine treatment in a rodent model of ADHD: Pro-cognitive effects in adolescence without an impact on cocaine cue reactivity in adulthood.

    Science.gov (United States)

    Jordan, Chloe J; Taylor, Danielle M; Dwoskin, Linda P; Kantak, Kathleen M

    2016-01-15

    Attention-deficit/hyperactivity disorder (ADHD) is comorbid with cocaine abuse. Whereas initiating ADHD medication in childhood does not alter later cocaine abuse risk, initiating medication during adolescence may increase risk. Preclinical work in the Spontaneously Hypertensive Rat (SHR) model of ADHD found that adolescent methylphenidate increased cocaine self-administration in adulthood, suggesting a need to identify alternatively efficacious medications for teens with ADHD. We examined effects of adolescent d-amphetamine treatment on strategy set shifting performance during adolescence and on cocaine self-administration and reinstatement of cocaine-seeking behavior (cue reactivity) during adulthood in male SHR, Wistar-Kyoto (inbred control), and Wistar (outbred control) rats. During the set shift phase, adolescent SHR needed more trials and had a longer latency to reach criterion, made more regressive errors and trial omissions, and exhibited slower and more variable lever press reaction times. d-Amphetamine improved performance only in SHR by increasing choice accuracy and decreasing errors and latency to criterion. In adulthood, SHR self-administered more cocaine, made more cocaine-seeking responses, and took longer to extinguish lever responding than control strains. Adolescent d-amphetamine did not alter cocaine self-administration in adult rats of any strain, but reduced cocaine seeking during the first of seven reinstatement test sessions in adult SHR. These findings highlight utility of SHR in modeling cognitive dysfunction and comorbid cocaine abuse in ADHD. Unlike methylphenidate, d-amphetamine improved several aspects of flexible learning in adolescent SHR and did not increase cocaine intake or cue reactivity in adult SHR. Thus, adolescent d-amphetamine was superior to methylphenidate in this ADHD model. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Mitochondrial reactive oxygen species mediate the lipopolysaccharide-induced pro-inflammatory response in human gingival fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xue; Wang, Xiaoxuan [Department of Periodontology, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Zheng, Ming, E-mail: zhengm@bjmu.edu.cn [Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191 (China); Luan, Qing Xian, E-mail: kqluanqx@126.com [Department of Periodontology, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China)

    2016-09-10

    Although periodontal diseases are initiated by bacteria that colonize the tooth surface and gingival sulcus, the host response is believed to play an essential role in the breakdown of connective tissue and bone. Mitochondrial reactive oxygen species (mtROS) have been proposed to regulate the activation of the inflammatory response by the innate immune system. However, the role of mtROS in modulating the response of human gingival fibroblasts (HGFs) to immune stimulation by lipopolysaccharides (LPS) has yet to be fully elucidated. Here, we showed that LPS from Porphyromonas gingivalis stimulated HGFs to increase mtROS production, which could be inhibited by treatment with a mitochondrial-targeted exogenous antioxidant (mito-TEMPO) or transfection with manganese superoxide dismutase (MnSOD). A time-course study revealed that an increase in the concentration of mtROS preceded the expression of inflammatory cytokines in HGFs. Mito-TEMPO treatment or MnSOD transfection also significantly prevented the LPS-induced increase of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. Furthermore, suppressing LPS-induced mtROS generation inhibited the activation of p38, c-Jun N-terminal kinase, and inhibitor of nuclear factor-κB kinase, as well as the nuclear localization of nuclear factor-κB. These results demonstrate that mtROS generation is a key signaling event in the LPS-induced pro-inflammatory response of HGFs. - Highlights: • Inflammation is thought to promote pathogenic changes in periodontitis. • We investigated mtROS as a regulator of inflammation in gingival fibroblasts. • Targeted antioxidants were used to inhibit mtROS production after LPS challenge. • Inhibiting mtROS generation suppressed the secretion of pro-inflammatory cytokines. • JNK, p38, IKK, and NF-κB were shown to act as transducers of mtROS signaling.

  13. Ursolic acid isolated from guava leaves inhibits inflammatory mediators and reactive oxygen species in LPS-stimulated macrophages.

    Science.gov (United States)

    Kim, Min-Hye; Kim, Jin Nam; Han, Sung Nim; Kim, Hye-Kyeong

    2015-06-01

    Psidium guajava (guava) leaves have been frequently used for the treatment of rheumatism, fever, arthritis and other inflammatory conditions. The purpose of this study was to identify major anti-inflammatory compounds from guava leaf extract. The methanol extract and its hexane-, dichloromethane-, ethylacetate-, n-butanol- and water-soluble phases derived from guava leaves were evaluated to determine their inhibitory activity on nitric oxide (NO) production by RAW 264.7 cells stimulated with lipopolysaccharide (LPS). The methanol extract decreased NO production in a dose-dependent manner without cytotoxicity at a concentration range of 0-100 μg/mL. The n-butanol soluble phase was the most potent among the five soluble phases. Four compounds were isolated by reversed-phase HPLC from the n-butanol soluble phase and identified to be avicularin, guaijaverin, leucocyanidin and ursolic acid by their NMR spectra. Among these compounds, ursolic acid inhibited LPS-induced NO production in a dose-dependent manner without cytotoxity at a concentration range of 1-10 µM, but the other three compounds had no effect. Ursolic acid also inhibited LPS-induced prostaglandin E2 production. A western blot analysis showed that ursolic acid decreased the LPS-stimulated inducible nitric oxide synthase and cyclooxygenase protein levels. In addition, ursolic acid suppressed the production of intracellular reactive oxygen species in LPS-stimulated RAW 264.7 cells, as measured by flow cytometry. Taken together, these results identified ursolic acid as a major anti-inflammatory compound in guava leaves.

  14. Mitochondrial reactive oxygen species mediate the lipopolysaccharide-induced pro-inflammatory response in human gingival fibroblasts

    International Nuclear Information System (INIS)

    Li, Xue; Wang, Xiaoxuan; Zheng, Ming; Luan, Qing Xian

    2016-01-01

    Although periodontal diseases are initiated by bacteria that colonize the tooth surface and gingival sulcus, the host response is believed to play an essential role in the breakdown of connective tissue and bone. Mitochondrial reactive oxygen species (mtROS) have been proposed to regulate the activation of the inflammatory response by the innate immune system. However, the role of mtROS in modulating the response of human gingival fibroblasts (HGFs) to immune stimulation by lipopolysaccharides (LPS) has yet to be fully elucidated. Here, we showed that LPS from Porphyromonas gingivalis stimulated HGFs to increase mtROS production, which could be inhibited by treatment with a mitochondrial-targeted exogenous antioxidant (mito-TEMPO) or transfection with manganese superoxide dismutase (MnSOD). A time-course study revealed that an increase in the concentration of mtROS preceded the expression of inflammatory cytokines in HGFs. Mito-TEMPO treatment or MnSOD transfection also significantly prevented the LPS-induced increase of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. Furthermore, suppressing LPS-induced mtROS generation inhibited the activation of p38, c-Jun N-terminal kinase, and inhibitor of nuclear factor-κB kinase, as well as the nuclear localization of nuclear factor-κB. These results demonstrate that mtROS generation is a key signaling event in the LPS-induced pro-inflammatory response of HGFs. - Highlights: • Inflammation is thought to promote pathogenic changes in periodontitis. • We investigated mtROS as a regulator of inflammation in gingival fibroblasts. • Targeted antioxidants were used to inhibit mtROS production after LPS challenge. • Inhibiting mtROS generation suppressed the secretion of pro-inflammatory cytokines. • JNK, p38, IKK, and NF-κB were shown to act as transducers of mtROS signaling.

  15. HYR1-mediated detoxification of reactive oxygen species is required for full virulence in the rice blast fungus.

    Directory of Open Access Journals (Sweden)

    Kun Huang

    2011-04-01

    Full Text Available During plant-pathogen interactions, the plant may mount several types of defense responses to either block the pathogen completely or ameliorate the amount of disease. Such responses include release of reactive oxygen species (ROS to attack the pathogen, as well as formation of cell wall appositions (CWAs to physically block pathogen penetration. A successful pathogen will likely have its own ROS detoxification mechanisms to cope with this inhospitable environment. Here, we report one such candidate mechanism in the rice blast fungus, Magnaporthe oryzae, governed by a gene we refer to as MoHYR1. This gene (MGG_07460 encodes a glutathione peroxidase (GSHPx domain, and its homologue in yeast was reported to specifically detoxify phospholipid peroxides. To characterize this gene in M. oryzae, we generated a deletion mutantΔhyr1 which showed growth inhibition with increased amounts of hydrogen peroxide (H₂O₂. Moreover, we observed that the fungal mutants had a decreased ability to tolerate ROS generated by a susceptible plant, including ROS found associated with CWAs. Ultimately, this resulted in significantly smaller lesion sizes on both barley and rice. In order to determine how this gene interacts with other (ROS scavenging-related genes in M. oryzae, we compared expression levels of ten genes in mutant versus wild type with and without H₂O₂. Our results indicated that the HYR1 gene was important for allowing the fungus to tolerate H₂O₂ in vitro and in planta and that this ability was directly related to fungal virulence.

  16. Reactive oxygen species mediate Cr(VI)-induced carcinogenesis through PI3K/AKT-dependent activation of GSK-3β/β-catenin signaling

    International Nuclear Information System (INIS)

    Son, Young-Ok; Pratheeshkumar, Poyil; Wang, Lei; Wang, Xin; Fan, Jia; Kim, Dong-Hern; Lee, Ju-Yeon; Zhang, Zhuo; Lee, Jeong-Chae; Shi, Xianglin

    2013-01-01

    Cr(VI) compounds are known human carcinogens that primarily target the lungs. Cr(VI) produces reactive oxygen species (ROS), but the exact effects of ROS on the signaling molecules involved in Cr(VI)-induced carcinogenesis have not been extensively studied. Chronic exposure of human bronchial epithelial cells to Cr(VI) at nanomolar concentrations (10–100 nM) for 3 months not only induced cell transformation, but also increased the potential of these cells to invade and migrate. Injection of Cr(VI)-stimulated cells into nude mice resulted in the formation of tumors. Chronic exposure to Cr(VI) increased levels of intracellular ROS and antiapoptotic proteins. Transfection with catalase or superoxide dismutase (SOD) prevented Cr(VI)-mediated increases in colony formation, cell invasion, migration, and xenograft tumors. While chronic Cr(VI) exposure led to activation of signaling cascades involving PI3K/AKT/GSK-3β/β-catenin and PI3K/AKT/mTOR, transfection with catalase or SOD markedly inhibited Cr(VI)-mediated activation of these signaling proteins. Inhibitors specific for AKT or β-catenin almost completely suppressed the Cr(VI)-mediated increase in total and active β-catenin proteins and colony formation. In particular, Cr(VI) suppressed autophagy of epithelial cells under nutrition deprivation. Furthermore, there was a marked induction of AKT, GSK-3β, β-catenin, mTOR, and carcinogenic markers in tumor tissues formed in mice after injection with Cr(VI)-stimulated cells. Collectively, our findings suggest that ROS is a key mediator of Cr(VI)-induced carcinogenesis through the activation of PI3K/AKT-dependent GSK-3β/β-catenin signaling and the promotion of cell survival mechanisms via the inhibition of apoptosis and autophagy. - Highlights: • Chronic exposure to Cr(VI) induces carcinogenic properties in BEAS-2B cells. • ROS play an important role in Cr(VI)-induced tumorigenicity of BEAS-2B cells. • PI3K/AKT/GSK-3β/β-catenin signaling involved in Cr

  17. Reactive oxygen species mediate Cr(VI)-induced carcinogenesis through PI3K/AKT-dependent activation of GSK-3β/β-catenin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Son, Young-Ok; Pratheeshkumar, Poyil; Wang, Lei; Wang, Xin; Fan, Jia; Kim, Dong-Hern; Lee, Ju-Yeon; Zhang, Zhuo [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536-0305 (United States); Lee, Jeong-Chae [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536-0305 (United States); School of Dentistry and Institute of Oral Biosciences, Research Center of Bioactive Materials, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Shi, Xianglin, E-mail: xshi5@email.uky.edu [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536-0305 (United States)

    2013-09-01

    Cr(VI) compounds are known human carcinogens that primarily target the lungs. Cr(VI) produces reactive oxygen species (ROS), but the exact effects of ROS on the signaling molecules involved in Cr(VI)-induced carcinogenesis have not been extensively studied. Chronic exposure of human bronchial epithelial cells to Cr(VI) at nanomolar concentrations (10–100 nM) for 3 months not only induced cell transformation, but also increased the potential of these cells to invade and migrate. Injection of Cr(VI)-stimulated cells into nude mice resulted in the formation of tumors. Chronic exposure to Cr(VI) increased levels of intracellular ROS and antiapoptotic proteins. Transfection with catalase or superoxide dismutase (SOD) prevented Cr(VI)-mediated increases in colony formation, cell invasion, migration, and xenograft tumors. While chronic Cr(VI) exposure led to activation of signaling cascades involving PI3K/AKT/GSK-3β/β-catenin and PI3K/AKT/mTOR, transfection with catalase or SOD markedly inhibited Cr(VI)-mediated activation of these signaling proteins. Inhibitors specific for AKT or β-catenin almost completely suppressed the Cr(VI)-mediated increase in total and active β-catenin proteins and colony formation. In particular, Cr(VI) suppressed autophagy of epithelial cells under nutrition deprivation. Furthermore, there was a marked induction of AKT, GSK-3β, β-catenin, mTOR, and carcinogenic markers in tumor tissues formed in mice after injection with Cr(VI)-stimulated cells. Collectively, our findings suggest that ROS is a key mediator of Cr(VI)-induced carcinogenesis through the activation of PI3K/AKT-dependent GSK-3β/β-catenin signaling and the promotion of cell survival mechanisms via the inhibition of apoptosis and autophagy. - Highlights: • Chronic exposure to Cr(VI) induces carcinogenic properties in BEAS-2B cells. • ROS play an important role in Cr(VI)-induced tumorigenicity of BEAS-2B cells. • PI3K/AKT/GSK-3β/β-catenin signaling involved in Cr

  18. Reactive oxygen species mediate soft corals-derived sinuleptolide-induced antiproliferation and DNA damage in oral cancer cells

    Directory of Open Access Journals (Sweden)

    Chang YT

    2017-07-01

    Full Text Available Yung-Ting Chang,1,2,* Chiung-Yao Huang,3,* Jen-Yang Tang,4,5 Chih-Chuang Liaw,1,3 Ruei-Nian Li,6 Jing-Ru Liu,6 Jyh-Horng Sheu,1,3,7,8 Hsueh-Wei Chang6,9–12 1Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University, Kaohsiung, Taiwan; 2Doctoral Degree Program in Marine Biotechnology, Academia Sinica, Taipei, Taiwan; 3Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan; 4Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Radiation Oncology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; 6Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; 8Frontier Center for Ocean Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan; 9Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan; 10Cancer Center, Kaohsiung Medical University Hospital; Kaohsiung Medical University, Kaohsiung, Taiwan; 11Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 12Research Center for Natural Products and Drug Development, Kaohsiung Medical University, Kaohsiung, Taiwan *These authors contributed equally to this work Abstract: We previously reported that the soft coral-derived bioactive substance, sinuleptolide, can inhibit the proliferation of oral cancer cells in association with oxidative stress. The functional role of oxidative stress in the cell-killing effect of sinuleptolide on oral cancer cells was not investigated as yet. To address this question, we introduced the reactive oxygen species (ROS scavenger (N-acetylcysteine [NAC] in a pretreatment to evaluate the sinuleptolide-induced changes to cell viability, morphology, intracellular

  19. Cellular corepressor TLE2 inhibits replication-and-transcription- activator-mediated transactivation and lytic reactivation of Kaposi's sarcoma-associated herpesvirus.

    Science.gov (United States)

    He, Zhiheng; Liu, Yunhua; Liang, Deguang; Wang, Zhuo; Robertson, Erle S; Lan, Ke

    2010-02-01

    Replication and transcription activator (RTA) encoded by open reading frame 50 (ORF50) of Kaposi's sarcoma-associated herpesvirus (KSHV) is essential and sufficient to initiate lytic reactivation. RTA activates its target genes through direct binding with high affinity to its responsive elements or by interaction with cellular factors, such as RBP-Jkappa, Ap-1, C/EBP-alpha, and Oct-1. In this study, we identified transducin-like enhancer of split 2 (TLE2) as a novel RTA binding protein by using yeast two-hybrid screening of a human spleen cDNA library. The interaction between TLE2 and RTA was confirmed by glutathione S-transferase (GST) binding and coimmunoprecipitation assays. Immunofluorescence analysis showed that TLE2 and RTA were colocalized in the same nuclear compartment in KSHV-infected cells. This interaction recruited TLE2 to RTA bound to its recognition sites on DNA and repressed RTA auto-activation and transactivation activity. Moreover, TLE2 also inhibited the induction of lytic replication and virion production driven by RTA. We further showed that the Q (Gln-rich), SP (Ser-Pro-rich), and WDR (Trp-Asp repeat) domains of TLE2 and the Pro-rich domain of RTA were essential for this interaction. RBP-Jkappa has been shown previously to bind to the same Pro-rich domain of RTA, and this binding can be subject to competition by TLE2. In addition, TLE2 can form a complex with RTA to access the cognate DNA sequence of the RTA-responsive element at different promoters. Intriguingly, the transcription level of TLE2 could be upregulated by RTA during the lytic reactivation process. In conclusion, we identified a new RTA binding protein, TLE2, and demonstrated that TLE2 inhibited replication and transactivation mediated by RTA. This provides another potentially important mechanism for maintenance of KSHV viral latency through interaction with a host protein.

  20. Intracellular zinc flux causes reactive oxygen species mediated mitochondrial dysfunction leading to cell death in Leishmania donovani.

    Directory of Open Access Journals (Sweden)

    Anjali Kumari

    Full Text Available Leishmaniasis caused by Leishmania parasite is a global threat to public health and one of the most neglected tropical diseases. Therefore, the discovery of novel drug targets and effective drug is a major challenge and an important goal. Leishmania is an obligate intracellular parasite that alternates between sand fly and human host. To survive and establish infections, Leishmania parasites scavenge and internalize nutrients from the host. Nevertheless, host cells presents mechanism like nutrient restriction to inhibit microbial growth and control infection. Zinc is crucial for cellular growth and disruption in its homeostasis hinders growth and survival in many cells. However, little is known about the role of zinc in Leishmania growth and survival. In this study, the effect of zinc on the growth and survival of L.donovani was analyzed by both Zinc-depletion and Zinc-supplementation using Zinc-specific chelator N, N, N', N'-tetrakis (2-pyridylmethyl ethylenediamine (TPEN and Zinc Sulfate (ZnSO4. Treatment of parasites with TPEN rather than ZnSO4 had significantly affected the growth in a dose- and time-dependent manner. The pre-treatment of promastigotes with TPEN resulted into reduced host-parasite interaction as indicated by decreased association index. Zn depletion resulted into flux in intracellular labile Zn pool and increased in ROS generation correlated with decreased intracellular total thiol and retention of plasma membrane integrity without phosphatidylserine exposure in TPEN treated promastigotes. We also observed that TPEN-induced Zn depletion resulted into collapse of mitochondrial membrane potential which is associated with increase in cytosolic calcium and cytochrome-c. DNA fragmentation analysis showed increased DNA fragments in Zn-depleted cells. In summary, intracellular Zn depletion in the L. donovani promastigotes led to ROS-mediated caspase-independent mitochondrial dysfunction resulting into apoptosis-like cell death

  1. Role of cytochrome P450-mediated metabolism and involvement of reactive metabolite formations on antiepileptic drug-induced liver injuries.

    Science.gov (United States)

    Sasaki, Eita; Yokoi, Tsuyoshi

    2018-01-01

    Several drugs have been withdrawn from the market or restricted to avoid unexpected adverse outcomes. Drug-induced liver injury (DILI) is a serious issue for drug development. Among DILIs, idiosyncratic DILIs have been a serious problem in drug development and clinical uses. Idiosyncratic DILI is most often unrelated to pharmacological effects or the dosing amount of a drug. The number of drugs that cause idiosyncratic DILI continue to grow in part because no practical preclinical tests have emerged that can identify drug candidates with the potential for developing idiosyncratic DILIs. Nevertheless, the implications of drug metabolism-related factors and immune-related factors on idiosyncratic DILIs has not been fully clarified because this toxicity can not be reproduced in animals. Therefore, accumulated evidence for the mechanisms of the idiosyncratic toxicity has been limited to only in vitro studies. This review describes current knowledge of the effects of cytochrome P450 (CYP)-mediated metabolism and its detoxification abilities based on studies of idiosyncratic DILI animal models developed recently. This review also focused on antiepileptic drugs, phenytoin (diphenyl hydantoin, DPH) and carbamazepine (CBZ), which have rarely caused severe adverse reactions, such as fulminant hepatitis, and have been recognized as sources of idiosyncratic DILI. The studies of animal models of idiosyncratic DILIs have produced new knowledge of chronic administration, CYP inductions/inhibitions, glutathione contents, and immune-related factors for the initiation of idiosyncratic DILIs. Considering changes in the drug metabolic profile and detoxification abilities, idiosyncratic DILIs caused by antiepileptic drugs will lead to understanding the mechanisms of these DILIs.

  2. Mindfulness facets as differential mediators of short and long-term effects of Mindfulness-Based Cognitive Therapy in diabetes outpatients

    DEFF Research Database (Denmark)

    Haenen, Sharon; Nyklíček, Ivan; VAN Son, Jenny

    2016-01-01

    BACKGROUND: There is increasing evidence that mindfulness-based interventions reduce psychological distress in various medical populations. However, it has hardly been studied if these effects are mediated by an increase in mindfulness. The aim of this study was to examine mediating effects...... of various mindfulness facets on effects of a Mindfulness Based Cognitive Therapy (MBCT) on perceived stress and mood. METHODS: Outpatients with diabetes types 1 and 2 and low levels of emotional wellbeing were randomized into a group receiving MBCT (n=70) or a waiting-list control group (n=69). Primary...... outcomes were mood and perceived stress. Before, after and at follow-up (6months post intervention) relevant questionnaires were completed. RESULTS: Mediation analysis using bootstrap resampling indicated that increases in total mindfulness and the facets observing and nonreactivity mediated the effects...

  3. Structural insights into 2,2'-azino-Bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)-mediated degradation of reactive blue 21 by engineered Cyathus bulleri Laccase and characterization of degradation products.

    Science.gov (United States)

    Kenzom, T; Srivastava, P; Mishra, S

    2014-12-01

    Advanced oxidation processes are currently used for the treatment of different reactive dyes which involve use of toxic catalysts. Peroxidases are reported to be effective on such dyes and require hydrogen peroxide and/or metal ions. Cyathus bulleri laccase, expressed in Pichia pastoris, catalyzes efficient degradation (78 to 85%) of reactive azo dyes (reactive black 5, reactive orange 16, and reactive red 198) in the presence of synthetic mediator ABTS [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)]. This laccase was engineered to degrade effectively reactive blue 21 (RB21), a phthalocyanine dye reported to be decolorized only by peroxidases. The 816-bp segment (toward the C terminus) of the lcc gene was subjected to random mutagenesis and enzyme variants (Lcc35, Lcc61, and Lcc62) were selected based on increased ABTS oxidizing ability. Around 78 to 95% decolorization of RB21 was observed with the ABTS-supplemented Lcc variants in 30 min. Analysis of the degradation products by mass spectrometry indicated the formation of several low-molecular-weight compounds. Mapping the mutations on the modeled structure implicated residues both near and far from the T1 Cu site that affected the catalytic efficiency of the mutant enzymes on ABTS and, in turn, the rate of oxidation of RB21. Several inactive clones were also mapped. The importance of geometry as well as electronic changes on the reactivity of laccases was indicated. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  4. Structural Insights into 2,2′-Azino-Bis(3-Ethylbenzothiazoline-6-Sulfonic Acid) (ABTS)-Mediated Degradation of Reactive Blue 21 by Engineered Cyathus bulleri Laccase and Characterization of Degradation Products

    Science.gov (United States)

    Kenzom, T.; Srivastava, P.

    2014-01-01

    Advanced oxidation processes are currently used for the treatment of different reactive dyes which involve use of toxic catalysts. Peroxidases are reported to be effective on such dyes and require hydrogen peroxide and/or metal ions. Cyathus bulleri laccase, expressed in Pichia pastoris, catalyzes efficient degradation (78 to 85%) of reactive azo dyes (reactive black 5, reactive orange 16, and reactive red 198) in the presence of synthetic mediator ABTS [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)]. This laccase was engineered to degrade effectively reactive blue 21 (RB21), a phthalocyanine dye reported to be decolorized only by peroxidases. The 816-bp segment (toward the C terminus) of the lcc gene was subjected to random mutagenesis and enzyme variants (Lcc35, Lcc61, and Lcc62) were selected based on increased ABTS oxidizing ability. Around 78 to 95% decolorization of RB21 was observed with the ABTS-supplemented Lcc variants in 30 min. Analysis of the degradation products by mass spectrometry indicated the formation of several low-molecular-weight compounds. Mapping the mutations on the modeled structure implicated residues both near and far from the T1 Cu site that affected the catalytic efficiency of the mutant enzymes on ABTS and, in turn, the rate of oxidation of RB21. Several inactive clones were also mapped. The importance of geometry as well as electronic changes on the reactivity of laccases was indicated. PMID:25261507

  5. Tumor-Derived Microvesicles Modulate Antigen Cross-Processing via Reactive Oxygen Species-Mediated Alkalinization of Phagosomal Compartment in Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Federico Battisti

    2017-09-01

    Full Text Available Dendritic cells (DCs are the only antigen-presenting cells able to prime naïve T cells and cross-prime antigen-specific CD8+ T cells. Their functionality is a requirement for the induction and maintenance of long-lasting cancer immunity. Albeit intensively investigated, the in vivo mechanisms underlying efficient antigen cross-processing and presentation are not fully understood. Several pieces of evidence indicate that antigen transfer to DCs mediated by microvesicles (MVs enhances antigen immunogenicity. This mechanism is also relevant for cross-presentation of those tumor-associated glycoproteins such as MUC1 that are blocked in HLA class II compartment when internalized by DCs as soluble molecules. Here, we present pieces of evidence that the internalization of tumor-derived MVs modulates antigen-processing machinery of DCs. Employing MVs derived from ovarian cancer ascites fluid and established tumor cell lines, we show that MV uptake modifies DC phagosomal microenvironment, triggering reactive oxygen species (ROS accumulation and early alkalinization. Indeed, tumor MVs carry radical species and the MV uptake by DCs counteracts the chemically mediated acidification of the phagosomal compartment. Further pieces of evidence suggest that efficacious antigen cross-priming of the MUC1 antigen carried by the tumor MVs results from the early signaling induced by MV internalization and the function of the antigen-processing machinery of DCs. These results strongly support the hypothesis that tumor-derived MVs impact antigen immunogenicity by tuning the antigen-processing machinery of DCs, besides being carrier of tumor antigens. Furthermore, these findings have important implications for the exploitation of MVs as antigenic cell-free immunogen for DC-based therapeutic strategies.

  6. 5-lipoxygenase mediates docosahexaenoyl ethanolamide and N-arachidonoyl-L-alanine-induced reactive oxygen species production and inhibition of proliferation of head and neck squamous cell carcinoma cells.

    Science.gov (United States)

    Park, Seok-Woo; Hah, J Hun; Oh, Sang-Mi; Jeong, Woo-Jin; Sung, Myung-Whun

    2016-07-13

    Endocannabinoids have recently drawn attention as promising anti-cancer agents. We previously observed that anandamide (AEA), one of the representative endocannabinoids, effectively inhibited the proliferation of head and neck squamous cell carcinoma (HNSCC) cell lines in a receptor-independent manner. In this study, using HNSCC cell lines, we examined the anti-cancer effects and the mechanisms of action of docosahexaenoyl ethanolamide (DHEA) and N-arachidonoyl-L-alanine (NALA), which are polyunsaturated fatty acid (PUFA)-based ethanolamides like AEA. DHEA and NALA were found to effectively inhibit HNSCC cell proliferation. These anti-proliferative effects seemed to be mediated in a cannabinoid receptor-independent manner, since the antagonist of cannabinoid receptor-1 (CB1) and vanilloid receptor-1 (VR1), two endocannabinoid receptors, did not reverse the ability of DHEA and NALA to induce cell death. Instead, we observed an increase in reactive oxygen species (ROS) production and a decrease of phosphorylated Akt as a result of DHEA and NALA treatment. Antioxidants efficiently reversed the inhibition of cell proliferation and the decrease of phosphorylated Akt induced by DHEA and NALA; inhibition of 5-lipoxygenase (5-LO), which is expected to be involved in DHEA- and NALA-degradation pathway, also partially blocked the ability of DHEA and NALA to inhibit cell proliferation and phosphorylated Akt. Interestingly, ROS production as a result of DHEA and NALA treatment was decreased by inhibition of 5-LO. From these findings, we suggest that ROS production induced by the 5-LO pathway mediates the anti-cancer effects of DHEA and NALA on HNSCC cells. Finally, our findings suggest the possibility of a new cancer-specific therapeutic strategy, which utilizes 5-LO activity rather than inhibiting it.

  7. 5-lipoxygenase mediates docosahexaenoyl ethanolamide and N-arachidonoyl-L-alanine-induced reactive oxygen species production and inhibition of proliferation of head and neck squamous cell carcinoma cells

    International Nuclear Information System (INIS)

    Park, Seok-Woo; Hah, J. Hun; Oh, Sang-Mi; Jeong, Woo-Jin; Sung, Myung-Whun

    2016-01-01

    Endocannabinoids have recently drawn attention as promising anti-cancer agents. We previously observed that anandamide (AEA), one of the representative endocannabinoids, effectively inhibited the proliferation of head and neck squamous cell carcinoma (HNSCC) cell lines in a receptor-independent manner. In this study, using HNSCC cell lines, we examined the anti-cancer effects and the mechanisms of action of docosahexaenoyl ethanolamide (DHEA) and N-arachidonoyl-L-alanine (NALA), which are polyunsaturated fatty acid (PUFA)-based ethanolamides like AEA. DHEA and NALA were found to effectively inhibit HNSCC cell proliferation. These anti-proliferative effects seemed to be mediated in a cannabinoid receptor-independent manner, since the antagonist of cannabinoid receptor-1 (CB1) and vanilloid receptor-1 (VR1), two endocannabinoid receptors, did not reverse the ability of DHEA and NALA to induce cell death. Instead, we observed an increase in reactive oxygen species (ROS) production and a decrease of phosphorylated Akt as a result of DHEA and NALA treatment. Antioxidants efficiently reversed the inhibition of cell proliferation and the decrease of phosphorylated Akt induced by DHEA and NALA; inhibition of 5-lipoxygenase (5-LO), which is expected to be involved in DHEA- and NALA-degradation pathway, also partially blocked the ability of DHEA and NALA to inhibit cell proliferation and phosphorylated Akt. Interestingly, ROS production as a result of DHEA and NALA treatment was decreased by inhibition of 5-LO. From these findings, we suggest that ROS production induced by the 5-LO pathway mediates the anti-cancer effects of DHEA and NALA on HNSCC cells. Finally, our findings suggest the possibility of a new cancer-specific therapeutic strategy, which utilizes 5-LO activity rather than inhibiting it. The online version of this article (doi:10.1186/s12885-016-2499-3) contains supplementary material, which is available to authorized users

  8. Effects of false feedback on affect, cognition, behavior, and postevent processing: the mediating role of self-focused attention.

    Science.gov (United States)

    Makkar, Steve R; Grisham, Jessica R

    2013-03-01

    Current social phobia models (e.g., Clark & Wells, 1995; Leary & Kowalski, 1995) postulate that socially anxious individuals negatively appraise their anxiety sensations (e.g., sweating, heart racing, blushing) as evidence of poor social performance, and thus fear these anxiety symptoms will be noticed and judged negatively by others. Consequently, they become self-focused and hypervigilant of these sensations and use them to judge how they appear to others. To test this model, high (N=41) and low (N=38) socially anxious participants were shown false physiological feedback regarding an increase or decrease in heart rate prior to and during an impromptu speech task. Relative to participants who observed a false heart rate decrease, those in the increase condition reported higher levels of negative affect, more negative performance appraisals, and more frequent negative ruminative thoughts, and these effects were mediated by an increase in self-focused attention. The unhelpful effects of the physiological feedback were not specific to high socially anxious participants. The results have implications for current cognitive models as well as the treatment of social phobia. Copyright © 2012. Published by Elsevier Ltd.

  9. Electroacupuncture ameliorates cognitive impairment through inhibition of NF-κB-mediated neuronal cell apoptosis in cerebral ischemia-reperfusion injured rats.

    Science.gov (United States)

    Feng, Xiaodong; Yang, Shanli; Liu, Jiao; Huang, Jia; Peng, Jun; Lin, Jiumao; Tao, Jing; Chen, Lidian

    2013-05-01

    Cognitive impairment is a serious mental deficit following stroke that severely affects the quality of life of stroke survivors. Nuclear factor‑κB (NF-κB)-mediated neuronal cell apoptosis is involved in the development of post-stroke cognitive impairment; therefore, it has become a promising target for the treatment of impaired cognition. Acupuncture at the Baihui (DU20) and Shenting (DU24) acupoints is commonly used in China to clinically treat post‑stroke cognitive impairment; however, the precise mechanism of its action is largely unknown. In the present study, we evaluated the therapeutic efficacy of electroacupuncture against post-stroke cognitive impairment and investigated the underlying molecular mechanisms using a rat model of focal cerebral ischemia-reperfusion (I/R) injury. Electroacupuncture at Baihui and Shenting was identified to significantly ameliorate neurological deficits and reduce cerebral infarct volume. Additionally, electroacupuncture improved learning and memory ability in cerebral I/R injured rats, demonstrating its therapeutic efficacy against post-stroke cognitive impairment. Furthermore, electroacupuncture significantly suppressed the I/R-induced activation of NF-κB signaling in ischemic cerebral tissues. The inhibitory effect of electroacupuncture on NF-κB activation led to the inhibition of cerebral cell apoptosis. Finally, electroacupuncture markedly downregulated the expression of pro-apoptotic Bax and Fas, two critical downstream target genes of the NF-κB pathway. Collectively, our findings suggest that inhibition of NF-κB‑mediated neuronal cell apoptosis may be one mechanism via which electroacupuncture at Baihui and Shenting exerts a therapeutic effect on post-stroke cognitive impairment.

  10. Myricetin-induced apoptosis of triple-negative breast cancer cells is mediated by the iron-dependent generation of reactive oxygen species from hydrogen peroxide.

    Science.gov (United States)

    Knickle, Allison; Fernando, Wasundara; Greenshields, Anna L; Rupasinghe, H P Vasantha; Hoskin, David W

    2018-05-06

    Myricetin is a dietary phytochemical with anticancer activity; however, the effect of myricetin on breast cancer cells remains unclear. Here, we show that myricetin inhibited the growth of triple-negative breast cancer (TNBC) cells but was less inhibitory for normal cells. The effect of myricetin was comparable to epigallocatechin gallate and doxorubicin, and greater than resveratrol and cisplatin. Myricetin-treated TNBC cells showed evidence of early and late apoptosis/necrosis, which was associated with intracellular reactive oxygen species (ROS) accumulation, extracellular regulated kinase 1/2 and p38 mitogen-activated protein kinase activation, mitochondrial membrane destabilization and cytochrome c release, and double-strand DNA breaks. The antioxidant N-acetyl-cysteine protected myricetin-treated TNBC cells from cytotoxicity due to DNA damage. Myricetin also induced hydrogen peroxide (H 2 O 2 ) production in cell-free culture medium, as well as in the presence of TNBC cells and normal cells. In addition, deferriprone-mediated inhibition of intracellular ROS generation via the iron-dependent Fenton reaction and inhibition of extracellular ROS accumulation with superoxide dismutase plus catalase prevented myricetin-induced cytotoxicity in TNBC cell cultures. We conclude that the cytotoxic effect of myricetin on TNBC cells was due to oxidative stress initiated by extracellular H 2 O 2 formed by autoxidation of myricetin, leading to intracellular ROS production via the Fenton reaction. Copyright © 2018. Published by Elsevier Ltd.

  11. Natriuretic peptide receptor A inhibition suppresses gastric cancer development through reactive oxygen species-mediated G2/M cell cycle arrest and cell death.

    Science.gov (United States)

    Li, Zheng; Wang, Ji-Wei; Wang, Wei-Zhi; Zhi, Xiao-Fei; Zhang, Qun; Li, Bo-Wen; Wang, Lin-Jun; Xie, Kun-Ling; Tao, Jin-Qiu; Tang, Jie; Wei, Song; Zhu, Yi; Xu, Hao; Zhang, Dian-Cai; Yang, Li; Xu, Ze-Kuan

    2016-10-01

    Natriuretic peptide receptor A (NPRA), the major receptor for atrial natriuretic peptide (ANP), has been implicated in tumorigenesis; however, the role of ANP-NPRA signaling in the development of gastric cancer remains unclear. Immunohistochemical analyses indicated that NPRA expression was positively associated with gastric tumor size and cancer stage. NPRA inhibition by shRNA induced G2/M cell cycle arrest, cell death, and autophagy in gastric cancer cells, due to accumulation of reactive oxygen species (ROS). Either genetic or pharmacologic inhibition of autophagy led to caspase-dependent cell death. Therefore, autophagy induced by NPRA silencing may represent a cytoprotective mechanism. ROS accumulation activated c-Jun N-terminal kinase (JNK) and AMP-activated protein kinase (AMPK). ROS-mediated activation of JNK inhibited cell proliferation by disturbing cell cycle and decreased cell viability. In addition, AMPK activation promoted autophagy in NPRA-downregulated cancer cells. Overall, our results indicate that the inhibition of NPRA suppresses gastric cancer development and targeting NPRA may represent a promising strategy for the treatment of gastric cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. 2-Deoxy-D-glucose treatment of endothelial cells induces autophagy by reactive oxygen species-mediated activation of the AMP-activated protein kinase.

    Directory of Open Access Journals (Sweden)

    Qilong Wang

    2011-02-01

    Full Text Available Autophagy is a cellular self-digestion process activated in response to stresses such as energy deprivation and oxidative stress. However, the mechanisms by which energy deprivation and oxidative stress trigger autophagy remain undefined. Here, we report that activation of AMP-activated protein kinase (AMPK by mitochondria-derived reactive oxygen species (ROS is required for autophagy in cultured endothelial cells. AMPK activity, ROS levels, and the markers of autophagy were monitored in confluent bovine aortic endothelial cells (BAEC treated with the glycolysis blocker 2-deoxy-D-glucose (2-DG. Treatment of BAEC with 2-DG (5 mM for 24 hours or with low concentrations of H(2O(2 (100 µM induced autophagy, including increased conversion of microtubule-associated protein light chain 3 (LC3-I to LC3-II, accumulation of GFP-tagged LC3 positive intracellular vacuoles, and increased fusion of autophagosomes with lysosomes. 2-DG-treatment also induced AMPK phosphorylation, which was blocked by either co-administration of two potent anti-oxidants (Tempol and N-Acetyl-L-cysteine or overexpression of superoxide dismutase 1 or catalase in BAEC. Further, 2-DG-induced autophagy in BAEC was blocked by overexpressing catalase or siRNA-mediated knockdown of AMPK. Finally, pretreatment of BAEC with 2-DG increased endothelial cell viability after exposure to hypoxic stress. Thus, AMPK is required for ROS-triggered autophagy in endothelial cells, which increases endothelial cell survival in response to cell stress.

  13. Inhibitory effects on the production of inflammatory mediators and reactive oxygen species by Mori folium in lipopolysaccharide-stimulated macrophages and zebrafish

    Directory of Open Access Journals (Sweden)

    DA HYE KWON

    Full Text Available ABSTRACT Mori folium, the leaf of Morus alba L. (Moraceae, has been traditionally used for various medicinal purposes from ancient times to the present. In this study, we examined the effects of water extract of Mori folium (WEMF on the production of inflammatory mediators, such as nitric oxide (NO and prostaglandin E2 (PGE2, and reactive oxygen species (ROS in lipopolysaccharide (LPS-stimulated murine RAW 264.7 macrophages. Our data indicated that WEMF significantly suppressed the secretion of NO and PGE2 in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects were accompanied by a marked reduction in their regulatory gene expression at the transcription level. WEMF attenuated LPS-induced intracellular ROS production in RAW 264.7 macrophages. It inhibited the nuclear translocation of the nuclear factor-kappa B p65 subunit and the activation of mitogen-activated protein kinases in LPS-treated RAW 264.7 macrophages. Furthermore, WEMF reduced LPS-induced NO production and ROS accumulation in zebrafish. Although more efforts are needed to fully understand the critical role of WEMF in the inhibition of inflammation, the findings of the present study may provide insights into the approaches for Mori folium as a potential therapeutic agent for inflammatory and antioxidant disorders.

  14. Mangosenone F, A Furanoxanthone from Garciana mangostana, Induces Reactive Oxygen Species-Mediated Apoptosis in Lung Cancer Cells and Decreases Xenograft Tumor Growth.

    Science.gov (United States)

    Seo, Kyung Hye; Ryu, Hyung Won; Park, Mi Jin; Park, Ki Hun; Kim, Jin Hyo; Lee, Mi-Ja; Kang, Hyeon Jung; Kim, Sun Lim; Lee, Jin Hwan; Seo, Woo Duck

    2015-11-01

    Mangosenone F (MSF), a natural xanthone, was isolated form Carcinia mangotana, and a few studies have reported its glycosidase inhibitor effect. In this study we investigated the anti lung cancer effect of MSF both in vitro and in vivo. MSF inhibited cancer cell cytotoxicity and induced and induced apoptosis via reactive oxygen species (ROS) generation in NCI-H460. MSF treatment also showed in pronounced release of apoptogenic cytochrome c from the mitochondria to the cytosol, downregulation of Bcl-2 and Bcl-xL, and upregulation of Bax, suggesting that caspase-mediated pathways were involved in MSF-induced apoptosis. ROS activation of the mitogen-activated protein kinase signaling pathway was shown to play a predominant role in the apoptosis mechanism of MSF. Compared with cisplatin treatment, MSF treatment showed significantly increased inhibition of the growth of NCI-H460 cells xenografted in nude mice. Together, these results indicate the potential of MSF as a candidate natural anticancer drug by promoting ROS production. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Honokiol induces autophagic cell death in malignant glioma through reactive oxygen species-mediated regulation of the p53/PI3K/Akt/mTOR signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chien-Ju [Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan (China); Comprehensive Cancer Center, Taipei Medical University, Taipei, Taiwan (China); Chen, Ta-Liang [Anesthetics and Toxicology Research Center, Taipei Medical University Hospital, Taipei, Taiwan (China); Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan (China); Tseng, Yuan-Yun [Department of Neurosurgery, Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan (China); Wu, Gong-Jhe [Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Hsieh, Ming-Hui [Anesthetics and Toxicology Research Center, Taipei Medical University Hospital, Taipei, Taiwan (China); Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan (China); Lin, Yung-Wei [Brain Disease Research Center, Taipei Medical University Wan-Fang Hospital, Taipei, Taiwan (China); Chen, Ruei-Ming, E-mail: rmchen@tmu.edu.tw [Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan (China); Anesthetics and Toxicology Research Center, Taipei Medical University Hospital, Taipei, Taiwan (China); Brain Disease Research Center, Taipei Medical University Wan-Fang Hospital, Taipei, Taiwan (China); Comprehensive Cancer Center, Taipei Medical University, Taipei, Taiwan (China)

    2016-08-01

    Honokiol, an active constituent extracted from the bark of Magnolia officinalis, possesses anticancer effects. Apoptosis is classified as type I programmed cell death, while autophagy is type II programmed cell death. We previously proved that honokiol induces cell cycle arrest and apoptosis of U87 MG glioma cells. Subsequently in this study, we evaluated the effect of honokiol on autophagy of glioma cells and examined the molecular mechanisms. Administration of honokiol to mice with an intracranial glioma increased expressions of cleaved caspase 3 and light chain 3 (LC3)-II. Exposure of U87 MG cells to honokiol also induced autophagy in concentration- and time-dependent manners. Results from the addition of 3-methyladenine, an autophagy inhibitor, and rapamycin, an autophagy inducer confirmed that honokiol-induced autophagy contributed to cell death. Honokiol decreased protein levels of PI3K, phosphorylated (p)-Akt, and p-mammalian target of rapamycin (mTOR) in vitro and in vivo. Pretreatment with a p53 inhibitor or transfection with p53 small interfering (si)RNA suppressed honokiol-induced autophagy by reversing downregulation of p-Akt and p-mTOR expressions. In addition, honokiol caused generation of reactive oxygen species (ROS), which was suppressed by the antioxidant, vitamin C. Vitamin C also inhibited honokiol-induced autophagic and apoptotic cell death. Concurrently, honokiol-induced alterations in levels of p-p53, p53, p-Akt, and p-mTOR were attenuated following vitamin C administration. Taken together, our data indicated that honokiol induced ROS-mediated autophagic cell death through regulating the p53/PI3K/Akt/mTOR signaling pathway. - Highlights: • Exposure of mice with intracranial gliomas to honokiol induces cell apoptosis and autophagy. • Honokiol triggers autophagy of human glioma cells via the PISK/AKT/mTOR signaling pathway. • P53 induces autophagy via regulating the AKT/mTOR pathway in honokiol-treated glioma cells. • ROS participates

  16. Stress and sleep reactivity: a prospective investigation of the stress-diathesis model of insomnia.

    Science.gov (United States)

    Drake, Christopher L; Pillai, Vivek; Roth, Thomas

    2014-08-01

    To prospectively assess sleep reactivity as a diathesis of insomnia, and to delineate the interaction between this diathesis and naturalistic stress in the development of insomnia among normal sleepers. Longitudinal. Community-based. 2,316 adults from the Evolution of Pathways to Insomnia Cohort (EPIC) with no history of insomnia or depression (46.8 ± 13.2 y; 60% female). None. Participants reported the number of stressful events they encountered at baseline (Time 1), as well as the level of cognitive intrusion they experienced in response to each stressor. Stressful events (OR = 1.13; P stress-induced cognitive intrusion (OR = 1.61; P stressful events on risk for insomnia (P sleep reactivity significantly increased risk for insomnia (OR = 1.78; P sleep reactivity moderated the effects of stress-induced intrusion (P sleep reactivity. Trait sleep reactivity also constituted a significant risk for depression (OR = 1.67; P sleep reactivity is a significant risk factor for incident insomnia, and that it triggers insomnia by exacerbating the effects of stress-induced intrusion. Sleep reactivity is also a precipitant of depression, as mediated by insomnia. These findings support the stress-diathesis model of insomnia, while highlighting sleep reactivity as an important diathesis. Drake CL, Pillai V, Roth T. Stress and sleep reactivity: a prospective investigation of the stress-diathesis model of insomnia.

  17. Cognitive Bias as a Mediator in the Relation Between Fear-Enhancing Parental Behaviors and Anxiety Symptoms in Children: A Cross-Sectional Study.

    Science.gov (United States)

    Fliek, Lorraine; Dibbets, Pauline; Roelofs, Jeffrey; Muris, Peter

    2017-02-01

    The present cross-sectional study explored the relations between fear-enhancing parenting behaviors (modeling and threat information transmission) and children's cognitive biases and anxiety symptoms. Participants were 258 children aged 7-12 years (132 boys and 126 girls), and their mothers (n = 199) and/or fathers (n = 117). Children and parents completed the Parental Enhancement of Anxious Cognitions questionnaire, which measures parental modeling and threat information transmission, while children also filled in a scale for assessing anxiety symptoms. In addition, children conducted a number of computerized tasks for measuring confirmation and interpretation bias. The data indicated that both biases mediated the relationship between threat information transmission (of both parents) and children's anxiety symptoms. Only interpretation bias significantly mediated the relationship between modeling (of mothers) and anxiety symptoms. These findings give partial support for the hypothesis that cognitive biases play a mediating role in the relation between fear-enhancing parental behaviors and children's anxiety symptoms.

  18. Social Cognitive Constructs Did Not Mediate the BEAT Cancer Intervention Effects on Objective Physical Activity Behavior Based on Multivariable Path Analysis.

    Science.gov (United States)

    Rogers, Laura Q; Courneya, Kerry S; Anton, Phillip M; Hopkins-Price, Patricia; Verhulst, Steven; Robbs, Randall S; Vicari, Sandra K; McAuley, Edward

    2017-04-01

    Most breast cancer survivors do not meet physical activity recommendations. Understanding mediators of physical activity behavior change can improve interventions designed to increase physical activity in this at-risk population. Study aims were to determine the 3-month Better Exercise Adherence after Treatment for Cancer (BEAT Cancer) behavior change intervention effects on social cognitive theory constructs and the mediating role of any changes on the increase in accelerometer-measured physical activity previously reported. Post-treatment breast cancer survivors (N = 222) were randomized to BEAT Cancer or usual care. Assessments occurred at baseline, 3 months (M3), and 6 months (M6). Adjusted linear mixed model analysis of variance determined intervention effects on walking self-efficacy, outcome expectations, goal setting, and perceived barrier interference at M3. Path analysis determined mediation of intervention effects on physical activity at M6 by changes in social cognitive constructs during the intervention (i.e., baseline to M3). BEAT Cancer significantly improved self-efficacy, goals, negative outcome expectations, and barriers. Total path analysis model explained 24 % of the variance in M6 physical activity. There were significant paths from randomized intervention group to self-efficacy (β = 0.15, p social cognitive constructs, no significant indirect effects on physical activity improvements 3 months post-intervention were observed (NCT00929617).

  19. Engagement with Cognitively-Based Compassion Training is associated with reduced salivary C-reactive protein from before to after training in foster care program adolescents.

    Science.gov (United States)

    Pace, Thaddeus W W; Negi, Lobsang Tenzin; Dodson-Lavelle, Brooke; Ozawa-de Silva, Brendan; Reddy, Sheethal D; Cole, Steven P; Danese, Andrea; Craighead, Linda W; Raison, Charles L

    2013-02-01

    Children exposed to early life adversity (ELA) have been shown to have elevated circulating concentrations of inflammatory markers that persist into adulthood. Increased inflammation in individuals with ELA is believed to drive the elevated risk for medical and psychiatric illness in the same individuals. This study sought to determine whether Cognitively Based Compassion Training (CBCT) reduced C-reactive protein (CRP) in adolescents in foster care with high rates of ELA, and to evaluate the relationship between CBCT engagement and changes in CRP given prior evidence from our group for an effect of practice on inflammatory markers. It was hypothesized that increasing engagement would be associated with reduced CRP from baseline to the 6-week assessment. Seventy-one adolescents in the Georgia foster care system (31 females), aged 13-17, were randomized to either 6 weeks of CBCT or a wait-list condition. State records were used to obtain information about each participant's history of trauma and neglect, as well as reason for placement in foster care. Saliva was collected before and again after 6 weeks of CBCT or the wait-list condition. Participants in the CBCT group completed practice diaries as a means of assessing engagement with the CBCT. No difference between groups was observed in salivary CRP concentrations. Within the CBCT group, practice sessions during the study correlated with reduced CRP from baseline to the 6-week assessment. Engagement with CBCT may positively impact inflammatory measures relevant to health in adolescents at high risk for poor adult functioning as a result of significant ELA, including individuals placed in foster care. Longer term follow-up will be required to evaluate if these changes are maintained and translate into improved health outcomes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Soyasaponins can blunt inflammation by inhibiting the reactive oxygen species-mediated activation of PI3K/Akt/NF-kB pathway.

    Science.gov (United States)

    Zha, Longying; Chen, Jiading; Sun, Suxia; Mao, Limei; Chu, Xinwei; Deng, Hong; Cai, Junwei; Li, Xuefeng; Liu, Zhenqi; Cao, Wenhong

    2014-01-01

    We and others have recently shown that soyasaponins abundant in soybeans can decrease inflammation by suppressing the nuclear factor kappa B (NF-kB)-mediated inflammation. However, the exact molecular mechanisms by which soyasaponins inhibit the NF-kB pathway have not been established. In this study in macrophages, soyasaponins (A1, A2 and I) inhibited the lipopolysaccharide (LPS)-induced release of inflammatory marker prostaglandin E2 (PGE2) to a similar extent as the NF-kB inhibitor (BAY117082). Soyasaponins (A1, A2 and I) also suppressed the LPS-induced expression of cyclooxygenase 2 (COX-2), another inflammatory marker, in a dose-dependent manner by inhibiting NF-kB activation. In defining the associated mechanisms, we found that soyasaponins (A1, A2 and I) blunted the LPS-induced IKKα/β phosphorylation, IkB phosphorylation and degradation, and NF-kB p65 phosphorylation and nuclear translocation. In studying the upstream targets of soyasaponins on the NF-kB pathway, we found that soyasaponins (A1, A2 and I) suppressed the LPS-induced activation of PI3K/Akt similarly as the PI3K inhibitor LY294002, which alone blocked the LPS-induced activation of NF-kB. Additionally, soyasaponins (A1, A2 and I) reduced the LPS-induced production of reactive oxygen species (ROS) to the same extent as the anti-oxidant N-acetyl-L-cysteine, which alone inhibited the LPS-induced phosphorylation of Akt, IKKα/β, IkBα, and p65, transactivity of NF-kB, PGE2 production, and malondialdehyde production. Finally, our results show that soyasaponins (A1, A2 and I) elevated SOD activity and the GSH/GSSG ratio. Together, these results show that soyasaponins (A1, A2 and I) can blunt inflammation by inhibiting the ROS-mediated activation of the PI3K/Akt/NF-kB pathway.

  1. Cognitive and Reactive Control Processes

    Science.gov (United States)

    Jarrett, Matthew A.; Gilpin, Ansley Tullos; Pierucci, Jillian M.; Rondon, Ana T.

    2016-01-01

    Attention-deficit/hyperactivity disorder (ADHD) can be identified in the preschool years, but little is known about the correlates of ADHD symptoms in preschool children. Research to date suggests that factors such as temperament, personality, and neuropsychological functioning may be important in understanding the development of early ADHD…

  2. Ampelopsin-induced reactive oxygen species enhance the apoptosis of colon cancer cells by activating endoplasmic reticulum stress-mediated AMPK/MAPK/XAF1 signaling

    Science.gov (United States)

    Park, Ga Bin; Jeong, Jee-Yeong; Kim, Daejin

    2017-01-01

    Ampelopsin (Amp) is bioactive natural product and exerts anti-cancer effects against several cancer types. The present study investigated the anti-colon cancer activity of Amp and explored its mechanism of action. The treatment of colon cancer cells with Amp resulted in the dose- and time-dependent induction of apoptosis via the activation of endoplasmic reticulum (ER) stress, 5′ adenosine monophosphate-activated protein kinase (AMPK), and c-Jun N-terminal protein kinase (JNK)/p38 mitogen-activated protein kinases (MAPKs). Salubrinal, an ER stress inhibitor, prevented the upregulation of ER stress-associated proteins, including phosphorylated protein kinase RNA-like ER kinase, phosphorylated eukaryotic translation initiation factor 2α, glucose-regulated protein 78, and CCAAT/enhancer-binding protein homologous protein, as well as suppressing AMPK activation and the MAPK signaling pathway. Knockdown of AMPK by RNA interference failed to block ER stress. Additionally, SP600125 (a JNK inhibitor) and SB203580 (a p38-MAPK inhibitor) effectively inhibited apoptosis and attenuated the expression of X-linked IAP-associated factor 1 (XAF1) and apoptotic Bcl-2 family proteins (BCL2 antagonist/killer 1 and BCL2-associated X protein) in Amp-treated colon cancer cells. Furthermore, reactive oxygen species (ROS)-mediated ER stress/AMPK apoptotic signaling pathway in Amp-treated colon cancer cells were markedly inhibited by treatment with N-acetyl-L-cysteine, a ROS scavenger. These results demonstrate that treatment with Amp induces the apoptotic death of colon cancer cells through ER stress-initiated AMPK/MAPK/XAF1 signaling. These results also provide experimental information for developing Amp as therapeutic drug against colon cancer. PMID:29250183

  3. The mechanism of Intralipid®-mediated cardioprotection complex IV inhibition by the active metabolite, palmitoylcarnitine, generates reactive oxygen species and activates reperfusion injury salvage kinases.

    Directory of Open Access Journals (Sweden)

    Phing-How Lou

    Full Text Available Intralipid® administration at reperfusion elicits protection against myocardial ischemia-reperfusion injury. However, the underlying mechanisms are not fully understood.Sprague-Dawley rat hearts were exposed to 15 min of ischemia and 30 min of reperfusion in the absence or presence of Intralipid® 1% administered at the onset of reperfusion. In separate experiments, the reactive oxygen species (ROS scavenger N-(2-mercaptopropionyl-glycine was added either alone or with Intralipid®. Left ventricular work and activation of Akt, STAT3, and ERK1/2 were used to evaluate cardioprotection. ROS production was assessed by measuring the loss of aconitase activity and the release of hydrogen peroxide using Amplex Red. Electron transport chain complex activities and proton leak were measured by high-resolution respirometry in permeabilized cardiac fibers. Titration experiments using the fatty acid intermediates of Intralipid® palmitoyl-, oleoyl- and linoleoylcarnitine served to determine concentration-dependent inhibition of complex IV activity and mitochondrial ROS release.Intralipid® enhanced postischemic recovery and activated Akt and Erk1/2, effects that were abolished by the ROS scavenger N-(2-mercaptopropionylglycine. Palmitoylcarnitine and linoleoylcarnitine, but not oleoylcarnitine concentration-dependently inhibited complex IV. Only palmitoylcarnitine reached high tissue concentrations during early reperfusion and generated significant ROS by complex IV inhibition. Palmitoylcarnitine (1 µM, administered at reperfusion, also fully mimicked Intralipid®-mediated protection in an N-(2-mercaptopropionyl-glycine -dependent manner.Our data describe a new mechanism of postconditioning cardioprotection by the clinically available fat emulsion, Intralipid®. Protection is elicited by the fatty acid intermediate palmitoylcarnitine, and involves inhibition of complex IV, an increase in ROS production and activation of the RISK pathway.

  4. Linking hydrogen-mediated boron toxicity tolerance with improvement of root elongation, water status and reactive oxygen species balance: a case study for rice.

    Science.gov (United States)

    Wang, Yu; Duan, Xingliang; Xu, Sheng; Wang, Ren; Ouyang, Zhaozeng; Shen, Wenbiao

    2016-12-01

    Boron is essential for plant growth but hazardous when present in excess. As the antioxidant properties of hydrogen gas (H 2 ) were recently described in plants, oxidative stress induced by excess boron was investigated along with other biological responses during rice (Oryza sativa) seed germination to study the beneficial role of H 2 METHODS: Rice seeds were pretreated with exogenous H 2 Using physiological, pharmacological and molecular approaches, the production of endogenous H 2 , growth status, reactive oxygen species (ROS) balance and relative gene expression in rice were measured under boron stress to investigate mechanisms of H 2 -mediated boron toxicity tolerance. In our test, boron-inhibited seed germination and seedling growth, and endogenous H 2 production, were obviously blocked by exogenously applying H 2 The re-establishment of ROS balance was confirmed by reduced lipid peroxidation and ROS accumulation. Meanwhile, activities of catalase (CAT) and peroxidase (POX) were increased. Suppression of pectin methylesterase (PME) activity and downregulation of PME transcripts by H 2 were consistent with the alleviation of root growth inhibition caused by boron. Water status was improved as well. This result was confirmed by the upregulation of genes encoding specific aquaporins (AQPs), the maintenance of low osmotic potential and high content of soluble sugar. Increased transcription of representative AQP genes (PIP2;7 in particular) and BOR2 along with decreased BOR1 mRNA may contribute to lowering boron accumulation. Hydrogen provides boron toxicity tolerance mainly by improving root elongation, water status and ROS balance. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Mitochondrial DNA deletion and impairment of mitochondrial biogenesis are mediated by reactive oxygen species in ionizing radiation-induced premature senescence

    International Nuclear Information System (INIS)

    Eom, Hyeon Soo; Jung, U Hee; Jo, Sung Kee; Kim, Young Sang

    2011-01-01

    Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging, and contributes to harmful effects in cultured cells and animal tissues. mtDNA biogenesis genes (NRF-1, TFAM) are essential for the maintenance of mtDNA, as well as the transcription and replication of mitochondrial genomes. Considering that oxidative stress is known to affect mitochondrial biogenesis, we hypothesized that ionizing radiation (IR)-induced reactive oxygen species (ROS) causes mtDNA deletion by modulating the mitochondrial biogenesis, thereby leading to cellular senescence. Therefore, we examined the effects of IR on ROS levels, cellular senescence, mitochondrial biogenesis, and mtDNA deletion in IMR-90 human lung fibroblast cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated at 4 or 8 Gy. Old cells at PD55, and H2O2-treated young cells at PD 39, were compared as a positive control. The IR increased the intracellular ROS level, senescence-associated β-galactosidase (SA-β-gal) activity, and mtDNA common deletion (4977 bp), and it decreased the mRNA expression of NRF-1 and TFAM in IMR-90 cells. Similar results were also observed in old cells (PD 55) and H 2 O 2 -treated young cells. To confirm that a increase in ROS level is essential for mtDNA deletion and changes of mitochondrial biogenesis in irradiated cells, the effects of N-acetylcysteine (NAC) were examined. In irradiated and H 2 O 2 -treated cells, 5 mM NAC significantly attenuated the increases of ROS, mtDNA deletion, and SA-β-gal activity, and recovered from decreased expressions of NRF-1 and TFAM mRNA. These results suggest that ROS is a key cause of IR-induced mtDNA deletion, and the suppression of the mitochondrial biogenesis gene may mediate this process.

  6. Mitochondrial DNA deletion and impairment of mitochondrial biogenesis are mediated by reactive oxygen species in ionizing radiation-induced premature senescence

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Hyeon Soo; Jung, U Hee; Jo, Sung Kee [Radiation Biotechnology Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Young Sang [College of Natural Sciences, Chungnam National University, Daejeon (Korea, Republic of)

    2011-09-15

    Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging, and contributes to harmful effects in cultured cells and animal tissues. mtDNA biogenesis genes (NRF-1, TFAM) are essential for the maintenance of mtDNA, as well as the transcription and replication of mitochondrial genomes. Considering that oxidative stress is known to affect mitochondrial biogenesis, we hypothesized that ionizing radiation (IR)-induced reactive oxygen species (ROS) causes mtDNA deletion by modulating the mitochondrial biogenesis, thereby leading to cellular senescence. Therefore, we examined the effects of IR on ROS levels, cellular senescence, mitochondrial biogenesis, and mtDNA deletion in IMR-90 human lung fibroblast cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated at 4 or 8 Gy. Old cells at PD55, and H2O2-treated young cells at PD 39, were compared as a positive control. The IR increased the intracellular ROS level, senescence-associated {beta}-galactosidase (SA-{beta}-gal) activity, and mtDNA common deletion (4977 bp), and it decreased the mRNA expression of NRF-1 and TFAM in IMR-90 cells. Similar results were also observed in old cells (PD 55) and H{sub 2}O{sub 2}-treated young cells. To confirm that a increase in ROS level is essential for mtDNA deletion and changes of mitochondrial biogenesis in irradiated cells, the effects of N-acetylcysteine (NAC) were examined. In irradiated and H{sub 2}O{sub 2}-treated cells, 5 mM NAC significantly attenuated the increases of ROS, mtDNA deletion, and SA-{beta}-gal activity, and recovered from decreased expressions of NRF-1 and TFAM mRNA. These results suggest that ROS is a key cause of IR-induced mtDNA deletion, and the suppression of the mitochondrial biogenesis gene may mediate this process.

  7. The impact of early shame memories in Binge Eating Disorder: The mediator effect of current body image shame and cognitive fusion.

    Science.gov (United States)

    Duarte, Cristiana; Pinto-Gouveia, José

    2017-12-01

    This study examined the phenomenology of shame experiences from childhood and adolescence in a sample of women with Binge Eating Disorder. Moreover, a path analysis was investigated testing whether the association between shame-related memories which are traumatic and central to identity, and binge eating symptoms' severity, is mediated by current external shame, body image shame and body image cognitive fusion. Participants in this study were 114 patients, who were assessed through the Eating Disorder Examination and the Shame Experiences Interview, and through self-report measures of external shame, body image shame, body image cognitive fusion and binge eating symptoms. Shame experiences where physical appearance was negatively commented or criticized by others were the most frequently recalled. A path analysis showed a good fit between the hypothesised mediational model and the data. The traumatic and centrality qualities of shame-related memories predicted current external shame, especially body image shame. Current shame feelings were associated with body image cognitive fusion, which, in turn, predicted levels of binge eating symptomatology. Findings support the relevance of addressing early shame-related memories and negative affective and self-evaluative experiences, namely related to body image, in the understanding and management of binge eating. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Associations of Early- and Later-Childhood Poverty With Child Cognitive Function in Indonesia: Effect Decomposition in the Presence of Exposure-Induced Mediator-Outcome Confounding.

    Science.gov (United States)

    Maika, Amelia; Mittinty, Murthy N; Brinkman, Sally; Lynch, John

    2017-05-15

    The amount of family financial resources available in early life influences child health and development. Using data from the 2000 and 2007 waves of the Indonesian Family Life Survey, we estimated the associations of early-life poverty (at age early intervention to support household income has a larger effect than intervention later in childhood; both seemed equally important. We also decomposed the effect of poverty at age child cognitive function at age 7-14 years (i.e., joint mediators β = -0.07, 95% confidence interval: -0.12, -0.02) than the indirect effects mediated through later poverty at age 7-14 years (β = -0.01, 95% confidence interval: -0.04, 0.01) and school attendance/home environment at age 7-14 years. The effect of poverty on cognitive function was small; nevertheless, financial intervention may still benefit children's cognitive function. © The Author 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.

  9. Changes in Frontal EEG Coherence across Infancy Predict Cognitive Abilities at Age 3: The Mediating Role of Attentional Control

    Science.gov (United States)

    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…

  10. Can individual conditions during childhood mediate or moderate the long-term cognitive effects of poor economic environments at birth?

    NARCIS (Netherlands)

    Fritze, T.; Doblhammer, G.; van den Berg, G.J.

    2014-01-01

    Recent analyses revealed that the business cycle at the time of birth influences cognitive functioning at older ages, and that those individuals born during economic boom periods on average display better cognitive functioning later in life. The current study examines the impact of childhood

  11. Alcohol-specific parenting, adolescent alcohol use and the mediating effect of adolescent alcohol-related cognitions

    NARCIS (Netherlands)

    Mares, S.H.W.; Lichtwarck-Aschoff, A.; Engels, R.C.M.E.

    2013-01-01

    Objectives : Previous research indicated that alcohol-specific parenting is an important precursor of adolescent alcohol use, but failed to define the underlying mechanism. Based on social cognitive theory, alcohol-related cognitions such as alcohol refusal self-efficacy and alcohol-related

  12. Life course socioeconomic position and C-reactive protein: mediating role of health-risk behaviors and metabolic alterations. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil.

    Directory of Open Access Journals (Sweden)

    Lidyane V Camelo

    Full Text Available BACKGROUND: Chronic inflammation has been postulated to be one mediating mechanism explaining the association between low socioeconomic position (SEP and cardiovascular disease (CVD. We sought to examine the association between life course SEP and C-reactive protein (CRP levels in adulthood, and to evaluate the extent to which health-risk behaviors and metabolic alterations mediate this association. Additionally, we explored the possible modifying influence of gender. METHODS AND FINDINGS: Our analytical sample comprised 13,371 participants from ELSA-Brasil baseline, a multicenter prospective cohort study of civil servants. SEP during childhood, young adulthood, and adulthood were considered. The potential mediators between life course SEP and CRP included clusters of health-risk behaviors (smoking, low leisure time physical activity, excessive alcohol consumption, and metabolic alterations (obesity, hypertension, low HDL, hypertriglyceridemia, and diabetes. Linear regression models were performed and structural equation modeling was used to evaluate mediation. Although lower childhood SEP was associated with higher levels of CRP in adult life, this association was not independent of adulthood SEP. However, CRP increased linearly with increasing number of unfavorable social circumstances during the life course (p trend <0.001. The metabolic alterations were the most important mediator between cumulative SEP and CRP. This mediation path accounted for 49.5% of the total effect of cumulative SEP on CRP among women, but only 20.2% among men. In consequence, the portion of the total effect of cumulative SEP on CRP that was mediated by risk behaviors and metabolic alterations was higher among women (55.4% than among men (36.8%. CONCLUSIONS: Cumulative SEP across life span was associated with elevated systemic inflammation in adulthood. Although health-risk behaviors and metabolic alterations were important mediators of this association, a sizable

  13. γ-Oryzanol suppresses COX-2 expression by inhibiting reactive oxygen species-mediated Erk1/2 and Egr-1 signaling in LPS-stimulated RAW264.7 macrophages.

    Science.gov (United States)

    Shin, Soon Young; Kim, Heon-Woong; Jang, Hwan-Hee; Hwang, Yu-Jin; Choe, Jeong-Sook; Kim, Jung-Bong; Lim, Yoongho; Lee, Young Han

    2017-09-16

    Cyclooxygenase (COX)-2 produces prostanoids, which contribute to inflammatory responses. Nuclear factor (NF)-κB is a key transcription factor mediating COX-2 expression. γ-Oryzanol is an active component in rice bran oil, which inhibits lipopolysaccharide (LPS)-mediated COX-2 expression by inhibiting NF-κB. However, the inhibition of COX-2 expression by γ-oryzanol independently of NF-κB is poorly understood. We found that LPS upregulated Egr-1 expression at the transcriptional level. Forced expression of Egr-1 trans-activated the Cox-2 promoter independently of NF-κB. In contrast, silencing of Egr-1 abrogated LPS-mediated COX-2 expression. LPS produced reactive oxygen species (ROS), which, in turn, induced Egr-1 expression via the Erk1/2 MAPK pathway. ROS scavenging activity of γ-oryzanol suppressed Egr-1 expression by inhibiting the Erk1/2 MAPK pathway. Our results suggest that γ-oryzanol inhibits LPS-mediated COX-2 expression by suppressing Erk1/2-mediated Egr-1 expression. This study supports that γ-oryzanol may be useful for ameliorating LPS-mediated inflammatory responses. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Work Stress and Depressive Symptoms in Fishermen With a Smoking Habit: A Mediator Role of Nicotine Dependence and Possible Moderator Role of Expressive Suppression and Cognitive Reappraisal.

    Science.gov (United States)

    Jiang, Hongjuan; Li, Sailan; Yang, Juan

    2018-01-01

    This study examined pathways of influence between work stress, depressive symptoms, nicotine dependence, expressive suppression, and cognitive reappraisal in fishermen with smoking habits in Qionghai, Hainan province, China (N = 1068). These fishermen responded to multiple assessments a week before leaving on a deep-sea fishing trip, including a Mental Stressor Investigation Questionnaire (MSIQ), the Center for Epidemiological Studies Depression Scale (CES-D), the Russell Reason for Smoking Questionnaire (RRSQ), and an Emotion Regulation Questionnaire (ERQ). Structural equation modeling (SEM) analyses of the collected data in Mplus 7 showed that work stress and nicotine dependence were independent predictors of depressive symptoms. The relationship between work stress and depressive symptoms was found to be partially mediated by nicotine dependence and be moderated by cognitive reappraisal. The evidence suggests it advantageous to examine the need of work stress, nicotine dependence, and cognitive reappraisal when attempting to understand depressive symptoms in fishermen with a smoking habit. These findings suggest that improving nicotine dependence through work stress management and training in cognitive reappraisal could be utilized as effective modalities for improving depressive symptoms.

  15. Psychological mediators related to clinical outcome in cognitive behavioural therapy for coronary heart disease: A sub-analysis from the SUPRIM trial.

    Science.gov (United States)

    Norlund, Fredrika; Olsson, Erik Mg; Pingel, Ronnie; Held, Claes; Svärdsudd, Kurt; Gulliksson, Mats; Burell, Gunilla

    2017-06-01

    Background The Secondary Prevention in Uppsala Primary Healthcare Project (SUPRIM) was a randomized controlled trial of a group-based cognitive behavioural therapy stress management programme for patients with coronary heart disease. The project was successful in reducing the risk of fatal or non-fatal first recurrent cardiovascular events. The aim of this study was to analyse the effect of cognitive behavioural therapy on self-rated stress, somatic anxiety, vital exhaustion and depression and to study the associations of these factors with the reduction in cardiovascular events. Methods A total of 362 patients were randomly assigned to intervention or usual care groups. The psychological outcomes were assessed five times during 24 months and analysed using linear mixed models. The mediating roles of the outcomes were analysed using joint modelling of the longitudinal and time to event data. Results The intervention had a positive effect on somatic anxiety ( p < 0.05), reflecting a beneficial development over time compared with the controls. Stress, vital exhaustion and depression did not differ between the groups over time. Mediator analysis suggested that somatic anxiety may have mediated the effect of treatment on cardiovascular events. Conclusions The intervention had a small positive effect on somatic anxiety, but did not affect stress, vital exhaustion or depression in patients with coronary heart disease. Somatic anxiety was associated with an increased risk of cardiovascular events and might act as a partial mediator in the treatment effect on cardiovascular events. However, the mechanisms between the intervention and the protective cardiovascular outcome remain to be identified.

  16. Effects of The Coach Approach Intervention on Adherence to Exercise in Obese Women: Assessing Mediation of Social Cognitive Theory Factors

    Science.gov (United States)

    Annesi, James J.; Unruh, Jennifer L.; Marti, C. Nathan; Gorjala, Srinivasa; Tennant, Gisele

    2011-01-01

    The link between physical activity and weight loss has precipitated interest in interventions to foster adherence to exercise. It has been suggested that treatment effects, when significant, should be analyzed to determine theory-based mediators. This research assessed possible mediation of changes in Physical Self-Concept, Exercise Self-Efficacy,…

  17. Stress, Psychosocial Mediators, and Cognitive Mediators in Parents of Child Cancer Patients and Cancer Survivors: Attention and Working Memory Pathway Perspectives.

    Science.gov (United States)

    Vander Haegen, Marie; Luminet, Olivier

    2015-01-01

    This review examines stress and its consequences on attention and working memory, stress symptoms in parents of child cancer patients and survivors and long-term consequences of stress on cognitive processing in parents of child cancer survivors. Eligible studies were experimental, meta-analyses, and qualitative (2000-2013) from Pubmed, Medline, the Cochrane Library, PsycArticles, and Google Scholar. We identified 92 eligible papers. They showed that elevated stress can impede performances on tasks requiring attention and memory patterns. In pediatric oncology, parental stress increased shortly after diagnosis involving depression and anxiety. Consequences of stress on cognitive performances were observed mainly among depressed individuals. As regards parents of child cancer survivors, female gender, low Socioeconomic Status (SES), and innate traits of anxiety/anger predicted the development of PTSS. Evidence of stress on attention and working memory processes in parents of child cancer survivors is insufficiently developed.

  18. Non-cognitive development in infancy: the influence of maternal employment and the mediating role of childcare

    OpenAIRE

    McDonnell, Thérèse

    2016-01-01

    This paper examines the relationship between maternal employment during infancy and the non-cognitive development of pre-school children. Noncognitive skills such as self-control, emotional regulation, empathy and patience are at least as important as cognitive skills for personal development and later labour market success. Drawing on recent advances in the economics literature on the theory of skill formation, this study uses data on Irish pre-school children (Growing Up in Ireland, Infant ...

  19. Fear, Negative Cognition, and Depression Mediate the Relationship Between Traumatic Exposure and Sleep Problems Among Flood Victims in China.

    Science.gov (United States)

    Zhen, Rui; Quan, Lijuan; Zhou, Xiao

    2017-10-09

    To examine the prerequisites of sleep problems among a traumatized population, and assess the underlying mechanisms of sleep problems following trauma. The current study investigated 187 flood victims from 5 makeshift shelters in the Wuhu city of Anhui province after a major flood disaster that occurred in July 2016. A traumatic exposure questionnaire, a fear questionnaire, a posttraumatic cognition inventory, a depression inventory, and a sleep problems questionnaire were used. Traumatic exposure had a direct and positive association with sleep problems and could also be indirectly associated with sleep problems through fear, depression, but not negative cognitions. The positive association could be the result of a path from negative cognitions to depression, but not from fear to negative cognition, or from fear to depression. Furthermore, a threefold multipath from fear to depression via negative cognitions could also link traumatic exposure to sleep problems. Flood victims' sleep problems are elicited by the combined role of fear, negative cognitions, and depression following trauma. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. Stress and Sleep Reactivity: A Prospective Investigation of the Stress-Diathesis Model of Insomnia

    Science.gov (United States)

    Drake, Christopher L.; Pillai, Vivek; Roth, Thomas

    2014-01-01

    Study Objectives: To prospectively assess sleep reactivity as a diathesis of insomnia, and to delineate the interaction between this diathesis and naturalistic stress in the development of insomnia among normal sleepers. Design: Longitudinal. Setting: Community-based. Participants: 2,316 adults from the Evolution of Pathways to Insomnia Cohort (EPIC) with no history of insomnia or depression (46.8 ± 13.2 y; 60% female). Interventions: None. Measurements and Results: Participants reported the number of stressful events they encountered at baseline (Time 1), as well as the level of cognitive intrusion they experienced in response to each stressor. Stressful events (OR = 1.13; P insomnia one year hence (Time 2). Intrusion mediated the effects of stressful events on risk for insomnia (P insomnia (OR = 1.78; P insomnia as a function of intrusion was significantly higher in individuals with high sleep reactivity. Trait sleep reactivity also constituted a significant risk for depression (OR = 1.67; P Insomnia at Time 2 significantly mediated this effect (P insomnia, and that it triggers insomnia by exacerbating the effects of stress-induced intrusion. Sleep reactivity is also a precipitant of depression, as mediated by insomnia. These findings support the stress-diathesis model of insomnia, while highlighting sleep reactivity as an important diathesis. Citation: Drake CL, Pillai V, Roth T. Stress and sleep reactivity: a prospective investigation of the stress-diathesis model of insomnia. SLEEP 2014;37(8):1295-1304. PMID:25083009

  1. Development of personal narratives as a mediator of the impact of deficits in social cognition and social withdrawal on negative symptoms in schizophrenia.

    Science.gov (United States)

    Lysaker, Paul H; Erikson, Molly; Macapagal, Kathryn R; Tunze, Chloe; Gilmore, Emily; Ringer, Jamie M

    2012-04-01

    Although negative symptoms are a barrier to recovery from schizophrenia, little is understood about the psychological processes that reinforce and sustain them. To explore this issue, this study used structural equation modeling to test whether the impact of social withdrawal and emotion recognition deficits upon negative symptoms is mediated by the richness or poverty of personal narratives. The participants were 99 adults with schizophrenia spectrum disorders. Social cognition was assessed using the Bell-Lysaker Emotional Recognition Task; social withdrawal, using the Quality of Life Scale; narrative coherence, using the Scale To Assess Narrative Development; and negative symptoms, using the Positive and Negative Syndrome Scale. The findings reveal that although social cognition deficits and social withdrawal are significantly associated with negative symptom severity, these relationships become nonsignificant when personal narrative integrity is examined as a mediating factor. These results indicate that the development of personal narratives may be directly linked to the severity of negative symptoms; this construct may be a useful target for future interventions.

  2. [Which route leads from chronic back pain to depression? A path analysis on direct and indirect effects using the cognitive mediators catastrophizing and helplessness/hopelessness in a general population sample].

    Science.gov (United States)

    Fahland, R A; Kohlmann, T; Hasenbring, M; Feng, Y-S; Schmidt, C O

    2012-12-01

    Chronic pain and depression are highly comorbid; however, the longitudinal link is only partially understood. This study examined direct and indirect effects of chronic back pain on depression using path analysis in a general population sample, focussing on cognitive mediator variables. Analyses are based on 413 participants (aged 18-75 years) in a population-based postal survey on back pain who reported chronic back pain at baseline. Follow-up data were collected after 1 year. Depression was measured with the Center for Epidemiologic Studies Depression Scale (CES-D). Fear-avoidance-beliefs (FABQ), catastrophizing and helplessness/hopelessness (KRSS) were considered as cognitive mediators. Data were analyzed using path analysis. Chronic back pain had no direct effect on depression at follow-up when controlling for cognitive mediators. A mediating effect emerged for helplessness/hopelessness but not for catastrophizing or fear-avoidance beliefs. These results support the cognitive mediation hypothesis which assumes that psychological variables mediate the association between pain and depression. The importance of helplessness/hopelessness is of relevance for the treatment of patients with chronic back pain.

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

    Science.gov (United States)

    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.

  4. Post-Traumatic Cognition Mediates the Relationship between a History of Sexual Abuse and the Post-Traumatic Stress Symptoms in Sexual Assault Victims.

    Science.gov (United States)

    Shin, Kyoung Min; Chung, Young Ki; Shin, Yee Jin; Kim, Miran; Kim, Nam Hee; Kim, Kyoung Ah; Lee, Hanbyul; Chang, Hyoung Yoon

    2017-10-01

    More than half of all sexual assault victims report experiencing sexual victimization more than once. The aim of this paper was to determine the role post-traumatic cognition plays in the relationship between a history of sexual abuse and post-traumatic stress symptoms in sexual assault victims. The relationship between a history of sexual assault and the severity of post-traumatic stress symptoms was investigated retrospectively using data from a sexual assault crisis center in Korea. Data on psychological symptoms were collected in person at the initial assessment and by telephone 1 month later using the Post-traumatic Cognitions Inventory and the Post-traumatic Stress Disorder Symptoms Scale: Self-report Version. Of 105 women included in the analysis, 10 (9.5%) reported prior sexual abuse and were classified as sexually revictimized. Revictimized women had more post-traumatic negative cognition at initial assessment (t = -2.98; P = 0.004) and more post-traumatic symptoms at 1 month follow-up (t = -2.39; P = 0.019) than singly victimized women. At 1 month follow-up, the severity of post-traumatic stress symptoms had increased in revictimized women but had decreased slightly in singly victimized women. Negative post-traumatic cognition fully mediated the association between a history of sexual abuse and the severity of post-traumatic stress symptoms. Early detection of sexually revictimized women and tailored service and treatment intervention is needed to better serve this group of victims. Interventions targeted at preventing revictimization or post crime victimization may also help victims recover from the trauma and prevent future abuse. © 2017 The Korean Academy of Medical Sciences.

  5. Post-Traumatic Cognition Mediates the Relationship between a History of Sexual Abuse and the Post-Traumatic Stress Symptoms in Sexual Assault Victims

    Science.gov (United States)

    2017-01-01

    More than half of all sexual assault victims report experiencing sexual victimization more than once. The aim of this paper was to determine the role post-traumatic cognition plays in the relationship between a history of sexual abuse and post-traumatic stress symptoms in sexual assault victims. The relationship between a history of sexual assault and the severity of post-traumatic stress symptoms was investigated retrospectively using data from a sexual assault crisis center in Korea. Data on psychological symptoms were collected in person at the initial assessment and by telephone 1 month later using the Post-traumatic Cognitions Inventory and the Post-traumatic Stress Disorder Symptoms Scale: Self-report Version. Of 105 women included in the analysis, 10 (9.5%) reported prior sexual abuse and were classified as sexually revictimized. Revictimized women had more post-traumatic negative cognition at initial assessment (t = −2.98; P = 0.004) and more post-traumatic symptoms at 1 month follow-up (t = −2.39; P = 0.019) than singly victimized women. At 1 month follow-up, the severity of post-traumatic stress symptoms had increased in revictimized women but had decreased slightly in singly victimized women. Negative post-traumatic cognition fully mediated the association between a history of sexual abuse and the severity of post-traumatic stress symptoms. Early detection of sexually revictimized women and tailored service and treatment intervention is needed to better serve this group of victims. Interventions targeted at preventing revictimization or post crime victimization may also help victims recover from the trauma and prevent future abuse. PMID:28875614

  6. Sensitivity to cognitive effort mediates psychostimulant effects on a novel rodent cost/benefit decision-making task.

    Science.gov (United States)

    Cocker, Paul J; Hosking, Jay G; Benoit, James; Winstanley, Catharine A

    2012-07-01

    Amotivational states and insufficient recruitment of mental effort have been observed in a variety of clinical populations, including depression, traumatic brain injury, post-traumatic stress disorder, and attention deficit hyperactivity disorder. Previous rodent models of effort-based decision making have utilized physical costs whereas human studies of effort are primarily cognitive in nature, and it is unclear whether the two types of effortful decision making are underpinned by the same neurobiological processes. We therefore designed a novel rat cognitive effort task (rCET) based on the 5-choice serial reaction time task, a well-validated measure of attention and impulsivity. Within each trial of the rCET, rats are given the choice between an easy or hard visuospatial discrimination, and successful hard trials are rewarded with double the number of sugar pellets. Similar to previous human studies, stable individual variation in choice behavior was observed, with 'workers' choosing hard trials significantly more than their 'slacker' counterparts. Whereas workers 'slacked off' in response to administration of amphetamine and caffeine, slackers 'worked harder' under amphetamine, but not caffeine. Conversely, these stimulants increased motor impulsivity in all animals. Ethanol did not affect animals' choice but invigorated behavior. In sum, we have shown for the first time that rats are differentially sensitive to cognitive effort when making decisions, independent of other processes such as impulsivity, and these baseline differences can influence the cognitive response to psychostimulants. Such findings could inform our understanding of impairments in effort-based decision making and contribute to treatment development.

  7. Visual function and cognitive speed of processing mediate age-related decline in memory span and fluid intelligence.

    Science.gov (United States)

    Clay, Olivio J; Edwards, Jerri D; Ross, Lesley A; Okonkwo, Ozioma; Wadley, Virginia G; Roth, David L; Ball, Karlene K

    2009-06-01

    To evaluate the relationship between sensory and cognitive decline, particularly with respect to speed of processing, memory span, and fluid intelligence. In addition, the common cause, sensory degradation and speed of processing hypotheses were compared. Structural equation modeling was used to investigate the complex relationships among age-related decrements in these areas. Cross-sectional data analyses included 842 older adult participants (M = 73 years). After accounting for age-related declines in vision and processing speed, the direct associations between age and memory span and between age and fluid intelligence were nonsignificant. Older age was associated with visual decline, which was associated with slower speed of processing, which in turn was associated with greater cognitive deficits. The findings support both the sensory degradation and speed of processing accounts of age-related, cognitive decline. Furthermore, the findings highlight positive aspects of normal cognitive aging in that older age may not be associated with a loss of fluid intelligence if visual sensory functioning and processing speed can be maintained.

  8. Processes of Change in Acceptance and Commitment Therapy and Cognitive Therapy for Depression: A Mediation Reanalysis of Zettle and Rains

    Science.gov (United States)

    Zettle, Robert D.; Rains, Jeanetta C.; Hayes, Steven C.

    2011-01-01

    Several articles have recently questioned the distinction between acceptance and commitment therapy (ACT) and traditional cognitive therapy (CT). This study presents a reanalysis of data from Zettle and Rains that compared 12 weeks of group CT with group ACT. For theoretical reasons, Zettle and Rains also included a modified form of CT that did…

  9. Different Perspectives of Cultural Mediation: Implications for the Research Design on Studies Examining Its Effect on Students' Cognition

    Science.gov (United States)

    Teo, Tang Wee

    2013-01-01

    In this forum, I extend Tao, Oliver, and Venville's paper "Chinese and Australian children's understanding of the earth: a cross cultural study of conceptual development" to discuss the different views on culture and cultural mediation. I tease out nuances in the viewpoints to suggest three ways to theoretically frame studies examining cultural…

  10. Negative Posttrauma Cognitions Mediate the Association Between Morally Injurious Events and Trauma‐Related Psychopathology in Treatment‐Seeking Veterans

    OpenAIRE

    Held, Philip; Klassen, Brian J.; Zou, Denise S.; Schroedter, Blake S.; Karnik, Niranjan S.; Pollack, Mark H.; Zalta, Alyson K.

    2017-01-01

    Abstract Exposure to potentially morally injurious events has been shown to be associated with posttraumatic stress disorder (PTSD) and depression symptoms in military personnel. Few studies have examined factors that help to explain how potentially morally injurious events may contribute to the development of trauma‐related psychopathology. Negative posttrauma cognitions are thought to play a role in the etiology of PTSD and depression following trauma; however, it is unclear whether more gl...

  11. Client interpersonal impacts as mediators of long-term outcome in cognitive-behavioral therapy integrated with motivational interviewing for generalized anxiety disorder.

    Science.gov (United States)

    Constantino, Michael J; Romano, Felicia M; Coyne, Alice E; Westra, Henny A; Antony, Martin M

    2017-03-24

    A recent trial of generalized anxiety disorder treatment (Westra, H. A., Constantino, M. J., & Antony, M. M. (2016). Integrating Motivational Interviewing With Cognitive-Behavioral Therapy for Severe Generalized Anxiety Disorder: An Allegiance-Controlled Randomized Clinical Trial. Journal of Consulting and Clinical Psychology, 84, 768-782. doi: 10.1037/ccp0000098 ) revealed that cognitive-behavioral therapy (CBT) integrated with motivational interviewing (MI) outperformed CBT alone across a 12-month follow up. The present study examined whether this treatment effect was mediated by MI-CBT clients engaging over time in during-session interpersonal behaviors reflecting more friendly dominance, or agentic actions, and less friendly submissiveness (FS), or trustingly compliant actions both theory-specific MI mechanisms. Clients received 15 sessions of MI-CBT (n = 42) or CBT alone (n = 43). Therapists rated client interpersonal behavior following five sessions, and clients rated their worry at baseline, each session, and 6- and 12-month follow up. Mediator and outcome variables were derived from multilevel models. Mediation was tested using a bootstrapping procedure. There was a significant indirect effect for FS. As expected, CBT clients evidenced greater increases in FS than MI-CBT clients, which in turn, though unexpectedly, related to lower 12-month worry. However, long-term CBT outcomes remained inferior to MI-CBT outcomes even with CBT clients'greater increase in FS. Results suggest that CBT outcomes are more positive when clients trustingly comply; however, MI-CBT remained superior, but for as yet unexplained reasons. Clinical or methodological significance of this article: The findings highlight the clinical importance of GAD clients becoming more friendly dominant in the therapy relationship irrespective of whether they received CBT or integrative MI-CBT. Moreover, it seems clinically indicated to incorporate MI spirit and techniques into CBT when

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

    Science.gov (United States)

    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

  13. How and why affective and reactive virtual agents will bring new insights on social cognitive disorders in schizophrenia? An illustration with a virtual card game paradigm

    Directory of Open Access Journals (Sweden)

    Ali eOker

    2015-03-01

    Full Text Available In recent decades, many studies have shown that schizophrenia is associated with severe social cognitive impairments affecting key components, such as the recognition of emotions, theory of mind, attributional style and metacognition. Most studies investigated each construct separately, precluding analysis of the interactive and immersive nature of real-life situation. Specialized batteries of tests are under investigation to assess social cognition which is thought now as a link between neurocognitive disorders and impaired functioning. However, this link accounts for a limited part of the variance of real life functioning. To fill this gap, advances in virtual reality and affective computing have made it possible to carry out experimental investigations of naturalistic social cognition, in controlled conditions, with good reproducibility. This approach is illustrated with the description of a new paradigm based on an original virtual card game in which subjects interpret emotional displays from a female virtual agent, and decipher her helping intentions. Independent variables concerning emotional expression in terms of valence and intensity were manipulated. We show how several useful dependant variables, ranging from classic experimental psychology data to metacognition or subjective experiences records, may be extracted from a single experiment. Methodological issues about the immersion into a simulated intersubjective situation are considered. The example of this new flexible experimental setting with regards to the many constructs recognized in social neurosciences, constitutes a rationale for focusing on this potential intermediate link between standardized tests and real life functioning, and also for using it as an innovative media for cognitive remediation.

  14. How and why affective and reactive virtual agents will bring new insights on social cognitive disorders in schizophrenia? An illustration with a virtual card game paradigm.

    Science.gov (United States)

    Oker, Ali; Prigent, Elise; Courgeon, Matthieu; Eyharabide, Victoria; Urbach, Mathieu; Bazin, Nadine; Amorim, Michel-Ange; Passerieux, Christine; Martin, Jean-Claude; Brunet-Gouet, Eric

    2015-01-01

    In recent decades, many studies have shown that schizophrenia is associated with severe social cognitive impairments affecting key components, such as the recognition of emotions, theory of mind, attributional style, and metacognition. Most studies investigated each construct separately, precluding analysis of the interactive and immersive nature of real-life situation. Specialized batteries of tests are under investigation to assess social cognition, which is thought now as a link between neurocognitive disorders and impaired functioning. However, this link accounts for a limited part of the variance of real-life functioning. To fill this gap, advances in virtual reality and affective computing have made it possible to carry out experimental investigations of naturalistic social cognition, in controlled conditions, with good reproducibility. This approach is illustrated with the description of a new paradigm based on an original virtual card game in which subjects interpret emotional displays from a female virtual agent, and decipher her helping intentions. Independent variables concerning emotional expression in terms of valence and intensity were manipulated. We show how several useful dependant variables, ranging from classic experimental psychology data to metacognition or subjective experiences records, may be extracted from a single experiment. Methodological issues about the immersion into a simulated intersubjective situation are considered. The example of this new flexible experimental setting, with regards to the many constructs recognized in social neurosciences, constitutes a rationale for focusing on this potential intermediate link between standardized tests and real-life functioning, and also for using it as an innovative media for cognitive remediation.

  15. Poor nutrition at age 3 and schizotypal personality at age 23: the mediating role of age 11 cognitive functioning.

    Science.gov (United States)

    Venables, Peter H; Raine, Adrian

    2012-08-01

    Poor prenatal nutrition has been associated with schizophrenia spectrum disorders in the Netherlands and China, and it has been suggested that perinatal and postnatal nutritional factors lead to the development of schizophrenia and the exhibition of schizotypal traits later in life. There appears to be no prior research on the existence of possible factors that may mediate the relationship between malnutrition and schizophrenia spectrum disorders or whether this association is a direct one. The authors tested the hypothesis that low IQ mediates the relationship between early childhood malnutrition and adult schizotypal personality. Participants were drawn from a birth cohort of 1,795 boys and girls who were followed prospectively. Objective indicators of malnutrition (anemia and stunting) were assessed at age 3. Verbal and performance intelligence were assessed at age 11, and schizotypal personality was assessed at age 23. Both stunting and anemia at age 3 were associated with low IQ at age 11. Low performance IQ at age 11 was associated with increased interpersonal and disorganized features of schizotypal personality at age 23. Poor performance IQ was found to mediate the relationship between poor nutrition at age 3 and interpersonal and disorganized features of schizotypy at age 23. Findings in female participants were replicated in male participants. Given that poor nutrition is an alterable risk factor, these findings suggest that nutritional enhancements may improve brain functioning and possibly reduce some features of schizotypal personality disorder.

  16. Effects of Age and Initial Risk Perception on Balloon Analogue Risk Task: The Mediating Role of Processing Speed and Need for Cognitive Closure

    Directory of Open Access Journals (Sweden)

    Maciej eKoscielniak

    2016-05-01

    Full Text Available According to the dual-process theoretical perspective adopted in the presented research, the efficiency of deliberative processes in decision making declines with age, but experiential processes are relatively well-preserved. The age-related differences in deliberative and experiential processes in risky decision-making were examined in this research by applying the Balloon Analogue Risk Task (BART. We analyzed the influence of age on risk acceptance and decision-making performance in two age groups of female participants (younger adults, n = 81; older adults, n = 76, with additional experimental manipulation of initial risk perception. We predicted and confirmed that aging significantly worsens performance on the behavioral BART measures due to age-related decline in deliberative processes. Older participants were found to exhibit significantly higher risk aversion and lower BART performance, and the effect of age was mediated by cognitive (processing speed and motivational (need for cognitive closure mechanisms. Moreover, older adults adapt to the initial failure (vs. success similarly as younger adults due to preserved efficiency of experiential processes. These results suggest future directions for minimizing negative effects of aging in risky decision-making and indicate compensatory processes, which are preserved during aging.

  17. AAV serotype 2/1-mediated gene delivery of anti-inflammatory interleukin-10 enhances neurogenesis and cognitive function in APP+PS1 mice.

    Science.gov (United States)

    Kiyota, T; Ingraham, K L; Swan, R J; Jacobsen, M T; Andrews, S J; Ikezu, T

    2012-07-01

    Brain inflammation is a double-edged sword. It is required for brain repair in acute damage, whereas chronic inflammation and autoimmune disorders are neuropathogenic. Certain proinflammatory cytokines and chemokines are closely related to cognitive dysfunction and neurodegeneration. Representative anti-inflammatory cytokines, such as interleukin (IL)-10, can suppress neuroinflammation and have significant therapeutic potentials in ameliorating neurodegenerative disorders such as Alzheimer's disease (AD). Here, we show that adeno-associated virus (AAV) serotype 2/1 hybrid-mediated neuronal expression of the mouse IL-10 gene ameliorates cognitive dysfunction in amyloid precursor protein+ presenilin-1 bigenic mice. AAV2/1 infection of hippocampal neurons resulted in sustained expression of IL-10 without its leakage into the blood, reduced astro/microgliosis, enhanced plasma amyloid-β peptide (Aβ) levels and enhanced neurogenesis. Moreover, increased levels of IL-10 improved spatial learning, as determined by the radial arm water maze. Finally, IL-10-stimulated microglia enhanced proliferation but not differentiation of primary neural stem cells in the co-culture system, whereas IL-10 itself had no effect. Our data suggest that IL-10 gene delivery has a therapeutic potential for a non-Aβ-targeted treatment of AD.

  18. Taurine Pretreatment Prevents Isoflurane-Induced Cognitive Impairment by Inhibiting ER Stress-Mediated Activation of Apoptosis Pathways in the Hippocampus in Aged Rats.

    Science.gov (United States)

    Zhang, Yanan; Li, Dongliang; Li, Haiou; Hou, Dailiang; Hou, Jingdong

    2016-10-01

    Isoflurane, a commonly used inhalation anesthetic, may induce neurocognitive deficits, especially in elderly patients after surgery. Recent study demonstrated that isoflurane caused endoplasmic reticulum (ER) stress and subsequent neuronal apoptosis in the brain, contributing to cognitive deficits. Taurine, a major intracellular free amino acid, has been shown to inhibit ER stress and neuronal apoptosis in several neurological disorders. Here, we examined whether taurine can prevent isoflurane-induced ER stress and cognitive impairment in aged rats. Thirty minutes prior to a 4-h 1.3 % isoflurane exposure, aged rats were treated with vehicle or taurine at low, middle and high doses. Aged rats without any treatment served as control. The brains were harvested 6 h after isoflurane exposure for molecular measurements, and behavioral study was performed 2 weeks later. Compared with control, isoflurane increased expression of hippocampal ER stress biomarkers including glucose-regulated protein 78, phosphorylated (P-) inositol-requiring enzyme 1, P-eukaryotic initiation factor 2-α (EIF2α), activating transcription factor 4 (ATF-4), cleaved ATF-6 and C/EBP homologous protein, along with activation of apoptosis pathways as indicated by decreased B cell lymphoma 2 (BCL-2)/BCL2-associated X protein, increased expressions of cytochrome-c and cleaved caspase-3. Taurine pretreatment dose-dependently inhibited isoflurane-induced increase in expression of ER stress biomarkers except for P-EIF2α and ATF-4, and reversed isoflurane-induced changes in apoptosis-related proteins. Moreover, isoflurane caused spatial working memory deficits in aged rats, which were prevented by taurine pretreatment. The results indicate that taurine pretreatment prevents anesthetic isoflurane-induced cognitive impairment by inhibiting ER stress-mediated activation of apoptosis pathways in the hippocampus in aged rats.

  19. Receptor for advanced glycation end products mediates sepsis-triggered amyloid-β accumulation, Tau phosphorylation, and cognitive impairment.

    Science.gov (United States)

    Gasparotto, Juciano; Girardi, Carolina S; Somensi, Nauana; Ribeiro, Camila T; Moreira, José C F; Michels, Monique; Sonai, Beatriz; Rocha, Mariane; Steckert, Amanda V; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe; Gelain, Daniel P

    2018-01-05

    Patients recovering from sepsis have higher rates of CNS morbidities associated with long-lasting impairment of cognitive functions, including neurodegenerative diseases. However, the molecular etiology of these sepsis-induced impairments is unclear. Here, we investigated the role of the receptor for advanced glycation end products (RAGE) in neuroinflammation, neurodegeneration-associated changes, and cognitive dysfunction arising after sepsis recovery. Adult Wistar rats underwent cecal ligation and perforation (CLP), and serum and brain (hippocampus and prefrontal cortex) samples were obtained at days 1, 15, and 30 after the CLP. We examined these samples for systemic and brain inflammation; amyloid-β peptide (Aβ) and Ser-202-phosphorylated Tau (p-Tau Ser-202 ) levels; and RAGE, RAGE ligands, and RAGE intracellular signaling. Serum markers associated with the acute proinflammatory phase of sepsis (TNFα, IL-1β, and IL-6) rapidly increased and then progressively decreased during the 30-day period post-CLP, concomitant with a progressive increase in RAGE ligands (S100B, N ϵ-[carboxymethyl]lysine, HSP70, and HMGB1). In the brain, levels of RAGE and Toll-like receptor 4, glial fibrillary acidic protein and neuronal nitric-oxide synthase, and Aβ and p-Tau Ser-202 also increased during that time. Of note, intracerebral injection of RAGE antibody into the hippocampus at days 15, 17, and 19 post-CLP reduced Aβ and p-Tau Ser-202 accumulation, Akt/mechanistic target of rapamycin signaling, levels of ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein, and behavioral deficits associated with cognitive decline. These results indicate that brain RAGE is an essential factor in the pathogenesis of neurological disorders following acute systemic inflammation. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden

    Directory of Open Access Journals (Sweden)

    Abisambra Jose F

    2010-11-01

    Full Text Available Abstract Background It has traditionally been thought that the pathological accumulation of tau in Alzheimer's disease and other tauopathies facilitates neurodegeneration, which in turn leads to cognitive impairment. However, recent evidence suggests that tau tangles are not the entity responsible for memory loss, rather it is an intermediate tau species that disrupts neuronal function. Thus, efforts to discover therapeutics for tauopathies emphasize soluble tau reductions as well as neuroprotection. Results Here, we found that neuroprotection alone caused by methylene blue (MB, the parent compound of the anti-tau phenothiaziazine drug, Rember™, was insufficient to rescue cognition in a mouse model of the human tauopathy, progressive supranuclear palsy (PSP and fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP17: Only when levels of soluble tau protein were concomitantly reduced by a very high concentration of MB, was cognitive improvement observed. Thus, neurodegeneration can be decoupled from tau accumulation, but phenotypic improvement is only possible when soluble tau levels are also reduced. Conclusions Neuroprotection alone is not sufficient to rescue tau-induced memory loss in a transgenic mouse model. Development of neuroprotective agents is an area of intense investigation in the tauopathy drug discovery field. This may ultimately be an unsuccessful approach if soluble toxic tau intermediates are not also reduced. Thus, MB and related compounds, despite their pleiotropic nature, may be the proverbial "magic bullet" because they not only are neuroprotective, but are also able to facilitate soluble tau clearance. Moreover, this shows that neuroprotection is possible without reducing tau levels. This indicates that there is a definitive molecular link between tau and cell death cascades that can be disrupted.

  1. Single-cell analysis of dihydroartemisinin-induced apoptosis through reactive oxygen species-mediated caspase-8 activation and mitochondrial pathway in ASTC-a-1 cells using fluorescence imaging techniques

    Science.gov (United States)

    Lu, Ying-Ying; Chen, Tong-Sheng; Wang, Xiao-Ping; Li, Li

    2010-07-01

    Dihydroartemisinin (DHA), a front-line antimalarial herbal compound, has been shown to possess promising anticancer activity with low toxicity. We have previously reported that DHA induced caspase-3-dependent apoptosis in human lung adenocarcinoma cells. However, the cellular target and molecular mechanism of DHA-induced apoptosis is still poorly defined. We use confocal fluorescence microscopy imaging, fluorescence resonance energy transfer, and fluorescence recovery after photobleaching techniques to explore the roles of DHA-elicited reactive oxygen species (ROS) in the DHA-induced Bcl-2 family proteins activation, mitochondrial dysfunction, caspase cascade, and cell death. Cell Counting Kit-8 assay and flow cytometry analysis showed that DHA induced ROS-mediated apoptosis. Confocal imaging analysis in a single living cell and Western blot assay showed that DHA triggered ROS-dependent Bax translocation, mitochondrial membrane depolarization, alteration of mitochondrial morphology, cytochrome c release, caspase-9, caspase-8, and caspase-3 activation, indicating the coexistence of ROS-mediated mitochondrial and death receptor pathway. Collectively, our findings demonstrate for the first time that DHA induces cell apoptosis by triggering ROS-mediated caspase-8/Bid activation and the mitochondrial pathway, which provides some novel insights into the application of DHA as a potential anticancer drug and a new therapeutic strategy by targeting ROS signaling in lung adenocarcinoma therapy in the future.

  2. The mediating role of social support, cognitive appraisal, and quality health care in black mothers' stress-resilience process following loss to gun violence.

    Science.gov (United States)

    Bailey, Annette; Sharma, Manoj; Jubin, Michelle

    2013-01-01

    Although much attention has been granted to the perpetrators and victims of gun violence, limitations exist in our understanding of the psychological well-being of parents grieving children lost to gun violence. The purpose of this study was to examine the mediating effects of social support, cognitive appraisal, and quality health care on the relationship between traumatic stress and resilience among Black mothers bereaving children to gun violence. A cross-sectional design and network sampling method were used to recruit 48 Black mothers living in a large Canadian city. Participants completed a survey either by phone or in person. Social support and positive appraisal were found to be protective factors of resilience for study participants. The traumatic stress experienced by the sample decreased with increased social support (beta = -.291, p = .045), leading to an increase of their resilience (beta = .297, p = .032). With positive appraisal of the loss, the stress levels of study participants decreased (beta = -.334, p = .023), leading to increased resilience (beta = .441, p = .003). Quality health care showed a significant positive relationship with the resilience of the women (beta = .313, p = .023) but did not mediate the relationship between their stress and resilience. For Black mothers who experience loss of a child to gun violence, policy and social change efforts should focus on strengthening their access to formal and informal supports and improving their abilities to find meaning in their loss.

  3. Common sense model of mental illness: Understanding the impact of cognitive and emotional representations of mental illness on recovery through the mediation of self-stigma.

    Science.gov (United States)

    Chan, Randolph C H; Mak, Winnie W S

    2016-12-30

    The present study applied the common sense model to understand the underlying mechanism of how cognitive and emotional representations of mental illness among people in recovery of mental illness would impact their endorsement of self-stigma, and how that would, in turn, affect clinical and personal recovery. A cross-sectional survey was administered to 376 people in recovery. Participants were recruited from seven public specialty outpatient clinics and substance abuse assessment clinics across various districts in Hong Kong. They were asked to report their perception towards their mental illness, self-stigma, symptom severity, and personal recovery. The results of structural equation modeling partially supported the hypothesized mediation model indicating that controllability, consequences, and emotional concern of mental illness, but not cause, timeline, and identity, were associated with self-stigma, which was subsequently negatively associated with clinical and personal recovery. The present study demonstrated the mediating role of self-stigma in the relationship between individuals' illness representations towards their mental illness and their recovery. Illness management programs aimed at addressing the maladaptive mental illness-related beliefs and emotions are recommended. Implications on developing self-directed and empowering mental health services are discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Cooking birch pollen-related food: divergent consequences for IgE- and T cell-mediated reactivity in vitro and in vivo

    NARCIS (Netherlands)

    Bohle, Barbara; Zwölfer, Bettina; Heratizadeh, Annice; Jahn-Schmid, Beatrice; Antonia, Yuliya Dall; Alter, Mareike; Keller, Walter; Zuidmeer, Laurian; van Ree, Ronald; Werfel, Thomas; Ebner, Christof

    2006-01-01

    BACKGROUND: The major birch pollen allergen Bet v 1 cross-reacts with homologous food allergens, resulting in IgE-mediated oral allergy syndromes (OASs). To avoid this food, allergy allergologists and guidebooks advise patients to consume birch pollen-related foods after heating. OBJECTIVE: We

  5. Health enhancing coping as a mediator in relationships of positive emotionality and cognitive curiosity with quality of life among type 2 diabetes patients

    Directory of Open Access Journals (Sweden)

    Kalka Dorota

    2015-09-01

    Full Text Available The number of people suffering from type 2 diabetes has been growing recently. This chronic disease is connected with lower perceived quality of life and experiencing a lot of stressful situations. Some of these situations can be anticipated. Thus, it is possible to prepare oneself for future difficult situations by using proactive coping strategies. The aim of this research was to verify the level of satisfaction with various areas of life, the frequency of use of proactive coping strategies in the case of type 2 diabetes patients and healthy individuals, as well as mediation role of these strategies in the relationship between positive emotionality, cognitive curiosity and perceived quality of life. One hundred and seventy four persons took part in the research: 85 persons with diabetes and 89 healthy individuals. We used instruments with recognized psychometric properties: The Proactive Coping Inventory, The World Health Organization Quality of Life Instrument-BREF, PANAS Questionnaire and State-Trait Personality Inventory. The analysis of the results showed, among other things, that people suffering from type 2 diabetes are the least satisfied with their health, and the most with their treatment and knowledge about the disease. Healthy individuals are the most satisfied with the physical domain and one’s present life, whereas the least satisfied with the environmental domain. Both groups differ in terms of using proactive coping strategies. People with diabetes most often adopt a preventive strategy, whereas healthy individuals a reflective one. Two strategies turned out to be able to mediate in the relationship of positive emotionality and life satisfaction in the diabetes group. It was a strictly proactive and preventive coping strategy. No mediation effect was found in the group of healthy people. The results show that in the face of anticipated difficulties, people with type 2 diabetes try to protect their current resources by

  6. Impact of stuttering severity on adolescents' domain-specific and general self-esteem through cognitive and emotional mediating processes.

    Science.gov (United States)

    Adriaensens, Stefanie; Beyers, Wim; Struyf, Elke

    2015-01-01

    The theory that self-esteem is substantially constructed based on social interactions implies that having a stutter could have a negative impact on self-esteem. Specifically, self-esteem during adolescence, a period of life characterized by increased self-consciousness, could be at risk. In addition to studying mean differences between stuttering and non-stuttering adolescents, this article concentrates on the influence of stuttering severity on domain-specific and general self-esteem. Subsequently, we investigate if covert processes on negative communication attitudes, experienced stigma, non-disclosure of stuttering, and (mal)adaptive perfectionism mediate the relationship between stuttering severity and self-esteem. Our sample comprised 55 stuttering and 76 non-stuttering adolescents. They were asked to fill in a battery of questionnaires, consisting of: Subjective Screening of Stuttering, Self-Perception Profile for Adolescents, Erickson S-24, Multidimensional Perfectionism Scale, and the Stigmatization and Disclosure in Adolescents Who Stutter Scale. SEM (structural equation modeling) analyses showed that stuttering severity negatively influences adolescents' evaluations of social acceptance, school competence, the competence to experience a close friendship, and global self-esteem. Maladaptive perfectionism and especially negative communication attitudes fully mediate the negative influence of stuttering severity on self-esteem. Group comparison showed that the mediation model applies to both stuttering and non-stuttering adolescents. We acknowledge the impact of having a stutter on those domains of the self in which social interactions and communication matter most. We then accentuate that negative attitudes about communication situations and excessive worries about saying things in ways they perceive as wrong are important processes to consider with regard to the self-esteem of adolescents who stutter. Moreover, we provide evidence that these covert

  7. 'There's a letter called ef' on Challenges and Repair in Interpreter-Mediated Tests of Cognitive Functioning in Dementia Evaluations

    DEFF Research Database (Denmark)

    Plejert, Charlotta; Antelius, Eleonor; Yazdanpanah, Maziar

    2015-01-01

    with memory problems and other dementia symptoms are referred for examination and evaluation. Very many elderly people with a foreign background require the assistance of an interpreter in their encounter with health-care facilities. The use of, and work by an interpreter is crucial in facilitating a smooth......In the Scandinavian countries Sweden, Denmark, Norway, and Finland, the number of first generation migrants reaching an old age, who will be in need of age-related health-care, is rapidly increasing. This situation poses new demands on health-care facilities, such as memory clinics, where patients...... the test of cognitive functioning. Special attention will be paid to the phenomenon 'repair', i.e., participants' joint attempts to solve upcoming difficulties during the course of interaction. Results show that sources of trouble may be related to the lack of cultural, linguistic, and educational...

  8. EM23, a natural sesquiterpene lactone from Elephantopus mollis H.B.K., induces apoptosis in human myeloid leukemia cells through thioredoxin- and reactive oxygen species-mediated signaling pathways

    Directory of Open Access Journals (Sweden)

    Hongyu eLi

    2016-03-01

    Full Text Available Elephantopus mollis H.B.K. (EM is a traditional herbal medicine with multiple pharmacological activities. However, the efficacy of EM in treating human leukemia is currently unknown. In the current study, we report that EM23, a natural sesquiterpene lactone isolated from EM, inhibits the proliferation of human chronic myeloid leukemia K562 cells and acute myeloid leukemia HL-60 cells by inducing apoptosis. Translocation of membrane-associated phospholipid phosphatidylserines, changes in cell morphology, activation of caspases and cleavage of PARP were concomitant with this inhibition. The involvement of the mitochondrial pathway in EM23-mediated apoptosis was suggested by observed disruptions in mitochondrial membrane potential (MMP. Mechanistic studies indicated that EM23 caused a marked increase in the level of reactive oxygen species (ROS. Pretreatment with N-acetyl-L-cysteine (NAC, a ROS scavenger, almost fully reversed EM23-mediated apoptosis. In EM23-treated cells, the expression levels of thioredoxin (Trx and thioredoxinreductase (TrxR, two components of the Trx system involved in maintaining cellular redox homeostasis, were significantly down-regulated. Concomitantly, Trx regulated the activation of apoptosis signal-regulating kinase 1 (ASK1 and its downstream regulatory targets, the p38, JNK, and ERK MAPKs. EM23-mediated activation of ASK1/MAPKs was significantly inhibited in the presence of NAC. Furthermore, tumor necrosis factor alpha (TNF-α-mediated activation of nuclear factor-κB (NF-κB was suppressed by EM23, as suggested by the observed blockage of p65 nuclear translocation, phosphorylation and reversion of IκBα degradation following EM23 treatment. Taken together, these results provide important insights into the anticancer activities of the EM component EM23 against human chronic myeloid leukemia K562 cells and acute myeloid leukemia HL-60 cells.

  9. Lactation and Reactivity to Physical and Psychological Stress

    National Research Council Canada - National Science Library

    Carter, C

    1998-01-01

    .... Studies of basal cortisol levels, cognitive performance and reactivity to stressors were conducted in human subjects during late pregnancy and immediately postpartum in women that were lactating...

  10. Reactive Arthritis

    Directory of Open Access Journals (Sweden)

    Eren Erken

    2013-06-01

    Full Text Available Reactive arthritis is an acute, sterile, non-suppurative and inflammatory arthropaty which has occured as a result of an infectious processes, mostly after gastrointestinal and genitourinary tract infections. Reiter syndrome is a frequent type of reactive arthritis. Both reactive arthritis and Reiter syndrome belong to the group of seronegative spondyloarthropathies, associated with HLA-B27 positivity and characterized by ongoing inflammation after an infectious episode. The classical triad of Reiter syndrome is defined as arthritis, conjuctivitis and urethritis and is seen only in one third of patients with Reiter syndrome. Recently, seronegative asymmetric arthritis and typical extraarticular involvement are thought to be adequate for the diagnosis. However, there is no established criteria for the diagnosis of reactive arthritis and the number of randomized and controlled studies about the therapy is not enough. [Archives Medical Review Journal 2013; 22(3.000: 283-299

  11. Neighborhood Economic Disadvantage and Children's Cognitive and Social-Emotional Development: Exploring Head Start Classroom Quality as a Mediating Mechanism.

    Science.gov (United States)

    McCoy, Dana Charles; Connors, Maia C; Morris, Pamela A; Yoshikawa, Hirokazu; Friedman-Krauss, Allison H

    Past research has shown robust relationships between neighborhood socioeconomic disadvantage and children's school achievement and social-emotional outcomes, yet the mechanisms for explaining these relationships are poorly understood. The present study uses data from 1,904 Head Start participants enrolled in the Head Start Impact Study to examine the role that classroom structural and relational quality play in explaining the association between neighborhood poverty and children's developmental gains over the preschool year. Results suggest that neighborhood poverty is directly related to lower levels of classroom quality, and lower gains in early literacy and math scores. Indirect relationships were also found between neighborhood poverty and children's social-emotional outcomes (i.e., approaches to learning and behavior problems) via differences in the physical resources and negative student-teacher relationships within classrooms. These findings highlight the need for policy initiatives to consider community characteristics as potential predictors of disparities in classroom quality and children's cognitive and social-emotional development in Head Start.

  12. Ghrelin-induced hippocampal neurogenesis and enhancement of cognitive function are mediated independently of GH/IGF-1 axis: lessons from the spontaneous dwarf rats.

    Science.gov (United States)

    Li, Endan; Kim, Yumi; Kim, Sehee; Park, Seungjoon

    2013-01-01

    We recently have reported that ghrelin modulates adult hippocampal neurogenesis. However, there is a possibility that the action of ghrelin on hippocampal neurogenesis could be, in part, due to the ability of ghrelin to stimulate the GH/insulin-like growth factor (IGF)-1 axis, where both GH and IGF-1 infusions are known to increase hippocampal neurogenesis. To explore this possibility, we assessed the impact of ghrelin on progenitor cell proliferation and differentiation in the dentate gyrus (DG) of spontaneous dwarf rats (SDRs), a dwarf strain with a mutation of the GH gene resulting in total loss of GH. Double immunohistochemical staining revealed that Ki-67-positive progenitor cells and doublecortin (DCX)-positive neuroblasts in the DG of the SDRs expressed ghrelin receptors. We found that ghrelin treatment in the SDRs significantly increased the number of proliferating cell nuclear antigen- and BrdU-labeled cells in the DG. The number of DCX-labeled cells in the DG of ghrelin-treated SDRs was also significantly increased compared with the vehicle-treated controls. To test whether ghrelin has a direct effect on cognitive performance independently of somatotropic axis, hippocampus-dependent learning and memory were assessed using the Y-maze and novel object recognition (NOR) test in the SDRs. Ghrelin treatment for 4 weeks by subcutaneous osmotic pump significantly increased alternation rates in the Y-maze and exploration time for novel object in the NOR test compared to vehicle-treated controls. Our results indicate that ghrelin-induced adult hippocampal neurogenesis and enhancement of cognitive function are mediated independently of somatotropic axis.

  13. Exploration as a Mediator of the Relation between the Attainment of Motor Milestones and the Development of Spatial Cognition and Spatial Language

    Science.gov (United States)

    Oudgenoeg-Paz, Ora; Leseman, Paul P. M.; Volman, M. J. M.

    2015-01-01

    The embodied-cognition approach views cognition and language as grounded in daily sensorimotor child-environment interactions. Therefore, the attainment of motor milestones is expected to play a role in cognitive-linguistic development. Early attainment of unsupported sitting and independent walking indeed predict better spatial cognition and…

  14. Punica granatum L. Fruit Aqueous Extract Suppresses Reactive Oxygen Species-Mediated p53/p65/miR-145 Expressions followed by Elevated Levels of irs-1 in Alloxan-Diabetic Rats.

    Science.gov (United States)

    Gharib, Ehsan; Montasser Kouhsari, Shideh; Izad, Maryam

    2018-01-01

    Reactive oxygen species (ROS) is an apoptosis inducer in pancreatic β-cells that stimulates p53/p65 mediated microRNA (miR)-145 expression. Punica granatum L. (pomegranate) is an antioxidant fruit that attenuates ROS generation. This study examines the effects of pomegranate fruit aqueous extract (PGE) on the levels of ROS, p53, p65, miR-145, and its target insulin receptor substrate 1 (irs-1) mRNA in Alloxan-diabetic male Wistar rats. In this experimental study, diabetic rats received different doses of PGE. The effects of the PGE polyphenols were examined through a long-term PGE treatment period model, followed by an evaluation of the plasma and tissue contents of free fatty acids (FFAs), triglycerides (TG), and glycogen compared with diabetic controls (DC) and normal controls (NC). We used real-time polymerase chain reaction (PCR) to investigate the modulation of p53, p65, miR-145, and irs-1 expression levels. There was a noticeable reduction in fasting blood glucose (FBG) and ROS generation compared to DC. We observed marked decreases in p53, p65, miR-145 expression levels followed by an elevated level of irs-1, which contributed to improvement in insulin sensitivity. PGE administration downregulated miR-145 levels in Alloxan-diabetic Wistar rats by suppression of ROS-mediated p53 and p65 overexpression. Copyright© by Royan Institute. All rights reserved.

  15. Intermittent hypoxia-induced cognitive deficits are mediated by NADPH oxidase activity in a murine model of sleep apnea.

    Directory of Open Access Journals (Sweden)

    Deepti Nair

    Full Text Available In rodents, exposure to intermittent hypoxia (IH, a hallmark of obstructive sleep apnea (OSA, is associated with neurobehavioral impairments, increased apoptosis in the hippocampus and cortex, as well as increased oxidant stress and inflammation. Excessive NADPH oxidase activity may play a role in IH-induced CNS dysfunction.The effect of IH during light period on two forms of spatial learning in the water maze and well as markers of oxidative stress was assessed in mice lacking NADPH oxidase activity (gp91phox(_/Y and wild-type littermates. On a standard place training task, gp91phox(_/Y displayed normal learning, and were protected from the spatial learning deficits observed in wild-type littermates exposed to IH. Moreover, anxiety levels were increased in wild-type mice exposed to IH as compared to room air (RA controls, while no changes emerged in gp91phox(_/Y mice. Additionally, wild-type mice, but not gp91phox(_/Y mice had significantly elevated levels of NADPH oxidase expression and activity, as well as MDA and 8-OHDG in cortical and hippocampal lysates following IH exposures.The oxidative stress responses and neurobehavioral impairments induced by IH during sleep are mediated, at least in part, by excessive NADPH oxidase activity, and thus pharmacological agents targeting NADPH oxidase may provide a therapeutic strategy in sleep-disordered breathing.

  16. Estrogen-Related Receptor Alpha Confers Methotrexate Resistance via Attenuation of Reactive Oxygen Species Production and P53 Mediated Apoptosis in Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Peng Chen

    2014-01-01

    Full Text Available Osteosarcoma (OS is a malignant tumor mainly occurring in children and adolescents. Methotrexate (MTX, a chemotherapy agent, is widely used in treating OS. However, treatment failures are common due to acquired chemoresistance, for which the underlying molecular mechanisms are still unclear. In this study, we report that overexpression of estrogen-related receptor alpha (ERRα, an orphan nuclear receptor, promoted cell survival and blocked MTX-induced cell death in U2OS cells. We showed that MTX induced ROS production in MTX-sensitive U2OS cells while ERRα effectively blocked the ROS production and ROS associated cell apoptosis. Our further studies demonstrated that ERRα suppressed ROS induction of tumor suppressor P53 and its target genes NOXA and XAF1 which are mediators of P53-dependent apoptosis. In conclusion, this study demonstrated that ERRα plays an important role in the development of MTX resistance through blocking MTX-induced ROS production and attenuating the activation of p53 mediated apoptosis signaling pathway, and points to ERRα as a novel target for improving osteosarcoma therapy.

  17. Adeno-associated virus-mediated rescue of the cognitive defects in a mouse model for Angelman syndrome.

    Directory of Open Access Journals (Sweden)

    Jennifer L Daily

    Full Text Available Angelman syndrome (AS, a genetic disorder occurring in approximately one in every 15,000 births, is characterized by severe mental retardation, seizures, difficulty speaking and ataxia. The gene responsible for AS was discovered to be UBE3A and encodes for E6-AP, an ubiquitin ligase. A unique feature of this gene is that it undergoes maternal imprinting in a neuron-specific manner. In the majority of AS cases, there is a mutation or deletion in the maternally inherited UBE3A gene, although other cases are the result of uniparental disomy or mismethylation of the maternal gene. While most human disorders characterized by severe mental retardation involve abnormalities in brain structure, no gross anatomical changes are associated with AS. However, we have determined that abnormal calcium/calmodulin-dependent protein kinase II (CaMKII regulation is seen in the maternal UBE3A deletion AS mouse model and is responsible for the major phenotypes. Specifically, there is an increased αCaMKII phosphorylation at the autophosphorylation sites Thr(286 and Thr(305/306, resulting in an overall decrease in CaMKII activity. CaMKII is not produced until after birth, indicating that the deficits associated with AS are not the result of developmental abnormalities. The present studies are focused on exploring the potential to rescue the learning and memory deficits in the adult AS mouse model through the use of an adeno-associated virus (AAV vector to increase neuronal UBE3A expression. These studies show that increasing the levels of E6-AP in the brain using an exogenous vector can improve the cognitive deficits associated with AS. Specifically, the associative learning deficit was ameliorated in the treated AS mice compared to the control AS mice, indicating that therapeutic intervention may be possible in older AS patients.

  18. Normative Cognition in Culture and Religion

    DEFF Research Database (Denmark)

    Jensen, Jeppe Sinding

    2013-01-01

    "Normative Cognition" is a theoretical model of human cognition as driven, modulated and governed by symbolically mediated inter-subjective norms and conventions......"Normative Cognition" is a theoretical model of human cognition as driven, modulated and governed by symbolically mediated inter-subjective norms and conventions...

  19. Autophagy is activated in compression-induced cell degeneration and is mediated by reactive oxygen species in nucleus pulposus cells exposed to compression.

    Science.gov (United States)

    Ma, K-G; Shao, Z-W; Yang, S-H; Wang, J; Wang, B-C; Xiong, L-M; Wu, Q; Chen, S-F

    2013-12-01

    To determine whether autophagy contributes to the pathogenesis of degenerative disc disease (DDD) or retards the intervertebral disc (IVD) degeneration, and investigate the possible relationship between compression-induced autophagy and intracellular reactive oxygen species (ROS) in nucleus pulposus (NP) cells in vitro. The autophagosome and autophagy-related markers were used to explore the role of autophagy in rat NP cells under compressive stress, which were measured directly by electronic microscopy, monodansylcadaverine (MDC) staining, immunofluorescence, western blot, and indirectly by analyzing the impact of pharmacological inhibitors of autophagy such as 3-methyladenine (3-MA) and chloroquine (CQ). And the relationship between autophagy and apoptosis was investigated by Annexin-V/propidium iodide (PI)-fluorescein staining. In addition, ROS were measured to determine whether these factors are responsible for the development of compression-induced autophagy. Our results indicated that rat NP cells activated autophagy in response to the same strong apoptotic stimuli that triggered apoptosis by compression. Autophagy and apoptosis were interconnected and coordinated in rat NP cells exposed to compression stimuli. Compression-induced autophagy was closely related to intracellular ROS production. Enhanced degradation of damaged components of NP cells by autophagy may be a crucial survival response against mechanical overload, and extensive autophagy may trigger autophagic cell death. Regulating autophagy and reducing the generation of intracellular ROS may retard IVD degeneration. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  20. Catechol Groups Enable Reactive Oxygen Species Scavenging-Mediated Suppression of PKD-NFkappaB-IL-8 Signaling Pathway by Chlorogenic and Caffeic Acids in Human Intestinal Cells

    Directory of Open Access Journals (Sweden)

    Hee Soon Shin

    2017-02-01

    Full Text Available Chlorogenic acid (CHA and caffeic acid (CA are phenolic compounds found in coffee, which inhibit oxidative stress-induced interleukin (IL-8 production in intestinal epithelial cells, thereby suppressing serious cellular injury and inflammatory intestinal diseases. Therefore, we investigated the anti-inflammatory mechanism of CHA and CA, both of which inhibited hydrogen peroxide (H2O2-induced IL-8 transcriptional activity. They also significantly suppressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB transcriptional activity, nuclear translocation of the p65 subunit, and phosphorylation of IκB kinase (IKK. Additionally, upstream of IKK, protein kinase D (PKD was also suppressed. Finally, we found that they scavenged H2O2-induced reactive oxygen species (ROS and the functional moiety responsible for the anti-inflammatory effects of CHA and CA was the catechol group. Therefore, we conclude that the presence of catechol groups in CHA and CA allows scavenging of intracellular ROS, thereby inhibiting H2O2-induced IL-8 production via suppression of PKD-NF-κB signaling in human intestinal epithelial cells.

  1. Morin Inhibits Proliferation of SW480 Colorectal Cancer Cells by Inducing Apoptosis Mediated by Reactive Oxygen Species Formation and Uncoupling of Warburg Effect

    Directory of Open Access Journals (Sweden)

    Thomas Sithara

    2017-09-01

    Full Text Available The study under investigation focuses on in vitro antiproliferative efficacy of the flavonoid morin and the mechanisms by which it inhibits the growth of colon cancer using SW480 colon cancer cells with emphasis on Warburg effect. It was found that the cell proliferation was significantly inhibited by morin in a dose and time dependent manner. Morin induced apoptosis that was correlated with increased levels of reactive oxygen species formation and loss of mitochondrial membrane potential of the cells. In addition, an increase in cleaved PARP, cleaved caspase 3, cleaved caspase 8, cleaved caspase 9 and Bax as well as a decrease in Bcl 2 was observed, indicating morin is inducing both intrinsic as well as extrinsic pathway of apoptosis. This was further confirmed by using downstream caspase 3 inhibitor which indicated that caspase 3 inhibition reduces morin induced cell death. Moreover, the impact of morin on over all energy status when determined in terms of total cellular ATP level showed a decline with low level of glucose uptake and Glut1 expression. The results indicate that morin exerts antiproliferative activity by inducing apoptosis and by reducing Warburg effect in the evaluated cell lines and provide preliminary evidence for its anticancer activity.

  2. Inhibition of Neuroblastoma cancer cells viability by ferromagnetic Mn doped CeO_2 monodisperse nanoparticles mediated through reactive oxygen species

    International Nuclear Information System (INIS)

    Abbas, Fazal; Jan, Tariq; Iqbal, Javed; Haider Naqvi, M. Sajjad; Ahmad, Ishaq

    2016-01-01

    Here we report the Mn doping induced effects on structural, Raman, optical, magnetic and anticancer properties of CeO_2 nanoparticles prepared via soft chemical route. Structural and microstructural results infer that the synthesized nanoparticles have single phase cubic fluorite structure of CeO_2 and that Mn doping results in enhancement of the structural defects. Scanning electron microscopy results reveal the formation of monodisperse nanoparticles having average particle size ranging from 30 to 41 nm. The optical absorbance spectroscopy analysis discloses the band gap energy tailoring of CeO_2 nanoparticles via Mn doping. Room temperature ferromagnetism (RTFM) has been found in both as-prepared and Mn doped CeO_2 nanoparticles. This RTFM of the synthesized nanoparticles have been attributed to the Mn ions and surface defects such as oxygen vacancies. Finally, the influence of Mn dopant on the cell viability and reactive oxygen species (ROS) generation levels of CeO_2 nanoparticles in the presence of healthy and cancerous cells have been studied. It has been observed that the differential cytotoxicity of the synthesized nanoparticles is strongly correlated with level of ROS generation. - Highlights: • Mn doped CeO_2 nanoparticles with cubic fluorite structure were synthesized. • Mn dopant significantly tailored the band gap of CeO_2 nanoparticles. • The synthesized nanoparticles exhibited room temperature ferromagnetic behavior. • The cytotoxicity of these nanoparticles was reported for the first time. • The synthesized nanoparticles exhibited differential cytotoxicity.

  3. Bamboo vinegar decreases inflammatory mediator expression and NLRP3 inflammasome activation by inhibiting reactive oxygen species generation and protein kinase C-α/δ activation.

    Directory of Open Access Journals (Sweden)

    Chen-Lung Ho

    Full Text Available Bamboo vinegar (BV, a natural liquid derived from the condensation produced during bamboo charcoal production, has been used in agriculture and as a food additive, but its application to immune modulation has not been reported. Here, we demonstrated that BV has anti-inflammatory activities both in vitro and in vivo. BV reduced inducible nitric oxide synthase expression and nitric oxide levels in, and interleukin-6 secretion by, lipopolysaccharide-activated macrophages without affecting tumor necrosis factor-α secretion and cyclooxygenase-2 expression. The mechanism for the anti-inflammatory effect of BV involved decreased reactive oxygen species production and protein kinase C-α/δ activation. Furthermore, creosol (2-methoxy-4-methylphenol was indentified as the major anti-inflammatory compound in BV. Impaired cytokine expression and NLR family, pyrin domain-containing 3 (NLRP3 inflammasome activation was seen in mice treated with creosol. These findings provide insights into how BV regulates inflammation and suggest that it may be a new source for the development of anti-inflammatory agents or a healthy supplement for preventing and ameliorating inflammation- and NLRP3 inflammasome-related diseases, including metabolic syndrome.

  4. A WRKY gene from Tamarix hispida, ThWRKY4, mediates abiotic stress responses by modulating reactive oxygen species and expression of stress-responsive genes.

    Science.gov (United States)

    Zheng, Lei; Liu, Guifeng; Meng, Xiangnan; Liu, Yujia; Ji, Xiaoyu; Li, Yanbang; Nie, Xianguang; Wang, Yucheng

    2013-07-01

    WRKY transcription factors are involved in various biological processes, such as development, metabolism and responses to stress. However, their exact roles in abiotic stress tolerance are largely unknown. Here, we demonstrated a working model for the function of a WRKY gene (ThWRKY4) from Tamarix hispida in the stress response. ThWRKY4 is highly induced by abscisic acid (ABA), salt and drought in the early period of stress (stress for 3, 6, or 9 h), which can be regulated by ABF (ABRE binding factors) and Dof (DNA binding with one finger), and also can be crossregulated by other WRKYs and autoregulated as well. Overexpression of ThWRKY4 conferred tolerance to salt, oxidative and ABA treatment in transgenic plants. ThWRKY4 can improve the tolerance to salt and ABA treatment by improving activities of superoxide dismutase and peroxidase, decreasing levels of O2 (-) and H2O2, reducing electrolyte leakage, keeping the loss of chlorophyll, and protecting cells from death. Microarray analyses showed that overexpression of ThWRKY4 in Arabidopsis leads to 165 and 100 genes significantly up- and downregulated, respectively. Promoter scanning analysis revealed that ThWRKY4 regulates the gene expression via binding to W-box motifs present in their promoter regions. This study shows that ThWRKY4 functions as a transcription factor to positively modulate abiotic stress tolerances, and is involved in modulating reactive oxygen species.

  5. Magnesium Lithospermate B from Salvia miltiorrhiza Bunge Ameliorates Aging-Induced Renal Inflammation and Senescence via NADPH Oxidase-Mediated Reactive Oxygen Generation.

    Science.gov (United States)

    Park, Chan Hum; Shin, Sung Ho; Lee, Eun Kyeong; Kim, Dae Hyun; Kim, Min-Jo; Roh, Seong-Soo; Yokozawa, Takako; Chung, Hae Young

    2017-05-01

    The present study was conducted to examine whether magnesium lithospermate B (MLB) extracted from Salviae miltiorrhizae radix was renoprotective in pathways related to age-related oxidative stress in aged rats. Magnesium lithospermate B was orally administered at a dose of 2- or 8-mg/kg body weight for 16 consecutive days, and the effects were compared with those of vehicle in old and young rats. Magnesium lithospermate B administration to old rats ameliorated renal oxidative stress through reduction of reactive oxygen species. The old rats exhibited a dysregulation of the expression of proteins related to oxidative stress and inflammation in the kidneys, and MLB administration significantly reduced the protein expression of major subunits of nicotinamide adenine dinucleotide phosphate oxidase (Nox4 and p22 phox ), phospho-p38, nuclear factor-kappa B p65, cyclooxygenase-2, and inducible nitric oxide synthase. In addition, MLB-treated old rats showed lower levels of senescence-related proteins such as p16, ADP-ribosylation factor 6, p53, and p21 through effects on the mitogen-activated protein kinase pathway. Magnesium lithospermate B administration also significantly attenuated the age-related increase in serum urea nitrogen, reflecting renal dysfunction, up-regulated podocyte structural proteins, and reduced renal structural injury. Our results provide important evidence that MLB reduces the renal damage of oxidative stress in old rats. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  6. Chrysophanol-induced cell death (necrosis) in human lung cancer A549 cells is mediated through increasing reactive oxygen species and decreasing the level of mitochondrial membrane potential.

    Science.gov (United States)

    Ni, Chien-Hang; Yu, Chun-Shu; Lu, Hsu-Feng; Yang, Jai-Sing; Huang, Hui-Ying; Chen, Po-Yuan; Wu, Shin-Hwar; Ip, Siu-Wan; Chiang, Su-Yin; Lin, Jaung-Geng; Chung, Jing-Gung

    2014-05-01

    Chrysophanol (1,8-dihydroxy-3-methylanthraquinone) is one of the anthraquinone compounds, and it has been shown to induce cell death in different types of cancer cells. The effects of chrysophanol on human lung cancer cell death have not been well studied. The purpose of this study is to examine chrysophanol-induced cytotoxic effects and also to investigate such influences that involved apoptosis or necrosis in A549 human lung cancer cells in vitro. Our results indicated that chrysophanol decreased the viable A549 cells in a dose- and time-dependent manner. Chrysophanol also promoted the release of reactive oxygen species (ROS) and Ca(2+) and decreased the levels of mitochondria membrane potential (ΔΨm ) and adenosine triphosphate in A549 cells. Furthermore, chrysophanol triggered DNA damage by using Comet assay and DAPI staining. Importantly, chrysophanol only stimulated the cytocheome c release, but it did not activate other apoptosis-associated protein levels including caspase-3, caspase-8, Apaf-1, and AIF. In conclusion, human lung cancer A549 cells treated with chrysophanol exhibited a cellular pattern associated with necrotic cell death and not apoptosis in vitro. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 740-749, 2014. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

  7. Air-stable nZVI formation mediated by glutamic acid: solid-state storable material exhibiting 2D chain morphology and high reactivity in aqueous environment

    Science.gov (United States)

    Siskova, Karolina; Tucek, Jiri; Machala, Libor; Otyepkova, Eva; Filip, Jan; Safarova, Klara; Pechousek, Jiri; Zboril, Radek

    2012-03-01

    We report a new chemical approach toward air-stable nanoscale zero-valent iron (nZVI). The uniformly sized (approx. 80 nm) particles, formed by the reduction of Fe(II) salt by borohydride in the presence of glutamic acid, are coated by a thin inner shell of amorphous ferric oxide/hydroxide and a secondary shell consisting of glutamic acid. The as-prepared nanoparticles stabilized by the inorganic-organic double shell create 2D chain morphologies. They are storable for several months under ambient atmosphere without the loss of Fe(0) relative content. They show one order of magnitude higher rate constant for trichlorethene decomposition compared with the pristine particles possessing only the inorganic shell as a protective layer. This is the first example of the inorganic-organic (consisting of low-molecular weight species) double-shell stabilized nanoscale zero-valent iron material being safely transportable in solid-state, storable on long-term basis under ambient conditions, environmentally acceptable for in situ applications, and extraordinarily reactive if contacted with reducible pollutants, all in one.

  8. Wear Particles Promote Reactive Oxygen Species-Mediated Inflammation via the Nicotinamide Adenine Dinucleotide Phosphate Oxidase Pathway in Macrophages Surrounding Loosened Implants

    Directory of Open Access Journals (Sweden)

    Weishen Chen

    2015-03-01

    Full Text Available Background/Aims: Prosthesis loosening is closely associated with chronic inflammatory cytokine secretion by macrophages, which are activated by wear particles or inflammatory stimulants such as lipopolysaccharide (LPS. Reactive oxygen species (ROS are critical regulators of inflammation, but their enzymatic sources in response to wear particles and their effects on peri-implant LPS-tolerance remain unclear. Methods: Three ROS-related enzymes—nicotinamide adenine dinucleotide phosphate oxidase (NOX-1 and -2 and catalase—were investigated in interface membrane tissues and in titanium (Ti particle-stimulated macrophages in vitro. The generation of ROS and downstream inflammatory effects were measured with or without pre-incubation with apocynin, an NOX inhibitor. Results: Pre-exposure to Ti particles attenuated NF-κB activation in LPS-stimulated macrophages, indicating that wear particles suppress immune response, which may lead to chronic inflammation. NOX-1 and -2 were highly expressed in aseptically loosened interface membranes and in macrophages stimulated with Ti particles; the particles induced a moderate amount of ROS generation, NF-κB activation, and TNF-a secretion in macrophages, and these effects were suppressed by apocynin. Conclusion: Wear particles induce ROS generation through the NOX signaling pathway, resulting in persistent inflammation and delayed loosening. Thus, the suppression of NOX activity may be a useful strategy for preventing prosthesis loosening.

  9. NADPH oxidase 2-derived reactive oxygen species mediate FFAs-induced dysfunction and apoptosis of β-cells via JNK, p38 MAPK and p53 pathways.

    Directory of Open Access Journals (Sweden)

    Huiping Yuan

    2010-12-01

    Full Text Available Dysfunction of β-cell is one of major characteristics in the pathogenesis of type 2 diabetes. The combination of obesity and type 2 diabetes, characterized as 'diabesity', is associated with elevated plasma free fatty acids (FFAs. Oxidative stress has been implicated in the pathogenesis of FFA-induced β-cell dysfunction. However, molecular mechanisms linking between reactive oxygen species (ROS and FFA-induced β-cell dysfunction and apoptosis are less clear. In the present study, we test the hypothesis that NOX2-derived ROS may play a critical role in dysfunction and apoptosis of β-cells induced by FFA. Our results show that palmitate and oleate (0.5 mmol/L, 48 h induced JNK activation and AKT inhibition which resulted in decreased phosphorylation of FOXO1 following nuclear localization and the nucleocytoplasmic translocation of PDX-1, leading to the reducing of insulin and ultimately dysfunction of pancreatic NIT-1 cells. We also found that palmitate and oleate stimulated apoptosis of NIT-1 cells through p38MAPK, p53 and NF-κB pathway. More interestingly, our data suggest that suppression of NOX2 may restore FFA-induced dysfunction and apoptosis of NIT-1 cells. Our findings provide a new insight of the NOX2 as a potential new therapeutic target for preservation of β-cell mass and function.

  10. Cognitive issues in autonomous spacecraft-control operations: An investigation of software-mediated decision making in a scaled environment

    Science.gov (United States)

    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

  11. FB elements can promote exon shuffling: a promoter-less white allele can be reactivated by FB mediated transposition in Drosophila melanogaster.

    Science.gov (United States)

    Moschetti, R; Marsano, R M; Barsanti, P; Caggese, C; Caizzi, R

    2004-05-01

    Foldback ( FB) elements are transposable elements found in many eukaryotic genomes; they are thought to contribute significantly to genome plasticity. In Drosophila melanogaster, FBs have been shown to be involved in the transposition of large chromosomal regions and in the genetic instability of some alleles of the white gene. In this report we show that FB mediated transposition of w(67C23), a mutation that deletes the promoter of the white gene and its first exon, containing the start codon, can restore expression of the white gene. We have characterized three independent events in which a 14-kb fragment from the w(67C23) locus was transposed into an intron region in three different genes. In each case a local promoter drives the expression of white, producing a chimeric mRNA. These findings suggest that, on an evolutionary timescale, FB elements may contribute to the creation of new genes via exon shuffling.

  12. Depression is associated with sexual risk among men who have sex with men, but is mediated by cognitive escape and self-efficacy.

    Science.gov (United States)

    Alvy, Lisa M; McKirnan, David J; Mansergh, Gordon; Koblin, Beryl; Colfax, Grant N; Flores, Stephen A; Hudson, Sharon

    2011-08-01

    Men who have sex with men (MSM) show high rates of HIV infection, and higher rates of depression than non-MSM. We examined the association between depression and sexual risk among "high risk" MSM. Evidence has been mixed regarding the link between depression and risky sex, although researchers have rarely considered the role of psychosocial vulnerabilities such as self-efficacy for sexual safety or "escape" coping styles. In a national sample (N = 1,540) of HIV-positive and HIV-negative MSM who reported unprotected sex and drug use with sex partners, we found evidence that depression is related to HIV transmission risk. Self-efficacy for sexual safety and cognitive escape mediated the link between depression and risk behavior, suggesting that psychosocial vulnerability plays an important role in the association of depression with sexual risk. These findings may help us construct more accurate theories regarding depression and sexual behavior, and may inform the design of sexual safety interventions.

  13. 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.

    Science.gov (United States)

    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

  14. Comparison of MicroRNAs Mediated in Reactivation of the γ-Globin in β-Thalassemia Patients, Responders and Non-Responders to Hydroxyurea.

    Science.gov (United States)

    Hojjati, Mohammad T; Azarkeivan, Azita; Pourfathollah, Ali A; Amirizadeh, Naser

    2017-03-01

    Drug induction of Hb F seems to be an ideal therapy for patients with hemoglobin (Hb) disorders, and many efforts have been made to reveal the mechanism behind it. Thus, we examined in vivo expression of some microRNAs (miRNAs) that are thought to be involved in this process. Among β-thalassemia (β-thal) patients who were undergoing hydroxyurea (HU) therapy in the past 3 months and five healthy individuals, five responders and five non-responders, were also included in the study. Erythroid progenitors were isolated by magnetic activated cell sorting (MACS) and miRNA expression analyzed using reverse transcription-polymerase chain reaction (RT-PCR). We showed that γ-globin, miR-210 and miR-486-3p had higher levels in the responders than the non-responders group. Moreover, miR-150 and miR-320 had higher levels in the healthy group than both non-responders and responders groups, but the expression of miR-96 did not show any significant difference between the study groups. To the best of our knowledge, this is the first study proposing that 'induction of cellular hypoxic condition by Hb F inducing agents' could be the milestone of possible mechanisms that explain why responders are able to reactivate γ-globin genes and subsequently, more production of Hb F, in response to these agents in comparison to non-responders. However, further investigations need to be performed to verify this hypothesis.

  15. Reactive oxygen species generation mediated by NADPH oxidase and PI3K/Akt pathways contribute to invasion of Streptococcus agalactiae in human endothelial cells.

    Science.gov (United States)

    Oliveira, Jessica Silva Santos de; Santos, Gabriela da Silva; Moraes, João Alfredo; Saliba, Alessandra Mattos; Barja-Fidalgo, Thereza Christina; Mattos-Guaraldi, Ana Luíza; Nagao, Prescilla Emy

    2018-01-01

    BACKGROUND Streptococcus agalactiae can causes sepsis, pneumonia, and meningitis in neonates, the elderly, and immunocompromised patients. Although the virulence properties of S. agalactiae have been partially elucidated, the molecular mechanisms related to reactive oxygen species (ROS) generation in infected human endothelial cells need further investigation. OBJECTIVES This study aimed to evaluate the influence of oxidative stress in human umbilical vein endothelial cells (HUVECs) during S. agalactiae infection. METHODS ROS production during S. agalactiae-HUVEC infection was detected using the probe CM-H2DCFDA. Microfilaments labelled with phalloidin-FITC and p47phox-Alexa 546 conjugated were analysed by immunofluorescence. mRNA levels of p47phox (NADPH oxidase subunit) were assessed using Real Time qRT-PCR. The adherence and intracellular viability of S. agalactiae in HUVECs with or without pre-treatment of DPI, apocynin (NADPH oxidase inhibitors), and LY294002 (PI3K inhibitor) were evaluated by penicillin/gentamicin exclusion. Phosphorylation of p47phox and Akt activation by S. agalactiae were evaluated by immunoblotting analysis. FINDINGS Data showed increased ROS production 15 min after HUVEC infection. Real-Time qRT-PCR and western