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

PubMed

Wang, Mingzhong; Deng, Xueli; Du, Xiuxiu

2018-04-01

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

Does prolactin mediate parental and life-history decisions in response to environmental conditions in birds? A review.

PubMed

Angelier, Frédéric; Wingfield, John C; Tartu, Sabrina; Chastel, Olivier

2016-01-01

This article is part of a Special Issue "Parental Care". In vertebrates, adjustments of physiology and behavior to environmental changes are often mediated by central physiological mechanisms, and more specifically by hormonal mechanisms. As a consequence, these mechanisms are thought to orchestrate life-history decisions in wild vertebrates. For instance, investigating the hormonal regulation of parental behavior is relevant to evaluate how parents modulate their effort according to specific environmental conditions. Surprisingly and despite being classically known as the 'parental hormone', prolactin has been overlooked in birds relative to this context. Our aim is to review evidence that changes in prolactin levels can mediate, at least to some extent, the response of breeding birds to environmental conditions. To do so, we first examine current evidence and limits for the role of prolactin in mediating parental behavior in birds. Second, we emphasize the influence of environmental conditions and stressors on circulating prolactin levels. In addition, we review to what extent prolactin levels are a reliable predictor of breeding success in wild birds. By linking environmental conditions, prolactin regulation, parental behavior, and breeding success, we highlight the potential role of this hormone in mediating parental decisions in birds. Finally, we also review the potential role of prolactin in mediating other life history decisions such as clutch size, re-nesting, and the timing of molt. By evaluating the influence of stressors on circulating prolactin levels during these other life-history decisions, we also raise new hypotheses regarding the potential of the prolactin stress response to regulate the orchestration of the annual cycle when environmental changes occur. To sum up, we show in this review that prolactin regulation has a strong potential to allow ecological physiologists to better understand how individuals adjust their life-history decisions (clutch size, parental behavior, re-nesting, and onset of molt) according to the environmental conditions they encounter and we encourage further research on that topic. Copyright © 2015 Elsevier Inc. All rights reserved.

A Prospective Examination of the Path from Child Abuse and Neglect to Illicit Drug Use in Middle Adulthood: The Potential Mediating Role of Four Risk Factors

ERIC Educational Resources Information Center

Wilson, Helen W.; Widom, Cathy Spatz

2009-01-01

This study examines prostitution, homelessness, delinquency and crime, and school problems as potential mediators of the relationship between childhood abuse and neglect (CAN) and illicit drug use in middle adulthood. Children with documented cases of physical and sexual abuse and neglect (ages 0-11) during 1967-1971 were matched with…

Potential roles of WRKY transcription factors in resistance to Aspergillus flavus colonization of immature maize kernels

USDA-ARS?s Scientific Manuscript database

Resistance to Aspergillus flavus by maize (Zea mays L.) is mediated by several defense proteins; however the mechanism regulating the expression of these defenses is poorly understood. This study examined the potential roles of six maize WRKY transcription factors, ZmWRKY19, ZmWRKY21, ZmWRKY53, ZmW...

Exosome-Mediated Pathogen Transmission by Arthropod Vectors.

PubMed

Hackenberg, Michael; Kotsyfakis, Michail

2018-04-24

Recent molecular and cellular studies have highlighted a potentially important role for tick exosomes in parasite transmission. Here we summarize evolving hypotheses about the largely unknown cellular events that may take place at the tick-host-pathogen interface, focusing on a potential role for arthropod exosomes in this tripartite interaction. Copyright © 2018 Elsevier Ltd. All rights reserved.

Interparental conflict and adolescent dating relationships: the role of perceived threat and self-blame appraisals.

PubMed

Kim, Kerri L; Jackson, Yo; Hunter, Heather L; Conrad, Selby M

2009-05-01

In line with the cognitive-contextual framework proposed by Grych and Fincham (1990), evidence suggests that children exposed to interparental conflict (IPC) are at risk for experiencing conflict within their own intimate relationships. The mediating role of adolescent appraisal in the relation between IPC and adolescent dating behavior was examined in the current study. Specifically, it was hypothesized that self-blame and threat appraisals would mediate the relation between IPC and adolescent maladaptive dating behaviors. To examine the potential mediating role of appraisal, 169 high school students completed the Children's Perception of Interparental Conflict (Grych, Seid, & Fincham, 1992) and Child and Adolescent Dating Relationships Inventory (Wolfe, Scott, Reitzel-Jaffe, Wekerle, Grasley, & Straatman, 2004). Findings suggest that self-blame appraisal partially mediated the relation between IPC and adolescent sexual aggression, and between IPC and adolescent threatening behavior. In addition, perceived threat appraisal partially mediated the relation between IPC and adolescent sexual aggression. Implications for the current findings are discussed.

Intergenerational transmission of educational attainment: Three levels of parent-child communication as mediators.

PubMed

Chi, Liping

2013-04-01

Although the intergenerational transmission of educational attainment has been confirmed by many researchers, its mechanism still remains controversial. Parent-child communication has been regarded as one of the important mediators. The present study primarily aimed to examine the potentially mediating role of parent-child communication in the transmission of educational attainment, based on a sample of 366 Chinese fifth and sixth graders. Parent-child communication was measured against the three levels of the parents' communication ability, the quality of the father-child and mother-child communications, and the relation between the two dyadic communications. The results duplicated the positive effect of parents' educational attainment on children's academic achievement. Moreover, it was found that parents' communication ability alone played a mediating role, and that the three levels of parent-child communication constructed a "mediator chain" between the parents' educational attainment and the children's academic achievement. Finally, the intergenerational transmission of educational attainment in China and the mediating role of the three levels of parent-child communication were discussed. © 2012 The Institute of Psychology, Chinese Academy of Sciences and Blackwell Publishing Asia Pty Ltd.

PDGF-mediated protection of SH-SY5Y cells against Tat toxin involves regulation of extracellular glutamate and intracellular calcium

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

Zhu Xuhui; Department of Laboratory Medicine, Tongji Hospital and Tongji Medical College of Huazhong University of Science and Technology, Wuhan; Yao Honghong

2009-10-15

The human immunodeficiency virus (HIV-1) protein Tat has been implicated in mediating neuronal apoptosis, one of the hallmark features of HIV-associated dementia (HAD). Mitigation of the toxic effects of Tat could thus be a potential mechanism for reducing HIV toxicity in the brain. In this study we demonstrated that Tat-induced neurotoxicity was abolished by NMDA antagonist-MK801, suggesting the role of glutamate in this process. Furthermore, we also found that pretreatment of SH-SY5Y cells with PDGF exerted protection against Tat toxicity by decreasing extracellular glutamate levels. We also demonstrated that extracellular calcium chelator EGTA was able to abolish PDGF-mediated neuroprotection, therebymore » underscoring the role of calcium signaling in PDGF-mediated neuroprotection. We also showed that Erk signaling pathway was critical for PDGF-mediated protection of cells. Additionally, blocking calcium entry with EGTA resulted in suppression of PDGF-induced Erk activation. These findings thus underscore the role of PDGF-mediated calcium signaling and Erk phosphorylation in the protection of cells against HIV Tat toxicity.« less

Perceived Work Conditions and Turnover Intentions: The Mediating Role of Meaning of Work

PubMed Central

Arnoux-Nicolas, Caroline; Sovet, Laurent; Lhotellier, Lin; Di Fabio, Annamaria; Bernaud, Jean-Luc

2016-01-01

Perceived working conditions lead to various negative outcomes for employee behaviors, including turnover intentions. Although potential mediators for these relationships were previously identified, the importance of meaning of work has not yet been investigated. This study examines the role of this psychological resource as a mediator for the relationships between perceived working conditions and turnover intentions in a sample of 336 French workers from different job contexts. Results show that adverse working conditions were positively and significantly associated with turnover intentions. Meaning of work is negatively related to both perceived working conditions and turnover intentions. Mediation analyses for meaning of work demonstrated indirect effects of several adverse working conditions on turnover intentions. The role of meaning of work as a psychological resource for employees facing adverse working conditions is discussed, especially regarding its implications for research and practice within organizational contexts. PMID:27242616

Perceived Work Conditions and Turnover Intentions: The Mediating Role of Meaning of Work.

PubMed

Arnoux-Nicolas, Caroline; Sovet, Laurent; Lhotellier, Lin; Di Fabio, Annamaria; Bernaud, Jean-Luc

2016-01-01

Perceived working conditions lead to various negative outcomes for employee behaviors, including turnover intentions. Although potential mediators for these relationships were previously identified, the importance of meaning of work has not yet been investigated. This study examines the role of this psychological resource as a mediator for the relationships between perceived working conditions and turnover intentions in a sample of 336 French workers from different job contexts. Results show that adverse working conditions were positively and significantly associated with turnover intentions. Meaning of work is negatively related to both perceived working conditions and turnover intentions. Mediation analyses for meaning of work demonstrated indirect effects of several adverse working conditions on turnover intentions. The role of meaning of work as a psychological resource for employees facing adverse working conditions is discussed, especially regarding its implications for research and practice within organizational contexts.

Mindfulness and Counseling Self-Efficacy: The Mediating Role of Attention and Empathy

ERIC Educational Resources Information Center

Greason, Paige Bentley; Cashwell, Craig S.

2009-01-01

This study examined the predictive relationship between mindfulness and counseling self-efficacy and the potential mediating effects of attention and empathy. Master's-level counseling interns and doctoral counseling students (N = 179) were surveyed to determine levels of mindfulness, attention, empathy, and counseling self-efficacy. Pearson…

Zinc and Autophagy

PubMed Central

Liuzzi, Juan P.; Guo, Liang; Yoo, Changwon; Stewart, Tiffanie S

2014-01-01

Autophagy is a highly conserved degradative process through which cells overcome stressful conditions. Inasmuch as faulty autophagy has been associated with aging, neuronal degeneration disorders, diabetes, and fatty liver, autophagy is regarded as a potential therapeutic target. This review summarizes the present state of knowledge concerning the role of zinc in the regulation of autophagy, the role of autophagy in zinc metabolism, and the potential role of autophagy as a mediator of the protective effects of zinc. Data from in vitro studies consistently support the notion that zinc is critical for early and late autophagy. Studies have shown inhibition of early and late autophagy in cells cultured in medium treated with zinc chelators. Conversely, excess zinc added to the medium has shown to potentiate the stimulation of autophagy by tamoxifen, H2O2, ethanol and dopamine. The potential role of autophagy in zinc homeostasis has just begun to be investigated.Increasing evidence indicates that autophagy dysregulation causes significant changes in cellular zinc homeostasis. Autophagy may mediate the protective effect of zinc against lipid accumulation, apoptosis and inflammation by promoting degradation of lipid droplets, inflammasomes, p62/SQSTM1 and damaged mitochondria.Studies with humans and animal models are necessary to determine whether autophagy is influenced by zinc intake. PMID:25012760

AMPA receptor-induced local brain-derived neurotrophic factor signaling mediates motor recovery after stroke.

PubMed

Clarkson, Andrew N; Overman, Justine J; Zhong, Sheng; Mueller, Rudolf; Lynch, Gary; Carmichael, S Thomas

2011-03-09

Stroke is the leading cause of adult disability. Recovery after stroke shares similar molecular and cellular properties with learning and memory. A main component of learning-induced plasticity involves signaling through AMPA receptors (AMPARs). We systematically tested the role of AMPAR function in motor recovery in a mouse model of focal stroke. AMPAR function controls functional recovery beginning 5 d after the stroke. Positive allosteric modulators of AMPARs enhance recovery of limb control when administered after a delay from the stroke. Conversely, AMPAR antagonists impair motor recovery. The contributions of AMPARs to recovery are mediated by release of brain-derived neurotrophic factor (BDNF) in periinfarct cortex, as blocking local BDNF function in periinfarct cortex blocks AMPAR-mediated recovery and prevents the normal pattern of motor recovery. In contrast to a delayed AMPAR role in motor recovery, early administration of AMPAR agonists after stroke increases stroke damage. These findings indicate that the role of glutamate signaling through the AMPAR changes over time in stroke: early potentiation of AMPAR signaling worsens stroke damage, whereas later potentiation of the same signaling system improves functional recovery.

The importance of autonomy support and the mediating role of work motivation for well-being: testing self-determination theory in a Chinese work organisation.

PubMed

Nie, Youyan; Chua, Bee Leng; Yeung, Alexander Seeshing; Ryan, Richard M; Chan, Wai Yen

2015-08-01

We examine relations between perceived organisational autonomy support and different types of work motivation and well-being outcomes in 266 teachers from two government schools in China. We hypothesised that greater autonomy support would be associated with more autonomous forms of employee motivation, and that teacher motivation would in turn mediate the effects of autonomy support on indicators of work well-being (i.e., job satisfaction, work stress and physical ill symptoms). Results generally supported the hypothesised relations between perceived autonomy support and SDT's five types of motivations. Findings also showed that perceived autonomy support predicted job satisfaction directly and indirectly through the mediating roles of intrinsic motivation, identified regulation, introjected regulation and external regulation. Perceived autonomy support predicted work stress directly and indirectly through the mediating roles of external regulation and amotivation. Autonomy support also predicted illness symptoms via the mediating roles of intrinsic motivation, introjected regulation and amotivation. The current findings highlight how perceived organisational support for autonomy relates to motivational differences in a Chinese work context, and the potential relevance of autonomy support for employee well-being. © 2014 International Union of Psychological Science.

Family functioning mediates adaptation in caregivers of individuals with Rett syndrome.

PubMed

Lamb, Amanda E; Biesecker, Barbara B; Umstead, Kendall L; Muratori, Michelle; Biesecker, Leslie G; Erby, Lori H

2016-11-01

The objective of this study was to investigate factors related to family functioning and adaptation in caregivers of individuals with Rett syndrome (RS). A cross-sectional quantitative survey explored the relationships between demographics, parental self-efficacy, coping methods, family functioning and adaptation. A forward-backward, step-wise model selection procedure was used to evaluate variables associated with both family functioning and adaptation. Analyses also explored family functioning as a mediator of the relationship between other variables and adaptation. Bivariate analyses (N=400) revealed that greater parental self-efficacy, a greater proportion of problem-focused coping, and a lesser proportion of emotion-focused coping were associated with more effective family functioning. In addition, these key variables were significantly associated with greater adaptation, as was family functioning, while controlling for confounders. Finally, regression analyses suggest family functioning as a mediator of the relationships between three variables (parental self-efficacy, problem-focused coping, and emotion-focused coping) with adaptation. This study demonstrates the potentially predictive roles of expectations and coping methods and the mediator role of family functioning in adaptation among caregivers of individuals with RS, a chronic developmental disorder. A potential target for intervention is strengthening of caregiver competence in the parenting role to enhance caregiver adaptation. Published by Elsevier Ireland Ltd.

Role of water mediated interactions in protein-protein recognition landscapes.

PubMed

Papoian, Garegin A; Ulander, Johan; Wolynes, Peter G

2003-07-30

The energy landscape picture of protein folding and binding is employed to optimize a number of pair potentials for direct and water-mediated interactions in protein complex interfaces. We find that water-mediated interactions greatly complement direct interactions in discriminating against various types of trap interactions that model those present in the cell. We highlight the context dependent nature of knowledge-based binding potentials, as contrasted with the situation for autonomous folding. By performing a Principal Component Analysis (PCA) of the corresponding interaction matrixes, we rationalize the strength of the recognition signal for each combination of the contact type and reference trap states using the differential in the idealized "canonical" amino acid compositions of native and trap layers. The comparison of direct and water-mediated contact potential matrixes emphasizes the importance of partial solvation in stabilizing charged groups in the protein interfaces. Specific water-mediated interresidue interactions are expected to influence significantly the kinetics as well as thermodynamics of protein association.

Use of Hemadsorption in a Case of Pediatric Toxic Shock Syndrome.

PubMed

Berkes, Andrea; Szikszay, Edit; Kappelmayer, János; Kerényi, Adrienne; Szabó, Tamás; Ujhelyi, László; Bari, Krisztina; Balla, György; Balla, József

2017-01-01

Toxic shock syndrome is a potentially fatal toxin-mediated disease. The role of toxins in this clinical entity made us hypothesize that extracorporeal blood purification with CytoSorb® could play a beneficial role in the clinical management of toxic shock syndrome. This case report describes the successful treatment of toxic shock syndrome using a combination of renal replacement therapy and hemadsorption in a pediatric patient. A 5-year-old girl with Down's syndrome presented with an inflamed area surrounding an insect bite, signs of systemic inflammation, and multiple organ failure. As previous attempts of immune modulation therapy were unsuccessful, renal replacement therapy was supplemented by the cytokine absorber CytoSorb. Treatment using this combination was associated with a rapid and significant stabilization in the hemodynamic situation and a decrease in inflammatory mediators within hours after the initiation of therapy. The application of CytoSorb therapy was simple and safe. The use of extracorporeal blood purification with CytoSorb proved potentially beneficial by removing toxins and inflammatory mediators in this case and could therefore play a role in the clinical management of toxic shock syndrome. Whether CytoSorb has the potential to even positively influence mortality in patients with toxic shock syndrome still needs to be confirmed.

Use of Hemadsorption in a Case of Pediatric Toxic Shock Syndrome

PubMed Central

Berkes, Andrea; Szikszay, Edit; Kerényi, Adrienne; Szabó, Tamás; Ujhelyi, László; Bari, Krisztina; Balla, György

2017-01-01

Background Toxic shock syndrome is a potentially fatal toxin-mediated disease. The role of toxins in this clinical entity made us hypothesize that extracorporeal blood purification with CytoSorb® could play a beneficial role in the clinical management of toxic shock syndrome. This case report describes the successful treatment of toxic shock syndrome using a combination of renal replacement therapy and hemadsorption in a pediatric patient. Case Presentation A 5-year-old girl with Down's syndrome presented with an inflamed area surrounding an insect bite, signs of systemic inflammation, and multiple organ failure. As previous attempts of immune modulation therapy were unsuccessful, renal replacement therapy was supplemented by the cytokine absorber CytoSorb. Treatment using this combination was associated with a rapid and significant stabilization in the hemodynamic situation and a decrease in inflammatory mediators within hours after the initiation of therapy. The application of CytoSorb therapy was simple and safe. Conclusion The use of extracorporeal blood purification with CytoSorb proved potentially beneficial by removing toxins and inflammatory mediators in this case and could therefore play a role in the clinical management of toxic shock syndrome. Whether CytoSorb has the potential to even positively influence mortality in patients with toxic shock syndrome still needs to be confirmed. PMID:28791185

Autistic Traits in the General Population: What Mediates the Link with Depressive and Anxious Symptomatology?

ERIC Educational Resources Information Center

Rosbrook, Ainslie; Whittingham, Koa

2010-01-01

The high prevalence of anxiety disorders and depression within the autism spectrum disorder (ASD) population is widely recognised. This study examined the role of three potential mediating variables in the relationship between autistic traits and depressive/anxious symptomatology in the general population. Participants included 231 university…

Strategic Game Moves Mediate Implicit Science Learning

ERIC Educational Resources Information Center

Rowe, Elizabeth; Baker, Ryan S.; Asbell-Clarke, Jodi

2015-01-01

Educational games have the potential to be innovative forms of learning assessment, by allowing us to not just study their knowledge but the process that takes students to that knowledge. This paper examines the mediating role of players' moves in digital games on changes in their pre-post classroom measures of implicit science learning. We…

College Alcohol Beliefs and Drinking Consequences: A Multiple Mediation Analysis of Norms, Expectancies, and Willingness to Experience Drinking Consequences

ERIC Educational Resources Information Center

Osberg, Timothy M.; Boyer, Amber

2018-01-01

Objective: We explored the potential mediating role of willingness to experience drinking consequences and other traditional alcohol outcome predictors (descriptive norms, injunctive norms, positive alcohol expectancies) in explaining the association between college alcohol beliefs1 (CABs) and the actual experience of drinking consequences among…

Dendritic sodium spikes are required for long-term potentiation at distal synapses on hippocampal pyramidal neurons

PubMed Central

Kim, Yujin; Hsu, Ching-Lung; Cembrowski, Mark S; Mensh, Brett D; Spruston, Nelson

2015-01-01

Dendritic integration of synaptic inputs mediates rapid neural computation as well as longer-lasting plasticity. Several channel types can mediate dendritically initiated spikes (dSpikes), which may impact information processing and storage across multiple timescales; however, the roles of different channels in the rapid vs long-term effects of dSpikes are unknown. We show here that dSpikes mediated by Nav channels (blocked by a low concentration of TTX) are required for long-term potentiation (LTP) in the distal apical dendrites of hippocampal pyramidal neurons. Furthermore, imaging, simulations, and buffering experiments all support a model whereby fast Nav channel-mediated dSpikes (Na-dSpikes) contribute to LTP induction by promoting large, transient, localized increases in intracellular calcium concentration near the calcium-conducting pores of NMDAR and L-type Cav channels. Thus, in addition to contributing to rapid neural processing, Na-dSpikes are likely to contribute to memory formation via their role in long-lasting synaptic plasticity. DOI: http://dx.doi.org/10.7554/eLife.06414.001 PMID:26247712

Anxiety Mediates Perceived Discrimination and Health in African-American Women.

PubMed

Carter, Sierra E; Walker, Rheeda L; Cutrona, Carolyn E; Simons, Ronald L; Beach, Steven R H

2016-11-01

We examined the mediational role of symptoms of anxiety in accounting for the association of discrimination and chronic health conditions among African-American women. Participants were 646 African-American women who completed self-report measures of perceived racial discrimination, symptoms of anxiety, and diagnosed chronic health problems. We examined the mediation hypothesis using a path analytic procedure. Mediational analyses indicated that, above and beyond symptoms of depression, age, and education status, anxiety symptoms were associated with both racial discrimination (β = .03, SE = .01, p < .001) and chronic health problems (β = .33, SE = .09, p < .001) and significantly mediated the discrimination-health association (β = -.01, SE = .01, p = .16). These findings highlight the potentially vital role of symptoms of anxiety in the process that occurs from an individual's perception of discrimination to reported chronic health outcomes. Future research expanding our understanding of the interconnection of psychosocial stressors, discrimination, and their biological sequelae is needed.

Prospective relations between maternal autonomy support and child executive functioning: investigating the mediating role of child language ability.

PubMed

Matte-Gagné, Célia; Bernier, Annie

2011-12-01

Although emerging evidence suggests that parental behavior is related to the development of child executive functioning (EF), the mechanisms through which parenting affects child EF have yet to be investigated. The goal of this study was to examine the potential mediating role of child language in the prospective relation between maternal autonomy support and child EF. A total of 53 mother-infant dyads took part in three home visits at 15months, 2years, and 3years, allowing for the assessment of maternal autonomy support (T1), child expressive vocabulary (T2), and child EF (T3). The results suggested that child language played a mediating role in the relation between maternal autonomy support and child performance on EF tasks entailing a strong impulse control component above and beyond child previous EF and family socioeconomic status (SES). In contrast, no such mediating role of language was found with EF tasks tapping mostly into working memory and set shifting. Thus, this study highlights one pathway through which parenting can affect child executive control. Copyright © 2011 Elsevier Inc. All rights reserved.

Acid sphingomyelinase mediates human CD4+ T-cell signaling: potential roles in T-cell responses and diseases

PubMed Central

Bai, Aiping; Guo, Yuan

2017-01-01

Acid sphingomyelinase (ASM) is a lipid hydrolase. By generating ceramide, ASM had been reported to have an important role in regulating immune cell functions inclusive of macrophages, NK cells, and CD8+ T cells, whereas the role of ASM bioactivity in regulation of human CD4+ T-cell functions remained uncertain. Recent studies have provided novel findings in this field. Upon stimulation of CD3 and/or CD28, ASM-dependent ceramide signaling mediates intracellular downstream signal cascades of CD3 and CD28, and regulates CD4+ T-cell activation and proliferation. Meanwhile, CD39 and CD161 have direct interactions with ASM, which mediates downstream signals inclusive of STAT3 and mTOR and thus defines human Th17 cells. Intriguingly, ASM mediates Th1 responses, but negatively regulates Treg functions. In this review, we summarized the pivotal roles of ASM in regulation of human CD4+ T-cell activation and responses. ASM/sphingolipid signaling may be a novel target for the therapy of human autoimmune diseases. PMID:28749465

The Relation of Pro-Sociality to Self-Esteem: The Mediational Role of Quality of Friendships.

PubMed

Zuffianò, Antonio; Eisenberg, Nancy; Alessandri, Guido; Luengo Kanacri, Bernadette Paula; Pastorelli, Concetta; Milioni, Michela; Caprara, Gian Vittorio

2016-02-01

The present longitudinal study examined the role of quality of friendship in mediating the relation of pro-sociality to self-esteem over time. Participants were 424 Italian young adults (56% females) assessed at two waves (M(age) = 21.1 at Time 1; M(age) = 25 at Time 2). An autoregressive cross-lagged panel model was used to test the mediational model. Self- and friend-report measures of pro-sociality, quality of friendship, and self-esteem were included in the analyses. Results were in line with the hypothesized paths, with quality of friendship mediating the relation of pro-sociality to later self-esteem above and beyond its high stability. Self-esteem, in turn, predicted pro-sociality 4 years later. Overall, the present findings support the potential benefits of behaving pro-socially for an actor in terms of increased perceived self-worth and also expand previous work by outlining the specific mediational role of the quality of friendships. The theoretical and practical implications of these results are discussed. © 2014 Wiley Periodicals, Inc.

Core self-evaluation and burnout among Nurses: the mediating role of coping styles.

PubMed

Li, Xiaofei; Guan, Lili; Chang, Hui; Zhang, Bo

2014-01-01

This study aimed to determine the potential association between core self-evaluation and the burnout syndrome among Chinese nurses, and the mediating role of coping styles in this relationship. A cross-sectional survey was conducted in Shenyang, China, from May to July, 2013. A questionnaire which consisted of the Maslach Burnout Inventory-General Survey (MBI-GS), the Core Self-Evaluation Scale (CSE), and the Simplified Coping Style Questionnaire (CSQ), was completed by a total of 1,559 nurses. Hierarchical linear regression analyses and the Sobel test were performed to determine the mediating role of coping styles on the relationship between CSE and burnout. Nurses who had higher self-evaluation characteristics, reported less emotional exhaustion and cynicism, and higher professional efficacy. Coping style had a partial mediating effect on the relationship between CSE and the burnout syndrome among nurses. Core self-evaluation had effects on burnout and coping style was a mediating factor in this relationship among Chinese nurses. Therefore, the improvement of coping strategies may be helpful in the prevention of burnout among nurses, thus enhancing professional performance.

Core Self-Evaluation and Burnout among Nurses: The Mediating Role of Coping Styles

PubMed Central

Li, Xiaofei; Guan, Lili; Chang, Hui; Zhang, Bo

2014-01-01

Objectives This study aimed to determine the potential association between core self-evaluation and the burnout syndrome among Chinese nurses, and the mediating role of coping styles in this relationship. Methods A cross-sectional survey was conducted in Shenyang, China, from May to July, 2013. A questionnaire which consisted of the Maslach Burnout Inventory-General Survey (MBI-GS), the Core Self-Evaluation Scale (CSE), and the Simplified Coping Style Questionnaire (CSQ), was completed by a total of 1,559 nurses. Hierarchical linear regression analyses and the Sobel test were performed to determine the mediating role of coping styles on the relationship between CSE and burnout. Results Nurses who had higher self-evaluation characteristics, reported less emotional exhaustion and cynicism, and higher professional efficacy. Coping style had a partial mediating effect on the relationship between CSE and the burnout syndrome among nurses. Conclusions Core self-evaluation had effects on burnout and coping style was a mediating factor in this relationship among Chinese nurses. Therefore, the improvement of coping strategies may be helpful in the prevention of burnout among nurses, thus enhancing professional performance. PMID:25541990

Metacognitions as Mediators of Gender Identity-related Anxiety.

PubMed

Fernie, Bruce A; Wright, Talen; Caselli, Gabriele; Nikčević, Ana V; Spada, Marcantonio M

2017-01-01

Research has found that the prevalence of psychological distress is substantially higher in transgender compared to cisgender populations. This study explored the role of metacognitions as mediators of anxiety in a sample comprising of cisgender and transgender individuals. One-hundred and twenty-five individuals (19 trans-male; 24 male; 25 trans-female; 57 female) completed a series of measures that assessed metacognitions, worry and anxiety. Correlation analyses were used to identify potential mediators of the relationship between gender identity and anxiety. A mediation model indicated that beliefs about thoughts concerning uncontrollability and danger entirely mediated the relationship between gender identity and anxiety (b = 2.00, bias corrected and accelerated confidence interval [0.68, 3.49]). Metacognitions play an important role in anxiety in transgender individuals. -Metacognitions were found to mediate anxiety in transgender and cisgender individuals. -The exploration of metacognitions in transgender individuals experiencing psychological distress may have clinical utility. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Attitudinal Ambivalence as a Protective Factor Against Junk Food Advertisements: A Moderated Mediation Model of Behavioral Intention.

PubMed

Ran, Weina; Yamamoto, Masahiro

2015-08-01

This study investigates the role of attitudinal ambivalence in moderating the effects of junk food advertisements on behavioral intentions by tapping different facets of this construct-felt ambivalence, potential ambivalence, and affective-cognitive ambivalence. Results based on an online survey of college students indicate that attention to junk food advertisements has an indirect positive effect on intentions to eat junk food through its positive effect on attitudes toward junk food. A moderated mediation model reveals that this indirect effect of junk food advertisements is weakened as respondents' levels of felt ambivalence increase. This moderating role is not observed for the measures of potential ambivalence and affective-cognitive ambivalence. Implications are discussed for health interventions.

Taurine-induced attenuation of MPP+ neurotoxicity in vitro: a possible role for the GABA(A) subclass of GABA receptors.

PubMed

O'Byrne, M B; Tipton, K F

2000-05-01

Taurine is a sulphur-containing beta-amino acid found in high (millimolar) concentrations in excitable tissues such as brain and heart. Its suggested roles include osmoregulator, thermoregulator, neuromodulator, and potential neurotransmitter. This amino acid has also been shown to be released in large concentrations during ischaemia and excitotoxin-induced neuronal damage. Here we report a protective effect of taurine against MPP(+)-induced neurotoxicity in coronal slices from rat brain. Significant protective effects were observed at taurine concentrations of 20 and 1 mM, suggesting a potential role for taurine in cases of neuronal insult. Studies with the synthetic taurine analogues taurine phosphonate, guanidinoethane sulphonate, and trimethyltaurine suggested the observed effect to be mediated via an extracellular mechanism. The use of GABA receptor ligands muscimol and bicuculline indicated the effect to be mediated through activation of GABA(A) receptors.

The Role of Youth Problem Behaviors in the Path from Child Abuse and Neglect to Prostitution: A Prospective Examination

ERIC Educational Resources Information Center

Wilson, Helen W.; Widom, Cathy Spatz

2010-01-01

Behaviors beginning in childhood or adolescence may mediate the relationship between childhood maltreatment and involvement in prostitution. This paper examines 5 potential mediators: early sexual initiation, running away, juvenile crime, school problems, and early drug use. Using a prospective cohort design, abused and neglected children (ages…

The Measurement Paradigm and Role of Mediators in Dynamic Assessment: A Qualitative Meta-Synthesis

ERIC Educational Resources Information Center

Rezaee, Abbas Ali; Ghanbarpour, Mahsa

2016-01-01

As dynamic assessment (DA) continues to come to prominence as a procedure that endeavors to ameliorate learner performance and further development through mediators' assistance with the intent of discerning learning potential, a plethora of research has delved into the applicability of DA in second/foreign language education. This article employed…

Predicting Desire for Institutional Placement among Racially Diverse Dementia Family Caregivers: The Role of Quality of Care

ERIC Educational Resources Information Center

Sun, Fei; Durkin, Daniel W.; Hilgeman, Michelle M.; Harris, Grant; Gaugler, Joseph E.; Wardian, Jana; Allen, Rebecca S.; Burgio, Louis D.

2013-01-01

Purpose: Literature on institutionalization of patients with dementia has not considered the role of caregivers' quality of care, which encompasses caregivers' exemplary care (EC) behaviors and caregivers' potentially harmful behaviors (PHBs) toward care recipients. This study sought to understand the role of quality of care in mediating between…

The Role of Depression and Negative Affect Regulation Expectancies in Tobacco Smoking among College Students

ERIC Educational Resources Information Center

Schleicher, Holly E.; Harris, Kari Jo; Catley, Delwyn; Nazir, Niaman

2009-01-01

Objective: Expectancies about nicotine's ability to alleviate negative mood states may play a role in the relationship between smoking and depression. The authors examined the role of negative affect regulation expectancies as a potential mediator of depression (history of depression and depressive symptoms) and smoking among college students.…

Physical Activity and Bone Health in Schoolchildren: The Mediating Role of Fitness and Body Fat

PubMed Central

Torres-Costoso, Ana; Gracia-Marco, Luis; Sánchez-López, Mairena; Notario-Pacheco, Blanca; Arias-Palencia, Natalia; Martínez-Vizcaíno, Vicente

2015-01-01

Background The relationship between physical activity (PA) and bone health is well known, although the role of percent body fat (%BF) and fitness as confounders or mediators in this relationship remains uncertain. Objective To examine whether the association between PA and bone mineral content (BMC) is mediated by %BF and cardiorespiratory fitness (CRF). Methods In this cross sectional study, BMC, total %BF (by DXA), vigorous PA (VPA), CRF, age and height were measured in 132 schoolchildren (62 boys, aged 8–11 years). ANCOVA was used to test differences in BMC by %BF, CRF and VPA, controlling for different sets of confounders. Simple mediation analyses and serial multiple mediation analyses were fitted to examine whether the relationship between PA and BMC is mediated by %BF and fitness. Results Children with high %BF had higher total body BMC than their peers after controlling for all sets of confounders. Children with good CRF or VPA had significantly less total body BMC after controlling for age and sex but in children with good CRF this inverse relation disappeared after adjusting by %BF. %BF and CRF both act as a full mediator in the association between VPA and BMC, after inclusion of the potential confounders in the models. Conclusion Fitness and %BF seem to have a mediator role on the relationship between physical activity and bone mass. PMID:25915941

Hydrogen sulfide: role in ion channel and transporter modulation in the eye

PubMed Central

Njie-Mbye, Ya F.; Opere, Catherine A.; Chitnis, Madhura; Ohia, Sunny E.

2012-01-01

Hydrogen sulfide (H2S), a colorless gas with a characteristic smell of rotten eggs, has been portrayed for decades as a toxic environmental pollutant. Since evidence of its basal production in mammalian tissues a decade ago, H2S has attracted substantial interest as a potential inorganic gaseous mediator with biological importance in cellular functions. Current research suggests that, next to its counterparts nitric oxide and carbon monoxide, H2S is an important multifunctional signaling molecule with pivotal regulatory roles in various physiological and pathophysiological processes as diverse as learning and memory, modulation of synaptic activities, cell survival, inflammation, and maintenance of vascular tone in the central nervous and cardiovascular systems. In contrast, there are few reports of a regulatory role of H2S in the eye. Accumulating reports on the pharmacological role of H2S in ocular tissues indicate the existence of a functional trans-sulfuration pathway and a potential physiological role for H2S as a gaseous neuromodulator in the eye. Thus, understanding the role of H2S in vision-related processes is imperative to our expanding knowledge of this molecule as a gaseous mediator in ocular tissues. This review aims to provide a comprehensive and current understanding of the potential role of H2S as a signaling molecule in the eye. This objective is achieved by discussing the involvement of H2S in the regulation of (1) ion channels such as calcium (L-type, T-type, and intracellular stores), potassium (KATP and small conductance channels) and chloride channels, (2) glutamate transporters such as EAAT1/GLAST and the L-cystine/glutamate antiporter. The role of H2S as an important mediator in cellular functions and physiological processes that are triggered by its interaction with ion channels/transporters in the eye will also be discussed. PMID:22934046

Integrating Social-Contextual and Intrapersonal Mechanisms of "Maturing Out": Joint Influences of Familial-Role Transitions and Personality Maturation on Problem-Drinking Reductions.

PubMed

Lee, Matthew R; Ellingson, Jarrod M; Sher, Kenneth J

2015-09-01

"Maturing out" of problem drinking is associated with both role transitions (e.g., getting married) and personality development. However, little is known concerning how these 2 mechanisms jointly influence problem-drinking desistance. This study investigated whether salutary effects of role transitions and personality occur at different points in young-adult development and whether they mediate one another's effects. Participants were initially recruited as first-year undergraduates, with family history of alcoholism overrepresented by design (N = 489). Using 4 waves of data at roughly ages 21, 25, 29, and 34, cross-lagged panel models estimated prospective relations among familial-role transitions (marriage or parenthood), personality (disinhibition, conscientiousness, and neuroticism), and problem drinking. Mixed support was found for the prediction of roles being more strongly associated with earlier maturing out of problem drinking and personality being more strongly associated with later maturing out. Regarding mediation, no evidence was found for the expectation that role effects would be mediated by personality. However, results did support mediation of personality effects by role transitions. Specifically, lower disinhibition and higher conscientiousness in emerging adulthood predicted role adoption, which, in turn, predicted later problem-drinking reductions. Family history of alcoholism also distally influenced these mediation processes. The differential timing of role and personality effects is consistent with the notion of decreasing contextual influences and increasing intrapersonal influences across development. In light of role incompatibility theory, results suggest that, over the course of development, the association of familial roles with problem drinking may increasingly reflect problem-drinking effects on role entry (i.e., role selection) and decreasingly reflect role entry effects on problem drinking (i.e., role socialization). As emerging-adult disinhibition and conscientiousness were associated with an apparent developmental cascade of both direct and indirect effects, findings highlight their potential importance as etiologic mechanisms and intervention targets. Copyright © 2015 by the Research Society on Alcoholism.

Integrating Social-Contextual and Intrapersonal Mechanisms of “Maturing Out”: Joint Influences of Familial-Role Transitions and Personality Maturation on Problem-Drinking Reductions

PubMed Central

Lee, Matthew R.; Ellingson, Jarrod M.; Sher, Kenneth J.

2015-01-01

Background “Maturing out” of problem drinking is associated with both role transitions (e.g., getting married) and personality development. However, little is known concerning how these two mechanisms jointly influence problem-drinking desistance. This study investigated whether salutary effects of role transitions and personality occur at different points in young-adult development and whether they mediate one another’s effects. Methods Participants were initially recruited as first-year undergraduates, with family history of alcoholism overrepresented by design (N=489; Sher et al., 1991). Using four waves of data at roughly ages 21, 25, 29, and 34, cross-lagged panel models estimated prospective relations among familial-role transitions (marriage or parenthood), personality (disinhibition, conscientiousness, and neuroticism), and problem drinking. Results Mixed support was found for the prediction of roles being more strongly associated with earlier maturing out of problem drinking and personality being more strongly associated with later maturing out. Regarding mediation, no evidence was found for the expectation that role effects would be mediated by personality. However, results did support mediation of personality effects by role transitions. Specifically, lower disinhibition and higher conscientiousness in emerging adulthood predicted role adoption, which, in turn, predicted later problem-drinking reductions. Family history of alcoholism also distally influenced these mediation processes. Conclusions The differential timing of role and personality effects is consistent with the notion of decreasing contextual influences and increasing intrapersonal influences across development. In light of role incompatibility theory, results suggest that, over the course of development, the association of familial roles with problem drinking may increasingly reflect problem-drinking effects on role entry (i.e., role selection) and decreasingly reflect role entry effects on problem drinking (i.e., role socialization). As emerging-adult disinhibition and conscientiousness were associated with an apparent developmental cascade of both direct and indirect effects, findings highlight their potential importance as etiologic mechanisms and intervention targets. PMID:26247314

From CNTNAP2 to Early Expressive Language in Infancy: The Mediation Role of Rapid Auditory Processing.

PubMed

Riva, Valentina; Cantiani, Chiara; Benasich, April A; Molteni, Massimo; Piazza, Caterina; Giorda, Roberto; Dionne, Ginette; Marino, Cecilia

2018-06-01

Although it is clear that early language acquisition can be a target of CNTNAP2, the pathway between gene and language is still largely unknown. This research focused on the mediation role of rapid auditory processing (RAP). We tested RAP at 6 months of age by the use of event-related potentials, as a mediator between common variants of the CNTNAP2 gene (rs7794745 and rs2710102) and 20-month-old language outcome in a prospective longitudinal study of 96 Italian infants. The mediation model examines the hypothesis that language outcome is explained by a sequence of effects involving RAP and CNTNAP2. The ability to discriminate spectrotemporally complex auditory frequency changes at 6 months of age mediates the contribution of rs2710102 to expressive vocabulary at 20 months. The indirect effect revealed that rs2710102 C/C was associated with lower P3 amplitude in the right hemisphere, which, in turn, predicted poorer expressive vocabulary at 20 months of age. These findings add to a growing body of literature implicating RAP as a viable marker in genetic studies of language development. The results demonstrate a potential developmental cascade of effects, whereby CNTNAP2 drives RAP functioning that, in turn, contributes to early expressive outcome.

MicroRNA-133 mediates cardiac diseases: Mechanisms and clinical implications

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

Liu, Yi; Liang, Yan; Zhang, Jin-fang

MicroRNAs (miRNAs) belong to the family of small non-coding RNAs that mediate gene expression by post-transcriptional regulation. Increasing evidence have demonstrated that miR-133 is enriched in muscle tissues and myogenic cells, and its aberrant expression could induce the occurrence and development of cardiac disorders, such as cardiac hypertrophy, heart failure, etc. In this review, we summarized the regulatory roles of miR-133 in cardiac disorders and the underlying mechanisms, which suggest that miR-133 may be a potential diagnostic and therapeutic tool for cardiac disorders. - Highlights: • miR-218 is frequently downregulated in multiple cancers. • miR-218 plays pivotal roles in carcinogenesis.more » • miR-218 mediates proliferation, apoptosis, metastasis, invasion, etc. • miR-218 mediates tumorigenesis and metastasis via multiple pathways.« less

Father's and mother's perceptions of parenting styles as mediators of the effects of parental psychopathology on antisocial behavior in outpatient children and adolescents.

PubMed

Vera, Juan; Granero, Roser; Ezpeleta, Lourdes

2012-06-01

The aim was to examine the potential mediating role of father's and mother's parenting styles in the association between parental psychopathology and antisocial behavior in children, and whether this pathway was moderated by child's sex. Participants included both parents and 338 Spanish outpatient children between 8 and 17 years (56.5% boys). Parenting style had a mediating effect on the studied relationships. Maternal psychopathology was positively associated with antisocial behavior in children, either directly or partially by parenting style, while paternal psychopathology was positively associated with offspring antisocial behavior only through the mediator role of parenting style. Child's sex did not moderate these relationships. Parenting style could be a target for prevention and intervention of antisocial behavior in the offspring of parents with mental health problems.

Effect of socio-economic status, family smoking and mental health through social network on the substance use potential in adolescents: a mediation analysis.

PubMed

Sajjadi, H; Jorjoran Shushtari, Z; Mahboubi, S; Rafiey, H; Salimi, Y

2018-04-01

Understanding pathways that influence substance use potential (SUP) can help with effective substance use prevention interventions among adolescents. The aim of the present study is to contribute to a better understanding of the SUP of adolescents by examining the mediating role of social network quality in the SUP of Iranian adolescents. A cross-sectional study. Structural equation modeling was conducted to assess the hypothesized model that social network quality would mediate the association of family socio-economic status, a mental health disorder, and family smoking with addiction potential. The model shows a good fit to the data. Social network quality mediated the effect of family smoking on the SUP for boys. A mental health disorder had a positive significant direct effect on addiction potential for both girls and boys. Social network quality mediates the effect of family smoking on boys' addiction potential in the context of Iran. Educational programs based on local societal ways and cultural norms are recommended to change tobacco smoking behavior among family members. In addition, to prevent subsequent substance use among adolescents, more effort is needed to improve their mental health. Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Personality and Body-Mass-Index in School-Age Children: An Exploration of Mediating and Moderating Variables

PubMed Central

Allen, Mark S.; Vella, Stewart A.

2016-01-01

This study explored longitudinal associations between personality and body-mass-index (BMI) in school-age children, including the potential mediating role of screen time and physical activity, and the potential moderating roles of child demographics and neighbourhood socioeconomic position. Participants were the parents (and teachers) of 3857 ten-year-old children, who completed questionnaires at baseline with a two-year follow-up. After controlling for child demographics (e.g., sex, pubertal status), we found that personality was unimportant for concurrent BMI, but was important for subsequent BMI and change in BMI over two years. Low levels of introversion and persistence at baseline, and decreases in persistence over time, were associated with a higher BMI at follow-up and a greater increase in BMI over time. Moderator analyses showed that introversion was more strongly related to subsequent BMI for children listed as aboriginal or Torres Strait Islander. The relationship between personality and change in BMI was mediated by screen time, but not by physical activity. To conclude, findings demonstrate that personality is important for change in body mass in Australian children (particularly indigenous children), and that screen-based sedentary behaviour features an important role in this association. PMID:27486752

Personality and Body-Mass-Index in School-Age Children: An Exploration of Mediating and Moderating Variables.

PubMed

Allen, Mark S; Vella, Stewart A

2016-01-01

This study explored longitudinal associations between personality and body-mass-index (BMI) in school-age children, including the potential mediating role of screen time and physical activity, and the potential moderating roles of child demographics and neighbourhood socioeconomic position. Participants were the parents (and teachers) of 3857 ten-year-old children, who completed questionnaires at baseline with a two-year follow-up. After controlling for child demographics (e.g., sex, pubertal status), we found that personality was unimportant for concurrent BMI, but was important for subsequent BMI and change in BMI over two years. Low levels of introversion and persistence at baseline, and decreases in persistence over time, were associated with a higher BMI at follow-up and a greater increase in BMI over time. Moderator analyses showed that introversion was more strongly related to subsequent BMI for children listed as aboriginal or Torres Strait Islander. The relationship between personality and change in BMI was mediated by screen time, but not by physical activity. To conclude, findings demonstrate that personality is important for change in body mass in Australian children (particularly indigenous children), and that screen-based sedentary behaviour features an important role in this association.

Sweating the small stuff: Glycoproteins in human sweat and their unexplored potential for microbial adhesion.

PubMed

Peterson, Robyn A; Gueniche, Audrey; Adam de Beaumais, Ségolène; Breton, Lionel; Dalko-Csiba, Maria; Packer, Nicolle H

2016-03-01

There is increasing evidence that secretory fluids such as tears, saliva and milk play an important role in protecting the human body from infection via a washing mechanism involving glycan-mediated adhesion of potential pathogens to secretory glycoproteins. Interaction of sweat with bacteria is well established as the cause of sweat-associated malodor. However, the role of sweat glycoproteins in microbial attachment has received little, if any, research interest in the past. In this review, we demonstrate how recent published studies involving high-throughput proteomic analysis have inadvertently, and fortuitously, exposed an abundance of glycoproteins in sweat, many of which have also been identified in other secretory fluids. We bring together research demonstrating microbial adhesion to these secretory glycoproteins in tears, saliva and milk and suggest a similar role of the sweat glycoproteins in mediating microbial attachment to sweat and/or skin. The contribution of glycan-mediated microbial adhesion to sweat glycoproteins, and the associated impact on sweat derived malodor and pathogenic skin infections are unchartered new research areas that we are beginning to explore. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

NHERF-1 regulation of EGF and neurotensin signalling in HT-29 epithelial cells

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

Kruger, Wade A.; Monteith, Gregory R.; Poronnik, Philip, E-mail: philip.poronnik@sydney.edu.au

2013-03-22

Highlights: ► NHERF-1 expression was abundant throughout HT-29 cells consistent with a cancerous phenotype. ► Knockdown of NHERF-1 lead to a significant reduction in cell proliferation. ► EGF and neurotensin-mediated proliferation was inhibited by knockdown of NHERF-1. ► Neurotensin-mediated Ca{sup 2+} response was abolished by knockdown of NHERF-1. -- Abstract: Neurotensin receptors (NT-R) and the epidermal growth factor receptors (EGF-R) are commonly overexpressed in many epithelial origin tumours. In addition to their role as mitogenic mediators through specific cell signalling, recent studies indicate that the activity/expression of scaffold proteins responsible for the assembly and coordination of the signalling complexes maymore » also have central roles in epithelial transformation. In particular, the “epithelial” PSD-95/Dlg/Zo-1 (PDZ) scaffold/adapter protein, Na{sup +}/H{sup +} exchanger regulatory factor isoform one (NHERF-1), has been identified as a potential regulator of cellular transformation. NHERF-1 is a known regulator of EGF-R function and plays numerous roles in G-protein-coupled receptor signalling. Because of the synergistic signalling between these two potent mitogens, we investigated a potential role for NHERF-1 in the molecular mechanism linking the aberrant proliferative phenotype initiated by some G-Protein-coupled receptor activators in the colon adenocarcinoma HT-29 cell line. Knockdown (80%) of endogenous NHERF-1 leads to significant reduction in proliferation rate; an effect that could not be recovered by exogenous application of either NT or EGF. Inhibition of the EGF-R with AG1487 also inhibited proliferation and this effect could not be recovered with NT. Knockdown of NHERF-1 significantly altered the expression of the EGF-R, and almost completely abolished the NT-mediated increases in intracellular free Ca{sup 2+}. Knockdown of NHERF-1 also attenuated UTP-mediated purinergic Ca{sup 2+} signalling. Taken together, these data suggest that NHERF-1 plays a more central role in cell proliferation by modulating Gq-mediated signalling pathways.« less

The Role of Emotion Regulation in Children's Early Academic Success

ERIC Educational Resources Information Center

Graziano, Paulo A.; Reavis, Rachael D.; Keane, Susan P.; Calkins, Susan D.

2007-01-01

This study investigated the role of emotion regulation in children's early academic success using a sample of 325 kindergarteners. A mediational analysis addressed the potential mechanisms through which emotion regulation relates to children's early academic success. Results indicated that emotion regulation was positively associated with teacher…

Latino Adolescents' Academic Success: The Role of Discrimination, Academic Motivation, and Gender

ERIC Educational Resources Information Center

Alfaro, Edna C.; Umana-Taylor, Adriana J.; Gonzales-Backen, Melinda A.; Bamaca, Mayra Y.; Zeiders, Katharine H.

2009-01-01

Guided by the academic resilience perspective, the current longitudinal study examined whether academic motivation mediated the relation between Latino adolescents' (N = 221) experiences with discrimination and their academic success. The potential moderating role of gender was also examined. Using multiple group analysis in structural equation…

The role of protein O-linked beta-N-acetylglucosamine in mediating cardiac stress responses.

PubMed

Chatham, John C; Marchase, Richard B

2010-02-01

The modification of serine and threonine residues of nuclear and cytoplasmic proteins by O-linked beta-N-acetylglucosamine (O-GlcNAc) has emerged as a highly dynamic post-translational modification that plays a critical role in regulating numerous biological processes. Much of our understanding of the mechanisms underlying the role of O-GlcNAc on cellular function has been in the context of its adverse effects in mediating a range of chronic disease processes, including diabetes, cancer and neurodegenerative diseases. However, at the cellular level it has been shown that O-GlcNAc levels are increased in response to stress; augmentation of this response improved cell survival while attenuation decreased cell viability. Thus, it has become apparent that strategies that augment O-GlcNAc levels are pro-survival, whereas those that reduce O-GlcNAc levels decrease cell survival. There is a long history demonstrating the effectiveness of acute glucose-insulin-potassium (GIK) treatment and to a lesser extent glutamine in protecting against a range of stresses, including myocardial ischemia. A common feature of these approaches for metabolic cardioprotection is that they both have the potential to stimulate O-GlcNAc synthesis. Consequently, here we examine the links between metabolic cardioprotection with the ischemic cardioprotection associated with acute increases in O-GlcNAc levels. Some of the protective mechanisms associated with activation of O-GlcNAcylation appear to be transcriptionally mediated; however, there is also strong evidence to suggest that transcriptionally independent mechanisms also play a critical role. In this context we discuss the potential link between O-GlcNAcylation and cardiomyocyte calcium homeostasis including the role of non-voltage gated, capacitative calcium entry as a potential mechanism contributing to this protection. Copyright 2009 Elsevier B.V. All rights reserved.

Social Competence and Social Support as Mediators between Comorbid Depressive and Conduct Problems and Functional Outcomes in Middle School Children

ERIC Educational Resources Information Center

Rockhill, Carol M.; Vander Stoep, Ann; McCauley, Elizabeth; Katon, Wayne J.

2009-01-01

This study examined the roles of social competence and social support as potential mediators of the association between psychopathology and functional outcomes in a middle school sample (n = 521). Participants were stratified into four psychopathology risk groups (depression only, conduct problems only, comorbid depression and conduct problems,…

[6]-Gingerol Affects Glucose Metabolism by Dual Regulation via the AMPKα2-Mediated AS160-Rab5 Pathway and AMPK-Mediated Insulin Sensitizing Effects.

PubMed

Lee, Jung Ok; Kim, Nami; Lee, Hye Jeong; Moon, Ji Wook; Lee, Soo Kyung; Kim, Su Jin; Kim, Joong Kwan; Park, Sun Hwa; Kim, Hyeon Soo

2015-07-01

[6]-Gingerol has been used to control diabetes and dyslipidemia; however, its metabolic role is poorly understood. In this study, [6]-gingerol increased adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation in mouse skeletal muscle C2C12 cells. Stimulation of glucose uptake by [6]-gingerol was dependent on AMPKα2. Moreover, both Inhibition and knockdown of AMPKα2 blocked [6]-gingerol-induced glucose uptake. [6]-Gingerol significantly decreased the activity of protein phosphatase 2A (PP2A). Inhibition of PP2A activity with okadaic acid enhanced the phosphorylation of AMPKα2. Moreover, the interaction between AMPKα2 and PP2A was increased by [6]-gingerol, suggesting that PP2A mediates the effect of [6]-gingerol on AMPK phosphorylation. In addition, [6]-gingerol increased the phosphorylation of Akt-substrate 160 (AS160), which is a Rab GTPase-activating protein. Inhibition of AMPKα2 blocked [6]-gingerol-induced AS160 phosphorylation. [6]-gingerol increased the Rab5, and AMPKα2 knockdown blocked [6]-gingerol-induced expression of Rab5, indicating AMPK play as an upstream of Rab5. It also increased glucose transporter 4 (GLUT4) mRNA and protein expression and stimulated GLUT4 translocation. Furthermore, insulin-mediated glucose uptake and Akt phosphorylation were further potentiated by [6]-gingerol treatment. This potentiation was not observed in the presence of AMPK inhibitor compound C. In summary, our results suggest that [6]-gingerol plays an important role in glucose metabolism via the AMPKα2-mediated AS160-Rab5 pathway and through potentiation of insulin-mediated glucose regulation. © 2015 Wiley Periodicals, Inc.

Tumor Necrosis Factor-α, a Regulator and Therapeutic Agent on Breast Cancer.

PubMed

Liu, Dongwu; Wang, Xiaoqian; Chen, Zhiwei

2016-01-01

The cell-mediated immunity and cytotoxic agents play a significant role on tumor cell apoptosis. Tumor necrosis factor-α (TNF-α) is an intricate linker between inflammation and cancer through mediating the process of apoptosis and cell-mediated immunity. A variety of evidences have confirmed the critical role of TNF-α on tumor migration, proliferation, matrix degradation, tumor metastasis, invasion, and angiogenesis. Through binding to receptors, TNF-α participates in activating multiple cell signaling cascades that link inflammation, survival and evolution towards breast cancer. TNF-α is an important agent for tumor biotherapy, but its clinical application is limited for its severe fatal systemic toxicity. The poly-lactic acid microspheres (PLAM) with intratumoral cytokine release hold tremendous potential for the immunotherapy of breast cancer, and TNF-α antagonists may offer therapeutic potential in solid tumors. In addition, TNF-α is related with the blockage of estrogen and progesterone receptors. For breast cancer treatment, it is necessary to understand the molecular signaling pathways that mediate TNF-α and the aggressive behavior of negative breast cancer. The aim of present review is to summarize the effect of TNF-α on breast cancer cells.

Body image concern among Australian adolescent girls: the role of body comparisons with models and peers.

PubMed

Carey, Renee N; Donaghue, Ngaire; Broderick, Pia

2014-01-01

This study investigated the potential mediating roles of body comparisons with peers and models in the relationship between the internalization of thinness norms and body image concern. A total of 224 Western Australian girls aged 14-15 completed questionnaires assessing their endorsement of thinness norms, body image concerns, and frequency of body comparisons with peers and with models. Both targets of body comparisons were found to significantly mediate the relationship between the endorsement of thinness norms and body image concern, with body comparison with peers a stronger mediator than comparison with models. These findings show that body comparison with peers, in particular, plays a significant role in the experience of body image concerns among adolescent girls, and should be given a higher profile in programs designed to prevent or reduce body image concern. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pathways to social anxiety: the role of reinforcement sensitivities and emotion regulation.

PubMed

O'Connor, Elodie J; Staiger, Petra K; Kambouropoulos, Nicolas; Smillie, Luke D

2014-12-30

Past research has demonstrated a strong relationship between threat sensitivity and social anxiety; however, the relationship between reward sensitivity and social anxiety is less clear. Further, the role that emotion regulation (ER) may play in the expression of social anxiety disorder (SAD) is rarely considered. The current study tested whether two emotion regulation strategies (emotional suppression and cognitive reappraisal) mediated associations between threat sensitivity and reward sensitivity and social anxiety in a community sample (402 adults, 78% female; Mage=32.49, S.D.age=11.53). Path analyses indicated that low reappraisal mediated the relationship between high threat sensitivity and high social anxiety; and both low reappraisal and high suppression mediated the relationship between low reward sensitivity and high social anxiety. These results highlight the potential role that emotion regulation plays in the relationship between trait motivation and social anxiety. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Explaining sex differences in reactions to relationship infidelities: comparisons of the roles of sex, gender, beliefs, attachment, and sociosexual orientation.

PubMed

Brase, Gary L; Adair, Lora; Monk, Kale

2014-02-04

To the extent that sex differences are mediated by mechanisms such as sex-roles and beliefs, individual differences in these more proximate traits should account for significant portions of relevant sex differences. Differences between women and men in reactions to sexual and emotional infidelity were assessed in a large sample of participants (n = 477), and these target reactions were evaluated as a function of many potential proximate mediators (infidelity implications beliefs, gender-role beliefs, interpersonal trust, attachment style, sociosexuality, and culture of honor beliefs) and as a function of participant sex. Results found a consistent sex difference that was not mediated by any other variables, although a handful of other variables were related to male, but not female, individual differences. These findings suggest particularly promising directions for future research on integrating evolutionarily based sex differences and proximate individual differences.

Functional Roles of p38 Mitogen-Activated Protein Kinase in Macrophage-Mediated Inflammatory Responses

PubMed Central

Yang, Yanyan; Yu, Tao; Sung, Gi-Ho; Yoo, Byong Chul

2014-01-01

Inflammation is a natural host defensive process that is largely regulated by macrophages during the innate immune response. Mitogen-activated protein kinases (MAPKs) are proline-directed serine and threonine protein kinases that regulate many physiological and pathophysiological cell responses. p38 MAPKs are key MAPKs involved in the production of inflammatory mediators, including tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2). p38 MAPK signaling plays an essential role in regulating cellular processes, especially inflammation. In this paper, we summarize the characteristics of p38 signaling in macrophage-mediated inflammation. In addition, we discuss the potential of using inhibitors targeting p38 expression in macrophages to treat inflammatory diseases. PMID:24771982

From hatching to dispatching: the multiple cellular roles of the Hsp70 molecular chaperone machinery.

PubMed

Meimaridou, Eirini; Gooljar, Sakina B; Chapple, J Paul

2009-01-01

Molecular chaperones are best recognized for their roles in de novo protein folding and the cellular response to stress. However, many molecular chaperones, and in particular the Hsp70 chaperone machinery, have multiple diverse cellular functions. At the molecular level, chaperones are mediators of protein conformational change. To facilitate conformational change of client/substrate proteins, in manifold contexts, chaperone power must be closely regulated and harnessed to specific cellular locales--this is controlled by cochaperones. This review considers specialized functions of the Hsp70 chaperone machinery mediated by its cochaperones. We focus on vesicular trafficking, protein degradation and a potential role in G protein-coupled receptor processing.

Attachment insecurities and women's sexual function and satisfaction: the mediating roles of sexual self-esteem, sexual anxiety, and sexual assertiveness.

PubMed

Brassard, Audrey; Dupuy, Emmanuelle; Bergeron, Sophie; Shaver, Phillip R

2015-01-01

We examined the potential role of three mediators--sexual self-esteem, sexual anxiety, and sexual assertiveness--of the association between romantic attachment insecurities (anxiety and avoidance) and two aspects of women's sexual functioning: sexual function and sexual satisfaction. A sample of 556 women aged 18 to 30 agreed to complete an online series of validated questionnaires assessing attachment insecurities and several aspects of sexual functioning. Lower sexual self-esteem and higher sexual anxiety mediated the associations between attachment anxiety and lower sexual function and satisfaction. Lower sexual self-esteem and higher sexual anxiety also partially mediated the links between attachment-related avoidance and the two sexual functioning variables. Sexual assertiveness, however, did not mediate these associations. A significant interaction between attachment anxiety and avoidance was also found to predict sexual satisfaction, with women high in avoidance and low in anxiety being the least satisfied. Results are discussed in terms of theoretical and clinical implications.

A Potential Role for Acrolein in Neutrophil-Mediated Chronic Inflammation.

PubMed

Noerager, Brett D; Xu, Xin; Davis, Virginia A; Jones, Caleb W; Okafor, Svetlana; Whitehead, Alicia; Blalock, J Edwin; Jackson, Patricia L

2015-12-01

Neutrophils (PMNs) are key mediators of inflammatory processes throughout the body. In this study, we investigated the role of acrolein, a highly reactive aldehyde that is ubiquitously present in the environment and produced endogenously at sites of inflammation, in mediating PMN-mediated degradation of collagen facilitating proline-glycine-proline (PGP) production. We treated peripheral blood neutrophils with acrolein and analyzed cell supernatants and lysates for matrix metalloproteinase-9 (MMP-9) and prolyl endopeptidase (PE), assessed their ability to break down collagen and release PGP, and assayed for the presence of leukotriene A4 hydrolase (LTA4H) and its ability to degrade PGP. Acrolein treatment induced elevated production and functionality of collagen-degrading enzymes and generation of PGP fragments. Meanwhile, LTA4H levels and triaminopeptidase activity declined with increasing concentrations of acrolein thereby sparing PGP from enzymatic destruction. These findings suggest that acrolein exacerbates the acute inflammatory response mediated by neutrophils and sets the stage for chronic pulmonary and systemic inflammation.

Mechanistic studies of cancer cell mitochondria- and NQO1-mediated redox activation of beta-lapachone, a potentially novel anticancer agent

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

Li, Jason Z.; Ke, Yuebin; Misra, Hara P.

Beta-lapachone (beta-Lp) derived from the Lapacho tree is a potentially novel anticancer agent currently under clinical trials. Previous studies suggested that redox activation of beta-Lp catalyzed by NAD(P)H:quinone oxidoreductase 1 (NQO1) accounted for its killing of cancer cells. However, the exact mechanisms of this effect remain largely unknown. Using chemiluminescence and electron paramagnetic resonance (EPR) spin-trapping techniques, this study for the first time demonstrated the real-time formation of ROS in the redox activation of beta-lapachone from cancer cells mediated by mitochondria and NQO1 in melanoma B16–F10 and hepatocellular carcinoma HepG2 cancer cells. ES936, a highly selective NQO1 inhibitor, and rotenone,more » a selective inhibitor of mitochondrial electron transport chain (METC) complex I were found to significantly block beta-Lp meditated redox activation in B16–F10 cells. In HepG2 cells ES936 inhibited beta-Lp-mediated oxygen radical formation by ∼ 80% while rotenone exerted no significant effect. These results revealed the differential contribution of METC and NQO1 to beta-lapachone-induced ROS formation and cancer cell killing. In melanoma B16–F10 cells that do not express high NQO1 activity, both NOQ1 and METC play a critical role in beta-Lp redox activation. In contrast, in hepatocellular carcinoma HepG2 cells expressing extremely high NQO1 activity, redox activation of beta-Lp is primarily mediated by NQO1 (METC plays a minor role). These findings will contribute to our understanding of how cancer cells are selectively killed by beta-lapachone and increase our ability to devise strategies to enhance the anticancer efficacy of this potentially novel drug while minimizing its possible adverse effects on normal cells. - Highlights: • Both isolated mitochondria and purified NQO1 are able to generate ROS by beta-Lp. • The differential roles of mitochondria and NQO1 in mediating redox activation of beta-Lp • In cancer cells with low NQO1 expression, mitochondria play a critical role in beta-Lp redox activation. • In cancer cells with high NQO1 activity, redox activation of beta-Lp is primarily mediated by NQO1.« less

Associations of Organizational Justice with Tinnitus and the Mediating Role of Depressive Symptoms and Burnout-Findings from a Cross-Sectional Study.

PubMed

Herr, Raphael M; Loerbroks, Adrian; Bosch, Jos A; Seegel, Max; Schneider, Michael; Schmidt, Burkhard

2016-04-01

Tinnitus refers to the perception of a sound while an external source is absent. Research has identified work-related stress and its potential mental health-related sequelaes, i.e., depression and burnout, as risk factors for tinnitus. Perceived unfairness at work (organizational injustice), which is considered a psychosocial occupational stressor, has been shown to predict depression and burnout but its potential associations with tinnitus remains unaddressed. The aim was to determine the relationship of organizational injustice with tinnitus, and to examine depression and burnout as potential mediators. Cross-sectional data from a sample of 1632 employees were used. Tinnitus was assessed by self-report (n = 207; 13.9 %). Organizational justice and its subcomponents (interactional and procedural justice), burnout, and depressive symptoms were measured by validated questionnaires. Associations were assessed by logistic regressions, and mediation was assessed by maximum likelihood logistic regression estimations. Overall organizational justice, interactional and procedural justice were inversely related to tinnitus (z-score for overall justice: OR = 0.754; 95 % CI = 0.649 to 0.876). These associations were independent of demographics, socioeconomic status, job characteristics (including potential noise exposure), and health behaviors. Mediation analyses suggested a potential mediation by burnout (95 % CI indirect effect -0.188 to -0.066) and depressive symptoms (95 % CI indirect effect -0.160 to -0.043). Parallel multiple mediation analysis revealed that mediation through burnout was significantly larger than through depressive symptoms. Organizational justice appeared inversely related to tinnitus and this association was explained by individual differences in burnout symptoms, suggesting mediation. Longitudinal studies may further help to strengthen the evidence base for prevention of tinnitus through promotion of organizational justice and prevention of burnout.

Mitochondria-targeted esculetin alleviates mitochondrial dysfunction by AMPK-mediated nitric oxide and SIRT3 regulation in endothelial cells: potential implications in atherosclerosis.

PubMed

Karnewar, Santosh; Vasamsetti, Sathish Babu; Gopoju, Raja; Kanugula, Anantha Koteswararao; Ganji, Sai Krishna; Prabhakar, Sripadi; Rangaraj, Nandini; Tupperwar, Nitin; Kumar, Jerald Mahesh; Kotamraju, Srigiridhar

2016-04-11

Mitochondria-targeted compounds are emerging as a new class of drugs that can potentially alter the pathophysiology of those diseases where mitochondrial dysfunction plays a critical role. We have synthesized a novel mitochondria-targeted esculetin (Mito-Esc) with an aim to investigate its effect during oxidative stress-induced endothelial cell death and angiotensin (Ang)-II-induced atherosclerosis in ApoE(-/-) mice. Mito-Esc but not natural esculetin treatment significantly inhibited H2O2- and Ang-II-induced cell death in human aortic endothelial cells by enhancing NO production via AMPK-mediated eNOS phosphorylation. While L-NAME (NOS inhibitor) significantly abrogated Mito-Esc-mediated protective effects, Compound c (inhibitor of AMPK) significantly decreased Mito-Esc-mediated increase in NO production. Notably, Mito-Esc promoted mitochondrial biogenesis by enhancing SIRT3 expression through AMPK activation; and restored H2O2-induced inhibition of mitochondrial respiration. siSIRT3 treatment not only completely reversed Mito-Esc-mediated mitochondrial biogenetic marker expressions but also caused endothelial cell death. Furthermore, Mito-Esc administration to ApoE(-/-) mice greatly alleviated Ang-II-induced atheromatous plaque formation, monocyte infiltration and serum pro-inflammatory cytokines levels. We conclude that Mito-Esc is preferentially taken up by the mitochondria and preserves endothelial cell survival during oxidative stress by modulating NO generation via AMPK. Also, Mito-Esc-induced SIRT3 plays a pivotal role in mediating mitochondrial biogenesis and perhaps contributes to its anti-atherogenic effects.

The Regulatory Functions of Calcium and the Potential Role of Calcium in Mediating Gravitational Responses in Cells and Tissues

NASA Technical Reports Server (NTRS)

Roux, S. J. (Editor)

1983-01-01

The hypothesis that calcium plays an important part in regulating cellular response to gravity and to other environmental stimuli is explored. Topics covered include the role of calmodulin and other proteins, gravitropic responses, bone demineralization during space flight, and intracellular communication.

The mediation roles of discrepancy stress and self-esteem between masculine role discrepancy and mental health problems.

PubMed

Yang, Xue; Lau, Joseph T F; Wang, Zixin; Ma, Yee-Ling; Lau, Mason C M

2018-08-01

Masculine role discrepancy and discrepancy stress occur when men perceive that they fail to live up to the ideal manhood derived from societal prescriptions. The present study examined the associations between masculine role discrepancy and two emotional and mental health problems (social anxiety and depressive symptoms), and potential mediation effects through discrepancy stress and self-esteem in a male general population. Based on random population-based sampling, 2000 male residents in Hong Kong were interviewed. Levels of masculine role discrepancy, discrepancy stress, self-esteem, social anxiety, and depressive symptoms were assessed by using validated scales. Results of structural equation modeling analysis indicated that the proposed model fit the sample well. (χ 2 (118) = 832.34, p < .05, CFI = 0.94, NNFI = 0.91, RMSEA = 0.06). Those who were young, single and less educated were vulnerable to masculine role discrepancy, discrepancy stress, and emotional/mental health problems. We found that discrepancy stress significantly mediated the association between masculine role discrepancy and social anxiety, while self-esteem significantly mediated the associations between masculine role discrepancy and both social anxiety and depression. Study limitations mainly included the cross-sectional design and reliance on self-reported questionnaires. The associations between masculine discrepancy and social anxiety/depressive symptoms among men may be explained by the increase in discrepancy stress and decrease in self-esteem. The findings suggest needs and directions for future research for the relationship between masculine role discrepancy and men's mental health, mechanisms involved, and interventions for improvement. Copyright © 2018. Published by Elsevier B.V.

Activating RNAs associate with Mediator to enhance chromatin architecture and transcription.

PubMed

Lai, Fan; Orom, Ulf A; Cesaroni, Matteo; Beringer, Malte; Taatjes, Dylan J; Blobel, Gerd A; Shiekhattar, Ramin

2013-02-28

Recent advances in genomic research have revealed the existence of a large number of transcripts devoid of protein-coding potential in multiple organisms. Although the functional role for long non-coding RNAs (lncRNAs) has been best defined in epigenetic phenomena such as X-chromosome inactivation and imprinting, different classes of lncRNAs may have varied biological functions. We and others have identified a class of lncRNAs, termed ncRNA-activating (ncRNA-a), that function to activate their neighbouring genes using a cis-mediated mechanism. To define the precise mode by which such enhancer-like RNAs function, we depleted factors with known roles in transcriptional activation and assessed their role in RNA-dependent activation. Here we report that depletion of the components of the co-activator complex, Mediator, specifically and potently diminished the ncRNA-induced activation of transcription in a heterologous reporter assay using human HEK293 cells. In vivo, Mediator is recruited to ncRNA-a target genes and regulates their expression. We show that ncRNA-a interact with Mediator to regulate its chromatin localization and kinase activity towards histone H3 serine 10. The Mediator complex harbouring disease- displays diminished ability to associate with activating ncRNAs. Chromosome conformation capture confirmed the presence of DNA looping between the ncRNA-a loci and its targets. Importantly, depletion of Mediator subunits or ncRNA-a reduced the chromatin looping between the two loci. Our results identify the human Mediator complex as the transducer of activating ncRNAs and highlight the importance of Mediator and activating ncRNA association in human disease.

PINK1/Parkin-mediated mitophagy play a protective role in manganese induced apoptosis in SH-SY5Y cells.

PubMed

Zhang, Hong-Tao; Mi, Lan; Wang, Ting; Yuan, Lan; Li, Xue-Hui; Dong, Li-Sha; Zhao, Peng; Fu, Juan-Ling; Yao, Bi-Yun; Zhou, Zong-Can

2016-08-01

Manganese (Mn) as an environmental risk factor of Parkinson's disease (PD) is considered to cause manganism. Mitophagy is thought to play a key role in elimination the injured mitochondria. The goal of this paper was to explore whether the PINK1/Parkin-mediated mitophagy is activated and its role in Mn-induced mitochondrial dysfunction and cell death in SH-SY5Y cells. Here, we investigated effects of MnCl2 on ROS generation, mitochondrial membrane potential (MMP/ΔΨm) and apoptosis by FACS and examined PINK1/Parkin-mediated mitophagy by western-blotting and the co-localization of mitochondria and acidic lysosomes. Further, we explore the role of mitophagy in Mn-induced apoptosis by inhibition the mitophagy by knockdown Parkin level. Results show that MnCl2 dose-dependently caused ΔΨm decrease, ROS generation and apoptosis of dopaminergic SH-SY5Y cells. Moreover, Mn could induce mitophagy and PINK1/Parkin-mediated pathway was activated in SH-SY5Y cells. Transient transfection of Parkin siRNA knockdown the expressing level of parkin inhibited Mn-induced mitophagy and aggravated apoptosis of SH-SY5Y cells. In conclusion, our study demonstrated that Mn may induce PINK1/Parkin-mediated mitophagy, which may exert significant neuro-protective effect against Mn-induced dopaminergic neuronal cells apoptosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Anger and health in dementia caregivers: exploring the mediation effect of optimism.

PubMed

López, J; Romero-Moreno, R; Márquez-González, M; Losada, A

2015-04-01

Although previous studies indicate a negative association between caregivers' anger and health, the potential mechanisms linking this relationship are not yet fully understood. The aim of this study was to explore the potential mediating role of optimism in the relationship between anger and caregivers' physical health. Dementia caregivers (n = 108) were interviewed and filled out instruments assessing their anger (reaction), optimism and health (vitality). A mediational model was tested to determine whether optimism partially mediated the relationship between anger and vitality. Angry reaction was negatively associated with optimism and vitality; optimism was positively associated with vitality. Finally, the relationship between angry reaction and vitality decreased when optimism was entered simultaneously. A non-parametric bootstrap approach confirmed that optimism significantly mediated some of the relationship between angry reaction and vitality. These findings suggest that low optimism may help explain the association between caregivers' anger and reduced sense of vitality. The results provide a specific target for intervention with caregivers. Copyright © 2013 John Wiley & Sons, Ltd.

Contribution of Microglia-Mediated Neuroinflammation to Retinal Degenerative Diseases

PubMed Central

Madeira, Maria H.; Boia, Raquel; Santos, Paulo F.; Ambrósio, António F.; Santiago, Ana R.

2015-01-01

Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microglia-mediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy. PMID:25873768

Discrimination, Subjective Wellbeing, and the Role of Gender: A Mediation Model of LGB Minority Stress.

PubMed

Conlin, Sarah E; Douglass, Richard P; Ouch, Staci

2017-10-26

The present study examined the link between discrimination and the three components of subjective wellbeing (positive and negative affect and life satisfaction) among a cisgender sample of lesbian, gay, and bisexual (LGB) adults. Specifically, we investigated internalized homonegativity and expectations of rejection as potential mediators of the links between discrimination and subjective wellbeing among a sample of 215 participants. Results from our structural equation model demonstrated a strong, positive direct link between discrimination and negative affect. Discrimination also had small, negative indirect effects on life satisfaction through our two mediators. Interestingly, neither discrimination nor our two mediators were related with positive affect, demonstrating the need for future research to uncover potential buffers of this link. Finally, our model evidenced configural, metric, and scalar invariance, suggesting that our model applies well for both women and men. Practical implications and future directions for research are discussed.

Approaches to target IgE antibodies in allergic diseases.

PubMed

Balbino, Bianca; Conde, Eva; Marichal, Thomas; Starkl, Philipp; Reber, Laurent L

2018-06-15

IgE is the antibody isotype found at the lowest concentration in the circulation. However IgE can undeniably play an important role in mediating allergic reactions; best exemplified by the clinical benefits of anti-IgE monoclonal antibody (omalizumab) therapy for some allergic diseases. This review will describe our current understanding of the interactions between IgE and its main receptors FcεRI and CD23 (FcεRII). We will review the known and potential functions of IgE in health and disease: in particular, its detrimental roles in allergic diseases and chronic spontaneous urticaria, and its protective functions in host defense against parasites and venoms. Finally, we will present an overview of the drugs that are in clinical development or have therapeutic potential for IgE-mediated allergic diseases. Copyright © 2018. Published by Elsevier Inc.

Experimental Evidence of ω-3 Polyunsaturated Fatty Acid Modulation of Inflammatory Cytokines and Bioactive Lipid Mediators: Their Potential Role in Inflammatory, Neurodegenerative, and Neoplastic Diseases

PubMed Central

Calviello, Gabriella; Su, Hui-Min; Weylandt, Karsten H.; Fasano, Elena; Serini, Simona; Cittadini, Achille

2013-01-01

A large body of evidence has emerged over the past years to show the critical role played by inflammation in the pathogenesis of several diseases including some cardiovascular, neoplastic, and neurodegenerative diseases, previously not considered inflammation-related. The anti-inflammatory action of ω-3 polyunsaturated fatty acids (PUFAs), as well as their potential healthy effects against the development and progression of the same diseases, has been widely studied by our and others' laboratories. As a result, a rethinking is taking place on the possible mechanisms underlying the beneficial effects of ω-3 PUFAs against these disorders, and, in particular, on the influence that they may exert on the molecular pathways involved in inflammatory process, including the production of inflammatory cytokines and lipid mediators active in the resolving phase of inflammation. In the present review we will summarize and discuss the current knowledge regarding the modulating effects of ω-3 PUFAs on the production of inflammatory cytokines and proresolving or protective lipid mediators in the context of inflammatory, metabolic, neurodegenerative, and neoplastic diseases. PMID:23691510

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

Cha, Min-Ji; Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seongsanno, Seodamun-gu, Seoul 120-752; Jang, Jin-Kyung

Highlights: •CaMKIIδ mediates H{sub 2}O{sub 2}-induced Ca{sup 2+} overload in cardiomyocytes. •miR-145 can inhibit Ca{sup 2+} overload. •A luciferase assay confirms that miR-145 functions as a CaMKIIδ-targeting miRNA. •Overexpression of miR-145 regulates CaMKIIδ-related genes and ameliorates apoptosis. -- Abstract: A change in intracellular free calcium (Ca{sup 2+}) is a common signaling mechanism of reperfusion-induced cardiomyocyte death. Calcium/calmodulin dependent protein kinase II (CaMKII) is a critical regulator of Ca{sup 2+} signaling and mediates signaling pathways responsible for functions in the heart including hypertrophy, apoptosis, arrhythmia, and heart disease. MicroRNAs (miRNA) are involved in the regulation of cell response, including survival, proliferation,more » apoptosis, and development. However, the roles of miRNAs in Ca{sup 2+}-mediated apoptosis of cardiomyocytes are uncertain. Here, we determined the potential role of miRNA in the regulation of CaMKII dependent apoptosis and explored its underlying mechanism. To determine the potential roles of miRNAs in H{sub 2}O{sub 2}-mediated Ca{sup 2+} overload, we selected and tested 6 putative miRNAs that targeted CaMKIIδ, and showed that miR-145 represses CaMKIIδ protein expression and Ca{sup 2+} overload. We confirmed CaMKIIδ as a direct downstream target of miR-145. Furthermore, miR-145 regulates Ca{sup 2+}-related signals and ameliorates apoptosis. This study demonstrates that miR-145 regulates reactive oxygen species (ROS)-induced Ca{sup 2+} overload in cardiomyocytes. Thus, miR-145 affects ROS-mediated gene regulation and cellular injury responses.« less

Pain and symptoms of depression in older adults living in community and in nursing homes: the role of activity restriction as a potential mediator and moderator.

PubMed

López-Lopez, Almudena; González, José L; Alonso-Fernández, Miriam; Cuidad, Noelia; Matías, Borja

2014-10-01

Chronic pain is likely to lead to depressive symptoms, but the nature of this relationship is not completely clear. The aim of the present study is to analyze the role of activity restriction in the pain-depression relationship in older people, and to test the hypothesis that this role is more relevant in community-dwelling older people than in nursing home residents. Depressive symptoms, pain intensity, and activity restriction were measured in a sample of 208 older adults with osteoarthritis, 102 living in nursing homes (NH), and 106 in the community. Analyses were carried out using moderation and moderated mediation analyses approach, treating activity restriction as a confounder. RESULTS showed a significant confounding effect of activity restriction, interaction effect between pain intensity and activity restriction on depression, and modifying effect of pain intensity on depression by adding activity restriction into the model. These results suggest a potential mediating and moderating effects of activity restriction. Moreover, analyses suggest that, surprisingly, the strength of the mediation could be higher in nursing homes. Overall, it may be that what is really important to emotional well-being is not so much pain itself, but rather the way in which the pain alters older people's lives. The greater strength of the mediation in NH might be understood within the scope of self-determination theory. Generally speaking, the NH context has been considered as a coercive setting, promoting non-autonomous orientation. In this context, when events are objectively coercive, people may lack perceived autonomy and hence be at greater risk of depression.

A putative role for the plasma membrane potential in the control of the expression of the gene encoding the tomato high-affinity potassium transporter HAK5.

PubMed

Nieves-Cordones, Manuel; Miller, Anthony J; Alemán, Fernando; Martínez, Vicente; Rubio, Francisco

2008-12-01

A chimeric CaHAK1-LeHAK5 transporter with only 15 amino acids of CaHAK1 in the N-terminus mediates high-affinity K(+) uptake in yeast cells. Kinetic and expression analyses strongly suggest that LeHAK5 mediates a significant proportion of the high-affinity K(+) uptake shown by K(+)-starved tomato (Solanum lycopersicum) plants. The development of high-affinity K(+) uptake, putatively mediated by LeHAK5, was correlated with increased LeHAK5 mRNA levels and a more negative electrical potential difference across the plasma membrane of root epidermal and cortical cells. However, this increase in high-affinity K(+) uptake was not correlated with the root K(+) content. Thus, (i) growth conditions that result in a hyperpolarized root plasma membrane potential, such as K(+) starvation or growth in the presence of NH(4) (+), but which do not decrease the K(+) content, lead to increased LeHAK5 expression; (ii) the presence of NaCl in the growth solution, which prevents the hyperpolarization induced by K(+) starvation, also prevents LeHAK5 expression. Moreover, once the gene is induced, depolarization of the plasma membrane potential then produces a decrease in the LeHAK5 mRNA. On the basis of these results, we propose that the plant membrane electrical potential plays a role in the regulation of the expression of this gene encoding a high-affinity K(+) transporter.

Youth experiences of family violence and teen dating violence perpetration: cognitive and emotional mediators.

PubMed

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

2012-03-01

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 influences upon one another are described. Theory and research on the role of emotions and emotional processes in the relation between youths' exposure to family violence and teen dating violence perpetration are also reviewed. We present an integrated model that highlights how emotions and emotional processes work in tandem with hypothesized cognitive mediators to predict teen dating violence.

The role of exercise dependence for the relationship between exercise behavior and eating pathology: mediator or moderator?

PubMed

Cook, Brian J; Hausenblas, Heather A

2008-05-01

Our study examined the potential mediating or moderating effect of exercise dependence on the exercise-eating pathology relationship. Female university students (N = 330) completed Internet-based self-report measures of exercise behavior, exercise dependence, and eating pathology. Exercise dependence served as a mediator for the relationship between exercise and eating pathology. This unidirectional causal model suggests that an individual's pathological motivation or compulsion to exercise is the critical mediating component in the exercise-eating pathology relationship. The best target for removing the link between exercise behavior and eating pathology may be reformulating exercise dependence symptoms.

The mediating role of psychological capital on the association between occupational stress and job burnout among bank employees in China.

PubMed

Li, Xirui; Kan, Dan; Liu, Li; Shi, Meng; Wang, Yang; Yang, Xiaoshi; Wang, Jiana; Wang, Lie; Wu, Hui

2015-03-10

Although job burnout is common among bank employees, few studies have explored positive resources for combating burnout in this population. This study aims to explore the relationship between occupational stress and job burnout among Chinese bank employees, and particularly the mediating role of psychological capital. A cross-sectional study was conducted in Liaoning, China, during June to August of 2013. A questionnaire that included the effort-reward imbalance scale, the Psychological Capital Questionnaire and the Maslach Burnout Inventory-General Survey, as well as demographic and working factors, was distributed to 1739 employees of state-owned banks. This yielded 1239 effective respondents (467 men, 772 women). Asymptotic and resampling strategies explored the mediating role of psychological capital in the relationship between occupational stress and job burnout. Both extrinsic effort and overcommitment were positively associated with emotional exhaustion and depersonalisation. Meanwhile, reward was negatively associated with emotional exhaustion and depersonalisation, but positively associated with personal accomplishment. There was a gender difference in the mediating role of Psychological capital on the occupational stress-job burnout. In male bank employees, Psychological capital mediated the relationships of extrinsic effort and reward with emotional exhaustion and depersonalization; in female bank employees, it partially mediated the relationships of extrinsic effort, reward and overcommitment with emotional exhaustion and depersonalisation, as well as the relationship between reward and personal accomplishment. Psychological capital was generally a mediator between occupational stress and job burnout among Chinese bank employees. Psychological capital may be a potential positive resource in reducing the negative effects of occupational stress on job burnout and relieving job burnout among bank employees, especially female bank employees.

The Mediating Role of Psychological Capital on the Association between Occupational Stress and Job Burnout among Bank Employees in China

PubMed Central

Li, Xirui; Kan, Dan; Liu, Li; Shi, Meng; Wang, Yang; Yang, Xiaoshi; Wang, Jiana; Wang, Lie; Wu, Hui

2015-01-01

Although job burnout is common among bank employees, few studies have explored positive resources for combating burnout in this population. This study aims to explore the relationship between occupational stress and job burnout among Chinese bank employees, and particularly the mediating role of psychological capital. A cross-sectional study was conducted in Liaoning, China, during June to August of 2013. A questionnaire that included the effort-reward imbalance scale, the Psychological Capital Questionnaire and the Maslach Burnout Inventory-General Survey, as well as demographic and working factors, was distributed to 1739 employees of state-owned banks. This yielded 1239 effective respondents (467 men, 772 women). Asymptotic and resampling strategies explored the mediating role of psychological capital in the relationship between occupational stress and job burnout. Both extrinsic effort and overcommitment were positively associated with emotional exhaustion and depersonalisation. Meanwhile, reward was negatively associated with emotional exhaustion and depersonalisation, but positively associated with personal accomplishment. There was a gender difference in the mediating role of Psychological capital on the occupational stress-job burnout. In male bank employees, Psychological capital mediated the relationships of extrinsic effort and reward with emotional exhaustion and depersonalization; in female bank employees, it partially mediated the relationships of extrinsic effort, reward and overcommitment with emotional exhaustion and depersonalisation, as well as the relationship between reward and personal accomplishment. Psychological capital was generally a mediator between occupational stress and job burnout among Chinese bank employees. Psychological capital may be a potential positive resource in reducing the negative effects of occupational stress on job burnout and relieving job burnout among bank employees, especially female bank employees. PMID:25764060

Father's and Mother's Perceptions of Parenting Styles as Mediators of the Effects of Parental Psychopathology on Antisocial Behavior in Outpatient Children and Adolescents

ERIC Educational Resources Information Center

Vera, Juan; Granero, Roser; Ezpeleta, Lourdes

2012-01-01

The aim was to examine the potential mediating role of father's and mother's parenting styles in the association between parental psychopathology and antisocial behavior in children, and whether this pathway was moderated by child's sex. Participants included both parents and 338 Spanish outpatient children between 8 and 17 years (56.5% boys).…

Instagram addiction and the Big Five of personality: The mediating role of self-liking.

PubMed

Kircaburun, Kagan; Griffiths, Mark D

2018-03-01

Background and aims Recent research has suggested that social networking site use can be addictive. Although extensive research has been carried out on potential addiction to social networking sites, such as Facebook, Twitter, YouTube, and Tinder, only one very small study has previously examined potential addiction to Instagram. Consequently, the objectives of this study were to examine the relationships between personality, self-liking, daily Internet use, and Instagram addiction, as well as exploring the mediating role of self-liking between personality and Instagram addiction using path analysis. Methods A total of 752 university students completed a self-report survey, including the Instagram Addiction Scale (IAS), the Big Five Inventory (BFI), and the Self-Liking Scale. Results Results indicated that agreeableness, conscientiousness, and self-liking were negatively associated with Instagram addiction, whereas daily Internet use was positively associated with Instagram addiction. The results also showed that self-liking partially mediated the relationship of Instagram addiction with agreeableness and fully mediated the relationship between Instagram addiction with conscientiousness. Discussion and conclusions This study contributes to the small body of literature that has examined the relationship between personality and social networking site addiction and is one of only two studies to examine the addictive use of Instagram and the underlying factors related to it.

Workplace Bullying as a Risk Factor for Musculoskeletal Disorders: The Mediating Role of Job-Related Psychological Strain

PubMed Central

Vignoli, Michela; Guglielmi, Dina; Balducci, Cristian; Bonfiglioli, Roberta

2015-01-01

Workplace bullying is considered by the European Agency for Safety and Health at Work one of the emerging psychosocial risk factors that could negatively affect workers' health. Thus, the aim of this study was to analyze the process that leads from bullying to negative health (such as musculoskeletal disorders (MSDs)), testing the mediating role of job-related strain. Data were collected on 512 workers (62.9% female; mean age = 43.6 years) of a retail chain who filled in a self-report questionnaire after a one-hour training session on work-related stress. Data analyses were performed controlling for potentially confounding variables (i.e., gender, age, organizational role, type of contract, and perceived physical job demands). Preacher and Hayes analytical approach was used to test the indirect relationship between bullying and MSDs. Results showed that work-related strain mediates the relationship between bullying and MSDs considered (low back, upper back, and neck) except for MSDs of the shoulders. Our study confirms the role played by bullying and job-related strain in determining workers' MSDs. PMID:26557693

Workplace Bullying as a Risk Factor for Musculoskeletal Disorders: The Mediating Role of Job-Related Psychological Strain.

PubMed

Vignoli, Michela; Guglielmi, Dina; Balducci, Cristian; Bonfiglioli, Roberta

2015-01-01

Workplace bullying is considered by the European Agency for Safety and Health at Work one of the emerging psychosocial risk factors that could negatively affect workers' health. Thus, the aim of this study was to analyze the process that leads from bullying to negative health (such as musculoskeletal disorders (MSDs)), testing the mediating role of job-related strain. Data were collected on 512 workers (62.9% female; mean age = 43.6 years) of a retail chain who filled in a self-report questionnaire after a one-hour training session on work-related stress. Data analyses were performed controlling for potentially confounding variables (i.e., gender, age, organizational role, type of contract, and perceived physical job demands). Preacher and Hayes analytical approach was used to test the indirect relationship between bullying and MSDs. Results showed that work-related strain mediates the relationship between bullying and MSDs considered (low back, upper back, and neck) except for MSDs of the shoulders. Our study confirms the role played by bullying and job-related strain in determining workers' MSDs.

Role of L-Type Ca[superscript 2+] Channel Isoforms in the Extinction of Conditioned Fear

ERIC Educational Resources Information Center

Busquet, Perrine; Hetzenauer, Alfred; Sinnegger-Brauns, Martina J.; Striessnig, Jorg; Singewald, Nicolas

2008-01-01

Dihydropyridine (DHP) L-type Ca[superscript 2+] channel (LTCC) antagonists, such as nifedipine, have been reported to impair the extinction of conditioned fear without interfering with its acquisition. Identification of the LTCC isoforms mediating this DHP effect is an essential basis to reveal their role as potential drug targets for the…

Rasagiline protects against alpha-synuclein induced sensitivity to oxidative stress in dopaminergic cells

PubMed Central

Chau, K.Y.; Cooper, J.M.; Schapira, A.H.V.

2010-01-01

Rasagiline is a propargylamine and irreversible monoamine oxidase (MAO) B inhibitor used for the treatment of Parkinson's disease (PD). It has demonstrated neuroprotective properties in laboratory studies. Current concepts of PD aetiopathogenesis include the role of alpha-synuclein, protein aggregation, free radical metabolism and mitochondrial dysfunction in contributing to cell death. We have used a combination of alpha-synuclein and free radical mediated toxicity in a dopaminergic cell line to provide a model of nigral toxicity in order to investigate the potential molecular mechanisms that mediate rasagiline protection. We demonstrate that rasagiline protects against cell death induced by the combination of free radicals generated by paraquat and either wild-type or A53T mutant alpha-synuclein over-expression. This protection was associated with a reduction in caspase 3 activation, a reduction in superoxide generation and a trend to ameliorate the fall in mitochondrial membrane potential. Rasagiline induced an increase in cellular glutathione levels. The results support a role for rasagiline in protecting dopaminergic cells against free radical mediated damage and apoptosis in the presence of alpha-synuclein over-expression. The data are of relevance to the interpretation of the potential mechanisms of action of rasagiline in explaining the results of disease modification trials in PD. PMID:20624440

Insulin-mediated inhibition of p38 mitogen-activated protein kinase protects cardiomyocytes in severe burns.

PubMed

Lv, Gen-fa; Dong, Mao-long; Hu, Da-hai; Zhang, Wan-fu; Wang, Yun-chuan; Tang, Chao-wu; Zhu, Xiong-xiang

2011-01-01

Thermal injury inhibits Akt activation and upregulates p38 mitogen-activated protein kinase, which in turn induces inflammation and increases apoptosis. This study aimed to elucidate the mechanism underlying the cytoprotective role of insulin in severe burns by examining the effects of insulin on inflammation and apoptosis mediated by p38 mitogen-activated protein kinase in burn serum-challenged cardiomyocytes. Neonatal rat cardiomyocytes were exposed to burn serum for 6 hours in the presence or absence of insulin and pretreated with inhibitors to p38 mitogen-activated protein kinase (SB203580) and Akt (LY294002). The authors examined expression of myocardial tumor necrosis factor-alpha, cardiac myofilament proteins caspase-3 and Bcl2, and apoptosis. Burn serum-induced upregulation of tumor necrosis factor was inhibited by both SB203580 and insulin. LY294002 reversed insulin-mediated downregulation of tumor necrosis factor. Both SB203580 and insulin inhibited apoptosis, resulting in fewer pyknotic nuclei and inhibition of caspase-3 activation and Bcl2 downregulation. LY294002 reversed insulin-mediated inhibition of apoptosis. Insulin decreases inflammatory cytokine expression and apoptosis via PI3K/Akt-mediated inhibition of p38 mitogen-activated protein kinase. The cytoprotective role of insulin suggests that it may have a potential role in strategies for treating thermal injuries.

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

PubMed

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

2018-04-01

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

Education and indoor smoking among parents who smoke: the mediating role of perceived social norms of smoking.

PubMed

Saito, Junko; Shibanuma, Akira; Yasuoka, Junko; Kondo, Naoki; Takagi, Daisuke; Jimba, Masamine

2018-02-02

Parents with less formal education are more likely to smoke indoors, causing socioeconomic disparity in children's exposure to second-hand smoke. However, little is known about the roles of social factors in the socioeconomic gradients of indoor smoking. We tested the potential mediating role of perceived smoking norms on the associations between education and indoor smoking among parents who smoke. In this cross-sectional study, 822 smoking fathers and 823 smoking mothers, who lived with young children and were members of a Japanese online survey panel, participated. Structural equation modelling tested the mediating effects of perceived descriptive and subjective norms on the association between education and indoor smoking. Perceived pro-smoking norms, which were more prevalent among less-educated parents, mediated the association between education and indoor smoking. Household smoking status and worksite smoking ban also mediated this association via perceived norms, but only for fathers. Perceived descriptive norms explained 28.5% of the association for fathers and 37.6% for mothers; the corresponding percentages for perceived subjective norms were 9.8% and 26.6%, respectively. Perceived smoking norms, household smoking status, and a worksite smoking ban could be vital targets of a strategy aimed at reducing the socioeconomic disparity in parental home smoking behaviours.

Empirical solvent-mediated potentials hold for both intra-molecular and inter-molecular inter-residue interactions.

PubMed Central

Keskin, O.; Bahar, I.; Badretdinov, A. Y.; Ptitsyn, O. B.; Jernigan, R. L.

1998-01-01

Whether knowledge-based intra-molecular inter-residue potentials are valid to represent inter-molecular interactions taking place at protein-protein interfaces has been questioned in several studies. Differences in the chain connectivity effect and in residue packing geometry between interfaces and single chain monomers have been pointed out as possible sources of distinct energetics for the two cases. In the present study, the interfacial regions of protein-protein complexes are examined to extract inter-molecular inter-residue potentials, using the same statistical methods as those previously adopted for intra-molecular residue pairs. Two sets of energy parameters are derived, corresponding to solvent-mediation and "average residue" mediation. The former set is shown to be highly correlated (correlation coefficient 0.89) with that previously obtained for inter-residue interactions within single chain monomers, while the latter exhibits a weaker correlation (0.69) with its intra-molecular counterpart. In addition to the close similarity of intra- and inter-molecular solvent-mediated potentials, they are shown to be significantly more residue-specific and thereby discriminative compared to the residue-mediated ones, indicating that solvent-mediation plays a major role in controlling the effective inter-residue interactions, either at interfaces, or within single monomers. Based on this observation, a reduced set of energy parameters comprising 20 one-body and 3 two-body terms is proposed (as opposed to the 20 x 20 tables of inter-residue potentials), which reproduces the conventional 20 x 20 tables with a correlation coefficient of 0.99. PMID:9865952

Conservation and Divergence of Mediator Structure and Function: Insights from Plants.

PubMed

Dolan, Whitney L; Chapple, Clint

2017-01-01

The Mediator complex is a large, multisubunit, transcription co-regulator that is conserved across eukaryotes. Studies of the Arabidopsis Mediator complex and its subunits have shown that it functions in nearly every aspect of plant development and fitness. In addition to revealing mechanisms of regulation of plant-specific pathways, studies of plant Mediator complexes have the potential to shed light on the conservation and divergence of Mediator structure and function across Kingdoms and plant lineages. The majority of insights into plant Mediator function have come from Arabidopsis because it is the only plant from which Mediator has been purified and from which an array of Mediator mutants have been isolated by forward and reverse genetics. So far, these studies indicate that, despite low sequence similarity between many orthologous subunits, the overall structure and function of Mediator is well conserved between Kingdoms. Several studies have also expanded our knowledge of Mediator to other plant species, opening avenues of investigation into the role of Mediator in plant adaptation and fitness.

Didehydro-Cortistatin A inhibits HIV-1 Tat mediated neuroinflammation and prevents potentiation of cocaine reward in Tat transgenic mice

PubMed Central

Mediouni, Sonia; Jablonski, Joseph; Paris, Jason J.; Clementz, Mark A.; Thenin-Houssier, Suzie; McLaughlin, Jay P.; Valente, Susana T.

2015-01-01

HIV-1 Tat protein has been shown to have a crucial role in HIV-1-associated neurocognitive disorders (HAND), which includes a group of syndromes ranging from undetectable neurocognitive impairment to dementia. The abuse of psychostimulants, such as cocaine, by HIV infected individuals, may accelerate and intensify neurological damage. On the other hand, exposure to Tat potentiates cocaine-mediated reward mechanisms, which further promotes HAND. Here, we show that didehydro-Cortistatin A (dCA), an analog of a natural steroidal alkaloid, crosses the blood-brain barrier, cross-neutralizes Tat activity from several HIV-1 clades and decreases Tat uptake by glial cell lines. In addition, dCA potently inhibits Tat mediated dysregulation of IL-1β, TNF-α and MCP-1, key neuroinflammatory signaling proteins. Importantly, using a mouse model where doxycycline induces Tat expression, we demonstrate that dCA reverses the potentiation of cocaine-mediated reward. Our results suggest that adding a Tat inhibitor, such as dCA, to current antiretroviral therapy may reduce HIV-1-related neuropathogenesis. PMID:25613133

The roles of melanin-concentrating hormone in energy balance and reproductive function: Are they connected?

PubMed

Naufahu, Jane; Cunliffe, Adam D; Murray, Joanne F

2013-01-01

Melanin-concentrating hormone (MCH) is an anabolic neuropeptide with multiple and diverse physiological functions including a key role in energy homoeostasis. Rodent studies have shown that the ablation of functional MCH results in a lean phenotype, increased energy expenditure and resistance to diet-induced obesity. These findings have generated interest among pharmaceutical companies vigilant for potential anti-obesity agents. Nutritional status affects reproductive physiology and behaviours, thereby optimising reproductive success and the ability to meet energetic demands. This complex control system entails the integration of direct or indirect peripheral stimuli with central effector systems and involves numerous mediators. A role for MCH in the reproductive axis has emerged, giving rise to the premise that MCH may serve as an integratory mediator between those discrete systems that regulate energy balance and reproductive function. Hence, this review focuses on published evidence concerning i) the role of MCH in energy homoeostasis and ii) the regulatory role of MCH in the reproductive axis. The question as to whether the MCH system mediates the integration of energy homoeostasis with the neuroendocrine reproductive axis and, if so, by what means has received limited coverage in the literature; evidence to date and current theories are summarised herein.

Regulation of the Cardiovascular System by Histamine.

PubMed

Hattori, Yuichi; Hattori, Kohshi; Matsuda, Naoyuki

2017-01-01

Histamine mediates a wide range of cellular responses, including allergic and inflammatory reactions, gastric acid secretion, and neurotransmission in the central nervous system. Histamine also exerts a series of actions upon the cardiovascular system but may not normally play a significant role in regulating cardiovascular function. During tissue injury, inflammation, and allergic responses, mast cells (or non-mast cells) within the tissues can release large amounts of histamine that leads to noticeable cardiovascular effects. Owing to intensive research during several decades, the distribution, function, and pathophysiological role of cardiovascular H 1 - and H 2 -receptors has become recognized adequately. Besides the recognized H 1 - and H 2 -receptor-mediated cardiovascular responses, novel roles of H 3 - and H 4 -receptors in cardiovascular physiology and pathophysiology have been identified over the last decade. In this review, we describe recent advances in our understanding of cardiovascular function and dysfunction mediated by histamine receptors, including H 3 - and H 4 -receptors, their potential mechanisms of action, and their pathological significance.

HTLV-1 Tax protein cooperates with Ras in protecting cells from apoptosis.

PubMed

Vajente, Nicola; Trevisan, Roberta; Saggioro, Daniela

2009-02-01

Tax protein of the human T-cell leukemia virus type 1 (HTLV-1) plays a critical role in HTLV-I-correlated diseases through its ability to deregulate the expression of a vast array of cellular genes. We have previously shown that Tax counteracts apoptosis induced by stimuli triggering mitochondria apoptotic pathway, most likely by activating CREB-mediated transcription and affecting the phosphorylation levels of CREB at Ser-133. Here, we report data that indicate the oncoprotein Ras as a possible mediator of Tax-induced apoptosis protection and suggest a possible role of Tax in Ras activation. In addition, using inhibitors of down stream effectors of Ras, we found that ERK signaling is the most relevant for Tax-mediated apoptosis protection. As a whole, our findings provide intriguing evidence of a possible link between Ras signaling and Tax capability to counteract apoptosis and to enhance P-CREB levels, and implicates a potential role for Ras in HTLV-1-induced diseases.

The role of mastery in the relationship between perceived ethnic discrimination and depression: The HELIUS study.

PubMed

Slotman, Anne; Snijder, Marieke B; Ikram, Umar Z; Schene, Aart H; Stevens, Gonneke W J M

2017-04-01

This study examined the mediating and moderating role of one's sense of mastery in the relationship between perceived ethnic discrimination and depression. Questionnaire data from participants of the Healthy Life in an Urban Setting (HELIUS) study were used, containing responses from 9,141 Surinamese, Turkish, Moroccan, and Ghanaian immigrant adults, aged 18 to 70, living in Amsterdam, the Netherlands. Results of path modeling indicated that perceptions of ethnic discrimination were positively related to depression symptomatology, and this relationship was moderated and partially mediated by mastery. Results remained fairly robust across sex, educational level, immigrant generation, and ethnicity. This study indicated that mastery may both serve a moderating and mediating role in the relationship between perceived ethnic discrimination and depression, suggestive of a process in which the impact of perceiving discrimination becomes increasingly more deteriorating over time. Thus, interventions focused on mastery may potentially be beneficial to improve ethnic minority mental health. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Inflammatory Bowel Disease: Pathophysiology and Current Therapeutic Approaches.

PubMed

Abraham, Bincy P; Ahmed, Tasneem; Ali, Tauseef

2017-01-01

Inflammatory bowel diseases, most commonly categorized as Crohn's disease and ulcerative colitis, are immune mediated chronic inflammatory disorders of the gastrointestinal tract. The etiopathogenesis is multifactorial with different environmental, genetic, immune mediated, and gut microbial factors playing important role. The current goals of therapy are to improve clinical symptoms, control inflammation, prevent complications, and improve quality of life. Different therapeutic agents, with their indications, mechanisms of action, and side effects are discussed in this chapter. Anti-integrin therapy, a newer therapeutic class, with its potential beneficial role in both Crohn's disease and ulcerative colitis is also mentioned. In the end, therapeutic algorithms for both diseases are reviewed.

Evidence that theory of planned behaviour variables mediate the effects of socio-demographic variables on homeless people's participation in service programmes.

PubMed

Christian, Julie; Armitage, Christopher J; Abrams, Dominic

2007-09-01

This article reports findings from two studies (N = 88, N = 100) using Ajzen's theory of planned behaviour (TPB) to predict homeless people's uptake of service programmes. Study 1 was conducted with an opportunity sample whereas Study 2 employed a representative sample. Both studies provide support for the application of the TPB, and demonstrate that the effects of demographic characteristics on behaviour were mediated by TPB variables. The discussion focuses on the role of attitudinal and normative components in actual behaviour, and on the potential role of social normative processes and stigmatization in homeless people's uptake of services.

Cytokines in the central nervous system: regulatory roles in neuronal function, cell death and repair.

PubMed

Sei, Y; Vitković, L; Yokoyama, M M

1995-01-01

Recent evidence suggests that neurons and glia can synthesize and secrete cytokines, which play critical roles in maintaining homeostasis in the central nervous system (CNS) by mediating the interaction between cells via autocrine or paracrine mechanisms. Circulating cytokines and soluble receptors also regulate neuronal function via endocrine mechanisms. Disturbance of the cytokine-mediated interaction between cells may lead to neuronal dysfunction and/or cell death and contribute to the pathogenesis of the CNS diseases (e.g., ischemia, Alzheimer's disease and HIV encephalopathy). Defining the molecular pathways of cytokine dysregulation and neurotoxicity may help to elucidate potential therapeutic interventions for many devastating CNS diseases.

The role of leadership perception as a mediator between managers' self-monitoring and subordinate attitudes.

PubMed

Özalp Türetgen, Ilknur; Unsal, Pinar; Dural, Uzay

2017-01-01

Although the role of social cognition in leadership perception has been emphasized frequently in recent years, research using this approach in an organizational context is rare. This study investigated subordinates' perceptions of their managers as leaders (that is, to what extent they perceive their manager as a leader) as a potential mediating factor explaining the relationship between managers' self-monitoring and their subordinates' attitudes toward their organizations. The study was carried out with middle-level managers (N = 64) and their subordinates (N = 210) from various business organizations in Turkey. Results indicate that subordinates' leadership perceptions of their managers mediate the relationship between managers' self-monitoring and their subordinates' affective and normative organizational commitment. These results provide insight into some of the antecedents and outcomes of leadership perception.

Parent-adolescent attachment and procrastination: The mediating role of self-worth.

PubMed

Chen, Bin-Bin

2017-01-01

Within the theoretical framework of attachment theory, the author examined associations between adolescents' procrastination and their attachment relationships with both mothers and fathers, and explored the potential mediation role of self-worth in these associations. Participants were 384 Chinese adolescents (49.6% boys, average age 15.13 years) from public schools in Shanghai, China. They completed self-report measures of 3 dimensions of parental attachment (i.e., trust, communication, and alienation), general self-worth, and procrastination. The results indicated that both paternal and maternal trust and paternal communication were negatively associated with higher levels of procrastination whereas both paternal and maternal alienation were positively associated with procrastination. In addition, self-worth mediated the associations among 3 dimensions of parental attachment and procrastination. The findings highlighted the importance of parental attachment-based intervention strategies to reduce procrastination among adolescents.

New light on an old friend: targeting PUMA in radioprotection and therapy of cardiovascular and neurodegenerative diseases.

PubMed

Tichy, Ales; Marek, Jan; Havelek, Radim; Pejchal, Jaroslav; Seifrtova, Martina; Zarybnicka, Lenka; Filipova, Alzbeta; Rezacova, Martina; Sinkorova, Zuzana

2018-04-05

This review summarizes recent progress in understanding the role of p53-upregulated mediator of apoptosis (PUMA) in molecular pathways with respect to its potential therapeutic applications. Particular emphasis is given to the PUMA´s role in ionizing radiation-induced signalling as radiotoxicity of normal tissue is mediated mostly via apoptosis. PUMA and its p53-dependent and p53-independent induction is described and potential use as a new target for the development of radioprotective agents is suggested. Further implications, including targeting PUMA to prevent and treat cardiovascular and neurodegenerative diseases, are also discussed together with overview of other therapeutic applications. Finally, basic chemical structures for development of novel PUMA modulators such as pifithrine derivativeses, kinase inhibitors or modulators of Bcl-2 protein family are described. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The role of exosomes in hepatitis, liver cirrhosis and hepatocellular carcinoma.

PubMed

Shen, Jiliang; Huang, Chiung-Kuei; Yu, Hong; Shen, Bo; Zhang, Yaping; Liang, Yuelong; Li, Zheyong; Feng, Xu; Zhao, Jie; Duan, Lian; Cai, Xiujun

2017-05-01

Exosomes are small vesicles that were initially thought to be a mechanism for discarding unneeded membrane proteins from reticulocytes. Their mediation of intercellular communication appears to be associated with several biological functions. Current studies have shown that most mammalian cells undergo the process of exosome formation and utilize exosome-mediated cell communication. Exosomes contain various microRNAs, mRNAs and proteins. They have been reported to mediate multiple functions, such as antigen presentation, immune escape and tumour progression. This concise review highlights the findings regarding the roles of exosomes in liver diseases, particularly hepatitis B, hepatitis C, liver cirrhosis and hepatocellular carcinoma. However, further elucidation of the contributions of exosomes to intercellular information transmission is needed. The potential medical applications of exosomes in liver diseases seem practical and will depend on the ingenuity of future investigators and their insights into exosome-mediated biological processes. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Procrastination as a Self-Regulation Failure: The Role of Impulsivity and Intrusive Thoughts.

PubMed

Rebetez, Marie My Lien; Rochat, Lucien; Barsics, Catherine; Van der Linden, Martial

2018-02-01

Procrastination has been described as the quintessence of self-regulatory failure. This study examines the relationships between this self-regulatory failure and other manifestations of self-regulation problems, namely impulsivity and intrusive thoughts. One hundred and forty-one participants completed questionnaires assessing procrastination, impulsivity (in particular, the urgency and lack of perseverance dimensions), and intrusive thoughts (i.e., rumination and daydreaming). Main results show that urgency mediated the association between rumination and procrastination, whereas rumination did not mediate the relation between urgency and procrastination. Lack of perseverance mediated the association between daydreaming and procrastination, and daydreaming mediated the relation between lack of perseverance and procrastination. This study highlights the role of impulsivity and intrusive thoughts in procrastination, specifies the links between these self-regulation problems, and provides insights into their (potential) underlying mechanisms. It also opens interesting prospects for management strategies for implementing targeted psychological interventions to reduce impulsive manifestations and/or thought control difficulties accompanying procrastination.

Trauma exposure and the mediating role of posttraumatic stress on somatic symptoms in civilian war victims.

PubMed

Morina, Naser; Schnyder, Ulrich; Klaghofer, Richard; Müller, Julia; Martin-Soelch, Chantal

2018-04-10

It has been well documented that the exposure to war has a negative effect on the psychological health of civilian. However, little is known on the impact of war exposure on the physical health of the civilian population. In addition, the link between trauma exposure and somatic symptoms remain poorly understood. This cross-sectional study examined levels of somatic symptoms in the aftermath of war, and the mediating role of posttraumatic stress symptoms in the relationship between trauma exposure and somatic symptoms. Civilian war survivors (N = 142) from Kosovo were assessed for potentially traumatic events, posttraumatic stress symptoms, and somatic symptoms. Data were analyzed using mediation analyses. Posttraumatic stress disorder (PTSD) symptoms were categorized based on King's four factor model (Psychol Assessment. 10: 90-96, 1998). Participants reported on average more than 5 types of traumatic exposure. The cut-off indicative for PTSD was exceeded by 26.1% of participants. Symptom levels of PTSD were associated with somatic symptoms. The relationship between trauma exposure and somatic symptoms was partly mediated by the active avoidance and hyperarousal symptom clusters of PTSD. Active avoidance and hyperarousal symptoms seem to play a key role in traumatized people suffering from somatic symptoms.

Understanding the Relationship between Rainstorm-Related Experiences and PTSD among Chinese Adolescents after Rainstorm Disaster: The Roles of Rumination and Social Support.

PubMed

Zhen, Rui; Quan, Lijuan; Yao, Benxian; Zhou, Xiao

2016-01-01

Posttraumatic stress disorder (PTSD) is prevalent among adolescents following natural disasters, and the trauma experiences represent a critical risk factor for PTSD. Nevertheless, the underlying mechanism of adolescents' PTSD following trauma experiences remains unclear. Rumination appears to be a mediating factor between trauma experiences and PTSD, and social support may moderate this mediating relationship between trauma experiences, rumination, and PTSD, but few studies have examined these assumptions. Thus, this study aimed to assess the mediating role of rumination and the moderating role of social support in the relationship between rainstorm-related experiences and PTSD among adolescents, following a rainstorm in China. Nine hundred and fifty-one middle school students completed self-report questionnaires, and structural equation modeling was conducted to examine the potential moderated mediation effect. Rainstorm-related experiences had a direct and positive effect on PTSD, and also indirectly influenced PTSD via rumination. Moreover, social support work to buffer the direct effect of rainstorm-related experiences on PTSD, but not the effect of rumination on PTSD. Implications for clinical practice and research are discussed along with study limitations.

Understanding the Relationship between Rainstorm-Related Experiences and PTSD among Chinese Adolescents after Rainstorm Disaster: The Roles of Rumination and Social Support

PubMed Central

Zhen, Rui; Quan, Lijuan; Yao, Benxian; Zhou, Xiao

2016-01-01

Posttraumatic stress disorder (PTSD) is prevalent among adolescents following natural disasters, and the trauma experiences represent a critical risk factor for PTSD. Nevertheless, the underlying mechanism of adolescents’ PTSD following trauma experiences remains unclear. Rumination appears to be a mediating factor between trauma experiences and PTSD, and social support may moderate this mediating relationship between trauma experiences, rumination, and PTSD, but few studies have examined these assumptions. Thus, this study aimed to assess the mediating role of rumination and the moderating role of social support in the relationship between rainstorm-related experiences and PTSD among adolescents, following a rainstorm in China. Nine hundred and fifty-one middle school students completed self-report questionnaires, and structural equation modeling was conducted to examine the potential moderated mediation effect. Rainstorm-related experiences had a direct and positive effect on PTSD, and also indirectly influenced PTSD via rumination. Moreover, social support work to buffer the direct effect of rainstorm-related experiences on PTSD, but not the effect of rumination on PTSD. Implications for clinical practice and research are discussed along with study limitations. PMID:27695436

Cytotoxic-T-lymphocyte antigen 4 receptor signaling for lymphocyte adhesion is mediated by C3G and Rap1.

PubMed

Kloog, Yoel; Mor, Adam

2014-03-01

T-lymphocyte adhesion plays a critical role in both inflammatory and autoimmune responses. The small GTPase Rap1 is the key coordinator mediating T-cell adhesion to endothelial cells, antigen-presenting cells, and virus-infected cells. We describe a signaling pathway, downstream of the cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor, leading to Rap1-mediated adhesion. We identified a role for the Rap1 guanine nucleotide exchange factor C3G in the regulation of T-cell adhesion and showed that this factor is required for both T-cell receptor (TCR)-mediated and CTLA-4-mediated T-cell adhesion. Our data indicated that C3G translocates to the plasma membrane downstream of TCR signaling, where it regulates activation of Rap1. We also showed that CTLA-4 receptor signaling mediates tyrosine phosphorylation in the C3G protein, and that this is required for augmented activation of Rap1 and increased adhesion mediated by leukocyte function-associated antigen type 1 (LFA-1). Zap70 is required for C3G translocation to the plasma membrane, whereas the Src family member Hck facilitates C3G phosphorylation. These findings point to C3G and Hck as promising potential therapeutic targets for the treatment of T-cell-dependent autoimmune disorders.

Post-Traumatic Symptomatology and Compulsions as Potential Mediators of the Relation Between Child Sexual Abuse and Auditory Verbal Hallucinations.

PubMed

McCarthy-Jones, Simon

2018-05-01

Whilst evidence is mounting that childhood sexual abuse (CSA) can be a cause of auditory verbal hallucinations (AVH), it is unclear what factors mediate this relation. Recent evidence suggests that post-traumatic symptomatology may mediate the CSA-AVH relation in clinical populations, although this hypothesis has not yet been tested in the general population. There is also reason to believe that obsessive ideation could mediate the CSA-AVH relation. To test for evidence to falsify the hypotheses that post-traumatic symptomatology, obsessions, compulsions, anxiety and depression mediate the relation between CSA and AVH in a general population sample. Indirect effects of CSA on AVH via potential mediators were tested for, using a regression-based approach employing data from the 2007 Adult Psychiatric Morbidity Survey (n = 5788). After controlling for demographics, IQ and child physical abuse, it was found that CSA, IQ, post-traumatic symptomatology and compulsions predicted lifetime experience of AVH. Mediation analyses found significant indirect effects of CSA on AVH via post-traumatic symptomatology [odds ratio (OR): 1.11; 95% confidence interval (CI):1.00-1.29] and compulsions (OR: 1.10, 95% CI: 1.01-1.28). These findings offer further support for the hypothesis that post-traumatic symptomatology is a mediator of the CSA-AVH relation. Although no evidence was found for obsessional thoughts as a mediating variable, a potential mediating role for compulsions is theoretically intriguing. This study's findings reiterate the need to ask about experiences of childhood adversity and post-traumatic symptomology in people with AVH, as well as the likely therapeutic importance of trauma-informed and trauma-based interventions for this population.

The Role of Depression and Dissociation in the Relationship between Childhood Trauma and Bulimic Symptoms among Ethnically Diverse Female Undergraduates

ERIC Educational Resources Information Center

Gerke, Clarice K.; Mazzeo, Suzanne E.; Kliewer, Wendy

2006-01-01

Objective: The goals of this study were to examine the role of dissociation and depression as possible mediators of the relationship between several forms of childhood trauma and bulimic symptomatology and to explore potential ethnic differences in these relationships. Method: Four hundred seventeen female undergraduates participated in this…

8-oxoguanine DNA glycosylase 1-deficiency modifies allergic airway inflammation by regulating STAT6 and IL-4 in cells and in mice

USDA-ARS?s Scientific Manuscript database

Background: 8-oxoguanine-DNA glycosylase (OGG-1) is an enzyme involved in DNA repair. OGG-1 has a potential role in regulating inflammation but its function in modulating allergic diseases remains undefined. Objectives: To investigate the role of OGG-1 in mediating allergic inflammation, we used OGG...

Laccase from Pycnoporus cinnabarinus and phenolic compounds: can the efficiency of an enzyme mediator for delignifying kenaf pulp be predicted?

PubMed

Andreu, Glòria; Vidal, Teresa

2013-03-01

In this work, kenaf pulp was delignified by using laccase in combination with various redox mediators and the efficiency of the different laccase–mediator systems assessed in terms of the changes in pulp properties after bleaching. The oxidative ability of the individual mediators used (acetosyringone, syringaldehyde, p-coumaric acid, vanillin and actovanillone) and the laccase–mediator systems was determined by monitoring the oxidation–reduction potential (ORP) during process. The results confirmed the production of phenoxy radicals of variable reactivity and stressed the significant role of lignin structure in the enzymatic process. Although changes in ORP were correlated with the oxidative ability of the mediators, pulp properties as determined after the bleaching stage were also influenced by condensation and grafting reactions. As shown here, ORP measurements provide a first estimation of the delignification efficiency of a laccase–mediator system. Copyright © 2013 Elsevier Ltd. All rights reserved.

Exploring the link between clinical managers involvement in budgeting and performance: Insights from the Italian public health care sector.

PubMed

Macinati, Manuela S; Rizzo, Marco G

2016-01-01

The public health care sector has had an increase in initiatives, mostly inspired by New Public Management principles, aimed at assigning financial accountability to clinical managers. However, clinical managers might experience a scarce alignment between professional values and organizational requirements, which is a potentially important phenomena that may result in negative consequences on clinical managers' job performance. Building on Psychological Ownership Theory and adopting a psychology-based management accounting research approach, we focus on the managerial (nonmedical) role the clinical manager fulfills and explore the budgetary participation-performance link via the indirect effects of job-based psychological ownership, role clarity, and clinical managers' affective commitment toward managerial roles. The data were collected by a survey conducted in an Italian hospital. The research hypotheses were tested employing a path model. Our study revealed new insights that shed some light on underexplored processes through which mental states mediate the participation-performance link. Among these latter, the findings demonstrate that (a) budgetary participation has a direct effect on job-based psychological ownership; (b) role clarity mediates participation- and job-based psychological ownership link; (c) role clarity and job-based psychological ownership partially mediate the participation-commitment link; and (d) job-based psychological ownership, role clarity, and commitment fully mediate the participation-performance link. From a managerial viewpoint, an understanding of how clinical managers' feelings of ownership toward managerial roles could be enhanced is imperative in health care because ownership accounts for important attitudinal and organizational consequences. Results suggest that health care organizations that invest in budgetary participation will directly and indirectly affect clinical managers' psychological ownership, and this, along with role clarity, motivates clinical managers' managerial work attitudes and performance.

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

Burgess, Antony W., E-mail: burgess@ludwig.edu.au; Faux, Maree C.; Layton, Meredith J.

In this brief overview we discuss the association between Wnt signaling and colon cell biology and tumorigenesis. Our current understanding of the role of Apc in the {beta}-catenin destruction complex is compared with potential roles for Apc in cell adhesion and migration. The requirement for phosphorylation in the proteasomal-mediated degradation of {beta}-catenin is contrasted with roles for phospho-{beta}-catenin in the activation of transcription, cell adhesion and migration. The synergy between Myb and {beta}-catenin regulation of transcription in crypt stem cells during Wnt signaling is discussed. Finally, potential effects of growth factor regulatory systems, Apc or truncated-Apc on crypt morphogenesis, stemmore » cell localization and crypt fission are considered.« less

Ganglioside GM2 mediates migration of tumor cells by interacting with integrin and modulating the downstream signaling pathway.

PubMed

Kundu, Manjari; Mahata, Barun; Banerjee, Avisek; Chakraborty, Sohini; Debnath, Shibjyoti; Ray, Sougata Sinha; Ghosh, Zhumur; Biswas, Kaushik

2016-07-01

The definitive role of ganglioside GM2 in mediating tumor-induced growth and progression is still unknown. Here we report a novel role of ganglioside GM2 in mediating tumor cell migration and uncovered its mechanism. Data shows differential expression levels of GM2-synthase as well as GM2 in different human cancer cells. siRNA mediated knockdown of GM2-synthase in CCF52, A549 and SK-RC-26B cells resulted in significant inhibition of tumor cell migration as well as invasion in vitro without affecting cellular proliferation. Over-expression of GM2-synthase in low-GM2 expressing SK-RC-45 cells resulted in a consequent increase in migration thus confirming the potential role GM2 and its downstream partners play in tumor cell migration and motility. Further, treatment of SK-RC-45 cells with exogenous GM2 resulted in a dramatic increase in migratory and invasive capacity with no change in proliferative capacity, thereby confirming the role of GM2 in tumorigenesis specifically by mediating tumor migration and invasion. Gene expression profiling of GM2-synthase silenced cells revealed altered expression of several genes involved in cell migration primarily those controlling the integrin mediated signaling. GM2-synthase knockdown resulted in decreased phosphorylation of FAK, Src as well as Erk, while over-expression and/or exogenous GM2 treatment caused increased FAK and Erk phosphorylation respectively. Again, GM2 mediated invasion and Erk phosphorylation is blocked in integrin knockdown SK-RC-45 cells, thus confirming that GM2 mediated migration and phosphorylation of Erk is integrin dependent. Finally, confocal microscopy suggested co-localization while co-immunoprecipitation and surface plasmon resonance (SPR) confirmed direct interaction of membrane bound ganglioside, GM2 with the integrin receptor. Copyright © 2016 Elsevier B.V. All rights reserved.

Learning and Teaching in a Synchronous Collaborative Environment.

ERIC Educational Resources Information Center

Marjanovic, Olivera

1999-01-01

Describes a new synchronous collaborative environment that combines interactive learning and Group Support Systems for computer-mediated collaboration. Illustrates its potential to improve critical thinking, problem solving, and communication skills, and describes how teachers' roles are changed. (Author/LRW)

Genetic and Physical Interactions between Tel2 and the Med15 Mediator Subunit in Saccharomyces cerevisiae

PubMed Central

Grandin, Nathalie; Corset, Laetitia; Charbonneau, Michel

2012-01-01

Background In budding yeast, the highly conserved Tel2 protein is part of several complexes and its main function is now believed to be in the biogenesis of phosphatidyl inositol 3-kinase related kinases. Principal Findings To uncover potentially novel functions of Tel2, we set out to isolate temperature-sensitive (ts) mutant alleles of TEL2 in order to perform genetic screenings. MED15/GAL11, a subunit of Mediator, a general regulator of transcription, was isolated as a suppressor of these mutants. The isolated tel2 mutants exhibited a short telomere phenotype that was partially rescued by MED15/GAL11 overexpression. The tel2-15mutant was markedly deficient in the transcription of EST2, coding for the catalytic subunit of telomerase, potentially explaining the short telomere phenotype of this mutant. In parallel, a two-hybrid screen identified an association between Tel2 and Rvb2, a highly conserved member of the AAA+ family of ATPases further found by in vivo co-immunoprecipitation to be tight and constitutive. Transiently overproduced Tel2 and Med15/Gal11 associated together, suggesting a potential role for Tel2 in transcription. Other Mediator subunits, as well as SUA7/TFIIB, also rescued the tel2-ts mutants. Significance Altogether, the present data suggest the existence of a novel role for Tel2, namely in transcription, possibly in cooperation with Rvb2 and involving the existence of physical interactions with the Med15/Gal11 Mediator subunit. PMID:22291956

Multifunctional Curcumin Mediate Multitherapeutic Effects.

PubMed

Shehzad, Adeeb; Qureshi, Munibah; Anwar, Muhammad Nabeel; Lee, Young Sup

2017-09-01

Inflammation can promote the development of arthritis, obesity, cardiovascular, type II diabetes, pancreatitis, metabolic and neurodegenerative diseases, and certain types of cancer. Compounds isolated from plants have been practiced since ancient times for curing various ailments including inflammatory disorders and to support normal physiological functions. Curcumin (diferuloylmethane) is a yellow coloring agent, extracted from turmeric that has been used for the prevention and treatment of various inflammatory diseases. Numerous studies have shown that curcumin modulate multiple molecular targets and can be translated to the clinics for multiple therapeutic processes. There is compelling evidence that curcumin can block cell proliferation, invasion, and angiogenesis as well as reduced the prolonged survival of cancer cells. Curcumin mediates anti-inflammatory effect through downregulation of inflammatory cytokines, transcription factors, protein kinases, and enzymes that promote inflammation and development of chronic diseases. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways by activating caspase cascades. Curcumin is a safe and nontoxic drug that has been reported to be well tolerated. Available clinical trials support the potential role of curcumin for treatment of various inflammatory disorders. However, curcumin's efficacy is hindered by poor absorption and low bioavailability, which limit its translation into clinics. This review outlines the potential pharmacological and clinical role of curcumin, which provide a gateway for the beneficial role of plant isolated compounds in treatment of various inflammatory diseases and cancer. © 2017 Institute of Food Technologists®.

mTOR, a Potential Target to Treat Autism Spectrum Disorder.

PubMed

Sato, Atsushi

2016-01-01

Mammalian target of rapamycin (mTOR) is a key regulator in various cellular processes, including cell growth, gene expression, and synaptic functions. Autism spectrum disorder (ASD) is frequently accompanied by monogenic disorders, such as tuberous sclerosis complex, phosphatase and tensin homolog tumor hamartoma syndrome, neurofibromatosis 1, and fragile X syndrome, in which mTOR is hyperactive. Mutations in the genes involved in the mTOR-mediated signaling pathway have been identified in some cases of syndromic ASD. Evidences indicate a pathogenic role for hyperactive mTOR-mediated signaling in ASD associated with these monogenic disorders, and mTOR inhibitors are a potential pharmacotherapy for ASD. Abnormal synaptic transmission through metabotropic glutamate receptor 5 may underlie in a part of ASD associated with hyperactive mTOR-mediated signaling. In this review, the relationship between mTOR and ASD is discussed.

mTOR, a Potential Target to Treat Autism Spectrum Disorder

PubMed Central

Sato, Atsushi

2016-01-01

Mammalian target of rapamycin (mTOR) is a key regulator in various cellular processes, including cell growth, gene expression, and synaptic functions. Autism spectrum disorder (ASD) is frequently accompanied by monogenic disorders, such as tuberous sclerosis complex, phosphatase and tensin homolog tumor hamartoma syndrome, neurofibromatosis 1, and fragile X syndrome, in which mTOR is hyperactive. Mutations in the genes involved in the mTOR-mediated signaling pathway have been identified in some cases of syndromic ASD. Evidences indicate a pathogenic role for hyperactive mTOR-mediated signaling in ASD associated with these monogenic disorders, and mTOR inhibitors are a potential pharmacotherapy for ASD. Abnormal synaptic transmission through metabotropic glutamate receptor 5 may underlie in a part of ASD associated with hyperactive mTOR-mediated signaling. In this review, the relationship between mTOR and ASD is discussed. PMID:27071790

The role of proteosome-mediated proteolysis in modulating potentially harmful transcription factor activity in Saccharomyces cerevisiae

PubMed Central

Bonzanni, Nicola; Zhang, Nianshu; Oliver, Stephen G.; Fisher, Jasmin

2011-01-01

Motivation: The appropriate modulation of the stress response to variable environmental conditions is necessary to maintain sustained viability in Saccharomyces cerevisiae. Particularly, controlling the abundance of proteins that may have detrimental effects on cell growth is crucial for rapid recovery from stress-induced quiescence. Results: Prompted by qualitative modeling of the nutrient starvation response in yeast, we investigated in vivo the effect of proteolysis after nutrient starvation showing that, for the Gis1 transcription factor at least, proteasome-mediated control is crucial for a rapid return to growth. Additional bioinformatics analyses show that potentially toxic transcriptional regulators have a significantly lower protein half-life, a higher fraction of unstructured regions and more potential PEST motifs than the non-detrimental ones. Furthermore, inhibiting proteasome activity tends to increase the expression of genes induced during the Environmental Stress Response more than those in the rest of the genome. Our combined results suggest that proteasome-mediated proteolysis of potentially toxic transcription factors tightly modulates the stress response in yeast. Contact: jasmin.fisher@microsoft.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21685082

Health-Related Behavior Mediates the Association Between Personality and Memory Performance in Older Adults.

PubMed

Allen, Mark S; Laborde, Sylvain; Walter, Emma E

2017-03-01

This prospective study explored the potential mediating role of health-related behavior (alcohol involvement, diet, television viewing, and physical activity) in the association between personality and change in memory performance over 2 years. A nationally representative sample of 8,376 U.K. participants aged 55 years and older (4,572 women, 3,804 men) completed self-report measures of personality and health-related behavior in 2010, and completed a memory performance task in 2010 and 2012. After removing variance associated with potential confounding variables, neuroticism and agreeableness had negative associations, and openness and conscientiousness positive associations with change in memory performance. There were no moderation effects by age, sex, education level, or ethnicity. Multiple mediator models demonstrated that physical activity, television viewing, and alcohol intake mediated associations between personality and change in memory performance. These findings provide evidence that the association between personality and memory performance in older adults can be explained, in part, through health-related behavior.

NIDO, AMOP and vWD domains of MUC4 play synergic role in MUC4 mediated signaling

PubMed Central

Liu, Xian; Xie, Kun-Ling; Tang, Jie; Jiang, Kui-Rong; Gao, Wen-Tao; Tian, Lei; Zhang, Kai; Xu, Ze-Kuan; Miao, Yi

2017-01-01

MUC4 mucin is well known as an important potential target to overcome pancreatic cancer. Three unique domains (NIDO, AMOP, and vWD) with unclear roles only present in MUC4 but are not found in other membrane-bound mucins. Our previous studies first reported that its splice variant, MUC4/Y can be a model of MUC4 (MUC4 gene fragment is more than 30KB, too huge to clone and eukaryotic express) in pancreatic cancer. More importantly, based on MUC4/Y with the appropriate length of gene sequence, it is easy to construct the unique domain-lacking models of MUC4/Y (MUC4) for research. The present study focuses on investigation of the respective role of the unique NIDO, AMOP, and vWD domain or their synergistic effect on MUC4(MUC4/Y)-mediated functions and mechanisms by series of in vitro assays, sequence-based transcriptome analysis, validation of qRT-PCR & Western blot, and systematic comparative analysis. Our results demonstrate: 1) NIDO, AMOP, and vWD domain or their synergy play significant roles on MUC4/Y-mediated malignant function of pancreatic cancer, downstream of molecule mechanisms, particularly MUC4/Y-triggered malignancy-related positive feedback loops, respectively. 2) The synergistic roles of three unique domains on MUC4/Y-mediated functions and mechanisms are more prominent than the respective domain because the synergy of three domain plays the more remarkable effects on MUC4/Y-mediated signaling hub. Thus, to improve reversed effects of domain-lacking and break the synergism of domains will contribute to block MUC4/Y(MUC4) triggering various oncogenic signaling pathways. PMID:28060749

NIDO, AMOP and vWD domains of MUC4 play synergic role in MUC4 mediated signaling.

PubMed

Zhu, Yi; Zhang, Jing-Jing; Peng, Yun-Peng; Liu, Xian; Xie, Kun-Ling; Tang, Jie; Jiang, Kui-Rong; Gao, Wen-Tao; Tian, Lei; Zhang, Kai; Xu, Ze-Kuan; Miao, Yi

2017-02-07

MUC4 mucin is well known as an important potential target to overcome pancreatic cancer. Three unique domains (NIDO, AMOP, and vWD) with unclear roles only present in MUC4 but are not found in other membrane-bound mucins. Our previous studies first reported that its splice variant, MUC4/Y can be a model of MUC4 (MUC4 gene fragment is more than 30KB, too huge to clone and eukaryotic express) in pancreatic cancer. More importantly, based on MUC4/Y with the appropriate length of gene sequence, it is easy to construct the unique domain-lacking models of MUC4/Y (MUC4) for research. The present study focuses on investigation of the respective role of the unique NIDO, AMOP, and vWD domain or their synergistic effect on MUC4(MUC4/Y)-mediated functions and mechanisms by series of in vitro assays, sequence-based transcriptome analysis, validation of qRT-PCR & Western blot, and systematic comparative analysis. Our results demonstrate: 1) NIDO, AMOP, and vWD domain or their synergy play significant roles on MUC4/Y-mediated malignant function of pancreatic cancer, downstream of molecule mechanisms, particularly MUC4/Y-triggered malignancy-related positive feedback loops, respectively. 2) The synergistic roles of three unique domains on MUC4/Y-mediated functions and mechanisms are more prominent than the respective domain because the synergy of three domain plays the more remarkable effects on MUC4/Y-mediated signaling hub. Thus, to improve reversed effects of domain-lacking and break the synergism of domains will contribute to block MUC4/Y(MUC4) triggering various oncogenic signaling pathways.

Krüppel-like factor 4 is induced by rapamycin and mediates the anti-proliferative effect of rapamycin in rat carotid arteries after balloon injury.

PubMed

Wang, Ying; Zhao, Beilei; Zhang, Yi; Tang, Zhihui; Shen, Qiang; Zhang, Youyi; Zhang, Weizhen; Du, Jie; Chien, Shu; Wang, Nanping

2012-04-01

The transcription factor, Krüppel-like factor 4 (KLF4), plays an important role in regulating the proliferation of vascular smooth muscle cells. This study aimed to examine the effect of rapamycin on the expression of KLF4 and the role of KLF4 in arterial neointimal formation. Expression of KLF4 was monitored using real-time PCR and immunoblotting in cultured vascular smooth muscle cells. and in rat carotid arteries in vivo after balloon injury. Adenovirus-mediated overexpression and siRNA-mediated knockdown of KLF4 were used to examine the role of KLF4 in mediating the anti-proliferative role of rapamycin . KLF4-regulated genes were identified using cDNA microarray. Rapamycin induced the expression of KLF4 in vitro and in vivo. Overexpression of KLF4 inhibited cell proliferation and the activity of mammalian target of rapamycin (mTOR) and its downstream pathways, including 4EBP-1 and p70S6K in vascular smooth muscle cells and prevented the neointimal formation in the balloon-injured arteries. KLF4 up-regulated the expression of GADD45β, p57(kip2) and p27(kip1) . Furthermore, knockdown of KLF4 attenuated the anti-proliferative effect of rapamycin both in vitro and in vivo. KLF4 plays an important role in mediating the anti-proliferative effect of rapamycin in VSMCs and balloon-injured arteries. Thus, it is a potential target for the treatment of proliferative vascular disorders such as restenosis after angioplasty. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Cytochrome P450-Mediated Phytoremediation using Transgenic Plants: A Need for Engineered Cytochrome P450 Enzymes

PubMed Central

Kumar, Santosh; Jin, Mengyao; Weemhoff, James L

2013-01-01

There is an increasing demand for versatile and ubiquitous Cytochrome P450 (CYP) biocatalysts for biotechnology, medicine, and bioremediation. In the last decade there has been an increase in realization of the power of CYP biocatalysts for detoxification of soil and water contaminants using transgenic plants. However, the major limitations of mammalian CYP enzymes are that they require CYP reductase (CPR) for their activity, and they show relatively low activity, stability, and expression. On the other hand, bacterial CYP enzymes show limited substrate diversity and usually do not metabolize herbicides and industrial contaminants. Therefore, there has been a considerable interest for biotechnological industries and the scientific community to design CYP enzymes to improve their catalytic efficiency, stability, expression, substrate diversity, and the suitability of P450-CPR fusion enzymes. Engineered CYP enzymes have potential for transgenic plants-mediated phytoremediation of herbicides and environmental contaminants. In this review we discuss: 1) the role of CYP enzymes in phytoremediation using transgenic plants, 2) problems associated with wild-type CYP enzymes in phytoremediation, and 3) examples of engineered CYP enzymes and their potential role in transgenic plant-mediated phytoremediation. PMID:25298920

Dyslipidemia links obesity to early cerebral neurochemical alterations.

PubMed

Haley, Andreana P; Gonzales, Mitzi M; Tarumi, Takashi; Tanaka, Hirofumi

2013-10-01

To examine the role of hypertension, hyperglycemia, and dyslipidemia in potentially accounting for obesity-related brain vulnerability in the form of altered cerebral neurochemistry. Sixty-four adults, ages 40-60 years, underwent a health screen and proton magnetic resonance spectroscopy ((1) H MRS) of occipitoparietal gray matter to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (mI), and glutamate (Glu) relative to creatine (Cr). The causal steps approach and nonparametric bootstrapping were utilized to assess if fasting glucose, mean arterial pressure or peripheral lipid/lipoprotein levels mediate the relationship between body mass index (BMI) and cerebral neurochemistry. Higher BMI was significantly related to higher mI/Cr, independent of age and sex. BMI was also significantly related to two of the proposed mediators, triglyceride, and HDL-cholesterol, which were also independently related to increased mI/Cr. Finally, the relationship between BMI and mI/Cr was significantly attenuated after inclusion of triglyceride and HDL-cholesterol into the model, one at a time, indicating statistical mediation. Higher triglyceride and lower HDL levels statistically account for the association between BMI and myo-inositol, pointing toward a potentially critical role for dyslipidemia in the development of cerebral neurochemical alterations in obesity. Copyright © 2013 The Obesity Society.

Causes of CNS inflammation and potential targets for anticonvulsants.

PubMed

Falip, Mercé; Salas-Puig, Xavier; Cara, Carlos

2013-08-01

Inflammation is one of the most important endogenous defence mechanisms in an organism. It has been suggested that inflammation plays an important role in the pathophysiology of a number of human epilepsies and convulsive disorders, and there is clinical and experimental evidence to suggest that inflammatory processes within the CNS may either contribute to or be a consequence of epileptogenesis. This review discusses evidence from human studies on the role of inflammation in epilepsy and highlights potential new targets in the inflammatory cascade for antiepileptic drugs. A number of mechanisms have been shown to be involved in CNS inflammatory reactions. These include an inflammatory response at the level of the blood-brain barrier (BBB), immune-mediated damage to the CNS, stress-induced release of inflammatory mediators and direct neuronal dysfunction or damage as a result of inflammatory reactions. Mediators of inflammation in the CNS include interleukin (IL)-1β, tumour necrosis factor-α, nuclear factor-κB and toll-like receptor-4 (TLR4). IL-1β, BBB and high-mobility group box-1-TLR4 signalling appear to be the most promising targets for anticonvulsant agents directed at inflammation. Such agents may provide effective therapy for drug-resistant epilepsies in the future.

Cancer-related marketing centrality motifs acting as pivot units in the human signaling network and mediating cross-talk between biological pathways.

PubMed

Li, Wan; Chen, Lina; Li, Xia; Jia, Xu; Feng, Chenchen; Zhang, Liangcai; He, Weiming; Lv, Junjie; He, Yuehan; Li, Weiguo; Qu, Xiaoli; Zhou, Yanyan; Shi, Yuchen

2013-12-01

Network motifs in central positions are considered to not only have more in-coming and out-going connections but are also localized in an area where more paths reach the networks. These central motifs have been extensively investigated to determine their consistent functions or associations with specific function categories. However, their functional potentials in the maintenance of cross-talk between different functional communities are unclear. In this paper, we constructed an integrated human signaling network from the Pathway Interaction Database. We identified 39 essential cancer-related motifs in central roles, which we called cancer-related marketing centrality motifs, using combined centrality indices on the system level. Our results demonstrated that these cancer-related marketing centrality motifs were pivotal units in the signaling network, and could mediate cross-talk between 61 biological pathways (25 could be mediated by one motif on average), most of which were cancer-related pathways. Further analysis showed that molecules of most marketing centrality motifs were in the same or adjacent subcellular localizations, such as the motif containing PI3K, PDK1 and AKT1 in the plasma membrane, to mediate signal transduction between 32 cancer-related pathways. Finally, we analyzed the pivotal roles of cancer genes in these marketing centrality motifs in the pathogenesis of cancers, and found that non-cancer genes were potential cancer-related genes.

The cyclophilin D/Drp1 axis regulates mitochondrial fission contributing to oxidative stress-induced mitochondrial dysfunctions in SH-SY5Y cells

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

Xiao, Anqi; Gan, Xueqi; Chen, Ruiqi

Oxidative stress plays a central role in the pathogenesis of various neurodegenerative diseases. Increasing evidences have demonstrated that structural abnormalities in mitochondria are involved in oxidative stress related nerve cell damage. And Drp1 plays a critical role in mitochondrial dynamic imbalance insulted by oxidative stress-derived mitochondria. However, the status of mitochondrial fusion and fission pathway and its relationship with mitochondrial properties such as mitochondrial membrane permeability transition pore (mPTP) have not been fully elucidated. Here, we demonstrated for the first time the role of Cyclophilin D (CypD), a crucial component for mPTP formation, in the regulation of mitochondrial dynamics inmore » oxidative stress treated nerve cell. We observed that CypD-mediated phosphorylation of Drp1 and subsequently augmented Drp1 recruitment to mitochondria and shifts mitochondrial dynamics toward excessive fission, which contributes to the mitochondrial structural and functional dysfunctions in oxidative stress-treated nerve cells. CypD depletion or over expression accompanies mitochondrial dynamics/functions recovery or aggravation separately. We also demonstrated first time the link between the CypD to mitochondrial dynamics. Our data offer new insights into the mechanism of mitochondrial dynamics which contribute to the mitochondrial dysfunctions, specifically the role of CypD in Drp1-mediated mitochondrial fission. The protective effect of CsA, or other molecules affecting the function of CypD hold promise as a potential novel therapeutic strategy for governing oxidative stress pathology via mitochondrial pathways. - Highlights: • Demonstrated first time the link between the mPTP to mitochondrial dynamics. • The role of Cyclophilin D in the regulation of Drp1-mediated mitochondrial fission. • CsA as a potential target for governing oxidative stress related neuropathology.« less

Human osteopontin splicing isoforms: known roles, potential clinical applications and activated signaling pathways.

PubMed

Gimba, E R; Tilli, T M

2013-04-30

Human osteopontin is subject to alternative splicing, which generates three isoforms, termed OPNa, OPNb and OPNc. These variants show specific expression and roles in different cell contexts. We present an overview of current knowledge of the expression profile of human OPN splicing isoforms (OPN-SIs), their tissue-specific roles, and the pathways mediating their functional properties in different pathophysiological conditions. We also describe their putative application as biomarkers, and their potential use as therapeutic targets by using antibodies, oligonucleotides or siRNA molecules. This synthesis provides new clues for a better understanding of human OPN splice variants, their roles in normal and pathological conditions, and their possible clinical applications. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Epac2 Mediates cAMP-Dependent Potentiation of Neurotransmission in the Hippocampus

PubMed Central

Fernandes, Herman B.; Riordan, Sean; Nomura, Toshihiro; Remmers, Christine L.; Kraniotis, Stephen; Marshall, John J.; Kukreja, Lokesh; Vassar, Robert

2015-01-01

Presynaptic terminal cAMP elevation plays a central role in plasticity at the mossy fiber-CA3 synapse of the hippocampus. Prior studies have identified protein kinase A as a downstream effector of cAMP that contributes to mossy fiber LTP (MF-LTP), but the potential contribution of Epac2, another cAMP effector expressed in the MF synapse, has not been considered. We investigated the role of Epac2 in MF-CA3 neurotransmission using Epac2−/− mice. The deletion of Epac2 did not cause gross alterations in hippocampal neuroanatomy or basal synaptic transmission. Synaptic facilitation during short trains was not affected by loss of Epac2 activity; however, both long-term plasticity and forskolin-mediated potentiation of MFs were impaired, demonstrating that Epac2 contributes to cAMP-dependent potentiation of transmitter release. Examination of synaptic transmission during long sustained trains of activity suggested that the readily releasable pool of vesicles is reduced in Epac2−/− mice. These data suggest that cAMP elevation uses an Epac2-dependent pathway to promote transmitter release, and that Epac2 is required to maintain the readily releasable pool at MF synapses in the hippocampus. PMID:25904804

The relationship between experiences of discrimination and mental health among lesbians and gay men: An examination of internalized homonegativity and rejection sensitivity as potential mechanisms.

PubMed

Feinstein, Brian A; Goldfried, Marvin R; Davila, Joanne

2012-10-01

The current study used path analysis to examine potential mechanisms through which experiences of discrimination influence depressive and social anxiety symptoms. The sample included 218 lesbians and 249 gay men (total N = 467) who participated in an online survey about minority stress and mental health. The proposed model included 2 potential mediators-internalized homonegativity and rejection sensitivity-as well as a culturally relevant antecedent to experiences of discrimination-childhood gender nonconformity. Results indicated that the data fit the model well, supporting the mediating roles of internalized homonegativity and rejection sensitivity in the associations between experiences of discrimination and symptoms of depression and social anxiety. Results also supported the role of childhood gender nonconformity as an antecedent to experiences of discrimination. Although there were not significant gender differences in the overall model fit, some of the associations within the model were significantly stronger for gay men than lesbians. These findings suggest potential mechanisms through which experiences of discrimination influence well-being among sexual minorities, which has important implications for research and clinical practice with these populations. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

The mediating role of avoidance coping between intimate partner violence (IPV) victimization, mental health, and substance abuse among women experiencing bidirectional IPV.

PubMed

Flanagan, Julianne C; Jaquier, Véronique; Overstreet, Nicole; Swan, Suzanne C; Sullivan, Tami P

2014-12-15

Avoidance coping is consistently linked with negative mental health outcomes among women experiencing intimate partner violence (IPV). This study extended the literature examining the potentially mediating role of avoidance coping strategies on both mental health and substance use problems to a highly generalizable, yet previously unexamined population (i.e., women experiencing bidirectional IPV) and examined multiple forms of IPV (i.e., psychological, physical, and sexual) simultaneously. Among a sample of 362 women experiencing bidirectional IPV, four separate path models were examined, one for each outcome variable. Avoidance coping mediated the relationships between psychological and sexual IPV victimization and the outcomes of PTSD symptom severity, depression severity, and drug use problems. Findings indicate nuanced associations among IPV victimization, avoidance coping, and mental health and substance use outcomes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The role of body awareness and mindfulness in the relationship between exercise and eating behavior.

PubMed

Martin, Rachel; Prichard, Ivanka; Hutchinson, Amanda D; Wilson, Carlene

2013-12-01

This study examined the potential mediating roles of mindfulness and body awareness in the relationship between exercise and eating behavior. Female exercisers (N = 159) recruited from fitness centers, yoga centers, and the community completed a questionnaire incorporating measures of exercise behavior, body awareness, trait mindfulness, mindful eating, dietary intake, and disordered eating symptoms. Participation in yoga was associated with significantly lower disordered eating (mediated by body awareness), whereas the amount of time spent participating in cardio-based exercise was associated with greater eating disturbance. The relationships between amount of exercise and actual food intake were not mediated by trait mindfulness or body awareness. The differential findings for dietary intake and disordered eating indicate that the body awareness cultivated in different forms of exercise may be more beneficial for clinical populations or those at risk for eating disorders than for modifying actual dietary intake in the general population.

Body esteem and eating disorder symptomatology: the mediating role of appearance-motivated exercise in a non-clinical adult female sample.

PubMed

Vinkers, Charlotte D W; Evers, Catharine; Adriaanse, Marieke A; de Ridder, Denise T D

2012-08-01

Low body esteem poses a risk for the development of eating disorder symptomatology. Appearance-motivated exercise, as opposed to health-motivated exercise, has been associated with both low body esteem and eating disorder symptomatology. The aim of this study was to investigate the mediating role of appearance-motivated exercise in the link between body esteem and eating disorder symptomatology. Female fitness club members (N=81) reported their body esteem, eating disorder symptomatology and exercise motives. Appearance-motivated exercise partially mediated the link between low body esteem and eating disorder symptomatology. In contrast, health-motivated exercise was unrelated to both body esteem and eating disorder symptomatology. Results indicate that the motives underlying exercise in response to low body esteem have differential consequences for the potential development of eating disorders, signifying the clinical relevance of considering motives behind exercise. Copyright © 2012 Elsevier Ltd. All rights reserved.

MiR-218 Mediates tumorigenesis and metastasis: Perspectives and implications

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

Lu, Ying-fei; Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong; Zhang, Li

2015-05-15

MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. As a highly conserved miRNA across a variety of species, microRNA-218 (miR-218) was found to play pivotal roles in tumorigenesis and progression. A group of evidence has demonstrated that miR-218 acts as a tumor suppressor by targeting many oncogenes related to proliferation, apoptosis and invasion. In this review, we provide a complex overview of miR-218, including its regulatory mechanisms, known functions in cancer and future challenges as a potential therapeutic target in human cancers. - Highlights: • miR-218 is frequently down regulatedmore » in multiple cancers. • miR-218 plays pivotal roles in carcinogenesis. • miR-218 mediates proliferation, apoptosis, metastasis, invasion, etc. • miR-218 mediates tumorigenesis and metastasis via multiple pathways.« less

Role of Rho/ROCK and p38 MAP kinase pathways in transforming growth factor-beta-mediated Smad-dependent growth inhibition of human breast carcinoma cells in vivo.

PubMed

Kamaraju, Anil K; Roberts, Anita B

2005-01-14

TGF-beta is a multifunctional cytokine known to exert its biological effects through a variety of signaling pathways of which Smad signaling is considered to be the main mediator. At present, the Smad-independent pathways, their interactions with each other, and their roles in TGF-beta-mediated growth inhibitory effects are not well understood. To address these questions, we have utilized a human breast cancer cell line MCF10CA1h and demonstrate that p38 MAP kinase and Rho/ROCK pathways together with Smad2 and Smad3 are necessary for TGF-beta-mediated growth inhibition of this cell line. We show that Smad2/3 are indispensable for TGF-beta-mediated growth inhibition, and that both p38 and Rho/ROCK pathways affect the linker region phosphorylation of Smad2/3. Further, by using Smad3 mutated at the putative phosphorylation sites in the linker region, we demonstrate that phosphorylation at Ser203 and Ser207 residues is required for the full transactivation potential of Smad3, and that these residues are targets of the p38 and Rho/ROCK pathways. We demonstrate that activation of the p38 MAP kinase pathway is necessary for the full transcriptional activation potential of Smad2/Smad3 by TGF-beta, whereas activity of Rho/ROCK is necessary for both down-regulation of c-Myc protein and up-regulation of p21waf1 protein, directly interfering with p21waf1 transcription. Our results not only implicate Rho/ROCK and p38 MAPK pathways as necessary for TGF-beta-mediated growth inhibition, but also demonstrate their individual contributions and the basis for their cooperation with each other.

Review article: the potential mechanisms of action of rifaximin in the management of inflammatory bowel diseases.

PubMed

Sartor, R B

2016-01-01

Gut microbiota dysbiosis contributes to the pathogenesis of inflammatory bowel diseases (IBD). Although the microbiota's role in IBD pathogenesis, specifically Crohn's disease (CD), provides a rationale for antibiotic treatment, antibiotic use in CD remains controversial. Rifaximin, traditionally identified as a nonsystemic bactericidal antibiotic, may be therapeutically beneficial for inducing CD remission. To examine the role of rifaximin in the management of IBD and its potential mechanisms of action. A literature search using the following strategy: ('inflammatory bowel disease' OR 'Crohn's' OR 'ulcerative'), 'rifaximin' AND ('barrier' OR 'translocation' OR 'adhesion' OR 'internalization' OR 'pregnane X'), AND 'pregnane X' AND ('Crohn's' OR 'ulcerative colitis' OR 'inflammatory bowel disease'). In vitro data suggest rifaximin mediates changes in epithelial cell physiology and reduces bacterial attachment and internalisation. In experimental colitis models, rifaximin antagonised the effects of tumour necrosis factor-α on intestinal epithelial cells by activating pregnane X receptor, which inhibits nuclear factor-κB-mediated proinflammatory mediators and induces detoxification genes (e.g. multidrug resistance 1 and cytochrome P450 3A4). Rifaximin also inhibits bacterial translocation into the mesenteric lymph nodes. Accumulating evidence suggests that mechanisms of action of rifaximin in IBD may not be limited to direct bactericidal activity; therefore, rifaximin could potentially be redefined as a gut environment modulator. © 2015 John Wiley & Sons Ltd.

Brown adipose tissue: The heat is on the heart.

PubMed

Thoonen, Robrecht; Hindle, Allyson G; Scherrer-Crosbie, Marielle

2016-06-01

The study of brown adipose tissue (BAT) has gained significant scientific interest since the discovery of functional BAT in adult humans. The thermogenic properties of BAT are well recognized; however, data generated in the last decade in both rodents and humans reveal therapeutic potential for BAT against metabolic disorders and obesity. Here we review the current literature in light of a potential role for BAT in beneficially mediating cardiovascular health. We focus mainly on BAT's actions in obesity, vascular tone, and glucose and lipid metabolism. Furthermore, we discuss the recently discovered endocrine factors that have a potential beneficial role in cardiovascular health. These BAT-secreted factors may have a favorable effect against cardiovascular risk either through their metabolic role or by directly affecting the heart. Copyright © 2016 the American Physiological Society.

Quality of clinical supervision and counselor emotional exhaustion: the potential mediating roles of organizational and occupational commitment.

PubMed

Knudsen, Hannah K; Roman, Paul M; Abraham, Amanda J

2013-01-01

Counselor emotional exhaustion has negative implications for treatment organizations as well as the health of counselors. Quality clinical supervision is protective against emotional exhaustion, but research on the mediating mechanisms between supervision and exhaustion is limited. Drawing upon data from 934 counselors affiliated with treatment programs in the National Institute on Drug Abuse's Clinical Trials Network (CTN), this study examined commitment to the treatment organization and commitment to the counseling occupation as potential mediators of the relationship between quality clinical supervision and emotional exhaustion. The final ordinary least squares (OLS) regression model, which accounted for the nesting of counselors within treatment organizations, indicated that these two types of commitment were plausible mediators of the association between clinical supervision and exhaustion. Higher quality clinical supervision was strongly correlated with commitment to the treatment organization as well as commitment to the occupation of SUD counseling. These findings suggest that quality clinical supervision has the potential to yield important benefits for counselor well-being by strengthening ties to both their employing organization as well the larger treatment field, but longitudinal research is needed to establish these causal relationships. Copyright © 2013 Elsevier Inc. All rights reserved.

Quality of clinical supervision and counselor emotional exhaustion: The potential mediating roles of organizational and occupational commitment

PubMed Central

Knudsen, Hannah K.; Roman, Paul M.; Abraham, Amanda J.

2013-01-01

Counselor emotional exhaustion has negative implications for treatment organizations as well as the health of counselors. Quality clinical supervision is protective against emotional exhaustion, but research on the mediating mechanisms between supervision and exhaustion is limited. Drawing upon data from 934 counselors affiliated with treatment programs in the National Institute on Drug Abuse’s Clinical Trials Network (CTN), this study examined commitment to the treatment organization and commitment to the counseling occupation as potential mediators of the relationship between quality clinical supervision and emotional exhaustion. The final ordinary least squares (OLS) regression model, which accounted for the nesting of counselors within treatment organizations, indicated that these two types of commitment were plausible mediators of the association between clinical supervision and exhaustion. Higher quality clinical supervision was strongly correlated with commitment to the treatment organization as well as commitment to the occupation of SUD counseling. These findings suggest that quality clinical supervision has the potential to yield important benefits for counselor well-being by strengthening ties to both their employing organization as well the larger treatment field, but longitudinal research is needed to establish these causal relationships. PMID:23312873

Endomorphins potentiate acid-sensing ion channel currents and enhance the lactic acid-mediated increase in arterial blood pressure: effects amplified in hindlimb ischaemia.

PubMed

Farrag, Mohamed; Drobish, Julie K; Puhl, Henry L; Kim, Joyce S; Herold, Paul B; Kaufman, Marc P; Ruiz-Velasco, Victor

2017-12-01

Chronic limb ischaemia, characterized by inflammatory mediator release and a low extracellular pH, leads to acid-sensing ion channel (ASIC) activation and reflexively increases mean arterial pressure; endomorphin release is also increased under inflammatory conditions. We examined the modulation of ASIC currents by endomorphins in sensory neurons from rats with freely perfused and ligated femoral arteries: peripheral artery disease (PAD) model. Endomorphins potentiated sustained ASIC currents in both groups of dorsal root ganglion neurons, independent of mu opioid receptor stimulation or G protein activation. Intra-arterial administration of lactic acid (to simulate exercising muscle and evoke a pressor reflex), endomorphin-2 and naloxone resulted in a significantly greater pressor response than lactic acid alone, while administration of APETx2 inhibited endomorphin's enhancing effect in both groups. These results suggest a novel role for endomorphins in modulating ASIC function to effect lactic acid-mediated reflex increase in arterial pressure in patients with PAD. Chronic muscle ischaemia leads to accumulation of lactic acid and other inflammatory mediators with a subsequent drop in interstitial pH. Acid-sensing ion channels (ASICs), expressed in thin muscle afferents, sense the decrease in pH and evoke a pressor reflex known to increase mean arterial pressure. The naturally occurring endomorphins are also released by primary afferents under ischaemic conditions. We examined whether high affinity mu opioid receptor (MOR) agonists, endomorphin-1 (E-1) and -2 (E-2), modulate ASIC currents and the lactic acid-mediated pressor reflex. In rat dorsal root ganglion (DRG) neurons, exposure to E-2 in acidic solutions significantly potentiated ASIC currents when compared to acidic solutions alone. The potentiation was significantly greater in DRG neurons isolated from rats whose femoral arteries were ligated for 72 h. Sustained ASIC current potentiation was also observed in neurons pretreated with pertussis toxin, an uncoupler of G proteins and MOR. The endomorphin-mediated potentiation was a result of a leftward shift of the activation curve to higher pH values and a slight shift of the inactivation curve to lower pH values. Intra-arterial co-administration of lactic acid and E-2 led to a significantly greater pressor reflex than lactic acid alone in the presence of naloxone. Finally, E-2 effects were inhibited by pretreatment with the ASIC3 blocker APETx2 and enhanced by pretreatment with the ASIC1a blocker psalmotoxin-1. These findings have uncovered a novel role of endomorphins by which the opioids can enhance the lactic acid-mediated reflex increase in arterial pressure that is MOR stimulation-independent and APETx2-sensitive. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Relationship authenticity partially mediates the effects of attachment on relationship satisfaction.

PubMed

Rasco, Danney; Warner, Rebecca M

2017-01-01

Individuals with anxious and avoidant attachment tend to experience less satisfaction in their relationships. Past research suggests the negative effects of attachment on relationship satisfaction may be partially mediated by self-disclosure and self-concealment; the present study evaluated relationship authenticity as a potential additional mediator. Confirmatory factor analysis indicated that relationship authenticity is distinct from self-disclosure and self-concealment. Relationship authenticity predicted additional variance in relationship satisfaction controlling for attachment, self-disclosure, and self-concealment. The results were consistent with relationship authenticity, along with self-disclosure and self-concealment, partially mediating the effects of attachment on relationship satisfaction. These findings suggest that relationship authenticity may play a unique role in understanding how attachment influences relationship satisfaction. Theoretical and clinical implications are discussed.

Weight bias internalization, depression, and self-reported health among overweight binge eating disorder patients.

PubMed

Pearl, Rebecca L; White, Marney A; Grilo, Carlos M

2014-05-01

This study aimed to examine the relationship between internalization of weight bias, which has been linked to specific negative mental health outcomes, and overall mental and physical health among overweight patients with binge eating disorder (BED). The role of depressive symptoms as a potential mediator in this relationship was also tested. In a cross-sectional study, 255 individuals who were overweight and seeking treatment for BED completed the Weight Bias Internalization Scale (WBIS), Short-Form 36 Health Survey (SF-36), and Beck Depression Inventory-II (BDI). Regression analyses were conducted to evaluate the relationship between the WBIS and the SF-36, and bootstrapping mediation analyses were conducted to test whether BDI scores mediated this relationship. Higher weight bias internalization was associated with poorer self-reported health on all scales of the SF-36, and BDI scores mediated the relationship. Additional analyses revealed that WBIS scores also mediated the relationship between BDI scores and three SF-36 scales. Weight bias internalization is associated with poorer overall mental and physical health, and depressive symptoms may play a role in accounting for this relationship in treatment-seeking overweight patients with BED. © 2013 The Obesity Society.

Attachment style and suicide behaviors in high risk psychiatric inpatients following hospital discharge: The mediating role of entrapment.

PubMed

Li, Shuang; Galynker, Igor I; Briggs, Jessica; Duffy, Molly; Frechette-Hagan, Anna; Kim, Hae-Joon; Cohen, Lisa J; Yaseen, Zimri S

2017-11-01

Insecure attachment is associated with suicidal behavior. This relationship and its possible mediators have not been examined in high-risk psychiatric inpatients with respect to the critical high-risk period following hospital discharge. Attachment styles and perception of entrapment were assessed in 200 high-risk adult psychiatric inpatients hospitalized following suicidal ideation or suicide attempt. Suicidal behaviors were evaluated with the Columbia Suicide Severity Rating Scale at 1-2 months post-discharge. Associations between different attachment styles and suicidal behaviors were assessed and mediation of attachment effects by entrapment was modeled. Fearful attachment was associated with post-discharge suicidal behavior and there was a trend-level negative association for secure attachment. In addition, entrapment mediated the relationship between fearful attachment and suicidal behavior. The current study highlights the mediating role of perceptions of entrapment in the contribution of fearful attachment to suicidal behavior in high-risk patients, suggesting entrapment as potential therapeutic target to prevent suicidal behavior in these individuals. Further research is warranted to establish the mechanisms by which entrapment experiences emerge in patients with insecure attachment styles. Copyright © 2017 Elsevier B.V. All rights reserved.

Alveolar macrophages are critical for broadly-reactive antibody-mediated protection against influenza A virus in mice.

PubMed

He, Wenqian; Chen, Chi-Jene; Mullarkey, Caitlin E; Hamilton, Jennifer R; Wong, Christine K; Leon, Paul E; Uccellini, Melissa B; Chromikova, Veronika; Henry, Carole; Hoffman, Kevin W; Lim, Jean K; Wilson, Patrick C; Miller, Matthew S; Krammer, Florian; Palese, Peter; Tan, Gene S

2017-10-10

The aim of candidate universal influenza vaccines is to provide broad protection against influenza A and B viruses. Studies have demonstrated that broadly reactive antibodies require Fc-Fc gamma receptor interactions for optimal protection; however, the innate effector cells responsible for mediating this protection remain largely unknown. Here, we examine the roles of alveolar macrophages, natural killer cells, and neutrophils in antibody-mediated protection. We demonstrate that alveolar macrophages play a dominant role in conferring protection provided by both broadly neutralizing and non-neutralizing antibodies in mice. Our data also reveal the potential mechanisms by which alveolar macrophages mediate protection in vivo, namely antibody-induced inflammation and antibody-dependent cellular phagocytosis. This study highlights the importance of innate effector cells in establishing a broad-spectrum antiviral state, as well as providing a better understanding of how multiple arms of the immune system cooperate to achieve an optimal antiviral response following influenza virus infection or immunization.Broadly reactive antibodies that recognize influenza A virus HA can be protective, but the mechanism is not completely understood. Here, He et al. show that the inflammatory response and phagocytosis mediated by the interaction between protective antibodies and macrophages are essential for protection.

Consequences of cyberbullying behaviour in working life: The mediating roles of social support and social organisational climate.

PubMed

Muhonen, Tuija; Jönsson, Sandra; Bäckström, Martin

2017-01-01

The purpose of this paper is to explore health- and work-related outcomes of cyberbullying behaviour and the potential mediating role of social organisational climate, social support from colleagues and social support from superiors. Altogether 3,371 respondents participated in a questionnaire study. The results of this study indicate that social organisational climate can have a mediating role in the relationship between cyberbullying behaviour and health, well-being, work engagement and intention to quit. Contrary to earlier face-to-face bullying research, the current study showed that cyberbullying behaviour had stronger indirect than direct relationships to health, well-being, work engagement and intention to quit. Communication through digital devices in work life is becoming more prevalent, which in turn increases the risk for cyberbullying behaviour. Organisations need therefore to develop occupational health and safety policies concerning the use of digital communication and social media in order to prevent cyberbullying behaviour and its negative consequences. Cyberbullying behaviour among working adults is a relatively unexplored phenomenon and therefore this study makes valuable contribution to the research field.

Internalized Homophobia and Drug Use in a National Cohort of Gay and Bisexual Men: Examining Depression, Sexual Anxiety, and Gay Community Attachment as Mediating Factors.

PubMed

Moody, Raymond L; Starks, Tyrel J; Grov, Christian; Parsons, Jeffrey T

2018-05-01

The minority stress process of internalized homophobia (IH) has been associated with a range of adverse health outcomes among gay and bisexual men (GBM). However, evidence is mixed regarding the effect of IH on drug use, suggesting the potential role of multiple mediated pathways. Researchers have linked depression, sexual anxiety, and gay community attachment with IH. Depression, sexual anxiety, and gay community attachment have also been linked with drug use and drug-related problems suggesting potential mediating roles. A U.S. national sample of 1071 HIV-negative GBM completed at-home surveys, including measures of sociodemographic characteristics, IH, depression, sexual anxiety, gay community attachment, and drug use and associated problems. Adjusting for sociodemographic characteristics, depression mediated the association between IH and recent drug use. IH was positively associated with depression, and depression was positively associated with recent drug use. Gay community attachment partially mediated drug-related problems. IH had a positive direct association with drug-related problems and a negative direct association with gay community attachment. Gay community attachment had a positive association with drug-related problems. IH was positively associated with sexual anxiety, but sexual anxiety was not associated with either drug outcome. Efforts to reduce IH among HIV-negative GBM are likely to have a positive impact on mental health problems, as well as reduce risk for drug use and drug-related problems. Gay communities could provide the social support necessary for reducing IH; however, emphasis on community level interventions that address factors that increase risk for drug-related problems remains important.

Laccase-mediator catalyzed conversion of model lignin compounds

USDA-ARS?s Scientific Manuscript database

Identifying suitable reaction conditions remains an important task in the development of practical enzyme catalysts. Laccases play an important role in the biological break down of lignin and have great potential in the deconstruction of lignocellulosic feedstocks. We examined 16 laccases, both comm...

Cytotoxic-T-Lymphocyte Antigen 4 Receptor Signaling for Lymphocyte Adhesion Is Mediated by C3G and Rap1

PubMed Central

Kloog, Yoel

2014-01-01

T-lymphocyte adhesion plays a critical role in both inflammatory and autoimmune responses. The small GTPase Rap1 is the key coordinator mediating T-cell adhesion to endothelial cells, antigen-presenting cells, and virus-infected cells. We describe a signaling pathway, downstream of the cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor, leading to Rap1-mediated adhesion. We identified a role for the Rap1 guanine nucleotide exchange factor C3G in the regulation of T-cell adhesion and showed that this factor is required for both T-cell receptor (TCR)-mediated and CTLA-4-mediated T-cell adhesion. Our data indicated that C3G translocates to the plasma membrane downstream of TCR signaling, where it regulates activation of Rap1. We also showed that CTLA-4 receptor signaling mediates tyrosine phosphorylation in the C3G protein, and that this is required for augmented activation of Rap1 and increased adhesion mediated by leukocyte function-associated antigen type 1 (LFA-1). Zap70 is required for C3G translocation to the plasma membrane, whereas the Src family member Hck facilitates C3G phosphorylation. These findings point to C3G and Hck as promising potential therapeutic targets for the treatment of T-cell-dependent autoimmune disorders. PMID:24396067

Value congruence and depressive symptoms among critical care clinicians: The mediating role of moral distress.

PubMed

Lamiani, Giulia; Dordoni, Paola; Argentero, Piergiorgio

2018-02-01

Clinicians working in intensive care units are often exposed to several job stressors that can negatively affect their mental health. Literature has acknowledged the role of value congruence and job control in determining clinicians' psychological well-being and depressive symptoms. However, potential mediators of this association have been scarcely examined. This study aimed to test the mediating role of moral distress in the relationship between value congruence and job control, on the one hand, and depression, on the other hand. A cross-sectional study involving physicians, nurses, and residents working in 7 intensive care units in the north of Italy was conducted. Clinicians were administered in the Italian Moral Distress Scale-Revised, the value and control subscales of the Areas of Worklife Scale, and the Beck Depression Inventory II. Structural equation modeling was used to test the mediation model. Analysis on 170 questionnaires (response rate 72%) found no relations between job control and moral distress. A total indirect effect of value congruence on depression through moral distress (β = -.12; p = .02) was found. Moral distress contributes to the development of depressive symptoms among critical care clinicians who perceive a value incongruence with their organization and therefore should be addressed. Copyright © 2017 John Wiley & Sons, Ltd.

FXR: Big fish or small fry for drug-induced liver injury?

PubMed

Ballet, François

2016-02-01

By integrating network analysis and molecular modeling, a "system pharmacology" approach identified FXR as a potential off-target protein mediating non-steroidal anti-inflammatory drugs (NSAID)-induced liver injury. In vitro assays showed that NSAID are potent FXR antagonists that inhibit FXR transcriptional activity. Given the role of FXR in bile acid homeostasis, liver inflammation and cell proliferation, the data suggest that FXR antagonism could mediate, at least in part, NSAID-induced liver injury. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

More than meets the IR: the expanding roles of variant Ionotropic Glutamate Receptors in sensing odor, taste, temperature and moisture.

PubMed

van Giesen, Lena; Garrity, Paul A

2017-01-01

The ionotropic receptors (IRs) are a branch of the ionotropic glutamate receptor family and serve as important mediators of sensory transduction in invertebrates. Recent work shows that, though initially studied as olfactory receptors, the IRs also mediate the detection of taste, temperature, and humidity. Here, we summarize recent insights into IR evolution and its potential ecological significance as well as recent advances in our understanding of how IRs contribute to diverse sensory modalities.

More than meets the IR: the expanding roles of variant Ionotropic Glutamate Receptors in sensing odor, taste, temperature and moisture

PubMed Central

van Giesen, Lena; Garrity, Paul A.

2017-01-01

The ionotropic receptors (IRs) are a branch of the ionotropic glutamate receptor family and serve as important mediators of sensory transduction in invertebrates. Recent work shows that, though initially studied as olfactory receptors, the IRs also mediate the detection of taste, temperature, and humidity. Here, we summarize recent insights into IR evolution and its potential ecological significance as well as recent advances in our understanding of how IRs contribute to diverse sensory modalities. PMID:29034089

Synaptic plasticity in the medial vestibular nuclei: role of glutamate receptors and retrograde messengers in rat brainstem slices.

PubMed

Grassi, S; Pettorossi, V E

2001-08-01

The analysis of cellular-molecular events mediating synaptic plasticity within vestibular nuclei is an attempt to explain the mechanisms underlying vestibular plasticity phenomena. The present review is meant to illustrate the main results, obtained in vitro, on the mechanisms underlying long-term changes in synaptic strength within the medial vestibular nuclei. The synaptic plasticity phenomena taking place at the level of vestibular nuclei could be useful for adapting and consolidating the efficacy of vestibular neuron responsiveness to environmental requirements, as during visuo-vestibular recalibration and vestibular compensation. Following a general introduction on the most salient features of vestibular compensation and visuo-vestibular adaptation, which are two plastic events involving neuronal circuitry within the medial vestibular nuclei, the second and third sections describe the results from rat brainstem slice studies, demonstrating the possibility to induce long-term potentiation and depression in the medial vestibular nuclei, following high frequency stimulation of the primary vestibular afferents. In particular the mechanisms sustaining the induction and expression of vestibular long-term potentiation and depression, such as the role of various glutamate receptors and retrograde messengers have been described. The relevant role of the interaction between the platelet-activating factor, acting as a retrograde messenger, and the presynaptic metabotropic glutamate receptors, in determining the full expression of vestibular long-term potentiation is also underlined. In addition, the mechanisms involved in vestibular long-term potentiation have been compared with those leading to long-term potentiation in the hippocampus to emphasize the most significant differences emerging from vestibular studies. The fourth part, describes recent results demonstrating the essential role of nitric oxide, another retrograde messenger, in the induction of vestibular potentiation. Finally the fifth part suggests the possible functional significance of different action times of the two retrograde messengers and metabotropic glutamate receptors, which are involved in mediating the presynaptic mechanism sustaining vestibular long-term potentiation.

YY1 and HDAC9c transcriptionally regulate p38-mediated mesenchymal stem cell differentiation into osteoblasts

PubMed Central

Chen, Ya-Huey; Chung, Chiao-Chen; Liu, Yu-Chia; Lai, Wei-Chen; Lin, Zong-Shin; Chen, Tsung-Ming; Li, Long-Yuan; Hung, Mien-Chie

2018-01-01

Mesenchymal stem cells (MSCs) have a high self-renewal potential and can differentiate into various types of cells, including adipocytes, osteoblasts, and chondrocytes. Previously, we reported that the enhancer of zeste homolog 2 (EZH2), the catalytic component of the Polycomb-repressive complex 2, and HDAC9c mediate the osteogenesis and adipogenesis of MSCs. In the current study, we identify the role of p38 in osteogenic differentiation from a MAPK antibody array screen and investigate the mechanisms underlying its transcriptional regulation. Our data show that YY1, a ubiquitously expressed transcription factor, and HDAC9c coordinate p38 transcriptional activity to promote its expression to facilitate the osteogenic potential of MSCs. Our results show that p38 mediates osteogenic differentiation, and this has significant implications in bone-related diseases, bone tissue engineering, and regenerative medicine. PMID:29637005

The mediating sex-specific effect of psychological distress on the relationship between adverse childhood experiences and current smoking among adults

PubMed Central

2012-01-01

Background Research suggests that ACEs have a long-term impact on the behavioral, emotional, and cognitive development of children. These disruptions can lead to adoption of unhealthy coping behaviors throughout the lifespan. The present study sought to examine psychological distress as a potential mediator of sex-specific associations between adverse childhood experiences (ACEs) and adult smoking. Method Data from 7,210 Kaiser-Permanente members in San Diego California collected between April and October 1997 were used. Results Among women, psychological distress mediated a significant portion of the association between ACEs and smoking (21% for emotional abuse, 16% for physical abuse, 15% for physical neglect, 10% for parental separation or divorce). Among men, the associations between ACEs and smoking were not significant. Conclusions These findings suggest that for women, current smoking cessation strategies may benefit from understanding the potential role of childhood trauma. PMID:22788356

ER-mediated stress induces mitochondrial-dependent caspases activation in NT2 neuron-like cells.

PubMed

Arduino, Daniela M; Esteves, A Raquel; Domingues, A Filipa; Pereira, Claudia M F; Cardoso, Sandra M; Oliveira, Catarina R

2009-11-30

Recent studies have revealed that endoplasmic reticulum (ER) disturbance is involved in the pathophysiology of neurodegenerative disorders, contributing to the activation of the ER stress-mediated apoptotic pathway. Therefore, we investigated here the molecular mechanisms underlying the ER-mitochondria axis, focusing on calcium as a potential mediator of cell death signals. Using NT2 cells treated with brefeldin A or tunicamycin, we observed that ER stress induces changes in the mitochondrial function, impairing mitochondrial membrane potential and distressing mitochondrial respiratory chain complex Moreover, stress stimuli at ER level evoked calcium fluxes between ER and mitochondria. Under these conditions, ER stress activated the unfolded protein response by an overexpression of GRP78, and also caspase-4 and-2, both involved upstream of caspase-9. Our findings show that ER and mitochondria interconnection plays a prominent role in the induction of neuronal cell death under particular stress circumstances.

The mediating role of state maladaptive emotion regulation in the relation between social anxiety symptoms and self-evaluation bias.

PubMed

Sarfan, Laurel D; Cody, Meghan W; Clerkin, Elise M

2018-03-16

Although social anxiety symptoms are robustly linked to biased self-evaluations across time, the mechanisms of this relation remain unclear. The present study tested three maladaptive emotion regulation strategies - state post-event processing, state experiential avoidance, and state expressive suppression - as potential mediators of this relation. Undergraduate participants (N = 88; 61.4% Female) rated their social skill in an impromptu conversation task and then returned to the laboratory approximately two days later to evaluate their social skill in the conversation again. Consistent with expectations, state post-event processing and state experiential avoidance mediated the relation between social anxiety symptoms and worsening self-evaluations of social skill (controlling for research assistant evaluations), particularly for positive qualities (e.g. appeared confident, demonstrated social skill). State expressive suppression did not mediate the relation between social anxiety symptoms and changes in self-evaluation bias across time. These findings highlight the role that spontaneous, state experiential avoidance and state post-event processing may play in the relation between social anxiety symptoms and worsening self-evaluation biases of social skill across time.

Coping strategies as mediators of the relationship between sense of coherence and stress reactions: Israeli adolescents under missile attacks.

PubMed

Braun-Lewensohn, Orna; Sagy, Shifra; Roth, Guy

2011-05-01

This study aimed to explore the relationships between sense of coherence (SOC) and stress reactions as mediated by cognitive appraisal and coping strategies among adolescents facing the acute stressful situation of missile attacks. Employing the Salutogenic Model and the interactionist approach to coping, we asked what the roles of situational factors such as coping strategies and cognitive appraisal were in mediating the relationship between SOC and stress reactions. Data were gathered during January 2009 when hundreds of missiles fell in southern Israel. One hundred and thirty eight adolescents filled out questionnaires dealing with SOC, cognitive appraisal (endangerment feelings), Adolescent Coping Scale, state anxiety, state anger, and psychological distress. Overall, our model explained 55% of the variance in stress reactions. SOC had the strongest total direct and indirect effects. Previous findings have indicated SOC as playing only a limited role in explaining stress reactions in acute stress situations. The results of this study highlight the potential of SOC as a powerful resilience factor even in an acute situation, through mediation of situational factors.

Pathways to Self-Esteem in Late Adolescence: The Role of Parent and Peer Attachment, Empathy, and Social Behaviours

ERIC Educational Resources Information Center

Laible, Deborah J.; Carlo, Gustavo; Roesch, Scott C.

2004-01-01

The goal of this study was to examine both the direct and indirect relations of parent and peer attachment with self-esteem and to examine the potential mediating roles of empathy and social behaviour. 246 college students ("Mage" = 18.6 years, s.d. = 1.61) completed self-report measures of parent and peer attachment, empathy, social behaviour,…

Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel α2δ1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer.

PubMed

Yu, Jiangyong; Wang, Shuhang; Zhao, Wei; Duan, Jianchun; Wang, Zhijie; Chen, Hanxiao; Tian, Yanhua; Wang, Di; Zhao, Jun; An, Tongtong; Bai, Hua; Wu, Meina; Wang, Jie

2018-05-01

Purpose: Chemoresistance in small-cell lung cancer (SCLC) is reportedly attributed to the existence of resistant cancer stem cells (CSC). Studies involving CSC-specific markers and related mechanisms in SCLC remain limited. This study explored the role of the voltage-dependent calcium channel α2δ1 subunit as a CSC marker in chemoresistance of SCLC, and explored the potential mechanisms of α2δ1-mediated chemoresistance and strategies of overcoming the resistance. Experimental Design: α2δ1-positive cells were identified and isolated from SCLC cell lines and patient-derived xenograft (PDX) models, and CSC-like properties were subsequently verified. Transcriptome sequencing and Western blotting were carried out to identify pathways involved in α2δ1-mediated chemoresistance in SCLC. In addition, possible interventions to overcome α2δ1-mediated chemoresistance were examined. Results: Different proportions of α2δ1 + cells were identified in SCLC cell lines and PDX models. α2δ1 + cells exhibited CSC-like properties (self-renewal, tumorigenic, differentiation potential, and high expression of genes related to CSCs and drug resistance). Chemotherapy induced the enrichment of α2δ1 + cells instead of CD133 + cells in PDXs, and an increased proportion of α2δ1 + cells corresponded to increased chemoresistance. Activation and overexpression of ERK in the α2δ1-positive H1048 cell line was identified at the protein level. mAb 1B50-1 was observed to improve the efficacy of chemotherapy and delay relapse as maintenance therapy in PDX models. Conclusions: SCLC cells expressing α2δ1 demonstrated CSC-like properties, and may contribute to chemoresistance. ERK may play a key role in α2δ1-mediated chemoresistance. mAb 1B50-1 may serve as a potential anti-SCLC drug. Clin Cancer Res; 24(9); 2148-58. ©2018 AACR . ©2018 American Association for Cancer Research.

Cinnamon and immune actions: potential role in Tristetraprolin-Mediated inflamatory diseases

USDA-ARS?s Scientific Manuscript database

Inflammatory diseases have placed a heavy burden on the American health care system. Drug treatment for reducing inflammation and associated diseases has not been satisfactory. Complementary and alternative approaches are urgently needed. Bioactive plant extracts have been used for preventing and...

Laccase-mediator catalyzed conversion of model lignin compounds

USDA-ARS?s Scientific Manuscript database

Laccases play an important role in the biological breakdown of lignin and have great potential in the deconstruction of lignocellulosic feedstocks. We examined a variety of laccases, both commercially prepared and crude extracts, for their ability to oxidize three model lignol compounds (p-coumaryl...

Urban Adolescent Stress and Hopelessness

ERIC Educational Resources Information Center

Landis, Dana; Gaylord-Harden, Noni K.; Malinowski, Sara L.; Grant, Kathryn E.; Carleton, Russell A.; Ford, Rebecca E.

2007-01-01

This study sought to explore potential mechanisms through which uncontrollable, chronic stressors may lead to hopelessness in low-income, urban adolescents. In particular, the roles of specific coping strategies as moderators and/or mediators of the association between stressors and hopelessness were examined. Results suggest that chronic,…

Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

PubMed Central

Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

2011-01-01

To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

The Tlo Proteins Are Stoichiometric Components of Candida albicans Mediator Anchored via the Med3 Subunit

PubMed Central

Zhang, Anda; Petrov, Kostadin O.; Hyun, Emily R.; Liu, Zhongle; Gerber, Scott A.

2012-01-01

The amplification of the TLO (for telomere-associated) genes in Candida albicans, compared to its less pathogenic, close relative Candida dubliniensis, suggests a role in virulence. Little, however, is known about the function of the Tlo proteins. We have purified the Mediator coactivator complex from C. albicans (caMediator) and found that Tlo proteins are a stoichiometric component of caMediator. Many members of the Tlo family are expressed, and each is a unique member of caMediator. Protein expression analysis of individual Tlo proteins, as well as the purification of tagged Tlo proteins, demonstrate that there is a large free population of Tlo proteins in addition to the Mediator-associated population. Coexpression and copurification of Tloα12 and caMed3 in Escherichia coli established a direct physical interaction between the two proteins. We have also made a C. albicans med3Δ/Δ strain and purified an intact Mediator from this strain. The analysis of the composition of the med3Δ Mediator shows that it lacks a Tlo subunit. Regarding Mediator function, the med3Δ/Δ strain serves as a substitute for the difficult-to-make tloΔ/Δ C. albicans strain. A potential role of the TLO and MED3 genes in virulence is supported by the inability of the med3Δ/Δ strain to form normal germ tubes. This study of caMediator structure provides initial clues to the mechanism of action of the Tlo genes and a platform for further mechanistic studies of caMediator's involvement in gene regulatory patterns that underlie pathogenesis. PMID:22562472

In vitro and ex vivo vanadium antitumor activity in (TGF-β)-induced EMT. Synergistic activity with carboplatin and correlation with tumor metastasis in cancer patients.

PubMed

Petanidis, Savvas; Kioseoglou, Efrosini; Domvri, Kalliopi; Zarogoulidis, Paul; Carthy, Jon M; Anestakis, Doxakis; Moustakas, Aristidis; Salifoglou, Athanasios

2016-05-01

Epithelial to mesenchymal transition (EMT) plays a key role in tumor progression and metastasis as a crucial event for cancer cells to trigger the metastatic niche. Transforming growth factor-β (TGF-β) has been shown to play an important role as an EMT inducer in various stages of carcinogenesis. Previous reports had shown that antitumor vanadium inhibits the metastatic potential of tumor cells by reducing MMP-2 expression and inducing ROS-dependent apoptosis. However, the role of vanadium in (TGF-β)-induced EMT remains unclear. In the present study, we report for the first time on the inhibitory effects of vanadium on (TGF-β)-mediated EMT followed by down-regulation of ex vivo cancer stem cell markers. The results demonstrate blockage of (TGF-β)-mediated EMT by vanadium and reduction in the mitochondrial potential of tumor cells linked to EMT and cancer metabolism. Furthermore, combination of vanadium and carboplatin (a) resulted in synergistic antitumor activity in ex vivo cell cultures, and (b) prompted G0/G1 cell cycle arrest and sensitization of tumor cells to carboplatin-induced apoptosis. Overall, the findings highlight the multifaceted antitumor action of vanadium and its synergistic antitumor efficacy with current chemotherapy drugs, knowledge that could be valuable for targeting cancer cell metabolism and cancer stem cell-mediated metastasis in aggressive chemoresistant tumors. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Modified In vitro Invasion Assay to Determine the Potential Role of Hormones, Cytokines and/or Growth Factors in Mediating Cancer Cell Invasion.

PubMed

Bagati, Archis; Koch, Zethan; Bofinger, Diane; Goli, Haneesha; Weiss, Laura S; Dau, Rosie; Thomas, Megha; Zucker, Shoshanna N

2015-04-24

Blood serum serves as a chemoattractant towards which cancer cells migrate and invade, facilitating their intravasation into microvessels. However, the actual molecules towards which the cells migrate remain elusive. This modified invasion assay has been developed to identify targets which drive cell migration and invasion. This technique compares the invasion index under three conditions to determine whether a specific hormone, growth factor, or cytokine plays a role in mediating the invasive potential of a cancer cell. These conditions include i) normal fetal bovine serum (FBS), ii) charcoal-stripped FBS (CS-FBS), which removes hormones, growth factors, and cytokines and iii) CS-FBS + molecule (denoted "X"). A significant change in cell invasion with CS-FBS as compared to FBS, indicates the involvement of hormones, cytokines or growth factors in mediating the change. Individual molecules can then be added back to CS-FBS to assay their ability to reverse or rescue the invasion phenotype. Furthermore, two or more factors can be combined to evaluate the additive or synergistic effects of multiple molecules in driving or inhibiting invasion. Overall, this method enables the investigator to determine whether hormones, cytokines, and/or growth factors play a role in cell invasion by serving as chemoattractants or inhibitors of invasion for a particular type of cancer cell or a specific mutant. By identifying specific chemoattractants and inhibitors, this modified invasion assay may help to elucidate signaling pathways that direct cancer cell invasion.

Synaptic transmission at functionally identified synapses in the enteric nervous system: roles for both ionotropic and metabotropic receptors.

PubMed

Gwynne, R M; Bornstein, J C

2007-03-01

Digestion and absorption of nutrients and the secretion and reabsorption of fluid in the gastrointestinal tract are regulated by neurons of the enteric nervous system (ENS), the extensive peripheral nerve network contained within the intestinal wall. The ENS is an important physiological model for the study of neural networks since it is both complex and accessible. At least 20 different neurochemically and functionally distinct classes of enteric neurons have been identified in the guinea pig ileum. These neurons express a wide range of ionotropic and metabotropic receptors. Synaptic potentials mediated by ionotropic receptors such as the nicotinic acetylcholine receptor, P2X purinoceptors and 5-HT(3) receptors are seen in many enteric neurons. However, prominent synaptic potentials mediated by metabotropic receptors, like the P2Y(1) receptor and the NK(1) receptor, are also seen in these neurons. Studies of synaptic transmission between the different neuron classes within the enteric neural pathways have shown that both ionotropic and metabotropic synaptic potentials play major roles at distinct synapses within simple reflex pathways. However, there are still functional synapses at which no known transmitter or receptor has been identified. This review describes the identified roles for both ionotropic and metabotropic neurotransmission at functionally defined synapses within the guinea pig ileum ENS. It is concluded that metabotropic synaptic potentials act as primary transmitters at some synapses. It is suggested identification of the interactions between different synaptic potentials in the production of complex behaviours will require the use of well validated computer models of the enteric neural circuitry.

Transient receptor potential channel superfamily: Role in lower urinary tract function.

PubMed

Ogawa, Teruyuki; Imamura, Tetsuya; Nakazawa, Masaki; Hiragata, Shiro; Nagai, Takashi; Minagawa, Tomonori; Yokoyama, Hitoshi; Ishikawa, Masakuni; Domen, Takahisa; Ishizuka, Osamu

2015-11-01

Lower urinary tract symptoms associated with neurogenic bladder and overactive bladder syndrome are mediated in part by members of the transient receptor potential channel superfamily. The best studied member of this superfamily is the vanilloid receptor. Other transient receptor potential channels, such as the melastatin receptor and the ankyrin receptor, are also active in the pathogenesis of lower urinary tract dysfunction. However, the detailed mechanisms by which the transient receptor potential channels contribute to lower urinary tract symptoms are still not clear, and the therapeutic benefits of modulating transient receptor potential channel activity have not been proved in the clinical setting. In the present review, to better understand the pathophysiology and therapeutic potential for lower urinary tract symptoms, we summarize the presence and role of different members of the transient receptor potential channel superfamily in the lower urinary tract. © 2015 The Japanese Urological Association.

Potentiation of pulmonary reflex response to capsaicin 24h following whole-body acrolein exposure is mediated by TRPV1.

PubMed

Hazari, Mehdi S; Rowan, William H; Winsett, Darrell W; Ledbetter, Allen D; Haykal-Coates, Najwa; Watkinson, William P; Costa, Daniel L

2008-02-01

Pulmonary C-fibers are stimulated by irritant air pollutants producing apnea, bronchospasm, and decrease in HR. Chemoreflex responses resulting from C-fiber activation are sometimes mediated by TRPV1 and release of substance P. While acrolein has been shown to stimulate C-fibers, the persistence of acrolein effects and the role of C-fibers in these responses are unknown. These experiments were designed to determine the effects of whole-body acrolein exposure and pulmonary chemoreflex response post-acrolein. Rats were exposed to either air or 3 ppm acrolein for 3 h while ventilatory function and HR were measured; 1-day later response to capsaicin challenge was measured in anesthetized rats. Rats experienced apnea and decrease in HR upon exposure to acrolein, which was not affected by either TRPV1 antagonist or NK(1)R antagonist pretreatment. Twenty-four hours later, capsaicin caused apnea and bronchoconstriction in control rats, which was potentiated in rats exposed to acrolein. Pretreatment with TRPV1 antagonist or NK(1)R antagonist prevented potentiation of apneic response and bronchoconstriction 24h post-exposure. These data suggest that although potentiation of pulmonary chemoreflex response 24h post-acrolein is mediated by TRPV1 and release of substance P, cardiopulmonary inhibition during whole-body acrolein exposure is mediated through other mechanisms.

Does insecure attachment mediate the relationship between trauma and voice-hearing in psychosis?

PubMed

Pilton, Marie; Bucci, Sandra; McManus, James; Hayward, Mark; Emsley, Richard; Berry, Katherine

2016-12-30

This study extends existing research and theoretical developments by exploring the potential mediating role of insecure attachment within the relationship between trauma and voice-hearing. Fifty-five voice hearers with a psychosis-related diagnosis completed comprehensive assessments of childhood trauma, adult attachment, voice-related severity and distress, beliefs about voices and relationships with voices. Anxious attachment was significantly associated with the voice-hearing dimensions examined. More sophisticated analysis showed that anxious attachment mediated the relationship between childhood sexual and emotional abuse and voice-related severity and distress, voice-malevolence, voice-omnipotence, voice-resistance and hearer-dependence. Anxious attachment also mediated the relationship between childhood physical neglect and voice-related severity and distress and hearer-dependence. Furthermore, consistent with previous research, the relationship between anxious attachment and voice-related distress was mediated by voice-malevolence, voice-omnipotence and voice-resistance. We propose a model whereby anxious attachment mediates the well-established relationship between trauma and voice-hearing. In turn, negative beliefs about voices may mediate the association between anxious attachment and voice-related distress. Findings presented here highlight the need to assess and formulate the impact of attachment patterns upon the voice-hearing experience in psychosis and the potential to alleviate voice-related distress by fostering secure attachments to therapists or significant others. Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.

Bax Translocation Mediated Mitochondrial Apoptosis and Caspase Dependent Photosensitizing Effect of Ficus religiosa on Cancer Cells

PubMed Central

Thankayyan R, Santhosh Kumar; Sithul, Hima; Sreeharshan, Sreeja

2012-01-01

The main aim of the present work was to investigate the potential effect of acetone extract of Ficus religosa leaf (FAE) in multiple apoptosis signalling in human breast cancer cells. FAE treatment significantly induced dose and time dependent, irreversible inhibition of breast cancer cell growth with moderate toxicity to normal breast epithelial cells. This observation was validated using Sulforhodamine B assay. Cell cycle analysis by Flow cytometry showed cell cycle arrest in G1 phase and induction of sub-G0 peak. FAE induced chromatin condensation and displayed an increase in apoptotic population in Annexin V-FITC/PI (Fluorescein isothiocyanate/Propidium iodide) double staining. FAE stimulated the loss of mitochondrial membrane potential in multiple breast cancer cell lines when compared to normal diploid cells. To understand the role of Bax in FAE induced apoptosis, we employed a sensitive cell based platform of MCF-7 cells expressing Bax-EGFP. Bax translocation to mitochondria was accompanied by the disruption of mitochondrial membrane potential and marked elevation in LEHDase activity (Caspase 9). Consistent with this data, FAE induced Caspase activation as evidenced by ratio change in FRET Caspase sensor expressing MCF-7 cell line and cleavage of prominent Caspases and PARP. Interestingly, FAE accelerated cell death in a mitochondrial dependent manner in continuous live cell imaging mode indicating its possible photosensitizing effect. Intracellular generation of reactive oxygen species (ROS) by FAE played a critical role in mediating apoptotic cell death and photosensitizing activity. FAE induced dose and time dependent inhibition of cancer cell growth which was associated with Bax translocation and mitochondria mediated apoptosis with the activation of Caspase 9 dependent Caspase cascade. FAE also possessed strong photosensitizing effect on cancer cell line that was mediated through rapid mitochondrial transmembrane potential loss and partial Caspase activation involving generation of intracellular ROS. PMID:22792212

Cue-dependent interference in comprehension

PubMed Central

Van Dyke, Julie A.

2011-01-01

The role of interference as a primary determinant of forgetting in memory has long been accepted, however its role as a contributor to poor comprehension is just beginning to be understood. The current paper reports two studies, in which speed-accuracy tradeoff and eye-tracking methodologies were used with the same materials to provide converging evidence for the role of syntactic and semantic cues as mediators of both proactive (PI) and retroactive interference (RI) during comprehension. Consistent with previous work (e.g., Van Dyke & Lewis, 2003), we found that syntactic constraints at the retrieval site are among the cues that drive retrieval in comprehension, and that these constraints effectively limit interference from potential distractors with semantic/pragmatic properties in common with the target constituent. The data are discussed in terms of a cue-overload account, in which interference both arises from and is mediated through a direct-access retrieval mechanism that utilizes a linear, weighted cue-combinatoric scheme. PMID:21927535

Role of the Cysteinyl Leukotrienes in the Pathogenesis and Progression of Cardiovascular Diseases

PubMed Central

Colazzo, Francesca; Gelosa, Paolo

2017-01-01

Cysteinyl leukotrienes (CysLTs) are potent lipid inflammatory mediators synthesized from arachidonic acid, through the 5-lipoxygenase (5-LO) pathway. Owing to their properties, CysLTs play a crucial role in the pathogenesis of inflammation; therefore, CysLT modifiers as synthesis inhibitors or receptor antagonists, central in asthma management, may become a potential target for the treatment of other inflammatory diseases such as the cardiovascular disorders. 5-LO pathway activation and increased expression of its mediators and receptors are found in cardiovascular diseases. Moreover, the cardioprotective effects observed by using CysLT modifiers are promising and contribute to elucidate the link between CysLTs and cardiovascular disease. The aim of this review is to summarize the state of present research about the role of the CysLTs in the pathogenesis and progression of atherosclerosis and myocardial infarction. PMID:28932020

Transforming Growth Factor β1 Function in Airway Remodeling and Hyperresponsiveness. The Missing Link?

PubMed

Ojiaku, Christie A; Yoo, Edwin J; Panettieri, Reynold A

2017-04-01

The pathogenesis of asthma includes a complex interplay among airway inflammation, hyperresponsiveness, and remodeling. Current evidence suggests that airway structural cells, including bronchial smooth muscle cells, myofibroblasts, fibroblasts, and epithelial cells, mediate all three aspects of asthma pathogenesis. Although studies show a connection between airway remodeling and changes in bronchomotor tone, the relationship between the two remains unclear. Transforming growth factor β1 (TGF-β1), a growth factor elevated in the airway of patients with asthma, plays a role in airway remodeling and in the shortening of various airway structural cells. However, the role of TGF-β1 in mediating airway hyperresponsiveness remains unclear. In this review, we summarize the literature addressing the role of TGF-β1 in airway remodeling and shortening. Through our review, we aim to further elucidate the role of TGF-β1 in asthma pathogenesis and the link between airway remodeling and airway hyperresponsiveness in asthma and to define TGF-β1 as a potential therapeutic target for reducing asthma morbidity and mortality.

Antibodies are necessary for rVSV/ZEBOV-GP-mediated protection against lethal Ebola virus challenge in nonhuman primates.

PubMed

Marzi, Andrea; Engelmann, Flora; Feldmann, Friederike; Haberthur, Kristen; Shupert, W Lesley; Brining, Douglas; Scott, Dana P; Geisbert, Thomas W; Kawaoka, Yoshihiro; Katze, Michael G; Feldmann, Heinz; Messaoudi, Ilhem

2013-01-29

Ebola viruses cause hemorrhagic disease in humans and nonhuman primates with high fatality rates. These viruses pose a significant health concern worldwide due to the lack of approved therapeutics and vaccines as well as their potential misuse as bioterrorism agents. Although not licensed for human use, recombinant vesicular stomatitis virus (rVSV) expressing the filovirus glycoprotein (GP) has been shown to protect macaques from Ebola virus and Marburg virus infections, both prophylactically and postexposure in a homologous challenge setting. However, the immune mechanisms of protection conferred by this vaccine platform remain poorly understood. In this study, we set out to investigate the role of humoral versus cellular immunity in rVSV vaccine-mediated protection against lethal Zaire ebolavirus (ZEBOV) challenge. Groups of cynomolgus macaques were depleted of CD4+ T, CD8+ T, or CD20+ B cells before and during vaccination with rVSV/ZEBOV-GP. Unfortunately, CD20-depleted animals generated a robust IgG response. Therefore, an additional group of vaccinated animals were depleted of CD4+ T cells during challenge. All animals were subsequently challenged with a lethal dose of ZEBOV. Animals depleted of CD8+ T cells survived, suggesting a minimal role for CD8+ T cells in vaccine-mediated protection. Depletion of CD4+ T cells during vaccination caused a complete loss of glycoprotein-specific antibodies and abrogated vaccine protection. In contrast, depletion of CD4+ T cells during challenge resulted in survival of the animals, indicating a minimal role for CD4+ T-cell immunity in rVSV-mediated protection. Our results suggest that antibodies play a critical role in rVSV-mediated protection against ZEBOV.

Potential Role for a Carbohydrate Moiety in Anti-Candida Activity of Human Oral Epithelial Cells

PubMed Central

Steele, Chad; Leigh, Janet; Swoboda, Rolf; Ozenci, Hatice; Fidel, Paul L.

2001-01-01

Candida albicans is both a commensal and a pathogen at the oral mucosa. Although an intricate network of host defense mechanisms are expected for protection against oropharyngeal candidiasis, anti-Candida host defense mechanisms at the oral mucosa are poorly understood. Our laboratory recently showed that primary epithelial cells from human oral mucosa, as well as an oral epithelial cell line, inhibit the growth of blastoconidia and/or hyphal phases of several Candida species in vitro with a requirement for cell contact and with no demonstrable role for soluble factors. In the present study, we show that oral epithelial cell-mediated anti-Candida activity is resistant to gamma-irradiation and is not mediated by phagocytosis, nitric oxide, hydrogen peroxide, and superoxide oxidative inhibitory pathways or by nonoxidative components such as soluble defensin and calprotectin peptides. In contrast, epithelial cell-mediated anti-Candida activity was sensitive to heat, paraformaldehyde fixation, and detergents, but these treatments were accompanied by a significant loss in epithelial cell viability. Treatments that removed existing membrane protein or lipid moieties in the presence or absence of protein synthesis inhibitors had no effect on epithelial cell inhibitory activity. In contrast, the epithelial cell-mediated anti-Candida activity was abrogated after treatment of the epithelial cells with periodic acid, suggesting a role for carbohydrates. Adherence of C. albicans to oral epithelial cells was unaffected, indicating that the carbohydrate moiety is exclusively associated with the growth inhibition activity. Subsequent studies that evaluated specific membrane carbohydrate moieties, however, showed no role for sulfated polysaccharides, sialic acid residues, or glucose- and mannose-containing carbohydrates. These results suggest that oral epithelial cell-mediated anti-Candida activity occurs exclusively with viable epithelial cells through contact with C. albicans by an as-yet-undefined carbohydrate moiety. PMID:11598085

Evaluation of laccase-mediator system (LMS) in the oxidation of veratryl alcohol

USDA-ARS?s Scientific Manuscript database

Identifying suitable reaction conditions remains an important task in the development of enzyme catalysis. Laccases play an important role in the biological break down of lignin and have great potential in the deconstruction of lignocellulosic feedstocks. We examined 16 laccases, both commercially...

A Review of the Role of Female Gender in Autism Spectrum Disorders

ERIC Educational Resources Information Center

Kirkovski, Melissa; Enticott, Peter G.; Fitzgerald, Paul B.

2013-01-01

This paper reviews the literature exploring gender differences associated with the clinical presentation of autism spectrum disorders (ASD). The potentially mediating effect of comorbid psychopathology, biological and neurodevelopmental implications on these gender differences is also discussed. A vastly heterogeneous condition, while females on…

Dyslipidemia links obesity to early cerebral neurochemical alterations

PubMed Central

Haley, Andreana P.; Gonzales, Mitzi M.; Tarumi, Takashi; Tanaka, Hirofumi

2013-01-01

Objective To examine the role of hypertension, hyperglycemia and dyslipidemia in potentially accounting for obesity-related brain vulnerability in the form of altered cerebral neurochemistry. Design and Methods Sixty-four adults, ages 40 to 60 years, underwent a health screen and proton magnetic resonance spectroscopy (1H MRS) of occipitoparietal grey matter to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (mI) and glutamate (Glu) relative to creatine (Cr). The causal steps approach and non-parametric bootstrapping were utilized to assess if fasting glucose, mean arterial pressure or peripheral lipid/lipoprotein levels mediate the relationship between body mass index (BMI) and cerebral neurochemistry. Results Higher BMI was significantly related to higher mI/Cr, independent of age and sex. BMI was also significantly related to two of the proposed mediators, triglyceride and HDL-cholesterol, which were also independently related to increased mI/Cr. Finally, the relationship between BMI and mI/Cr, was significantly attenuated after inclusion of triglyceride and HDL-cholesterol into the model, one at a time, indicating statistical mediation. Conclusions Higher triglyceride and lower HDL levels statistically account for the association between BMI and myo-inositol, pointing towards a potentially critical role for dyslipidemia in the development of cerebral neurochemical alterations in obesity. PMID:23512296

Suppressive Effects of Pelargonidin on Endothelial Protein C Receptor Shedding via the Inhibition of TACE Activity and MAP Kinases.

PubMed

Kang, Hyejin; Lee, Taeho; Bae, Jong-Sup

2016-01-01

Beyond its role in the activation of protein C, the endothelial cell protein C receptor (EPCR) plays an important role in the cytoprotective pathway. EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-[Formula: see text] converting enzyme (TACE). Pelargonidin is a well-known red pigment found in plants, and has been reported to have important biological activities that are potentially beneficial to human health. However, little is known about the effects of pelargonidin on EPCR shedding. We investigated this issue by monitoring the effects of pelargonidin on phorbol-12-myristate 13-acetate (PMA)-, tumor necrosis factor (TNF)-[Formula: see text]-, interleukin (IL)-1β-, and cecal ligation and puncture (CLP)-mediated EPCR shedding and by investigating the underlying mechanism of pelargonidin action. Data demonstrate that pelargonidin induced potent inhibition of PMA-, TNF-[Formula: see text]-, IL-1β-, and CLP-induced EPCR shedding by inhibiting the phosphorylation of mitogen-activated protein kinases (MAPKs) such as p38, janus kinase (JNK), and extracellular signal-regulated kinase (ERK) 1/2. Pelargonidin also inhibited the expression and activity of PMA-induced TACE in endothelial cells. These results demonstrate the potential of pelargonidin as an anti-EPCR shedding reagent against PMA- and CLP-mediated EPCR shedding.

BRN2, a POUerful driver of melanoma phenotype switching and metastasis.

PubMed

Fane, Mitchell E; Chhabra, Yash; Smith, Aaron G; Sturm, Richard A

2018-05-21

The POU domain family of transcription factors play a central role in embryogenesis and are highly expressed in neural crest cells and the developing brain. BRN2 is a class III POU domain protein that is a key mediator of neuroendocrine and melanocytic development and differentiation. While BRN2 is a central regulator in numerous developmental programs, it has also emerged as a major player in the biology of tumourigenesis. In melanoma, BRN2 has been implicated as one of the master regulators of the acquisition of invasive behavior within the phenotype-switching model of progression. As a mediator of melanoma cell phenotype-switching it co-ordinates the transition to a de-differentiated, slow cycling and highly motile cell type. Its inverse expression relationship with MITF is believed to mediate tumour progression and metastasis within this model. Recent evidence has now outlined a potential epigenetic switching mechanism in melanoma cells driven by BRN2 expression that induces melanoma cell invasion. We summarise the role of BRN2 in tumour cell dissemination and metastasis in melanoma, while also examining it as a potential metastatic regulator in other tumour models. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

So depression is an inflammatory disease, but where does the inflammation come from?

PubMed Central

2013-01-01

Background We now know that depression is associated with a chronic, low-grade inflammatory response and activation of cell-mediated immunity, as well as activation of the compensatory anti-inflammatory reflex system. It is similarly accompanied by increased oxidative and nitrosative stress (O&NS), which contribute to neuroprogression in the disorder. The obvious question this poses is ‘what is the source of this chronic low-grade inflammation?’ Discussion This review explores the role of inflammation and oxidative and nitrosative stress as possible mediators of known environmental risk factors in depression, and discusses potential implications of these findings. A range of factors appear to increase the risk for the development of depression, and seem to be associated with systemic inflammation; these include psychosocial stressors, poor diet, physical inactivity, obesity, smoking, altered gut permeability, atopy, dental cares, sleep and vitamin D deficiency. Summary The identification of known sources of inflammation provides support for inflammation as a mediating pathway to both risk and neuroprogression in depression. Critically, most of these factors are plastic, and potentially amenable to therapeutic and preventative interventions. Most, but not all, of the above mentioned sources of inflammation may play a role in other psychiatric disorders, such as bipolar disorder, schizophrenia, autism and post-traumatic stress disorder. PMID:24228900

Neurovascular contributions to migraine: Moving beyond vasodilation.

PubMed

Jacobs, Blaine; Dussor, Gregory

2016-12-03

Migraine is the third most common disease worldwide, the most common neurological disorder, and one of the most common pain conditions. Despite its prevalence, the basic physiology and underlying mechanisms contributing to the development of migraine are still poorly understood and development of new therapeutic targets is long overdue. Until recently, the major contributing pathophysiological event thought to initiate migraine was cerebral and meningeal arterial vasodilation. However, the role of vasodilation in migraine is unclear and recent findings challenge its necessity. While vasodilation itself may not contribute to migraine, it remains possible that vessels play a role in migraine pathophysiology in the absence of vasodilation. Blood vessels consist of a variety of cell types that both release and respond to numerous mediators including growth factors, cytokines, adenosine triphosphate (ATP), and nitric oxide (NO). Many of these mediators have actions on neurons that can contribute to migraine. Conversely, neurons release factors such as norepinephrine and calcitonin gene-related peptide (CGRP) that act on cells native to blood vessels. Both normal and pathological events occurring within and between vascular cells could thus mediate bi-directional communication between vessels and the nervous system, without the need for changes in vascular tone. This review will discuss the potential contribution of the vasculature, specifically endothelial cells, to current neuronal mechanisms hypothesized to play a role in migraine. Hypothalamic activity, cortical spreading depression (CSD), and dural afferent input from the cranial meninges will be reviewed with a focus on how these mechanisms can influence or be impacted by blood vessels. Together, the data discussed will provide a framework by which vessels can be viewed as important potential contributors to migraine pathophysiology, even in light of the current uncertainty over the role of vasodilation in this disorder. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Neurovascular contributions to migraine: moving beyond vasodilation

PubMed Central

Jacobs, Blaine; Dussor, Gregory

2016-01-01

Migraine is the third most common disease worldwide, the most common neurological disorder, and one of the most common pain conditions. Despite its prevalence, the basic physiology and underlying mechanisms contributing to the development of migraine is still poorly understood and development of new therapeutic targets is long overdue. Until recently, the major contributing pathophysiological event thought to initiate migraine was cerebral and meningeal arterial vasodilation. However, the role of vasodilation in migraine is unclear and recent findings challenge its necessity. While vasodilation itself may not contribute to migraine, it remains possible that vessels play a role in migraine pathophysiology in the absence of vasodilation. Blood vessels consist of a variety of cell types that both release and respond to numerous mediators including growth factors, cytokines, adenosine triphosphate (ATP), and nitric oxide (NO). Many of these mediators have actions on neurons that can contribute to migraine. Conversely, neurons release factors such as norepinephrine and calcitonin gene-related peptide (CGRP) that act on cells native to blood vessels. Both normal and pathological events occurring within and between vascular cells could thus mediate bi-directional communication between vessels and the nervous system, without the need for changes in vascular tone. This review will discuss the potential contribution of the vasculature, specifically endothelial cells, to current neuronal mechanisms hypothesized to play a role in migraine. Hypothalamic activity, cortical spreading depression (CSD), and dural afferent input from the cranial meninges will be reviewed with a focus on how these mechanisms can influence or be impacted by blood vessels. Together, the data discussed will provide a framework by which vessels can be viewed as important potential contributors to migraine pathophysiology, even in light of the current uncertainty over the role of vasodilation in this disorder. PMID:27312704

Pathways From Bullying Perpetration, Victimization, and Bully Victimization to Suicidality Among School-Aged Youth: A Review of the Potential Mediators and a Call for Further Investigation.

PubMed

Hong, Jun Sung; Kral, Michael J; Sterzing, Paul R

2015-10-01

In the wake of several highly publicized adolescent suicides attributed to bullying victimization, national attention has been brought to bear on the profound public health problem of bullying. This article reviews the extant literature on the associations between bullying perpetration, victimization, and thoughts of or attempts at suicide and proposes five potential mediators, namely depression, anxiety, low self-esteem, loneliness, and hopelessness, that may explain this relationship. Numerous studies have found empirical support for the interrelations between internalizing behaviors and both bullying perpetration and victimization and suicide. We find that further longitudinal research needs to be conducted to more conclusively determine the role and causal ordering these various psychosocial factors may play in bullying perpetration, victimization, and suicide. Although the research literature implies causal directions among all these potential mediators, untangling the unique influence of bullying perpetration, victimization, and bully victimization on suicide and its mechanisms of action has major research and practice implications. © The Author(s) 2014.

IRBIT plays an important role in NHE3-mediated pHi regulation in HSG cells.

PubMed

Tran, Tien Manh; Park, Moon-Yong; Lee, Jiyeon; Bae, Jun-Seok; Hwang, Sung-Min; Choi, Se-Young; Mikoshiba, Katsuhiko; Park, Kyungpyo

2013-07-19

Expression of inositol-1,4,5-trisphosphate (IP3) receptor-binding protein (IRBIT) has been reported in epithelial cells. However, its role in pHi regulation is not well understood. In this study, we investigated the role of IRBIT in pHi regulation, mediated by Na(+)/H(+) exchangers (NHEs), in salivary glands. We measured pHi recovery from cell acidification in BCECF-loaded salivary HSG cells. Western blot and co-immunoprecipitation (CO-IP) assays were also performed, showing that NHE1, 2 and 3 are expressed, and IRBIT binds to NHE3. HOE642, a specific NHE1 blocker, inhibited pHi recovery, but 40% pH(i) recovery was still observed even at the highest concentration of HOE642. Furthermore, pretreatment of the cells with siIRBIT significantly inhibited pHi recovery, indicating that NHE3 potentially plays a role in pHi recovery as well. The amount of membrane-localized NHE3 and its interaction with IRBIT are also significantly increased by cell acidification. In addition, we found that Ste20p-related proline alanine-rich kinase (SPAK) reverses the effect of IRBIT on membrane NHE3 translocation. Taken together, we conclude that IRBIT plays an important role in pHi regulation, mediated by NHE3, and further regulated by SPAK. Copyright © 2013 Elsevier Inc. All rights reserved.

Violence Exposure as a Mediator Between Parenting and Adolescent Mental Health.

PubMed

Moed, Anat; Gershoff, Elizabeth T; Bringewatt, Elizabeth H

2017-04-01

For youth exposed to community violence, parenting has been found to play a significant role in protecting adolescents from associated mental health symptoms. Yet little is known about the potential of parenting to prevent such exposure in the first place and thereby reduce the likelihood of adolescents' mental health symptoms. This study examined two parental practices that have often been examined as moderators, but not yet as predictors, of youth exposure to community violence associations with adolescent mental health, namely parental control and parental harshness. Analyses of self-reported data from 908 adolescents (M age  = 16.5, SD = 1.71; 52 % girls; 13 % non-Hispanic White) revealed that harsh parenting was indirectly associated with youth mental health symptoms through higher levels of exposure to community violence, whereas links between controlling parenting and mental health symptoms were either non-significant or mediated through lower levels of adolescent violence exposure. These findings highlight the potential positive role parental control may play by preventing adolescents from exposure to potentially dangerous situations. Conversely, our results suggest that harsh parenting appears to pose a risk for adolescents by driving youth away from the home environment and potentially into places where violence may be more prevalent.

Epac2 Mediates cAMP-Dependent Potentiation of Neurotransmission in the Hippocampus.

PubMed

Fernandes, Herman B; Riordan, Sean; Nomura, Toshihiro; Remmers, Christine L; Kraniotis, Stephen; Marshall, John J; Kukreja, Lokesh; Vassar, Robert; Contractor, Anis

2015-04-22

Presynaptic terminal cAMP elevation plays a central role in plasticity at the mossy fiber-CA3 synapse of the hippocampus. Prior studies have identified protein kinase A as a downstream effector of cAMP that contributes to mossy fiber LTP (MF-LTP), but the potential contribution of Epac2, another cAMP effector expressed in the MF synapse, has not been considered. We investigated the role of Epac2 in MF-CA3 neurotransmission using Epac2(-/-) mice. The deletion of Epac2 did not cause gross alterations in hippocampal neuroanatomy or basal synaptic transmission. Synaptic facilitation during short trains was not affected by loss of Epac2 activity; however, both long-term plasticity and forskolin-mediated potentiation of MFs were impaired, demonstrating that Epac2 contributes to cAMP-dependent potentiation of transmitter release. Examination of synaptic transmission during long sustained trains of activity suggested that the readily releasable pool of vesicles is reduced in Epac2(-/-) mice. These data suggest that cAMP elevation uses an Epac2-dependent pathway to promote transmitter release, and that Epac2 is required to maintain the readily releasable pool at MF synapses in the hippocampus. Copyright © 2015 the authors 0270-6474/15/356544-10$15.00/0.

The role of transient receptor potential vanilloid type-2 ion channels in innate and adaptive immune responses

PubMed Central

Santoni, Giorgio; Farfariello, Valerio; Liberati, Sonia; Morelli, Maria B.; Nabissi, Massimo; Santoni, Matteo; Amantini, Consuelo

2013-01-01

The transient receptor potential vanilloid type-2 (TRPV2), belonging to the transient receptor potential channel family, is a specialized ion channel expressed in human and other mammalian immune cells. This channel has been found to be expressed in CD34+ hematopoietic stem cells, where its cytosolic Ca2+ activity is crucial for stem/progenitor cell cycle progression, growth, and differentiation. In innate immune cells, TRPV2 is expressed in granulocytes, macrophages, and monocytes where it stimulates fMet-Leu-Phe migration, zymosan-, immunoglobulin G-, and complement-mediated phagocytosis, and lipopolysaccharide-induced tumor necrosis factor-alpha and interleukin-6 production. In mast cells, activation of TRPV2 allows intracellular Ca2+ ions flux, thus stimulating protein kinase A-dependent degranulation. In addition, TRPV2 is highly expressed in CD56+ natural killer cells. TRPV2 orchestrates Ca2+ signal in T cell activation, proliferation, and effector functions. Moreover, messenger RNA for TRPV2 are expressed in CD4+ and CD8+ T lymphocytes. Finally, TRPV2 is expressed in CD19+ B lymphocytes where it regulates Ca2+ release during B cell development and activation. Overall, the specific expression of TRPV2 in immune cells suggests a role in immune-mediated diseases and offers new potential targets for immunomodulation. PMID:23420671

Sound stress-induced long-term enhancement of mechanical hyperalgesia in rats is maintained by sympathoadrenal catecholamines.

PubMed

Khasar, Sachia G; Dina, Olayinka A; Green, Paul G; Levine, Jon D

2009-10-01

Although stress plays an important role in chronic widespread pain syndromes, such as fibromyalgia, the underlying mechanism has remained elusive. We have recently demonstrated, in a model of chronic widespread pain, that prolonged enhancement of immune mediator hyperalgesia, induced by unpredictable sound stress, requires a contribution of both the sympathoadrenal (epinephrine) and the hypothalamic-pituitary adrenal (corticosterone) neuroendocrine stress axes. Because this stress protocol produced sustained elevation of plasma epinephrine, in the current study we tested the hypothesis that the sympathoadrenal axis also plays a role in maintenance of symptoms in this model of chronic widespread pain. After establishment, adrenal medullectomy abolished the enhancement of epinephrine-induced cutaneous and muscle hyperalgesia. Administration of stress levels of epinephrine to adrenal medullectomized rats reconstituted the pain phenotype. These observations suggest that the sympathoadrenal stress axis plays a major role in the induction as well as maintenance of stress-induced enhancement of mechanical hyperalgesia, mediated by prolonged elevation of circulating epinephrine. We present data showing mechanical hyperalgesia persisting for up to 28 days after exposure to sound stress, with evidence that the sympathoadrenal axis mediator epinephrine plays a major role. These findings could have clinical implications with regard to novel potential treatments for chronic widespread pain syndromes, such as fibromyalgia.

PINK1/Parkin-mediated mitophagy alleviates chlorpyrifos-induced apoptosis in SH-SY5Y cells.

PubMed

Dai, Hongmei; Deng, Yuanying; Zhang, Jie; Han, Hailong; Zhao, Mingyi; Li, Ying; Zhang, Chen; Tian, Jing; Bing, Guoying; Zhao, Lingling

2015-08-06

Chlorpyrifos (CPF) is one of the most widely used organophosphorous insecticides. There are links between CPF exposure and neurological disorders. Mitochondrial damage has been implicated to play a key role in CPF-induced neurotoxicity. Mitophagy, the selective autophagic elimination of mitochondria, is an important mitochondrial quality control mechanism. However, the role of mitophagy in CPF-induced neurotoxicity remains unclear. In this study, CPF-caused mitochondrial damage, role and mechanism of mitophagy on CPF-induced neuroapoptosis were extensively studied by using SH-SY5Y cells. We showed that CPF treatment caused mitochondrial fragmentation, excessive ROS generation and mitochondrial depolarization, thus led to cell apoptosis. Moreover, CPF treatment also resulted in increased colocalizaton of mitochondria with LC3, decreased levels of mitochondrial proteins, PINK1 stabilization and mitochondrial accumulation of Parkin. These data suggested that CPF treatment induced PINK1/Parkin-mediated mitophagy in SH-SY5Y cells. Furthermore, knockdown of Parkin dramatically increased CPF-induced neuroapoptosis. On the other hand, overexpression of Parkin markedly alleviated CPF-induced SH-SY5Y cell apoptosis. Together, these findings implicate a protective role of PINK1/Parkin-mediated mitophagy against neuroapoptosis and that enhancing mitophagy provides a potential therapeutic strategy for CPF-induced neurological disorders. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Galectin-3 in autoimmunity and autoimmune diseases

PubMed Central

de Oliveira, Felipe L; Gatto, Mariele; Bassi, Nicola; Luisetto, Roberto; Ghirardello, Anna; Punzi, Leonardo

2015-01-01

Galectin-3 (gal-3) is a β-galactoside-binding lectin, which regulates cell–cell and extracellular interactions during self/non-self-antigen recognition and cellular activation, proliferation, differentiation, migration and apoptosis. It plays a significant role in cellular and tissue pathophysiology by organizing niches that drive inflammation and immune responses. Gal-3 has some therapeutic potential in several diseases, including chronic inflammatory disorders, cancer and autoimmune diseases. Gal-3 exerts a broad spectrum of functions which differs according to its intra- or extracellular localization. Recombinant gal-3 strategy has been used to identify potential mode of action of gal-3; however, exogenous gal-3 may not reproduce the functions of the endogenous gal-3. Notably, gal-3 induces monocyte–macrophage differentiation, interferes with dendritic cell fate decision, regulates apoptosis on T lymphocytes and inhibits B-lymphocyte differentiation into immunoglobulin secreting plasma cells. Considering the influence of these cell populations in the pathogenesis of several autoimmune diseases, gal-3 seems to play a role in development of autoimmunity. Gal-3 has been suggested as a potential therapeutic agent in patients affected with some autoimmune disorders. However, the precise role of gal-3 in driving the inflammatory process in autoimmune or immune-mediated disorders remains elusive. Here, we reviewed the involvement of gal-3 in cellular and tissue events during autoimmune and immune-mediated inflammatory diseases. PMID:26142116

Understanding the Association Between Negative Life Events and Suicidal Risk in College Students: Examining Self-Compassion as a Potential Mediator.

PubMed

Chang, Edward C; Yu, Tina; Najarian, Alexandria S-M; Wright, Kaitlin M; Chen, Wenting; Chang, Olivia D; Du, Yifeng; Hirsch, Jameson K

2017-06-01

We tested a hypothesized model consistent with the notion that self-compassion mediates the association between negative life events and suicidal risk (viz., depressive symptoms and suicidal behaviors) in college students METHOD: The sample was comprised of 331 college students. Self-compassion facets (viz., self-kindness, self-judgment, common humanity, isolation, mindfulness, and overidentification) were used in testing for multiple mediation, controlling for sex. Common humanity, mindfulness, and overidentification were found to mediate the association between negative life events (NLE) and depressive symptoms. However, common humanity was found to be the only mediator of the association between NLE and suicidal behaviors. These findings suggest that there are specific facets of self-compassion that account for the association between NLE and suicidal risk in college students and that (loss of) common humanity plays a central role in this process. © 2016 Wiley Periodicals, Inc.

Hypnotherapy to Reduce Hot Flashes: Examination of Response Expectancies as a Mediator of Outcomes

PubMed Central

Sliwinski, Jim R.; Elkins, Gary R.

2017-01-01

The mechanism of action responsible for hypnotherapy’s effect in reducing hot flashes is not yet known. The purpose of this study was to examine the role of response expectancies as a potential mediator. Hypnotizability was also tested as an effect moderator. Data were collected from a sample of 172 postmenopausal women, who had been randomized to receive either a 5-week hypnosis intervention or structured attention counseling. Measures of response expectancies were analyzed to determine if the relationship between group assignment and hot flashes frequency was mediated by expectancies for treatment efficacy. A series of simple mediation and conditional process analyses did not support mediation of the relationship between treatment condition and hot flash frequency through response expectancy. The effect of hypnotherapy in reducing hot flashes does not appear to be due to placebo effects as determined by response expectancies. Implications for clinical practice and future research are discussed. PMID:28528570

Estrous Cycle Regulation of Extrasynaptic δ-Containing GABAA Receptor-Mediated Tonic Inhibition and Limbic Epileptogenesis

PubMed Central

Wu, Xin; Gangisetty, Omkaram; Carver, Chase Matthew

2013-01-01

The ovarian cycle affects susceptibility to behavioral and neurologic conditions. The molecular mechanisms underlying these changes are poorly understood. Deficits in cyclical fluctuations in steroid hormones and receptor plasticity play a central role in physiologic and pathophysiologic menstrual conditions. It has been suggested that synaptic GABAA receptors mediate phasic inhibition in the hippocampus and extrasynaptic receptors mediate tonic inhibition in the dentate gyrus. Here we report a novel role of extrasynaptic δ-containing GABAA receptors as crucial mediators of the estrous cycle–related changes in neuronal excitability in mice, with hippocampus subfield specificity. In molecular and immunofluorescence studies, a significant increase occurred in δ-subunit, but not α4- and γ2-subunits, in the dentate gyrus during diestrus. However, δ-subunit upregulation was not evident in the CA1 region. The δ-subunit expression was undiminished by age and ovariectomy and in mice lacking progesterone receptors, but it was significantly reduced by finasteride, a neurosteroid synthesis inhibitor. Electrophysiologic studies confirmed greater potentiation of GABA currents by progesterone-derived neurosteroid allopregnanolone in dissociated dentate gyrus granule cells in diestrus than in CA1 pyramidal cells. The baseline conductance and allopregnanolone potentiation of tonic currents in dentate granule cells from hippocampal slices were higher than in CA1 pyramidal cells. In behavioral studies, susceptibility to hippocampus kindling epileptogenesis was lower in mice during diestrus. These results demonstrate the estrous cycle–related plasticity of neurosteroid-sensitive, δ-containing GABAA receptors that mediate tonic inhibition and seizure susceptibility. These findings may provide novel insight on molecular cascades of menstrual disorders like catamenial epilepsy, premenstrual syndrome, and migraine. PMID:23667248

Effects of Exposure to Community Violence and Family Violence on School Functioning Problems among Urban Youth: The Potential Mediating Role of Posttraumatic Stress Symptoms

PubMed Central

McGill, Tia M.; Self-Brown, Shannon R.; Lai, Betty S.; Cowart-Osborne, Melissa; Tiwari, Ashwini; LeBlanc, Monique; Kelley, Mary Lou

2014-01-01

Adolescents who are exposed to violence during childhood are at an increased risk for developing posttraumatic stress (PTS) symptoms. The literature suggests that violence exposure might also have negative effects on school functioning, and that PTS might serve as a potential mediator in this association. The purpose of the current study was to replicate and extend prior research by examining PTS symptoms as a mediator of the relationship between two types of violence exposure and school functioning problems among adolescent youth from an urban setting. Participants included a sample of 121 junior high and high school students (M = 15 years; range = 13–16 years; 60 males, 61 females) within high-crime neighborhoods. Consistent with our hypotheses, community violence and family violence were associated with PTS symptoms and school functioning problems. Our data suggest that community and family violence were indirectly related to school functioning problems through PTS symptoms. Findings from this study demonstrate that PTS symptoms potentially mediate the relationship between violence exposure and school functioning problems across two settings (community and home). Future research should further examine protective factors that can prevent youth violence exposure as well as negative outcomes related to violence. PMID:24570897

Insulin-like growth factor 1: common mediator of multiple enterotrophic hormones and growth factors.

PubMed

Bortvedt, Sarah F; Lund, P Kay

2012-03-01

To summarize the recent evidence that insulin-like growth factor 1 (IGF1) mediates growth effects of multiple trophic factors and discuss clinical relevance. Recent reviews and original reports indicate benefits of growth hormone (GH) and long-acting glucagon-like peptide 2 (GLP2) analogs in short bowel syndrome and Crohn's disease. This review highlights the evidence that biomarkers of sustained small intestinal growth or mucosal healing and evaluation of intestinal epithelial stem cell biomarkers may improve clinical measures of intestinal growth or response to trophic hormones. Compelling evidence that IGF1 mediates growth effects of GH and GLP2 on intestine or linear growth in preclinical models of resection or Crohn's disease is presented, along with a concept that these hormones or IGF1 may enhance sustained growth if given early after bowel resection. Evidence that suppressor of cytokine signaling protein induction by GH or GLP2 in normal or inflamed intestine may limit IGF1-induced growth, but protect against risk of dysplasia or fibrosis, is reviewed. Whether IGF1 receptor mediates IGF1 action and potential roles of insulin receptors are addressed. IGF1 has a central role in mediating trophic hormone action in small intestine. Better understanding of benefits and risks of IGF1, receptors that mediate IGF1 action, and factors that limit undesirable growth are needed.

Potential Role of Rebamipide in Osteoclast Differentiation and Mandibular Condylar Cartilage Homeostasis.

PubMed

Izawa, Takashi; Hutami, Islamy Rahma; Tanaka, Eiji

2018-04-20

Temporomandibular joint osteoarthritis (TMJ-OA) is a degenerative disease that involves changes in subchondral bone and progressive degradation of cartilage. Currently, rebamipide, a gastroprotective drug, is administered to protect gastric mucosa and accelerate ulcer healing. Recent studies have shown that rebamipide also attenuates cartilage degeneration by suppressing oxidative damage and inducing homeostasis of the extracellular matrix of articular chondrocytes. Regarding the latter, reduced expression of cathepsin K, NFATc1, c-Src, and integrin β3, and increased expression of nuclear factor-kappa B, have been found to be mediated by the transcription factor, receptor activator of nuclear factor kappa-B ligand (RANKL). Treatment with rebamipide was also found to activate, mitogen-activated protein kinases such as p38, ERK, and JNK to reduce osteoclast differentiation. Taken together, these results strongly indicate that rebamipide mediates inhibitory effects on cartilage degradation and osteoclastogenesis in TMJ-OA. Here, we highlight recent evidence regarding the potential for rebamipide to affect osteoclast differentiation and TMJ-OA pathogenesis. We also discuss the potential role of rebamipide to serve as a new strategy for the treatment of TMJ-OA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Heparan sulfate proteoglycans mediate renal carcinoma metastasis.

PubMed

Qazi, Henry; Shi, Zhong-Dong; Song, Jonathan W; Cancel, Limary M; Huang, Peigen; Zeng, Ye; Roberge, Sylvie; Munn, Lance L; Tarbell, John M

2016-12-15

The surface proteoglycan/glycoprotein layer (glycocalyx) on tumor cells has been associated with cellular functions that can potentially enable invasion and metastasis. In addition, aggressive tumor cells with high metastatic potential have enhanced invasion rates in response to interstitial flow stimuli in vitro. Our previous studies suggest that heparan sulfate (HS) in the glycocalyx plays an important role in this flow mediated mechanostransduction and upregulation of invasive and metastatic potential. In this study, highly metastatic renal cell carcinoma cells were genetically modified to suppress HS production by knocking down its synthetic enzyme NDST1. Using modified Boyden chamber and microfluidic assays, we show that flow-enhanced invasion is suppressed in HS deficient cells. To assess the ability of these cells to metastasize in vivo, parental or knockdown cells expressing fluorescence reporters were injected into kidney capsules in SCID mice. Histological analysis confirmed that there was a large reduction (95%) in metastasis to distant organs by tumors formed from the NDST1 knockdown cells compared to control cells with intact HS. The ability of these cells to invade surrounding tissue was also impaired. The substantial inhibition of metastasis and invasion upon reduction of HS suggests an active role for the tumor cell glycocalyx in tumor progression. © 2016 UICC.

Pattern-recognition receptors: signaling pathways and dysregulation in canine chronic enteropathies-brief review.

PubMed

Heilmann, Romy M; Allenspach, Karin

2017-11-01

Pattern-recognition receptors (PRRs) are expressed by innate immune cells and recognize pathogen-associated molecular patterns (PAMPs) as well as endogenous damage-associated molecular pattern (DAMP) molecules. With a large potential for synergism or convergence between their signaling pathways, PRRs orchestrate a complex interplay of cellular mediators and transcription factors, and thus play a central role in homeostasis and host defense. Aberrant activation of PRR signaling, mutations of the receptors and/or their downstream signaling molecules, and/or DAMP/PAMP complex-mediated receptor signaling can potentially lead to chronic auto-inflammatory diseases or development of cancer. PRR signaling pathways appear to also present an interesting new avenue for the modulation of inflammatory responses and to serve as potential novel therapeutic targets. Evidence for a dysregulation of the PRR toll-like receptor (TLR)2, TLR4, TLR5, and TLR9, nucleotide-binding oligomerization domain-containing protein (NOD)2, and the receptor of advanced glycation end products (RAGE) exists in dogs with chronic enteropathies. We describe the TLR, NOD2, and RAGE signaling pathways and evaluate the current veterinary literature-in comparison to human medicine-to determine the role of TLRs, NOD2, and RAGE in canine chronic enteropathies.

Sleep associated monitoring on awakening mediates the relationship between cutaneous body image dissatisfaction and insomnia symptoms

PubMed Central

Akram, Umair

2017-01-01

INTRODUCTION This study examined the relationship between dissatisfaction with cutaneous body image and insomnia symptoms, incorporating the mediating role of monitoring for signs of poor-sleep on awakening and throughout the day. METHODS Two hundred twenty-one participants completed The Insomnia Severity Index, Cutaneous Body Image Scale, and subscales of the Sleep Associated Monitoring Index. RESULTS The results demonstrated that insomnia symptoms were significantly associated with a greater dissatisfaction with cutaneous body image. Moreover, this relationship was partially mediated by sleep associated monitoring on awakening, but not throughout the day. CONCLUSIONS These findings provide further understanding of the potential mechanisms underlying negative self-perceptions of physical appearance in insomnia. PMID:28966747

Addressing cancer patient and caregiver role transitions during home hospice nursing care.

PubMed

Hudson, Janella; Reblin, Maija; Clayton, Margaret F; Ellington, Lee

2018-05-15

Many family caregivers and hospice patients experience role changes resulting from advancing illness and the need for increased caregiver responsibility. Successful navigation of conflicts that arise because of these role transitions has been linked to higher quality of patient care and improved caregiver bereavement adjustment. Nursing communication with patients and their caregivers plays an important role in facilitating these transitions. Our objective is to describe patient-caregiver-nurse communication during transitions at end of life. A secondary, qualitative analysis was conducted on transcripts. Using an iterative process of constant comparison, coders inductively categorized nurse, caregiver, and patient communication behavior into overarching themes. Participants were home hospice nurses and cancer patient/spouse caregiver dyads; participants were >45 years of age, English speaking, and cognitively able to participate. Research took place in the home during nurse visits.ResultNineteen unique home hospice visits were analyzed. Patient-caregiver conflict occurred in two major content themes (1) negotiating transitions in patient independence and (2) navigating caregiver/patient emotions (e.g., frustration, sadness). Nurse responses to transition conflict included problem-solving, mediating, or facilitating discussions about conflicts. Nurse responses to emotional conflict included validation and reassurance.Significance of resultsOur findings provide insight into the topics and processes involved in patient and caregiver transitions in home hospice and the role hospice nursing communication plays in mediating potential conflict. Nurses are often asked to take on the role of mediator, often with little conflict resolution communication education; results can be used for nursing education.

Investigating the Effects of Mass Media Exposure on the Uptake of Preventive Measures by Hong Kong Residents during the 2015 MERS Outbreak: The Mediating Role of Interpersonal Communication and the Perception of Concern.

PubMed

Ludolph, Ramona; Schulz, Peter J; Chen, Ling

2018-01-01

In 2015, South Korea experienced the largest outbreak to date of the Middle East Respiratory Syndrome (MERS-CoV) outside the Middle East. Fears related to a potential spread of the disease led to an increased alert level as well as heightened media coverage in the neighboring Hong Kong. A cross-sectional survey (N = 533) among residents of Hong Kong was conducted to assess the relationships between the effects of outbreak-related mass media coverage, interpersonal communication, the perceived level of concern in one's close environment, and the uptake of preventive measures. A serial multiple mediator model finds that interpersonal communication and higher perceived concern indirectly influence the effects of media coverage on the engagement in preventive actions. These results expand previous research on the mediating role of interpersonal communication and support assumptions about a modified two-step flow of communication in the context of a public health emergency.

Adolescents choosing self-harm as an emotion regulation strategy: the protective role of trait emotional intelligence.

PubMed

Mikolajczak, Moïra; Petrides, K V; Hurry, Jane

2009-06-01

The present study seeks to extend the understanding of the role of dispositional factors in the aetiology of self-harm among adolescents. We hypothesized that higher trait emotional intelligence (trait EI) would be associated with a lower likelihood to harm oneself, and that this relationship would be mediated by the choice of coping strategies. Trait EI, coping styles and self-harm behaviours were assessed in 490 adolescents recruited from eight British schools. The results supported our hypothesis and showed that the relationship between trait EI and self-harm was partly mediated by the choice of coping strategies. Emotional coping was a particularly powerful mediator, suggesting that self-harm may be a way to decrease the negative emotions that are exacerbated by maladaptive emotional coping strategies, such as rumination, self-blame, and helplessness. Trait EI was correlated positively with adaptive coping styles and negatively with maladaptive coping styles, and depression. These findings emphasize the potential value of incorporating coping coaching programmes in the treatment of self-harm patients.

A regulatory governance perspective on health technology assessment (HTA) in France: the contextual mediation of common functional pressures.

PubMed

Barron, Anthony J G; Klinger, Corinna; Shah, Sara Mehmood Birchall; Wright, John S F

2015-02-01

The new regulatory governance perspective has introduced several insights to the study of health technology assessment (HTA): it has broadened the scope for the analysis of HTA; it has provided a more sophisticated account of national diversity and the potential for cross-border policy learning; and, it has dissolved the distinction between HTA assessment and appraisal processes. In this paper, we undertake a qualitative study of the French process for HTA with a view to introducing a fourth insight: that the emergence and continuing function of national agencies for HTA follows a broadly evolutionary pattern in which contextual factors play an important mediating role. We demonstrate that the French process for HTA is characterised by distinctive institutions, processes and evidential requirements. Consistent with the mediating role of this divergent policy context, we argue that even initiatives for the harmonisation of national approaches to HTA are likely to meet with divergent national policy responses. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The mediating role of internalized racism in the relationship between racist experiences and anxiety symptoms in a Black American sample.

PubMed

Graham, Jessica R; West, Lindsey M; Martinez, Jennifer; Roemer, Lizabeth

2016-07-01

The current study explores the potential mediating role of internalized racism in the relationship between racist experiences and anxiety symptomology in a Black American sample. One hundred and 73 Black American participants, between 18 and 62 years of age, completed a questionnaire packet containing measures of anxious arousal and stress symptoms, internalized racism, and experiences of racist events. Results indicated that internalized racism mediated the relationship between past-year frequency of racist events and anxious arousal as well as past-year frequency of racist events and stress symptoms. Internalized racism may be 1 mechanism that underlies the relationship between racism and anxious symptomology for Black Americans. These preliminary findings suggest that internalized racism may be an avenue through which clinicians can target the anxiety elicited by racist experiences. The clinical implications of these findings and future research directions are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The HDAC inhibitor SAHA regulates CBX2 stability via a SUMO-triggered ubiquitin-mediated pathway in leukemia.

PubMed

Di Costanzo, Antonella; Del Gaudio, Nunzio; Conte, Lidio; Dell'Aversana, Carmela; Vermeulen, Michiel; de Thé, Hugues; Migliaccio, Antimo; Nebbioso, Angela; Altucci, Lucia

2018-05-01

Polycomb group (PcG) proteins regulate transcription, playing a key role in stemness and differentiation. Deregulation of PcG members is known to be involved in cancer pathogenesis. Emerging evidence suggests that CBX2, a member of the PcG protein family, is overexpressed in several human tumors, correlating with lower overall survival. Unraveling the mechanisms regulating CBX2 expression may thus provide a promising new target for anticancer strategies. Here we show that the HDAC inhibitor SAHA regulates CBX2 stability via a SUMO-triggered ubiquitin-mediated pathway in leukemia. We identify CBX4 and RNF4 as the E3 SUMO and E3 ubiquitin ligase, respectively, and describe the specific molecular mechanism regulating CBX2 protein stability. Finally, we show that CBX2-depleted leukemic cells display impaired proliferation, underscoring its critical role in regulating leukemia cell tumorogenicity. Our results show that SAHA affects CBX2 stability, revealing a potential SAHA-mediated anti-leukemic activity though SUMO2/3 pathway.

Side effects, adherence self-efficacy, and adherence to antiretroviral treatment: a mediation analysis in a Chinese sample.

PubMed

Zhang, Liying; Li, Xiaoming; Lin, Zhenping; Jacques-Tiura, Angela J; Xu, Jinping; Zhou, Yuejiao; Qiao, Shan; Shen, Zhiyong; Stanton, Bonita

2016-07-01

Antiretroviral therapy (ART) is a lifelong treatment. To date, ART adherence is suboptimal for most patients in resource-poor settings. Previous research indicates that medication side effects are perceived to be a significant barrier of high ART adherence. Data regarding the role of adherence self-efficacy in mediating the relationship between side effects from ART and adherence to ART are limited; thus, this study examines this potential mediational role of self-efficacy. A cross-sectional survey of 2987 people living with HIV aged ≥18 years was conducted in 2012-2013 in Guangxi Autonomous Region (Guangxi) which has one of the fastest-growing HIV rates in China. Of the total sample, 2146 (72.1%) participants had initiated ART. Participants reported the number of days of completing the daily dose of ART in the past month; adherence was defined as completing the daily dose at least 28 days in the last month (≥90%). Side effects were significantly negatively related to adherence to ART. Mediation analyses indicated that adherence self-efficacy significantly mediated the side effects-adherence relationship. Future interventions to increase adherence self-efficacy and effective coping with side effects among HIV patients are needed in order to improve their ART adherence.

Febuxostat, an Inhibitor of Xanthine Oxidase, Suppresses Lipopolysaccharide-Induced MCP-1 Production via MAPK Phosphatase-1-Mediated Inactivation of JNK

PubMed Central

Nomura, Johji; Busso, Nathalie; Ives, Annette; Tsujimoto, Syunsuke; Tamura, Mizuho; So, Alexander; Yamanaka, Yoshihiro

2013-01-01

Excess reactive oxygen species (ROS) formation can trigger various pathological conditions such as inflammation, in which xanthine oxidase (XO) is one major enzymatic source of ROS. Although XO has been reported to play essential roles in inflammatory conditions, the molecular mechanisms underlying the involvement of XO in inflammatory pathways remain unclear. Febuxostat, a selective and potent inhibitor of XO, effectively inhibits not only the generation of uric acid but also the formation of ROS. In this study, therefore, we examined the effects of febuxostat on lipopolysaccharide (LPS)-mediated inflammatory responses. Here we show that febuxostat suppresses LPS-induced MCP-1 production and mRNA expression via activating MAPK phosphatase-1 (MKP-1) which, in turn, leads to dephosphorylation and inactivation of JNK in macrophages. Moreover, these effects of febuxostat are mediated by inhibiting XO-mediated intracellular ROS production. Taken together, our data suggest that XO mediates LPS-induced phosphorylation of JNK through ROS production and MKP-1 inactivation, leading to MCP-1 production in macrophages. These studies may bring new insights into the novel role of XO in regulating inflammatory process through MAPK phosphatase, and demonstrate the potential use of XO inhibitor in modulating the inflammatory processes. PMID:24086554

Suppression of experimental myasthenia gravis, a B cell-mediated autoimmune disease, by blockade of IL-18.

PubMed

Im, S H; Barchan, D; Maiti, P K; Raveh, L; Souroujon, M C; Fuchs, S

2001-10-01

Interleukin-18 (IL-18) is a pleiotropic proinflammatory cytokine that plays an important role in interferon gamma (IFN-gamma) production and IL-12-driven Th1 phenotype polarization. Increased expression of IL-18 has been observed in several autoimmune diseases. In this study we have analyzed the role of IL-18 in an antibody-mediated autoimmune disease and elucidated the mechanisms involved in disease suppression mediated by blockade of IL-18, using experimental autoimmune myasthenia gravis (EAMG) as a model. EAMG is a T cell-regulated, antibody-mediated autoimmune disease in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. Th1- and Th2-type responses are both implicated in EAMG development. We show that treatment by anti-IL-18 during ongoing EAMG suppresses disease progression. The protective effect can be adoptively transferred to naive recipients and is mediated by increased levels of the immunosuppressive Th3-type cytokine TGF-beta and decreased AChR-specific Th1-type cellular responses. Suppression of EAMG is accompanied by down-regulation of the costimulatory factor CD40L and up-regulation of CTLA-4, a key negative immunomodulator. Our results suggest that IL-18 blockade may potentially be applied for immunointervention in myasthenia gravis.

Transcription regulation by the Mediator complex.

PubMed

Soutourina, Julie

2018-04-01

Alterations in the regulation of gene expression are frequently associated with developmental diseases or cancer. Transcription activation is a key phenomenon in the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase II transcription (Mediator), a large complex with modular organization, is generally required for transcription by RNA polymerase II, and it regulates various steps of this process. The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation. Recent functional studies of Mediator with the use of structural biology approaches and functional genomics have revealed new insights into Mediator activity and its regulation during transcription initiation, including how Mediator is recruited to transcription regulatory regions and how it interacts and cooperates with PIC components to assist in PIC assembly. Novel roles of Mediator in the control of gene expression have also been revealed by showing its connection to the nuclear pore and linking Mediator to the regulation of gene positioning in the nuclear space. Clear links between Mediator subunits and disease have also encouraged studies to explore targeting of this complex as a potential therapeutic approach in cancer and fungal infections.

Proteome Profiling of BEAS-2B Cells Treated with Titanium Dioxide Reveals Potential Toxicity of and Detoxification Pathways for Nanomaterial

EPA Science Inventory

Oxidative stress is known to play important roles in nanomaterial-induced toxicities. However, the proteins and signaling pathways associated with nanomaterial-mediated oxidative stress and toxicity are largely unknown. To identify oxidative stress-responding toxicity pathways an...

Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Titanium Dioxide Nanoparticles

EPA Science Inventory

Oxidative stress is known to play important roles in engineered nanomaterial induced cellular toxicity. However, the proteins and signaling pathways associated with the engineered nanomaterial mediated oxidative stress and toxicity are largely unknown. To identify these toxicity ...

Longitudinal Associations across Prematurity, Attention, and Language in School-Age Children

ERIC Educational Resources Information Center

Mahurin-Smith, Jamie; DeThorne, Laura S.; Petrill, Stephen A.

2017-01-01

Purpose: This research note explores the potential role of attention in mediating previously reported associations between language outcomes and prematurity. Method: As a follow-up investigation to Mahurin Smith, DeThorne, Logan, Channell, and Petrill (2014), we employed multilevel modeling to analyze longitudinal data on language and attention…

Combinatorial evaluation of the laccase-mediator system (LMS) in the oxidation of veratryl alcohol

USDA-ARS?s Scientific Manuscript database

Identifying suitable reaction conditions remains an important task in the development of practical enzyme catalysts. Laccases play an important role in the biological break down of lignin and have great potential in the deconstruction of lignocellulosic feedstocks. We examined 16 laccases, both co...

Selective oxidation of lignin model compounds – a combinatorial application of the laccase-mediator system

USDA-ARS?s Scientific Manuscript database

Identifying suitable reaction conditions remains an important task in the development of practical enzyme catalysts. Laccases play an important role in the biological break down of lignin and have great potential in the deconstruction of lignocellulosic feedstocks. We examined 16 laccases, both comm...

Digital Media and "Girling" at an Elite Girls' School

ERIC Educational Resources Information Center

Charles, Claire

2007-01-01

In this article, I draw on Judith Butler's notion of performativity to investigate the role of digital technologies in processes of gendered subjectification (or "girling") in elite girls' education. Elite girls' schooling is a site where the potential of digital technologies in mediating student-led constructions and explorations of…

Tumor progression locus 2 ablation suppressed hepatocellular carcinoma development by inhibiting hepatic inflammation and steatosis in mice

USDA-ARS?s Scientific Manuscript database

Background: Tumor progression locus 2 (TPL2), a serine threonine kinase, functions as a critical regulator of inflammatory pathways and mediates oncogenic events. The potential role of Tpl2 in nonalcoholic fatty liver disease (NAFLD) associated hepatocellular carcinoma (HCC) development remains unkn...

Neuroinflammation in Parkinson's disease: role in neurodegeneration and tissue repair.

PubMed

Vivekanantham, Sayinthen; Shah, Savan; Dewji, Rizwan; Dewji, Abbas; Khatri, Chetan; Ologunde, Rele

2015-01-01

Neuroinflammation in Parkinson's disease [PD] is a process that occurs alongside the loss of dopaminergic neurons, and is associated with alterations to many cell types, most notably microglia. This review examines the key evidence contributing to our understanding of the role of inflammation-mediated degeneration of the dopaminergic (DA) nigrostriatal pathway in PD. It will consider the potential role inflammation plays in tissue repair within the brain, inflammation linked gene products that are associated with sporadic Parkinsonian phenotypes (alpha-synuclein, Parkin and Nurr 1), and developing anti-inflammatory drug treatments in PD. With growing evidence supporting the key role of neuroinflammation in PD pathogenesis, new molecular targets are being found that could potentially prevent or delay nigrostriatal DA neuron loss. Hence, this creates the opportunity for disease modifying treatment, to currently what is an incurable disease.

Predicting desire for institutional placement among racially diverse dementia family caregivers: the role of quality of care.

PubMed

Sun, Fei; Durkin, Daniel W; Hilgeman, Michelle M; Harris, Grant; Gaugler, Joseph E; Wardian, Jana; Allen, Rebecca S; Burgio, Louis D

2013-06-01

Literature on institutionalization of patients with dementia has not considered the role of caregivers' quality of care, which encompasses caregivers' exemplary care (EC) behaviors and caregivers' potentially harmful behaviors (PHBs) toward care recipients. This study sought to understand the role of quality of care in mediating between caregiving stressors and caregiver desire to institutionalize (DTI) a patient with dementia. A sample of 612 family caregivers from diverse racial/ethnic backgrounds was drawn from the baseline data of the Resources for Enhancing Alzheimer's Caregiver Heath (REACH II) project. Multiple mediator models were run using Preacher and Hayes asymptotic and resampling strategies to assess direct and indirect effects of caregiver stressors (daily care bother, behavioral bother, and burden) on caregiver desire to institutionalize a patient with dementia. Overall, PHB was positively related to caregiver desire to institutionalize their care recipients. Specifically, PHB was found to mediate the relationship between caregiving stressors and DTI in the Caucasian and Latino groups, whereas only the mediation effect of EC was significant in the African American group. Caregivers' perceptions of quality of care helped explain their desire to institutionalize their care recipients with dementia. Including assessment of EC and PHB in clinical and social service settings is recommended for all ethnic groups. Interventions should facilitate EC behaviors among African American caregivers and address concerns of PHBs in Caucasian and Latino caregivers.

Evaluating the Role of Drone-Produced Chemical Signals in Mediating Social Interactions in Honey Bees (Apis mellifera).

PubMed

Villar, Gabriel; Wolfson, Megan D; Hefetz, Abraham; Grozinger, Christina M

2018-01-01

Pheromones play a critical role in shaping societies of social insects, including honey bees, Apis mellifera. While diverse functions have been ascribed to queen- and worker-produced compounds, few studies have explored the identity and function of male-produced (drone) compounds. However, several lines of evidence suggest that drones engage in a variety of social interactions inside and outside of the colony. Here we elucidate the chemical composition of extracts of the drone mandibular gland, and test the hypothesis that compounds produced in these glands, or a synthetic blend consisting of the six main compounds, mediate drone social interactions in and out of the colony. Drone mandibular glands primarily produce a blend of saturated, unsaturated and methyl branched fatty acids ranging in chain length from nonanoic to docosanoic acids, and both gland extracts and synthetic blends of these chemicals serve to attract drones outside of the hive, but do not attract workers inside the hive. These studies shed light on the role drones and drone-produced chemicals have on mediating social interactions with other drones and highlight their potential importance in communicating with other castes.

Taming dendritic cells with TIM-3: another immunosuppressive strategy used by tumors.

PubMed

Patel, Jaina; Bozeman, Erica N; Selvaraj, Periasamy

2012-12-01

Evaluation of: Chiba S, Baghdadi M, Akiba H et al. Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat. Immunol. 13, 832-842 (2012). The identification of TIM-3 expression on tumor-associated dendritic cells (TADCs) provides insight into another aspect of tumor-mediated immunosuppression. The role of TIM-3 has been well characterized on tumor-infiltrating T cells; however, its role on TADCs was not previously known. The current paper demonstrated that TIM-3 was predominantly expressed by TADCs and its interaction with the nuclear protein HMGB1 suppressed nucleic acid-mediated activation of an effective antitumor immune response. The authors were able to show that TIM-3 interaction with HMGB1 prevented the localization of nucleic acids into endosomal vesicles. Furthermore, chemotherapy was found to be more effective in anti-TIM-3 monoclonal antibody-treated mice or mice depleted of all DCs, which indicated that a significant role is played by TADCs in inhibiting tumor regression. Taken together, these findings identify TIM-3 as a potential target for inducing antitumor immunity in conjunction with DNA vaccines and/or immunogenic chemotherapy in clinical settings.

Polycyclic aromatic hydrocarbons and cytochrome P450 in HIV pathogenesis

PubMed Central

Rao, P. S. S.; Kumar, Santosh

2015-01-01

High prevalence of cigarette smoking in HIV patients is associated with increased HIV pathogenesis and disease progression. While the effect of smoking on the occurrence of lung cancer has been studied extensively, the association between smoking and HIV pathogenesis is poorly studied. We have recently shown the possible role of cytochrome P450 (CYP) in smoking/nicotine-mediated viral replication. In this review, we focus on the potential role of CYP pathway in polycyclic aromatic hydrocarbons (PAH), important constituents of cigarette smoke, mediated HIV pathogenesis. More specifically, we will discuss the role of CYP1A1 and CYP1B1, which are the major PAH-activating CYP enzymes. Our results have shown that treatment with cigarette smoke condensate (CSC) increases viral replication in HIV-infected macrophages. CSC contains PAH, which are known to be activated by CYP1A1 and CYP1B1 into procarcinogens/toxic metabolites. The expression of these CYPs is regulated by aryl hydrocarbon receptors (AHR), the cellular target of PAH, and an important player in various diseases including cancer. We propose that PAH/AHR-mediated CYP pathway is a novel target to develop new interventions for HIV positive smokers. PMID:26082767

The Role of Adenosine A2A Receptor, CYP450s, and PPARs in the Regulation of Vascular Tone

PubMed Central

Khayat, Maan T.

2017-01-01

Adenosine is an endogenous mediator involved in a myriad of physiologic functions, including vascular tone regulation. It is also implicated in some pathologic conditions. Four distinct receptor subtypes mediate the effects of adenosine, such as its role in the regulation of the vascular tone. Vascular tone regulation is a complex and continuous process which involves many mechanisms and mediators that are not fully disclosed. The vascular endothelium plays a pivotal role in regulating blood flow to and from all body organs. Also, the vascular endothelium is not merely a physical barrier; it is a complex tissue with numerous functions. Among adenosine receptors, A2A receptor subtype (A2AAR) stands out as the primary receptor responsible for the vasodilatory effects of adenosine. This review focuses on important effectors of the vascular endothelium, including adenosine, adenosine receptors, EETs (epoxyeicosatrienoic acids), HETEs (hydroxyeicosatetraenoic acids), PPARs (peroxisome proliferator-activated receptors), and KATP channels. Given the impact of vascular tone regulation in cardiovascular physiology and pathophysiology, better understanding of the mechanisms affecting it could have a significant potential for developing therapeutic agents for cardiovascular diseases. PMID:28884118

Peer relationships and adolescents' academic and non-academic outcomes: same-sex and opposite-sex peer effects and the mediating role of school engagement.

PubMed

Liem, Gregory Arief D; Martin, Andrew J

2011-06-01

The literature has documented theoretical/conceptual models delineating the facilitating role of peer relationships in academic and non-academic outcomes. However, the mechanisms through which peer relationships link to those outcomes is an area requiring further research. The study examined the role of adolescents' perceptions of their relationships with same-sex and opposite-sex peers in predicting their academic performance and general self-esteem and the potentially mediating role of school engagement in linking these perceived peer relationships with academic and non-academic outcomes. The sample comprised 1,436 high-school students (670 boys, 756 girls; 711 early adolescents, 723 later adolescents). Self-report measures and objective achievement tests were used. Structural equation modelling (SEM) was performed to test the hypothesized model and its invariance across gender and age groups. Perceived same-sex peer relationships yielded positive direct and indirect links with academic performance and general self-esteem. Perceived opposite-sex peer relationships yielded positive direct and indirect links with general self-esteem and an indirect positive link with academic performance, but mediation via school engagement was not as strong as that of perceived same-sex peer relationships. These findings generalized across gender and age groups. Adolescents' same-sex and opposite-sex peer relationships seem to positively impact their academic performance and general self-esteem in distinct ways. It appears that school engagement plays an important role in mediating these peer relationship effects, particularly those of same-sex peer relationships, on academic and non-academic functioning. Implications for psycho-educational theory, measurement, and practice are discussed. ©2011 The British Psychological Society.

Hostage (crisis) negotiation: the potential role of negotiator personality, decision-making style, coping style and emotional intelligence on negotiator success.

PubMed

Grubb, Amy; Brown, Sarah

2012-01-01

This article explores the potential role of hostage negotiator characteristics and the impact of psychological constructs on negotiator success. It explores the role of Personality, Decision-Making Style, Coping Style, Cognitive Coping Style and Emotion Regulation and Emotional Intelligence within high stress environments and occupations. The findings suggest that certain individual traits and characteristics may play a role in negotiator success, via the mediation of specific styles, which are conducive to effective crisis negotiation skills. It is proposed that these findings have application within the field of hostage/crisis negotiation in the format of guidance regarding the recruitment and selection of hostage negotiators and the identification of potential training needs within individual negotiators in order to maximize their efficacy within the field. In line with this, it is argued that a psychometric tool that assesses these constructs is developed in order to aid the process of hostage negotiation selection.

Job security and work performance in Chinese employees: The mediating role of organisational identification.

PubMed

Ma, Bing; Liu, Shanshi; Liu, Donglai; Wang, Hongchun

2016-04-01

This research focuses on investigating whether organisational identification mediates the effects of job security on in-role behaviour and extra-role behaviour and how these mediation mechanisms differ according to gender. Through analysing 212 supervisor-subordinate dyads from a Chinese air transportation group, the research indicated that organisational identification partially mediated the effect of job security on in-role behaviour and fully mediated the effect of job security on extra-role behaviour. A multi-group analysis also showed that there were significant differences between male and female employees in these relationships. In addition, moderated mediation analyses showed that gender moderated the indirect effects of job security on in-role behaviour and extra-role behaviour through organisational identification. Limitations and implications of these findings are discussed. © 2015 International Union of Psychological Science.

Effects of ZD7288 on firing pattern of thermosensitive neurons isolated from hypothalamus.

PubMed

Cai, Chunqing; Meng, Xiaojing; He, Junchu; Wu, Hangyu; Zou, Fei

2012-01-11

The role of the hyperpolarization-activated current (Ih) mediated by HCN channels in temperature sensing by the hypothalamus was addressed. In warm-sensitive neurons (WSNs), exposure to ZD7288, an inhibitor of Ih mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, decreased their action potential amplitudes and frequencies significantly. By contrast, ZD7288 had little or no effect on temperature-insensitive neurons (TINs). Exposure of WSNs to ZD7288 led to a significant increase in the duration of the inter-spike interval and a reduction of Ih irreversibly. These results suggest that ZD7288 have the contrasting effects on the firing patterns of WSNs versus TINs, which implies HCN channels play a central role in temperature sensing by hypothalamic neurons. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The Long-term Effects of Self-Esteem on Depression: The Roles of Alcohol and Substance Uses during Young Adulthood1

PubMed Central

Park, Kiwoong; Yang, Tse-Chuan

2017-01-01

Using the National Longitudinal Surveys of Youth 1979, this study examines the roles of alcohol and substance use as mediators in the mechanism between self-esteem and depression, and investigates whether the mechanism works for both men and women. Results demonstrate that alcohol and substance use during young adulthood mediates the effect of self-esteem on depression among men. Furthermore, self-esteem during young adulthood remains a determinant of high depression in middle adulthood. However, we did not find evidence to support that same mechanism among women. Our findings provide insight into how self-esteem affects depression over the transition from young to middle adulthood, and elucidate potential gendered responsivity to low self-esteem. PMID:28936002

The relationship between vigorous physical activity and juvenile delinquency: a mediating role for self-esteem?

PubMed

Faulkner, Guy E J; Adlaf, Edward M; Irving, Hyacinth M; Allison, Kenneth R; Dwyer, John J M; Goodman, Jack

2007-04-01

Many policy-related reviews of the potential social value of sport and physical activity list the prevention of juvenile delinquency. We examined the relationships among vigorous physical activity, self-esteem, and delinquent behavior among adolescents in a large cross-sectional survey of Ontario adolescents. Data are based on questionnaires from 3,796 students (range 11-20 years) derived from the 2005 Ontario Student Drug Use Survey. Negative binominal regression methods were used to estimate both additive and interactive models predicting delinquent behavior. Vigorous physical activity was positively associated with delinquent behavior; however, this pattern of association was observed only among male adolescents. There was no evidence of a mediating role for self-esteem. Our findings suggest that physical activity is not the solution for reducing juvenile delinquency.

Pathways to self-esteem in late adolescence: the role of parent and peer attachment, empathy, and social behaviours.

PubMed

Laible, Deborah J; Carlo, Gustavo; Roesch, Scott C

2004-12-01

The goal of this study was to examine both the direct and indirect relations of parent and peer attachment with self-esteem and to examine the potential mediating roles of empathy and social behaviour. 246 college students (M age = 18.6 years, S.D. = 1.61) completed self-report measures of parent and peer attachment, empathy, social behaviour, and self-esteem. Structural equation modelling revealed that parental attachment had mostly direct effects on self-esteem. Among females, the links between peer attachment and self-esteem, however, were entirely mediated by empathy and prosocial behaviour. The findings from this study suggest that although close supportive relationships with parents and peers are related to adolescent self-esteem, these links are complex.

Latino adolescents' academic success: the role of discrimination, academic motivation, and gender.

PubMed

Alfaro, Edna C; Umaña-Taylor, Adriana J; Gonzales-Backen, Melinda A; Bámaca, Mayra Y; Zeiders, Katharine H

2009-08-01

Guided by the academic resilience perspective, the current longitudinal study examined whether academic motivation mediated the relation between Latino adolescents' (N=221) experiences with discrimination and their academic success. The potential moderating role of gender was also examined. Using multiple group analysis in structural equation modeling, findings indicated that perceived discrimination at Wave 2 significantly predicted academic motivation at Waves 2 and 3 for boys but not girls. Additionally, for boys, academic motivation significantly mediated the relation between perceived discrimination and academic success. Findings underscore the importance of considering the long-term implications of discrimination for Latino boys' academic success. Furthermore, findings encourage moving beyond the examination of gender differences in specific academic outcomes (e.g., academic success) and focusing on how the processes leading to academic success vary by gender.

Occupational imbalance and the role of perceived stress in predicting stress-related disorders.

PubMed

Håkansson, Carita; Ahlborg, Gunnar

2017-03-02

Stress-related disorders are the main reason for sick leave in many European countries. The aim of the present study was to explore whether perceived occupational imbalance predicts stress-related disorders, potential gender differences, and to explore the mediating role of perceived stress. Longitudinal data on 2223 employees in a public organization in Sweden were collected by surveys, and analyzed by logistic regression. Occupational imbalance predicted stress-related disorders among both women and men. However, what aspects of occupational imbalance which predicted stress-related disorders differ by gender. Perceived stress was not a mediator in these associations. How women and men perceived their occupational balance affected the risk of stress-related disorders. The results may be used to develop effective strategies to decrease stress-related disorders.

Narp Deletion Blocks Extinction of Morphine Place Preference Conditioning

PubMed Central

Crombag, Hans S; Dickson, Mercy; Dinenna, Megan; Johnson, Alexander W; Perin, Mark S; Holland, Peter C; Baraban, Jay M; Reti, Irving M

2008-01-01

As drug abuse can be viewed as a maladaptive form of neuronal plasticity, attention has focused on defining the synaptic plasticity mechanisms that mediate the long-term effects of these drugs. As Narp is secreted at synaptic sites and binds to the extracellular surface of AMPA receptors, it has been implicated in mediating enduring forms of synaptic plasticity. Accordingly, to assess its potential role in the long-lasting behavioral effects of drugs of abuse, we have investigated the impact of Narp deletion on sustained behavioral responses elicited by repeated morphine administration. Narp knockout mice display normal locomotor sensitization and conditioned place preference, but are markedly resistant to extinction of place preference. Thus, these findings indicate that Narp plays a selective role in extinction, possibly by its effects on AMPA receptor trafficking. PMID:18536700

Associations Between Race, Menthol, and Acute Tobacco Withdrawal

DTIC Science & Technology

2013-04-13

race differences in cessation. In the following section, the role of nicotine withdrawal as a potential mediator is examined.   7...NICOTINE ADDICTION AND WITHDRAWAL The nicotine withdrawal syndrome may potentially explain differences in cessation outcomes among African Americans...smokers,  nicotine  reduces  the  activity  of  Monoamine  Oxidase  A   and  B,  which  are   enzymes  that  break  down

Direct analysis by time-of-flight secondary ion mass spectrometry reveals action of bacterial laccase-mediator systems on both hardwood and softwood samples.

PubMed

Goacher, Robyn E; Braham, Erick J; Michienzi, Courtney L; Flick, Robert M; Yakunin, Alexander F; Master, Emma R

2017-12-29

The modification and degradation of lignin play a vital role in carbon cycling as well as production of biofuels and bioproducts. The possibility of using bacterial laccases for the oxidation of lignin offers a route to utilize existing industrial protein expression techniques. However, bacterial laccases are most frequently studied on small model compounds that do not capture the complexity of lignocellulosic materials. This work studied the action of laccases from Bacillus subtilis and Salmonella typhimurium (EC 1.10.3.2) on ground wood samples from yellow birch (Betula alleghaniensis) and red spruce (Picea rubens). The ability of bacterial laccases to modify wood can be facilitated by small molecule mediators. Herein, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), gallic acid and sinapic acid mediators were tested. Direct analysis of the wood samples was achieved by time-of-flight secondary ion mass spectrometry (ToF-SIMS), a surface sensitive mass spectrometry technique that has characteristic peaks for H, G and S lignin. The action of the bacterial laccases on both wood samples was demonstrated and revealed a strong mediator influence. The ABTS mediator led to delignification, evident in an overall increase of polysaccharide peaks in the residual solid, along with equal loss of G and S-lignin peaks. The gallic acid mediator demonstrated minimal laccase activity. Meanwhile, the sinapic acid mediator altered the S/G peak ratio consistent with mediator attaching to the wood solids. The current investigation demonstrates the action of bacterial laccase-mediator systems directly on woody materials, and the potential of using ToF-SIMS to uncover the fundamental and applied role of bacterial enzymes in lignocellulose conversion. © 2017 Scandinavian Plant Physiology Society.

Immunolocalization of hypochlorite-induced, catalase-bound free radical formation in mouse hepatocytes

PubMed Central

Bonini, Marcelo G.; Siraki, Arno G.; Atanassov, Boyko S.; Mason., Ronald P.

2007-01-01

The establishment of oxidants as mediators of signal transduction has renewed the interest of investigators in oxidant production and metabolism. In particular, H2O2 has been demonstrated to play pivotal roles in mediating cell differentiation, proliferation and death. Intracellular concentrations of H2O2 are modulated by its rate of production and its rate of decomposition by catalase and peroxidases. In inflammation and infection some of the H2O2 is converted to hypochlorous acid, a key mediator of the host immune response against pathogens. In vivo HOCl production is mediated by myeloperoxidase, which uses excess H2O2 to oxidize Cl−. Mashino and Fridovich (1988) observed that a high excess of HOCl over catalase inactivated the enzyme by mechanisms that remain unclear. The potential relevance of this as an alternative mechanism for catalase activity control and its potential impact on H2O2-mediated signaling and HOCl-production compelled us to explore in depth the HOCl-mediated catalase inactivation pathways. Here, we demonstrate that HOCl induces formation of catalase protein radicals and carbonyls, which are temporally correlated with catalase aggregation. Hypochlorite-induced catalase aggregation and free radical formation that paralleled the enzyme loss of function in vitro were also detected in mouse hepatocytes treated with the oxidant. Interestingly, the novel immunospin-trapping technique was applied to image radical production in the cells. Indeed, in HOCl-treated hepatocytes, catalase and protein-DMPO nitrone adducts were colocalized in the cells’ peroxisomes. In contrast, when hepatocytes from catalase-knockout mice were treated with hypochlorous acid, there was extensive production of free radicals in the plasma membrane. Because free radicals are short-lived species with fundamental roles in biology, the possibility of their detection and localization to cell compartments is expected to open new and stimulating research venues in the interface of chemistry, biology and medicine. PMID:17275685

Cystic fibrosis transmembrane conductance regulator regulates epithelial cell response to Aspergillus and resultant pulmonary inflammation.

PubMed

Chaudhary, Neelkamal; Datta, Kausik; Askin, Frederic B; Staab, Janet F; Marr, Kieren A

2012-02-01

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) alter epithelial cell (EC) interactions with multiple microbes, such that dysregulated inflammation and injury occur with airway colonization in people with cystic fibrosis (CF). Aspergillus fumigatus frequently colonizes CF airways, but it has been assumed to be an innocent saprophyte; its potential role as a cause of lung disease is controversial. To study the interactions between Aspergillus and EC, and the role of the fungus in evoking inflammatory responses. A. fumigatus expressing green fluorescent protein was developed for in vitro and in vivo models, which used cell lines and mouse tracheal EC. Fungal spores (conidia) are rapidly ingested by ECs derived from bronchial cell lines and murine tracheas, supporting a role for EC in early airway clearance. Bronchial ECs harboring CFTR mutations (ΔF508) or deletion demonstrate impaired uptake and killing of conidia, and ECs with CFTR mutation undergo more conidial-induced apoptosis. Germinated (hyphal) forms of the fungus evoke secretion of inflammatory mediators, with CFTR mutation resulting in increased airway levels of macrophage inflammatory protein 2 and KC, and higher lung monocyte chemotactic protein-1. After A. fumigatus inhalation, CFTR(-/-) mice develop exaggerated lymphocytic inflammation, mucin accumulation, and lung injury. Data demonstrate a critical role for CFTR in mediating EC responses to A. fumigatus. Results suggest that the fungus elicits aberrant pulmonary inflammation in the setting of CFTR mutation, supporting the potential role of antifungals to halt progressive CF lung disease.

Stress- and glucocorticoid-induced priming of neuroinflammatory responses: potential mechanisms of stress-induced vulnerability to drugs of abuse.

PubMed

Frank, Matthew G; Watkins, Linda R; Maier, Steven F

2011-06-01

Stress and stress-induced glucocorticoids (GCs) sensitize drug abuse behavior as well as the neuroinflammatory response to a subsequent pro-inflammatory challenge. Stress also predisposes or sensitizes individuals to develop substance abuse. There is an emerging evidence that glia and glia-derived neuroinflammatory mediators play key roles in the development of drug abuse. Drugs of abuse such as opioids, psychostimulants, and alcohol induce neuroinflammatory mediators such as pro-inflammatory cytokines (e.g. interleukin (IL)-1β), which modulate drug reward, dependence, and tolerance as well as analgesic properties. Drugs of abuse may directly activate microglial and astroglial cells via ligation of Toll-like receptors (TLRs), which mediate the innate immune response to pathogens as well as xenobiotic agents (e.g. drugs of abuse). The present review focuses on understanding the immunologic mechanism(s) whereby stress primes or sensitizes the neuroinflammatory response to drugs of abuse and explores whether stress- and GC-induced sensitization of neuroimmune processes predisposes individuals to drug abuse liability and the role of neuroinflammatory mediators in the development of drug addiction. Copyright © 2011 Elsevier Inc. All rights reserved.

Secure attachment and eudaimonic well-being in late adulthood: The mediating role of self-compassion.

PubMed

Homan, Kristin J

2018-03-01

Attachment style refers to a systematic pattern of emotions, behaviors, and expectations that people have for how others will respond in relationships. Extensive evidence has documented the importance of attachment security in infants, children, adolescents, and adults, but the effects of attachment among exclusively older adult populations have received less attention. The present study explored the relationships between attachment style in late adulthood and eudaimonic well-being, which refers to a life replete with meaning, productive activity, and striving to reach one's potential. It also explored the mediating role of self-compassion, which can be described as a kind and forgiving attitude toward the self. A sample of 126 community-dwelling older adults (mean age = 70.40 years) completed measures tapping adult attachment, self-compassion, and six theoretically derived markers of eudaimonic well-being. Attachment anxiety and avoidance were inversely related to self-acceptance, personal growth, interpersonal relationship quality, purpose in life, and environmental mastery. Mediation analyses showed that self-compassion mediated each of these relationships. Results support the importance of attachment orientation for psychological well-being in late life and indicate that secure attachment facilitates an attitude of kindness and acceptance toward the self.

MiR-218 inhibits HMGB1-mediated autophagy in endometrial carcinoma cells during chemotherapy.

PubMed

Ran, Xiaomin; Yang, Juan; Liu, Chaoxia; Zhou, Ping; Xiao, Linzhi; Zhang, Keqiang

2015-01-01

Endometrial carcinoma is the most common gynecological malignancy among women worldwide. Although treatment for EC has improved with the introduction of Paclitaxel (Tax) chemotherapy, the majority of patients will develop resistance to the treatment, leading to poor prognosis. One of the causes of chemoresistance is the increased ability to undergo autophagy. In this study, we identified that miR-218 was significantly down-regulated in Tax-resistant EC cells compared to the non-drug resistant cell lines, and overexpression of miR-218 sensitized paclitaxel resistant EC cells to paclitaxel. Moreover, we demonstrated that miR-218 directly binds to the 3'-UTR of HMGB1 gene. HMGB1 was upregulated in paclitaxel resistant EC cells, it mediated autophagy and contributed to chemotherapy resistance in endometrial carcinoma in vitro. HMGB1-mediated autophagy could be suppressed by miR-218 overexpression in Tax resistant EC cells. In summary, we determined the targeting role of miR-218 to HMGB1 and the regulation of miR-218 on the HMGB1-mediated cell autophagy during chemotherapy resistance in endometrial carcinoma cells. These results reveal novel potential role of miR-218 against chemotherapy resistance during the treatment of endometrial carcinoma.

Neutral endopeptidase inhibitors potentiate substance P- and capsaicin-induced cough in awake guinea pigs.

PubMed Central

Kohrogi, H; Graf, P D; Sekizawa, K; Borson, D B; Nadel, J A

1988-01-01

To study the roles of substance P and endogenous neutral endopeptidase in mediating cough, we measured cough responses in awake guinea pigs in response to exogenous substance P and capsaicin aerosols in the presence and absence of the neutral endopeptidase inhibitors leucine-thiorphan and phosphoramidon. Substance P stimulated cough in very low concentrations (10(-17)-10(-16) M). In a second study where the investigator did not know whether substance P or diluent alone was aerosolized, substance P (10(-16) M) caused cough. Leucine-thiorphan (10(-5) M) and phosphoramidon (10(-5) M) potentiated substance P-induced cough; NEP inhibitors also potentiated capsaicin-induced cough significantly. These findings suggest that substance P is a potent stimulator of cough responses, that capsaicin-induced cough is mediated by substance P or another similar neuropeptide, and that cough responses are modulated by endogenous neutral endopeptidase. PMID:2461967

Neutral endopeptidase inhibitors potentiate substance P- and capsaicin-induced cough in awake guinea pigs.

PubMed

Kohrogi, H; Graf, P D; Sekizawa, K; Borson, D B; Nadel, J A

1988-12-01

To study the roles of substance P and endogenous neutral endopeptidase in mediating cough, we measured cough responses in awake guinea pigs in response to exogenous substance P and capsaicin aerosols in the presence and absence of the neutral endopeptidase inhibitors leucine-thiorphan and phosphoramidon. Substance P stimulated cough in very low concentrations (10(-17)-10(-16) M). In a second study where the investigator did not know whether substance P or diluent alone was aerosolized, substance P (10(-16) M) caused cough. Leucine-thiorphan (10(-5) M) and phosphoramidon (10(-5) M) potentiated substance P-induced cough; NEP inhibitors also potentiated capsaicin-induced cough significantly. These findings suggest that substance P is a potent stimulator of cough responses, that capsaicin-induced cough is mediated by substance P or another similar neuropeptide, and that cough responses are modulated by endogenous neutral endopeptidase.

Role of the Renin–Angiotensin System in the Pathogenesis of Intimal Hyperplasia: Therapeutic Potential for Prevention of Vein Graft Failure?

PubMed Central

Osgood, Michael J.; Harrison, David G.; Sexton, Kevin W.; Hocking, Kyle M.; Voskresensky, Igor V.; Komalavilas, Padmini; Cheung-Flynn, Joyce; Guzman, Raul J.; Brophy, Colleen M.

2014-01-01

The saphenous vein remains the most widely used conduit for peripheral and coronary revascularization despite a high rate of vein graft failure. The most common cause of vein graft failure is intimal hyperplasia. No agents have been proven to be successful for the prevention of intimal hyperplasia in human subjects. The rennin–angiotensin system is essential in the regulation of vascular tone and blood pressure in physiologic conditions. However, this system mediates cardiovascular remodeling in pathophysiologic states. Angiotensin II is becoming increasingly recognized as a potential mediator of intimal hyperplasia. Drugs modulating the renin–angiotensin system include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. These drugs are powerful inhibitors of atherosclerosis and cardiovascular remodeling, and they are first-line agents for management of several medical conditions based on class I evidence that they delay progression of cardiovascular disease and improve survival. Several experimental models have demonstrated that these agents are capable of inhibiting intimal hyperplasia. However, there are no data supporting their role in prevention of intimal hyperplasia in patients with vein grafts. This review summarizes the physiology of the rennin–angiotensin system, the role of angiotensin II in the pathogenesis of cardiovascular remodeling, the medical indications for these agents, and the experimental data supporting an important role of the rennin–angiotensin system in the pathogenesis of intimal hyperplasia. PMID:22445245

The nematode homologue of Mediator complex subunit 28, F28F8.5, is a critical regulator of C. elegans development

PubMed Central

Kostrouchová, Markéta; Kostrouch, David; Kaššák, Filip; Kostrouchová, Veronika; Benda, Aleš; Krause, Michael W.; Saudek, Vladimír; Kostrouchová, Marta

2017-01-01

The evolutionarily conserved Mediator complex is a critical player in regulating transcription. Comprised of approximately two dozen proteins, the Mediator integrates diverse regulatory signals through direct protein-protein interactions that, in turn, modulate the influence of Mediator on RNA Polymerase II activity. One Mediator subunit, MED28, is known to interact with cytoplasmic structural proteins, providing a potential direct link between cytoplasmic dynamics and the control of gene transcription. Although identified in many animals and plants, MED28 is not present in yeast; no bona fide MED28 has been described previously in Caenorhabditis elegans. Here, we identify bioinformatically F28F8.5, an uncharacterized predicted protein, as the nematode homologue of MED28. As in other Metazoa, F28F8.5 has dual nuclear and cytoplasmic localization and plays critical roles in the regulation of development. F28F8.5 is a vital gene and its null mutants have severely malformed gonads and do not reproduce. F28F8.5 interacts on the protein level with the Mediator subunits MDT-6 and MDT-30. Our results indicate that F28F8.5 is an orthologue of MED28 and suggest that the potential to link cytoplasmic and nuclear events is conserved between MED28 vertebrate and nematode orthologues. PMID:28603670

WRKY23 is a component of the transcriptional network mediating auxin feedback on PIN polarity

PubMed Central

Vasileva, Mina; Sauer, Michael

2018-01-01

Auxin is unique among plant hormones due to its directional transport that is mediated by the polarly distributed PIN auxin transporters at the plasma membrane. The canalization hypothesis proposes that the auxin feedback on its polar flow is a crucial, plant-specific mechanism mediating multiple self-organizing developmental processes. Here, we used the auxin effect on the PIN polar localization in Arabidopsis thaliana roots as a proxy for the auxin feedback on the PIN polarity during canalization. We performed microarray experiments to find regulators of this process that act downstream of auxin. We identified genes that were transcriptionally regulated by auxin in an AXR3/IAA17- and ARF7/ARF19-dependent manner. Besides the known components of the PIN polarity, such as PID and PIP5K kinases, a number of potential new regulators were detected, among which the WRKY23 transcription factor, which was characterized in more detail. Gain- and loss-of-function mutants confirmed a role for WRKY23 in mediating the auxin effect on the PIN polarity. Accordingly, processes requiring auxin-mediated PIN polarity rearrangements, such as vascular tissue development during leaf venation, showed a higher WRKY23 expression and required the WRKY23 activity. Our results provide initial insights into the auxin transcriptional network acting upstream of PIN polarization and, potentially, canalization-mediated plant development. PMID:29377885

The nematode homologue of Mediator complex subunit 28, F28F8.5, is a critical regulator of C. elegans development.

PubMed

Kostrouchová, Markéta; Kostrouch, David; Chughtai, Ahmed A; Kaššák, Filip; Novotný, Jan P; Kostrouchová, Veronika; Benda, Aleš; Krause, Michael W; Saudek, Vladimír; Kostrouchová, Marta; Kostrouch, Zdeněk

2017-01-01

The evolutionarily conserved Mediator complex is a critical player in regulating transcription. Comprised of approximately two dozen proteins, the Mediator integrates diverse regulatory signals through direct protein-protein interactions that, in turn, modulate the influence of Mediator on RNA Polymerase II activity. One Mediator subunit, MED28, is known to interact with cytoplasmic structural proteins, providing a potential direct link between cytoplasmic dynamics and the control of gene transcription. Although identified in many animals and plants, MED28 is not present in yeast; no bona fide MED28 has been described previously in Caenorhabditis elegans. Here, we identify bioinformatically F28F8.5, an uncharacterized predicted protein, as the nematode homologue of MED28. As in other Metazoa, F28F8.5 has dual nuclear and cytoplasmic localization and plays critical roles in the regulation of development. F28F8.5 is a vital gene and its null mutants have severely malformed gonads and do not reproduce. F28F8.5 interacts on the protein level with the Mediator subunits MDT-6 and MDT-30. Our results indicate that F28F8.5 is an orthologue of MED28 and suggest that the potential to link cytoplasmic and nuclear events is conserved between MED28 vertebrate and nematode orthologues.

Protein kinase G confers survival advantage to Mycobacterium tuberculosis during latency-like conditions.

PubMed

Khan, Mehak Zahoor; Bhaskar, Ashima; Upadhyay, Sandeep; Kumari, Pooja; Rajmani, Raju S; Jain, Preeti; Singh, Amit; Kumar, Dhiraj; Bhavesh, Neel Sarovar; Nandicoori, Vinay Kumar

2017-09-29

Protein kinase G (PknG), a thioredoxin-fold-containing eukaryotic-like serine/threonine protein kinase, is a virulence factor in Mycobacterium tuberculosis , required for inhibition of phagolysosomal fusion. Here, we unraveled novel functional facets of PknG during latency-like conditions. We found that PknG mediates persistence under stressful conditions like hypoxia and abets drug tolerance. PknG mutant displayed minimal growth in nutrient-limited conditions, suggesting its role in modulating cellular metabolism. Intracellular metabolic profiling revealed that PknG is necessary for efficient metabolic adaptation during hypoxia. Notably, the PknG mutant exhibited a reductive shift in mycothiol redox potential and compromised stress response. Exposure to antibiotics and hypoxic environment resulted in higher oxidative shift in mycothiol redox potential of PknG mutant compared with the wild type. Persistence during latency-like conditions required kinase activity and thioredoxin motifs of PknG and is mediated through phosphorylation of a central metabolic regulator GarA. Finally, using a guinea pig model of infection, we assessed the in vivo role of PknG in manifestation of disease pathology and established a role for PknG in the formation of stable granuloma, hallmark structures of latent tuberculosis. Taken together, PknG-mediated GarA phosphorylation is important for maintenance of both mycobacterial physiology and redox poise, an axis that is dispensable for survival under normoxic conditions but is critical for non-replicating persistence of mycobacteria. In conclusion, we propose that PknG probably acts as a modulator of latency-associated signals. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Epigallocatechin-gallate (EGCG) regulates autophagy in human retinal pigment epithelial cells: A potential role for reducing UVB light-induced retinal damage

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

Li, Chao-Peng; Yao, Jin; Tao, Zhi-Fu

Highlights: •UVB irradiation induces RPE autophagy. •EGCG treatment represses UVB-mediated autophagy. •EGCG regulates UVB-mediated autophagy through mTOR signaling pathway. •EGCG sensitizes RPE cells to UVB-induced damage in an autophagy-dependent manner. -- Abstract: Autophagy is an intracellular catabolic process involved in protein and organelle degradation via the lysosomal pathway that has been linked in the pathogenesis of age-related macular degeneration (AMD). UVB irradiation-mediated degeneration of the macular retinal pigment epithelial (RPE) cells is an important hallmark of AMD, which is along with the change in RPE autophagy. Thus, pharmacological manipulation of RPE autophagy may offer an alternative therapeutic target in AMD.more » Here, we found that epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, plays a regulatory role in UVB irradiation-induced autophagy in RPE cells. UVB irradiation results in a marked increase in the amount of LC3-II protein in a dose-dependent manner. EGCG administration leads to a significant reduction in the formation of LC3-II and autophagosomes. mTOR signaling activation is required for EGCG-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation is significantly impaired by rapamycin administration. Moreover, EGCG significantly alleviates the toxic effects of UVB irradiation on RPE cells in an autophagy-dependent manner. Collectively, our study reveals a novel role of EGCG in RPE autophagy. EGCG may be exploited as a potential therapeutic reagent for the treatment of pathological conditions associated with abnormal autophagy.« less

Health behaviors as mediators for the effect of partner abuse on infant birth weight.

PubMed

Kearney, Margaret H; Munro, Barbara Hazard; Kelly, Ursula; Hawkins, Joellen W

2004-01-01

Intimate partner abuse of pregnant women has been linked to the delivery of low-birth-weight infants. Also, abused pregnant women have reported a greater prevalence of substance abuse, poor nutrition, and demographic risk factors for poor birth outcomes. These factors may play a role in the reported relation between intimate partner violence and birth weight. To explore the role of substance abuse (smoking, alcohol, and drug use) and weight gain of less than 15 pounds during pregnancy as potential mediators of the relation between recent partner abuse and infant birth weight, and to investigate the role of demographic risk factors as potential moderators for the impact of abuse on birth weight. Data were extracted on abuse screening results, demographics, birth outcomes, and a range of medical and obstetric risks and complications from the medical records of 1969 women who had been screened by clinicians for domestic abuse during pregnancy. Hypotheses were tested using multiple regression analysis. Recent physical or psychological abuse had a small but significant effect on birth weight in this sample. Smoking and low weight gain were weak but significant mediators of the relation between recent abuse and infant birth weight. Single marital status was the strongest demographic predictor of decreased birth weight. No moderator effects were found. Although prospective studies are warranted, nursing care to reduce smoking and promote adequate weight gain in all women along with support for women's efforts to seek safety from abuse may help to improve birth outcomes and promote maternal well-being.

Effects of traumatic experiences on obsessive-compulsive and internalizing symptoms: The role of avoidance and mindfulness.

PubMed

Kroska, Emily B; Miller, Michelle L; Roche, Anne I; Kroska, Sydney K; O'Hara, Michael W

2018-01-01

Trauma exposure is associated with adverse psychological outcomes including anxiety, depression, and obsessive-compulsive (OC) symptoms. Adolescence is increasingly recognized as a period of vulnerability for the onset of these types of psychological symptoms. The current study explored the mediating roles of experiential avoidance and mindfulness processes in the association between retrospective reports of childhood trauma and current internalizing and OC symptoms in adolescents. A group of at-risk adolescents (N = 51) and a group of college students (N = 400) reported on childhood trauma, experiential avoidance, mindfulness, anxiety, depressive, and OC symptoms. Mediation analyses were performed to examine the mechanistic roles of avoidance and mindfulness in the association between trauma and internalizing and OC-specific symptoms. In the group of at-risk adolescents, experiential avoidance and mindfulness both significantly mediated the association between childhood trauma and OC symptoms. In the college student sample, experiential avoidance mediated the association between trauma and OC symptoms. Experiential avoidance, as well as the observe, act with awareness, and nonjudgmental facets of mindfulness all significantly mediated the association between trauma and internalizing symptoms. The group of at-risk adolescents was small, and the college student group was demographically homogeneous. All data was self-report and cross-sectional. The current study demonstrated that experiential avoidance and mindfulness processes may be the mechanisms through which the association between trauma and obsessive-compulsive and trauma and internalizing symptoms exist in adolescents. These findings provide potential targets for clinical intervention to improve outcomes for adolescents who have experienced trauma. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of Traumatic Experiences on Obsessive-Compulsive and Internalizing Symptoms: The Role of Avoidance and Mindfulness

PubMed Central

Kroska, Emily B.; Miller, Michelle L.; Roche, Anne I.; Kroska, Sydney K.; O’Hara, Michael W.

2017-01-01

Background Trauma exposure is associated with adverse psychological outcomes including anxiety, depression, and obsessive-compulsive (OC) symptoms. Adolescence is increasingly recognized as a period of vulnerability for the onset of these types of psychological symptoms. The current study explored the mediating roles of experiential avoidance and mindfulness processes in the association between retrospective reports of childhood trauma and current internalizing and OC symptoms in adolescents. Method A group of at-risk adolescents (N =51) and a group of college students (N =400) reported on childhood trauma, experiential avoidance, mindfulness, anxiety, depressive, and OC symptoms. Mediation analyses were performed to examine the mechanistic roles of avoidance and mindfulness in the association between trauma and internalizing and OC-specific symptoms. Results In the group of at-risk adolescents, experiential avoidance and mindfulness both significantly mediated the association between childhood trauma and OC symptoms. In the college student sample, experiential avoidance mediated the association between trauma and OC symptoms. Experiential avoidance, as well as the observe, act with awareness, and nonjudgmental facets of mindfulness all significantly mediated the association between trauma and internalizing symptoms. Limitations The group of at-risk adolescents was small, and the college student group was demographically homogeneous. All data was self-report and cross-sectional. Conclusion The current study demonstrated that experiential avoidance and mindfulness processes may be the mechanisms through which the association between trauma and obsessive-compulsive and trauma and internalizing symptoms exist in adolescents. These findings provide potential targets for clinical intervention to improve outcomes for adolescents who have experienced trauma. PMID:28843915

Feline immunodeficiency virus envelope glycoprotein mediates apoptosis in activated PBMC by a mechanism dependent on gp41 function

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

Garg, Himanshu; Joshi, Anjali; Tompkins, Wayne A.

2004-12-20

Feline Immunodeficiency Virus (FIV) is a lentivirus that causes immunodeficiency in cats, which parallels HIV-1-induced immunodeficiency in humans. It has been established that HIV envelope (Env) glycoprotein mediates T cell loss via a mechanism that requires CXCR4 binding. The Env glycoprotein of FIV, similar to HIV, requires CXCR4 binding for viral entry, as well as inducing membrane fusion leading to syncytia formation. However, the role of FIV Env in T cell loss and the molecular mechanisms governing this process have not been elucidated. We studied the role of Env glycoprotein in FIV-mediated T cell apoptosis in an in vitro model.more » Our studies demonstrate that membrane-expressed FIV Env induces apoptosis in activated feline peripheral blood mononuclear cells (PBMC) by a mechanism that requires CXCR4 binding, as the process was inhibited by CXCR4 antagonist AMD3100 in a dose-dependent manner. Interestingly, studies regarding the role of CD134, the recently identified primary receptor of FIV, suggest that binding to CD134 may not be important for induction of apoptosis in PBMC. However, inhibiting Env-mediated fusion post CXCR4 binding by FIV gp41-specific fusion inhibitor also inhibited apoptosis. Under similar conditions, a fusion-defective gp41 mutant was unable to induce apoptosis in activated PBMC. Our findings are the first report suggesting the potential of FIV Env to mediate apoptosis in bystander cells by a process that is dependent on gp41 function.« less

Role of receptor-mediated endocytosis in the antiangiogenic effects of human T lymphoblastic cell-derived microparticles.

PubMed

Yang, Chun; Xiong, Wei; Qiu, Qian; Shao, Zhuo; Shao, Zuo; Hamel, David; Tahiri, Houda; Leclair, Grégoire; Lachapelle, Pierre; Chemtob, Sylvain; Hardy, Pierre

2012-04-15

Microparticles possess therapeutic potential regarding angiogenesis. We have demonstrated the contribution of apoptotic human CEM T lymphocyte-derived microparticles (LMPs) as inhibitors of angiogenic responses in animal models of inflammation and tumor growth. In the present study, we characterized the antivascular endothelial growth factor (VEGF) effects of LMPs on pathological angiogenesis in an animal model of oxygen-induced retinopathy and explored the role of receptor-mediated endocytosis in the effects of LMPs on human retinal endothelial cells (HRECs). LMPs dramatically inhibited cell growth of HRECs, suppressed VEGF-induced cell migration in vitro experiments, and attenuated VEGF-induced retinal vascular leakage in vivo. Intravitreal injections of fluorescently labeled LMPs revealed accumulation of LMPs in retinal tissue, with more than 60% reductions of the vascular density in retinas of rats with oxygen-induced neovascularization. LMP uptake experiments demonstrated that the interaction between LMPs and HRECs is dependent on temperature. In addition, endocytosis is partially dependent on extracellular calcium. RNAi-mediated knockdown of low-density lipoprotein receptor (LDLR) reduced the uptake of LMPs and attenuated the inhibitory effects of LMPs on VEGF-A protein expression and HRECs cell growth. Intravitreal injection of lentivirus-mediated RNA interference reduced LDLR protein expression in retina by 53% and significantly blocked the antiangiogenic effects of LMPs on pathological vascularization. In summary, the potent antiangiogenic LMPs lead to a significant reduction of pathological retinal angiogenesis through modulation of VEGF signaling, whereas LDLR-mediated endocytosis plays a partial, but pivotal, role in the uptake of LMPs in HRECs.

Child abuse potential in mothers with early life maltreatment, borderline personality disorder and depression.

PubMed

Dittrich, Katja; Boedeker, Katja; Kluczniok, Dorothea; Jaite, Charlotte; Hindi Attar, Catherine; Fuehrer, Daniel; Herpertz, Sabine C; Brunner, Romuald; Winter, Sibylle Maria; Heinz, Andreas; Roepke, Stefan; Heim, Christine; Bermpohl, Felix

2018-05-24

Early life maltreatment (ELM), borderline personality disorder (BPD) and major depressive disorder (MDD) have been shown to increase the potential of abuse. Emotion regulation is an identified mediator for the association of ELM and BPD with abuse potential. Until now, there has been no study to account for the co-occurrence of these risk factors in one analysis, although BPD and MDD are known as common sequelae of ELM. This is paired with a lack of studies investigating the effects of abuse potential on child well-being.AimsOur study aims at (a) disentangling the effects of maternal ELM, MDD and BPD on abuse potential; (b) exploring the role of emotion regulation as a mediator; and (c) testing for intergenerational effects of abuse potential on child psychopathology. The research design included 114 mothers with/without ELM, BPD and MDD in remission and their children, all of which were between 5 and 12 years of age. A path analysis was conducted to investigate the multiple associations between our variables. ELM, MDD and BPD were all associated with abuse potential, with emotion regulation acting as a mediator for BPD and MDD. Furthermore, an elevated abuse potential was related to higher psychopathology in the child. History of ELM as well as the common sequelae, BPD and MDD, pose risks for child abuse. Our findings suggest improvement of emotion regulation as a potential target for intervention programs. These programs should also aim at non-substantiated cases because even an elevated abuse potential affected child mental health.Declaration of interestNone.

The Neonatal Microbiome and Its Partial Role in Mediating the Association between Birth by Cesarean Section and Adverse Pediatric Outcomes.

PubMed

Montoya-Williams, Diana; Lemas, Dominick J; Spiryda, Lisa; Patel, Keval; Carney, O'neshia Olivia; Neu, Josef; Carson, Tiffany L

2018-05-22

Cesarean sections (CS) are among the most commonly performed surgical procedures in the world. Epidemiologic data has associated delivery by CS with an increased risk of certain adverse health outcomes in children, such as asthma and obesity. To explore what is known about the effect of mode of delivery on the development of the infant microbiome and discuss the potentially mediating role of CS-related microbial dysbiosis in the development of adverse pediatric health outcomes. Recommendations for future inquiry are also provided. This study provides a narrative overview of the literature synthesizing the findings of literature retrieved from searches of PubMed and other computerized databases and authoritative texts. Emerging evidence suggests that mode of delivery is involved in the development of the neonatal microbiome and may partially explain pediatric health outcomes associated with birth by CS. Specifically, the gut microbiome of vaginally delivered infants more closely resembles their mothers' vaginal microbiome and thus more commonly consists of potentially beneficial microbiota such as Lactobacillus, Bifidobacterium, and Bacteroides. Conversely, the microbiome of infants born via CS shows an increased prevalence of either skin flora or potentially pathogenic microbial communities such as Klebsiella, Enterococcus, and Clostridium. Mode of delivery plays an important role in the development of the postnatal microbiome but likely tells only part of the story. More comprehensive investigations into all the pre- and perinatal factors that have the potential to contribute to the neonatal microbiome are warranted. © 2018 S. Karger AG, Basel.

The Relationship of Spiritual Health with Quality of Life, Mental Health, and Burnout: The Mediating Role of Emotional Regulation.

PubMed

Akbari, Mehdi; Hossaini, Sayed Morteza

2018-01-01

Objective: The World Health Organization's definition of health now stands open to severe criticism due to changes in today's world and the accompanying mental void; in addition to physical, psychological, and social aspects, spiritual health and its interaction with the other aspects has been studied in scientific literature and recent research. The present study was conducted to investigate the mediating role of emotional regulation in the relationship between spiritual health with quality of life, psychological health, and burnout. Method : In this study, 231 staff from Baqiyatallah University of Medical Sciences completed Spiritual Well-Being Scale (SWBS), Difficulties in Emotion Regulation Scale (DERS), World Health Organization Quality of Life-BREF (WHOQOL-BREF), General Health Questionnaire-28 (GHQ-28), and Maslach Burnout Inventory (MBI). The gathered data were analyzed using Pearson correlation, Hierarchical Regression analysis, and Sobel's test. Results: All variables were correlated with one another (p<0.001). The hierarchical regression analysis and Sobel's test indicated that the emotional regulation have a relative mediating role in the relationship between spiritual health and quality of life (ß=0.53, Z=4.05, p<0.001) and a complete mediating role in the relationship between spiritual health with mental health (ß=0.68, Z=5.62, p<0.001) and burnout (ß=0.70, Z=6.12, p<0.001). Conclusion: There is a complex and non-linear relationship between spiritual health and the areas of quality of life, mental health and burnout. This relationship is potentially influenced by emotional regulation.

Environmental adversities and psychotic symptoms: The impact of timing of trauma, abuse, and neglect.

PubMed

Schalinski, Inga; Breinlinger, Susanne; Hirt, Vanessa; Teicher, Martin H; Odenwald, Michael; Rockstroh, Brigitte

2017-11-13

Trauma and adverse childhood experiences (ACE) occur more often in mental illness, including psychosis, than in the general population. Individuals with psychosis (cases) report a higher number and severity (dose) of adversities than healthy controls. While a dose-dependent increase of adversities has been related to more severe psychopathology, the role of type and timing is still insufficiently understood on the exacerbation of positive and negative psychotic symptoms. Moreover, dissociative symptoms were examined as potential mediator between adversities and severity of psychotic symptoms. Exposure to adversities were assessed by interviews in n=180 cases and n=70 controls. In cases, symptom severities were obtained for psychotic symptoms and dissociation. Conditioned random forest regression determined the importance of type and timing of ACE for positive and negative symptom severity, and mediator analyses evaluated the role of dissociative symptoms in the relationship between adversities and psychotic symptoms. Cases experienced substantially more abuse and neglect than controls. Adversities were related in a dose-dependent manner to psychotic disorder. An array of adversities was associated with more severe positive symptoms, while the conditioned random forest regression depicted neglect at age 10 as the most important predictor. Dissociative symptoms mediated the small relation of trauma load in childhood and positive symptoms. The role of trauma and ACE on psychotic symptoms can be specified by neglect during frontocortical development in the exacerbation of positive symptoms. The mediating role of dissociation is restricted to the relation of childhood trauma and positive symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.

The Relationship of Spiritual Health with Quality of Life, Mental Health, and Burnout: The Mediating Role of Emotional Regulation

PubMed Central

Akbari, Mehdi; Hossaini, Sayed Morteza

2018-01-01

Objective: The World Health Organization's definition of health now stands open to severe criticism due to changes in today's world and the accompanying mental void; in addition to physical, psychological, and social aspects, spiritual health and its interaction with the other aspects has been studied in scientific literature and recent research. The present study was conducted to investigate the mediating role of emotional regulation in the relationship between spiritual health with quality of life, psychological health, and burnout. Method : In this study, 231 staff from Baqiyatallah University of Medical Sciences completed Spiritual Well-Being Scale (SWBS), Difficulties in Emotion Regulation Scale (DERS), World Health Organization Quality of Life-BREF (WHOQOL-BREF), General Health Questionnaire-28 (GHQ-28), and Maslach Burnout Inventory (MBI). The gathered data were analyzed using Pearson correlation, Hierarchical Regression analysis, and Sobel’s test. Results: All variables were correlated with one another (p<0.001). The hierarchical regression analysis and Sobel’s test indicated that the emotional regulation have a relative mediating role in the relationship between spiritual health and quality of life (ß=0.53, Z=4.05, p<0.001) and a complete mediating role in the relationship between spiritual health with mental health (ß=0.68, Z=5.62, p<0.001) and burnout (ß=0.70, Z=6.12, p<0.001). Conclusion: There is a complex and non-linear relationship between spiritual health and the areas of quality of life, mental health and burnout. This relationship is potentially influenced by emotional regulation. PMID:29892314

The relative contributions of function, perceived psychological burden and partner support to cognitive distress in bladder cancer.

PubMed

Heyes, Susan M; Bond, Malcolm J; Harrington, Ann; Belan, Ingrid

2016-09-01

Bladder cancer is a genitourinary disease of increasing incidence. Despite improvements in treatment, outcomes remain equivocal with high recurrence rates. It is associated with poor psychosocial outcomes due to reduced functioning of the genitourinary system. The objective of these analyses was to query whether reported loss of function or the perception of psychological burden caused by this functional impedance was the key to understanding psychosocial outcomes. The sample comprised 119 participants with a confirmed diagnosis of bladder cancer. They completed a self-report questionnaire comprising the Bladder Cancer Index, Mini-mental Adjustment to Cancer Scale, Psychosocial Adjustment to Illness Scale and standard sociodemographic details. Simple mediation and serial mediation were used to explore the potential for psychological burden to mediate associations between loss of function and cognitive distress, and the potential additional contribution of positive partner support on these relationships. Age and duration of cancer were considered as covariates. Simple mediation demonstrated that the association between function and cognitive distress was fully mediated by perceived psychological burden. Serial mediation, which allowed for the addition of partner support, again demonstrated full mediation, with partner support being the key predictive variable. These analyses emphasise the importance of an appreciation of individuals' interpretation of the burden occasioned by bladder cancer and the role of a supportive partner. The implications for management discussions and support services in alleviating negative psychological outcomes in bladder cancer are highlighted. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Prosociality and negative emotionality mediate the association of serotonin transporter genotype with childhood ADHD and ODD.

PubMed

Brammer, Whitney A; Lee, Steve S

2013-01-01

Although there is evidence that the promoter polymorphism of the serotonin transporter (5-HTTLPR) gene is associated with attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), the pathways underlying these associations are largely unknown. Given their theoretical and biological plausibility, we tested whether individual differences in key temperament dimensions (i.e., prosociality, negative emotionality, daring) constituted potential pathways from 5-HTTLPR to ADHD and ODD. Using a well-characterized sample of 194 six to nine-year-old children with and without ADHD, we utilized multiple mediation procedures with bootstrapping to evaluate prosociality, negative emotionality, and daring as independent mediators of 5-HTTLPR with separate parent and teacher ratings of ADHD and ODD. Controlling for ODD, prosociality and negative emotionality significantly mediated the association of 5-HTTLPR and parent-reported ADHD. Similarly, controlling for ADHD, prosociality and negative emotionality each uniquely mediated the association of 5-HTTLPR and parent-reported ODD. For teacher-reported ADHD, prosociality significantly mediated the association of 5-HTTLPR (controlling for ODD) whereas controlling for ODD, negative emotionality significantly mediated the prediction of teacher-reported ODD from 5-HTTLPR. Specifically, the number of 5-HTTLPR long alleles was inversely associated with prosociality and positively associated with negative emotionality; prosociality was inversely associated and negative emotionality was positively associated with ADHD and ODD. We consider the role of temperament in genetically sensitive designs as well as its potential value in the development and delivery of effective interventions.

Moderated mediation analysis: An illustration using the association of gender with delinquency and mental health.

PubMed

Miles, Jeremy N V; Kulesza, Magdalena; Ewing, Brett; Shih, Regina A; Tucker, Joan S; D'Amico, Elizabeth J

When researchers find an association between two variables, it is useful to evaluate the role of other constructs in this association. While assessing these mediation effects, it is important to determine if results are equal for different groups. It is possible that the strength of a mediation effect may differ for males and females, for example - such an effect is known as moderated mediation. Participants were 2532 adolescents from diverse ethnic/racial backgrounds and equally distributed across gender. The goal of this study was to investigate parental respect as a potential mediator of the relationship between gender and delinquency and mental health, and to determine whether observed mediation is moderated by gender. Parental respect mediated the association between gender and both delinquency and mental health. Specifically, parental respect was a protective factor against delinquency and mental health problems for both females and males. Demonstrated the process of estimating models in Lavaan, using two approaches (i.e. single group regression and multiple group regression model), and including covariates in both models.

Moderated mediation analysis: An illustration using the association of gender with delinquency and mental health

PubMed Central

Miles, Jeremy N.V.; Kulesza, Magdalena; Ewing, Brett; Shih, Regina A.; Tucker, Joan S.; D’Amico, Elizabeth J.

2015-01-01

Purpose When researchers find an association between two variables, it is useful to evaluate the role of other constructs in this association. While assessing these mediation effects, it is important to determine if results are equal for different groups. It is possible that the strength of a mediation effect may differ for males and females, for example – such an effect is known as moderated mediation. Design Participants were 2532 adolescents from diverse ethnic/racial backgrounds and equally distributed across gender. The goal of this study was to investigate parental respect as a potential mediator of the relationship between gender and delinquency and mental health, and to determine whether observed mediation is moderated by gender. Findings Parental respect mediated the association between gender and both delinquency and mental health. Specifically, parental respect was a protective factor against delinquency and mental health problems for both females and males. Practical implications Demonstrated the process of estimating models in Lavaan, using two approaches (i.e. single group regression and multiple group regression model), and including covariates in both models. PMID:26500722

Dexamethasone enhances interaction of endogenous annexin 1 with L-selectin and triggers shedding of L-selectin in the monocytic cell line U-937.

PubMed

de Coupade, Catherine; Solito, Egle; Levine, Jon D

2003-09-01

(1) L-selectin, constitutively expressed by leukocytes, is involved in the initial binding of leukocytes to activated endothelium. Anti-inflammatory drugs like glucocorticoids can induce shedding of L-selectin, but the mechanism is still unknown. Annexin 1, a protein whose synthesis and externalization/secretion are induced during the inflammatory response, has been proposed as a mediator of the anti-inflammatory actions of glucocorticoids. (2) The monocytic cell line U-937 strongly expresses Annexin 1 after 24 h of phorbol 12-myristate 13-acetate (PMA, 1 nm) treatment and externalizes/releases the protein after additional 16 h of dexamethasone (1 microm) treatment. (3) This study investigated the possible regulation of cell surface L-selectin shedding by endogenous Annexin 1, and its role in glucocorticoid-induced L-selectin shedding in the U-937 cell line. (4) PMA- and dexamethasone treatment-induced L-selectin shedding was potentially mediated by Annexin 1, since neutralizing antibodies against Annexin 1 reduced dexamethasone- and Annexin 1-induced shedding. (5) Immunoprecipitation and binding assays provided support for the suggestion that this effect could be mediated by an interaction between externalized Annexin 1 and L-selectin. Such interaction involved the N-terminal domain of Annexin 1 and was calcium-dependent. Confocal microscopy studies demonstrated increased colocalization of Annexin 1 and L-selectin on the cell surface. (6) Overall, our study provides new insights into the potential role of endogenous ANXA1 as a mediator of dexamethasone-induced L-selectin shedding, which may contribute to the anti-inflammatory activity of glucocorticoids.

Anoctamin 1 contributes to inflammatory and nerve-injury induced hypersensitivity.

PubMed

Lee, Byeongjun; Cho, Hawon; Jung, Jooyoung; Yang, Young Duk; Yang, Dong-Jin; Oh, Uhtaek

2014-01-23

Various pathological conditions such as inflammation or injury can evoke pain hypersensitivity. That represents the response to innocuous stimuli or exaggerated response to noxious stimuli. The molecular mechanism based on the pain hypersensitivity is associated with changes in many of ion channels in dorsal-root ganglion (DRG) neurons. Anoctamin 1 (ANO1/TMEM16A), a Ca2+ activated chloride channel is highly visible in small DRG neurons and responds to heat. Mice with an abolished function of ANO1 in DRG neurons demonstrated attenuated pain-like behaviors when exposed to noxious heat, suggesting a role in acute thermal nociception. In this study, we further examined the function of ANO1 in mediating inflammation- or injury-induced hyperalgesia or allodynia. Using Advillin/Ano1fl/fl (Adv/Ano1fl/fl) mice that have a functional ablation of Ano1 mainly in DRG neurons, we were able to determine its role in mediating thermal hyperalgesia and mechanical allodynia induced by inflammation or nerve injury. The thermal hyperalgesia and mechanical allodynia induced by carrageenan injection and spared-nerve injury were significantly reduced in Adv/Ano1fl/fl mice. In addition, flinching or licking behavior after bradykinin or formalin injection was also significantly reduced in Adv/Ano1fl/fl mice. Since pathological conditions augment nociceptive behaviors, we expected ANO1's contribution to the excitability of DRG neurons. Indeed, the application of inflammatory mediators reduced the threshold for action potential (rheobase) or time for induction of the first action potential in DRG neurons isolated from control (Ano1fl/fl) mice. These parameters for neuronal excitability induced by inflammatory mediators were not changed in Adv/Ano1fl/fl mice, suggesting an active contribution of ANO1 in augmenting the neuronal excitability. In addition to ANO1's role in mediating acute thermal pain as a heat sensor, ANO1 is also capable of augmenting the excitability of DRG neurons under inflammatory or neuropathic conditions and thereby aggravates inflammation- or tissue injury-induced pathological pain.

Significance of the Centrally Expressed TRP Channel "Painless" in "Drosophila" Courtship Memory

ERIC Educational Resources Information Center

Sakai, Takaomi; Sato, Shoma; Ishimoto, Hiroshi; Kitamoto, Toshihiro

2013-01-01

Considerable evidence has demonstrated that transient receptor potential (TRP) channels play vital roles in sensory neurons, mediating responses to various environmental stimuli. In contrast, relatively little is known about how TRP channels exert their effects in the central nervous system to control complex behaviors. This is also true for the…

Pre- and Peri-Natal Environmental Risks for Attention-Deficit Hyperactivity Disorder (ADHD): The Potential Role of Epigenetic Processes in Mediating Susceptibility

ERIC Educational Resources Information Center

Mill, Jonathan; Petronis, Arturas

2008-01-01

Attention-deficit hyperactivity disorder (ADHD) is a common childhood neurobehavioural disorder defined by symptoms of developmentally inappropriate inattention, impulsivity and hyperactivity. As is the norm for most psychiatric phenotypes, traditional aetiological studies have focused primarily on the interplay between genetic and environmental…

Examining the Relationship between Family Meal Frequency and Individual Dietary Intake: Does Family Cohesion Play a Role?

ERIC Educational Resources Information Center

Welsh, Ericka M.; French, Simone A.; Wall, Melanie

2011-01-01

Objective: To confirm previously reported associations between family meal frequency and dietary intake, and to examine family cohesion as a potential mediator of this relationship. Design: Cross-sectional observational study. Data collected at baseline via questionnaire. Setting: Randomized, controlled household weight gain prevention trial.…

Work-Life Benefits and Job Pursuit Intentions: The Role of Anticipated Organizational Support

ERIC Educational Resources Information Center

Casper, Wendy J.; Buffardi, Louis C.

2004-01-01

The current study examined the impact of two work-life benefits, work schedule flexibility, and dependent care assistance, on applicants' intentions to pursue jobs with potential employers. The study also explored whether anticipated organizational support would mediate the relationships between these two work-life benefits and job pursuit…

Why Do Some Children Have Difficulty Learning Mathematics? Looking at Language for Answers

ERIC Educational Resources Information Center

Morin, Joseph E.; Franks, David J.

2009-01-01

Some students enter the world of mathematics with a disadvantage. The authors explored the causes for this from a language-processing perspective. They were particularly concerned with students with potential learning disabilities or specific language impairments. They also explored the role of language-mediated instruction in creating an…

Seasonal and spatial patterns in coupled nitrification-denitrification rates in a large Great Lakes coastal system: The St. Louis River Estuary

EPA Science Inventory

Anthropogenic inputs of excess nitrogen (N) to aquatic systems are detrimental, but aquatic plants and sediments have the potential to mitigate N-loading. Sediment processes are driven by microbially mediated N-cycling. Coastal embayments purportedly play a significant role in N-...

Re-Mediating Literacy: Culture, Difference, and Learning for Students from Nondominant Communities

ERIC Educational Resources Information Center

Gutierrez, Kris D.; Morales, P. Zitlali; Martinez, Danny C.

2009-01-01

Deficit notions about the cognitive potential of individuals from nondominant communities have persisted in social science inquiry, particularly where literacy is concerned. The intellectual trails of current conflicting ideas about literacy can be traced in part to theories about the role of literacy in society. For example, the great divide…

Basic and Advanced Numerical Performances Relate to Mathematical Expertise but Are Fully Mediated by Visuospatial Skills

ERIC Educational Resources Information Center

Sella, Francesco; Sader, Elie; Lolliot, Simon; Cohen Kadosh, Roi

2016-01-01

Recent studies have highlighted the potential role of basic numerical processing in the acquisition of numerical and mathematical competences. However, it is debated whether high-level numerical skills and mathematics depends specifically on basic numerical representations. In this study mathematicians and nonmathematicians performed a basic…

Digital Identity Formation: Socially Being Real and Present on Digital Networks

ERIC Educational Resources Information Center

Bozkurt, Aras; Tu, Chih-Hsiung

2016-01-01

Social networks have become popular communication and interaction environments recently. As digital environments, so as ecosystems, they have potential in terms of networked learning as they fulfill some roles such as mediating an environment for digital identity formation and providing social and emotional presence. Based on this phenomenon, the…

Peer Victimization and Adolescent Adjustment: Does School Belonging Matter?

ERIC Educational Resources Information Center

Wormington, Stephanie V.; Anderson, Kristen G.; Schneider, Ashley; Tomlinson, Kristin L.; Brown, Sandra A.

2016-01-01

Recent research highlights the role of peer victimization in students' adjustment across a variety of domains (e.g., academic, social), but less often identifies potential mediating variables. In the current study, we tested for direct effects from peer victimization to adolescents' academic behavior and alcohol use, as well as indirect effects…

The Politics of International League Tables: PISA in Japan's Achievement Crisis Debate

ERIC Educational Resources Information Center

Takayama, Keita

2008-01-01

Using the political-economic analysis of globalisation and education as well as a culturalist approach to education policy borrowing, the paper analyses the role of local actors, specifically, national newspapers and the Ministry of Education, in mediating the potentially homogenising curricular policy pressure of globalisation exerted through the…

Glutamine-mediated protection from neuronal cell death depends on mitochondrial activity.

PubMed

Stelmashook, E V; Lozier, E R; Goryacheva, E S; Mergenthaler, P; Novikova, S V; Zorov, D B; Isaev, N K

2010-09-27

The specific aim of this study was to elucidate the role of mitochondria in a neuronal death caused by different metabolic effectors and possible role of intracellular calcium ions ([Ca(2+)](i)) and glutamine in mitochondria- and non-mitochondria-mediated cell death. Inhibition of mitochondrial complex I by rotenone was found to cause intensive death of cultured cerebellar granule neurons (CGNs) that was preceded by an increase in intracellular calcium concentration ([Ca(2+)](i)). The neuronal death induced by rotenone was significantly potentiated by glutamine. In addition, inhibition of Na/K-ATPase by ouabain also caused [Ca(2+)](i) increase, but it induced neuronal cell death only in the absence of glucose. Treatment with glutamine prevented the toxic effect of ouabain and decreased [Ca(2+)](i). Blockade of ionotropic glutamate receptors prevented neuronal death and significantly decreased [Ca(2+)](i), demonstrating that toxicity of rotenone and ouabain was at least partially mediated by activation of these receptors. Activation of glutamate receptors by NMDA increased [Ca(2+)](i) and decreased mitochondrial membrane potential leading to markedly decreased neuronal survival under glucose deprivation. Glutamine treatment under these conditions prevented cell death and significantly decreased the disturbances of [Ca(2+)](i) and changes in mitochondrial membrane potential caused by NMDA during hypoglycemia. Our results indicate that glutamine stimulates glutamate-dependent neuronal damage when mitochondrial respiration is impaired. However, when mitochondria are functionally active, glutamine can be used by mitochondria as an alternative substrate to maintain cellular energy levels and promote cell survival. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases

PubMed Central

Sarkar, Avijit; De, Ronita; Mukhopadhyay, Asish K

2016-01-01

Curcumin, a yellow pigment and principal polyphenolic Curcuminoid obtained from the turmeric rhizome Curcuma longa, is commonly used as a food-coloring agent. Studies suggest that curcumin has a wide range of beneficial properties e.g., anti-inflammatory, anti-oxidant, anti-cancer, anti-proliferative, anti-fungal and anti-microbial. These pleiotropic activities prompted several research groups to elucidate the role of curcumin in Helicobacter pylori (H. pylori) infection. This is the first review with this heading where we discussed regarding the role of curcumin as an anti-H. pylori agent along with its potential in other gastrointestinal diseases. Based on several in vitro, early cell culture, animal research and few pre-clinical trials, curcumin projected as a potential therapeutic candidate against H. pylori mediated gastric pathogenesis. This review sheds light on the anti-H. pylori effects of curcumin in different models with meticulous emphasis on its anti-oxidant, anti-inflammatory and anti-carcinogenic effects as well as some critical signaling and effecter molecules. Remarkably, non-toxic molecule curcumin fulfills the characteristics for an ideal chemopreventive agent against H. pylori mediated gastric carcinogenesis but the foremost challenge is to obtain the optimum therapeutic levels of curcumin, due to its low solubility and poor bioavailability. Further, we have discussed about the possibilities for improving its efficacy and bioavailability. Lastly, we concluded with the anticipation that in near future curcumin may be used to develop a therapeutic drug against H. pylori mediated gastric ailments through improved formulation or delivery systems, facilitating its enhanced absorption and cellular uptake. PMID:26973412

Endogenous 17β-estradiol is required for activity-dependent long-term potentiation in the striatum: interaction with the dopaminergic system

PubMed Central

Tozzi, Alessandro; de Iure, Antonio; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Giampà, Carmela; Di Mauro, Michela; Mazzocchetti, Petra; Costa, Cinzia; Di Filippo, Massimiliano; Grassi, Silvarosa; Pettorossi, Vito Enrico; Calabresi, Paolo

2015-01-01

17β-estradiol (E2), a neurosteroid synthesized by P450-aromatase (ARO), modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs) and dopamine (DA) receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP) in both medium spiny neurons (MSNs) and cholinergic interneurons (ChIs). Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson’s disease. PMID:26074768

Victimization and depressive symptomology in transgender adults: The mediating role of avoidant coping

PubMed Central

Hughto, Jaclyn M. White; Pachankis, John E.; Willie, Tiara C.; Reisner, Sari L.

2016-01-01

Victimization and depressive distress symptoms represent serious and interconnected public health problems facing transgender communities. Avoidant coping is hypothesized to temporarily alleviate the stress of victimization, but has potential long-term mental and behavioral health costs, such as increasing the probability of depressive symptoms. A community sample of 412 transgender adults (M age = 32.7, SD = 12.8) completed a one-time survey capturing multiple forms of victimization (i.e., everyday discrimination, bullying, physical assault by family, verbal harassment by family, childhood sexual abuse, intimate partner violence), avoidant coping, and past-week depressive symptomology. Structural equation modeling examined the mediating role of avoidant coping in the association between victimization and depressive symptomology. A latent victimization variable composed of six measures of victimization was positively associated with avoidant coping, which in turn was positively associated with depressive symptoms. Victimization was also positively associated with depressive symptomology both directly and indirectly through avoidant coping. Avoidant coping represents a potentially useful intervention target for clinicians aiming to reduce the mental health sequelae of victimization in this highly stigmatized and vulnerable population. PMID:28068130

Sirtuin7 is involved in protecting neurons against oxygen-glucose deprivation and reoxygenation-induced injury through regulation of the p53 signaling pathway.

PubMed

Lv, Jianrui; Tian, Junbin; Zheng, Guoxi; Zhao, Jing

2017-10-01

Sirtuin7 (SIRT7) is known to regulate apoptosis and stress responses. So far, very little is known about the role of SIRT7 in cerebral ischemia/reperfusion injury. In this study, we aimed to investigate the potential role of SIRT7 in regulating oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury in neurons. We found a significant increase of SIRT7 expression in neurons in response to OGD/R treatment. Knockdown of SIRT7 aggravated OGD/R-induced injury. Knockdown of SIRT7 augmented the levels of total and acetylated p53 protein. Moreover, knockdown of SIRT7 markedly increased the transcriptional activity of p53 toward apoptosis and activated the p53-mediated proapoptotic signaling pathway. By contrast, overexpression of SIRT7 showed the opposite effects. Taken together, the results of our study suggest that SIRT7 is involved in protecting neurons against OGD/R-induced injury, possibly through regulation of the p53-mediated proapoptotic signaling pathway, indicating a potential therapeutic target for cerebral ischemia/reperfusion injury. © 2017 Wiley Periodicals, Inc.

Endogenous 17β-estradiol is required for activity-dependent long-term potentiation in the striatum: interaction with the dopaminergic system.

PubMed

Tozzi, Alessandro; de Iure, Antonio; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Giampà, Carmela; Di Mauro, Michela; Mazzocchetti, Petra; Costa, Cinzia; Di Filippo, Massimiliano; Grassi, Silvarosa; Pettorossi, Vito Enrico; Calabresi, Paolo

2015-01-01

17β-estradiol (E2), a neurosteroid synthesized by P450-aromatase (ARO), modulates various brain functions. We characterized the role of the locally synthesized E2 on striatal long-term synaptic plasticity and explored possible interactions between E2 receptors (ERs) and dopamine (DA) receptors in the dorsal striatum of adult male rats. Inhibition of E2 synthesis or antagonism of ERs prevented the induction of long-term potentiation (LTP) in both medium spiny neurons (MSNs) and cholinergic interneurons (ChIs). Activation of a D1-like DA receptor/cAMP/PKA-dependent pathway restored LTP. In MSNs exogenous E2 reversed the effect of ARO inhibition. Also antagonism of M1 muscarinic receptors prevented the D1-like receptor-mediated restoration of LTP confirming a role for ChIs in controlling the E2-mediated LTP of MSNs. A novel striatal interaction, occurring between ERs and D1-like receptors in both MSNs and ChIs, might be critical to regulate basal ganglia physiology and to compensate synaptic alterations in Parkinson's disease.

Aversive Startle Potentiation and Fear Pathology: Mediating Role of Threat Sensitivity and Moderating Impact of Depression

PubMed Central

Yancey, James R.; Vaidyanathan, Uma; Patrick, Christopher J.

2015-01-01

Enhanced startle during exposure to unpleasant cues (aversive startle potentiation; ASP) appears in the RDoC matrix as a physiological index of acute threat response. Increased ASP has been linked to focal fear disorders and to scale measures of dispositional fearfulness (i.e., threat sensitivity; THT+). However, some studies have reported reduced ASP for fear pathology accompanied by major depressive disorder (MDD) or pervasive distress. The current study evaluated whether (a) THT+ as indexed by reported dispositional fearfulness mediates the relationship between fear disorders (when unaccompanied by depression) and ASP, and (b) depression moderates relations of THT+ and fear disorders with ASP. Fear disorder participants without MDD showed enhanced ASP whereas those with MDD (or other distress conditions) showed evidence of reduced ASP. Continuous THT+ scores also predicted ASP, and this association: (a) was likewise moderated by depression/distress, and (b) accounted for the relationship between ASP and fear pathology without MDD. These findings point to a role for the RDoC construct of acute threat, operationalized dispositionally, in enhanced ASP shown by individuals with fear pathology unaccompanied by distress pathology. PMID:25448265

Publics in the making: mediating different methods of engagement and the publics these construct : commentary on: "Technologies of democracy: experiments and demonstrations".

PubMed

Mohr, Alison

2011-12-01

The potential for public engagement to democratise science has come under increasing scrutiny amid concerns that conflicting motivations have led to confusion about what engagement means to those who mediate science and publics. This raises important yet relatively unexplored questions regarding how publics are constituted by different forms of engagement used by intermediary scholars and other actors. It is possible to identify at least two possible 'rationalities of mediation' that mobilise different versions of the public and the roles they are assumed to play, as 'citizens' or 'users', in discussions around technology. However, combinations of rationalities are found in practice and these have significant implications for the 'new' scientific democracy.

Human Mucosal Mast Cells Capture HIV-1 and Mediate Viral trans-Infection of CD4+ T Cells.

PubMed

Jiang, Ai-Ping; Jiang, Jin-Feng; Wei, Ji-Fu; Guo, Ming-Gao; Qin, Yan; Guo, Qian-Qian; Ma, Li; Liu, Bao-Chi; Wang, Xiaolei; Veazey, Ronald S; Ding, Yong-Bing; Wang, Jian-Hua

2015-12-30

The gastrointestinal mucosa is the primary site where human immunodeficiency virus type 1 (HIV-1) invades, amplifies, and becomes persistently established, and cell-to-cell transmission of HIV-1 plays a pivotal role in mucosal viral dissemination. Mast cells are widely distributed in the gastrointestinal tract and are early targets for invasive pathogens, and they have been shown to have increased density in the genital mucosa in HIV-infected women. Intestinal mast cells express numerous pathogen-associated molecular patterns (PAMPs) and have been shown to combat various viral, parasitic, and bacterial infections. However, the role of mast cells in HIV-1 infection is poorly defined. In this study, we investigated their potential contributions to HIV-1 transmission. Mast cells isolated from gut mucosal tissues were found to express a variety of HIV-1 attachment factors (HAFs), such as DC-SIGN, heparan sulfate proteoglycan (HSPG), and α4β7 integrin, which mediate capture of HIV-1 on the cell surface. Intriguingly, following coculture with CD4(+) T cells, mast cell surface-bound viruses were efficiently transferred to target T cells. Prior blocking with anti-HAF antibody or mannan before coculture impaired viral trans-infection. Cell-cell conjunctions formed between mast cells and T cells, to which viral particles were recruited, and these were required for efficient cell-to-cell HIV-1 transmission. Our results reveal a potential function of gut mucosal mast cells in HIV-1 dissemination in tissues. Strategies aimed at preventing viral capture and transfer mediated by mast cells could be beneficial in combating primary HIV-1 infection. In this study, we demonstrate the role of human mast cells isolated from mucosal tissues in mediating HIV-1 trans-infection of CD4(+) T cells. This finding facilitates our understanding of HIV-1 mucosal infection and will benefit the development of strategies to combat primary HIV-1 dissemination. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Corticotropin-releasing factor (CRF) and α 2 adrenergic receptors mediate heroin withdrawal-potentiated startle in rats.

PubMed

Park, Paula E; Vendruscolo, Leandro F; Schlosburg, Joel E; Edwards, Scott; Schulteis, Gery; Koob, George F

2013-09-01

Anxiety is one of the early symptoms of opioid withdrawal and contributes to continued drug use and relapse. The acoustic startle response (ASR) is a component of anxiety that has been shown to increase during opioid withdrawal in both humans and animals. We investigated the role of corticotropin-releasing factor (CRF) and norepinephrine (NE), two key mediators of the brain stress system, on acute heroin withdrawal-potentiated ASR. Rats injected with heroin (2 mg/kg s.c.) displayed an increased ASR when tested 4 h after heroin treatment. A similar increase in ASR was found in rats 10-20 h into withdrawal from extended access (12 h) to i.v. heroin self-administration, a model that captures several aspects of heroin addiction in humans. Both the α 2 adrenergic receptor agonist clonidine (10 μg/kg s.c.) and CRF1 receptor antagonist N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5-a] pyrimidin-7-amine (MPZP; 20 mg/kg s.c.) blocked heroin withdrawal-potentiated startle. To investigate the relationship between CRF1 and α 2 adrenergic receptors in the potentiation of the ASR, we tested the effect of MPZP on yohimbine (1.25 mg/kg s.c.)-potentiated startle and clonidine on CRF (2 μg i.c.v.)-potentiated startle. Clonidine blocked CRF-potentiated startle, whereas MPZP partially attenuated but did not reverse yohimbine-potentiated startle, suggesting that CRF may drive NE release to potentiate startle. These results suggest that CRF1 and α 2 receptors play an important role in the heightened anxiety-like behaviour observed during acute withdrawal from heroin, possibly via CRF inducing the release of NE in stress-related brain regions.

Focal adhesion kinase regulates neuronal growth, synaptic plasticity and hippocampus-dependent spatial learning and memory.

PubMed

Monje, Francisco J; Kim, Eun-Jung; Pollak, Daniela D; Cabatic, Maureen; Li, Lin; Baston, Arthur; Lubec, Gert

2012-01-01

The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase abundantly expressed in the mammalian brain and highly enriched in neuronal growth cones. Inhibitory and facilitatory activities of FAK on neuronal growth have been reported and its role in neuritic outgrowth remains controversial. Unlike other tyrosine kinases, such as the neurotrophin receptors regulating neuronal growth and plasticity, the relevance of FAK for learning and memory in vivo has not been clearly defined yet. A comprehensive study aimed at determining the role of FAK in neuronal growth, neurotransmitter release and synaptic plasticity in hippocampal neurons and in hippocampus-dependent learning and memory was therefore undertaken using the mouse model. Gain- and loss-of-function experiments indicated that FAK is a critical regulator of hippocampal cell morphology. FAK mediated neurotrophin-induced neuritic outgrowth and FAK inhibition affected both miniature excitatory postsynaptic potentials and activity-dependent hippocampal long-term potentiation prompting us to explore the possible role of FAK in spatial learning and memory in vivo. Our data indicate that FAK has a growth-promoting effect, is importantly involved in the regulation of the synaptic function and mediates in vivo hippocampus-dependent spatial learning and memory. Copyright © 2011 S. Karger AG, Basel.

Experienced stigma and its impacts in psychosis: The role of social rank and external shame.

PubMed

Wood, Lisa; Irons, Chris

2017-09-01

Experienced stigma is detrimental to those who experience psychosis and can cause emotional distress and hinder recovery. This study aimed to explore the relationship between experienced stigma with emotional distress and recovery in people with psychosis. It explored the role of external shame and social rank as mediators in these relationships. A cross-sectional design was implemented. Fifty-two service users were administered a battery of questionnaires examining experienced stigma, external shame, social rank, personal recovery, positive symptoms, depression, and anxiety. Correlation and multiple regression analysis were conducted on the data. Where appropriate, mediation analysis was employed to explore social rank and external shame as mediatory variables. Experienced stigma was significantly related to shame (social rank and external shame), positive symptoms, emotional distress (depression and anxiety), and personal recovery. The impact of experienced stigma on depression was mediated by external shame. Social rank was a mediator between experienced stigma and personal recovery only. People with psychosis who have experienced stigma are likely to experience emotional distress and be inhibited in their recovery. This was found to be partly mediated by external shame and low social rank. Clinical approaches to stigma need to target these as potential maintenance factors. Experienced stigma is significantly related to shame (social rank and external shame) emotional distress, and reduced personal recovery. External shame mediated the relationship between experienced stigma and depression in psychosis. Social rank mediated the relationship between experienced stigma and personal recovery. Clinical approaches to stigma should include the assessment of external shame and low social rank. © 2017 The British Psychological Society.

Yeast Model Uncovers Dual Roles of Mitochondria in the Action of Artemisinin

PubMed Central

Li, Wei; Mo, Weike; Shen, Dan; Sun, Libo; Wang, Juan; Lu, Shan; Gitschier, Jane M; Zhou, Bing

2005-01-01

Artemisinins, derived from the wormwood herb Artemisia annua, are the most potent antimalarial drugs currently available. Despite extensive research, the exact mode of action of artemisinins has not been established. Here we use yeast, Saccharamyces cerevisiae, to probe the core working mechanism of this class of antimalarial agents. We demonstrate that artemisinin's inhibitory effect is mediated by disrupting the normal function of mitochondria through depolarizing their membrane potential. Moreover, in a genetic study, we identify the electron transport chain as an important player in artemisinin's action: Deletion of NDE1 or NDI1, which encode mitochondrial NADH dehydrogenases, confers resistance to artemisinin, whereas overexpression of NDE1 or NDI1 dramatically increases sensitivity to artemisinin. Mutations or environmental conditions that affect electron transport also alter host's sensitivity to artemisinin. Sensitivity is partially restored when the Plasmodium falciparum NDI1 ortholog is expressed in yeast ndi1 strain. Finally, we showed that artemisinin's inhibitory effect is mediated by reactive oxygen species. Our results demonstrate that artemisinin's effect is primarily mediated through disruption of membrane potential by its interaction with the electron transport chain, resulting in dysfunctional mitochondria. We propose a dual role of mitochondria played during the action of artemisinin: the electron transport chain stimulates artemisinin's effect, most likely by activating it, and the mitochondria are subsequently damaged by the locally generated free radicals. PMID:16170412

Melanopsin mediates light-dependent relaxation in blood vessels.

PubMed

Sikka, Gautam; Hussmann, G Patrick; Pandey, Deepesh; Cao, Suyi; Hori, Daijiro; Park, Jong Taek; Steppan, Jochen; Kim, Jae Hyung; Barodka, Viachaslau; Myers, Allen C; Santhanam, Lakshmi; Nyhan, Daniel; Halushka, Marc K; Koehler, Raymond C; Snyder, Solomon H; Shimoda, Larissa A; Berkowitz, Dan E

2014-12-16

Melanopsin (opsin4; Opn4), a non-image-forming opsin, has been linked to a number of behavioral responses to light, including circadian photo-entrainment, light suppression of activity in nocturnal animals, and alertness in diurnal animals. We report a physiological role for Opn4 in regulating blood vessel function, particularly in the context of photorelaxation. Using PCR, we demonstrate that Opn4 (a classic G protein-coupled receptor) is expressed in blood vessels. Force-tension myography demonstrates that vessels from Opn4(-/-) mice fail to display photorelaxation, which is also inhibited by an Opn4-specific small-molecule inhibitor. The vasorelaxation is wavelength-specific, with a maximal response at ∼430-460 nm. Photorelaxation does not involve endothelial-, nitric oxide-, carbon monoxide-, or cytochrome p450-derived vasoactive prostanoid signaling but is associated with vascular hyperpolarization, as shown by intracellular membrane potential measurements. Signaling is both soluble guanylyl cyclase- and phosphodiesterase 6-dependent but protein kinase G-independent. β-Adrenergic receptor kinase 1 (βARK 1 or GRK2) mediates desensitization of photorelaxation, which is greatly reduced by GRK2 inhibitors. Blue light (455 nM) regulates tail artery vasoreactivity ex vivo and tail blood blood flow in vivo, supporting a potential physiological role for this signaling system. This endogenous opsin-mediated, light-activated molecular switch for vasorelaxation might be harnessed for therapy in diseases in which altered vasoreactivity is a significant pathophysiologic contributor.

GPER1 mediates estrogen-induced neuroprotection against oxygen-glucose deprivation in the primary hippocampal neurons.

PubMed

Zhao, Tian-Zhi; Shi, Fei; Hu, Jun; He, Shi-Ming; Ding, Qian; Ma, Lian-Ting

2016-07-22

It is well-known that the neuroprotective effects of estrogen have potential in the prevention and amelioration of ischemic and degenerative neurological disorders, while the underlying mechanisms for estrogen actions are undefined. As an important mediator for the non-genomic functions of estrogen, GPER1 (G Protein-coupled Estrogen Receptor 1) has been suggested to involve in the beneficial roles of estrogen in neural cells. Here our studies on primary hippocampal neurons have focused on GPER1 in an in vitro model of ischemia using oxygen-glucose deprivation (OGD). GPER1 expression in the primary hippocampal neurons was stimulated by the OGD treatments. Both E2 (estradiol) and E2-BSA (membrane impermeable estradiol by covalent conjugation of bovine serum albumin) attenuated OGD-induced cell death in primary cultures of hippocampal neurons. Importantly, this membrane-mediated estrogen function requires GPER1 protein. Knocking down of GPER1 diminished, while overexpression of GPER1 potentiated, the protective roles of E2/E2-BSA following OGD. Additionally, the downstream mechanisms employed by membrane-associated estrogen signaling were found to include PI3K/Akt-dependent Ask1 inhibition in the primary hippocampal neurons. Overall, these research results could enhance our understanding of the neuroprotective actions for estrogen, and provide a new therapeutic target for improving stroke outcome and ameliorating degenerative neurological diseases. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Hedgehog signaling regulates nociceptive sensitization.

PubMed

Babcock, Daniel T; Shi, Shanping; Jo, Juyeon; Shaw, Michael; Gutstein, Howard B; Galko, Michael J

2011-09-27

Nociceptive sensitization is a tissue damage response whereby sensory neurons near damaged tissue enhance their responsiveness to external stimuli. This sensitization manifests as allodynia (aversive withdrawal to previously nonnoxious stimuli) and/or hyperalgesia (exaggerated responsiveness to noxious stimuli). Although some factors mediating nociceptive sensitization are known, inadequacies of current analgesic drugs have prompted a search for additional targets. Here we use a Drosophila model of thermal nociceptive sensitization to show that Hedgehog (Hh) signaling is required for both thermal allodynia and hyperalgesia following ultraviolet irradiation (UV)-induced tissue damage. Sensitization does not appear to result from developmental changes in the differentiation or arborization of nociceptive sensory neurons. Genetic analysis shows that Hh signaling acts in parallel to tumor necrosis factor (TNF) signaling to mediate allodynia and that distinct transient receptor potential (TRP) channels mediate allodynia and hyperalgesia downstream of these pathways. We also demonstrate a role for Hh in analgesic signaling in mammals. Intrathecal or peripheral administration of cyclopamine (CP), a specific inhibitor of Sonic Hedgehog signaling, blocked the development of analgesic tolerance to morphine (MS) or morphine antinociception in standard assays of inflammatory pain in rats and synergistically augmented and sustained morphine analgesia in assays of neuropathic pain. We demonstrate a novel physiological role for Hh signaling, which has not previously been implicated in nociception. Our results also identify new potential therapeutic targets for pain treatment. Copyright © 2011 Elsevier Ltd. All rights reserved.

The association between injustice perception and psychological outcomes in an inpatient spinal cord injury sample: the mediating effects of anger.

PubMed

Trost, Z; Scott, W; Buelow, M T; Nowlin, L; Turan, B; Boals, A; Monden, K R

2017-10-01

Cross-sectional study design involving completion of self-report measures. To investigate the relationship between perceived injustice, post-traumatic stress symptoms and depression in a sample of individuals receiving inpatient rehabilitation care following hospitalization for acute spinal cord injury (SCI), as well as the mediating role of anger variables. Inpatient rehabilitation program in a large urban city in the Southwestern United States. A sample of 53 participants with an average of 204.51 days (s.d.=410.67, median=56) post injury occurrence completed measures of perceived injustice, depression and post-traumatic stress symptoms as well as measures of trait anger, state anger, anger inhibition and anger expression. Perceived injustice was significantly correlated with depression and post-traumatic stress symptoms, and accounted for unique variance in depression and post-traumatic stress symptoms when controlling for demographic and injury-related variables. Anger inhibition was found to mediate the relationship between perceived injustice and depression. Trait anger and anger expression were found to mediate the relationship between perceived injustice and post-traumatic stress symptoms. Consistent with previous research, perceived injustice was associated with greater depression and post-traumatic stress symptoms. The results support previous findings that anger inhibition mediates between perceived injustice and depression, and provides novel findings regarding mediation of post-traumatic stress symptoms. Results provide preliminary evidence for the role of perceived injustice in SCI and potential mechanisms by which it may exert its effects.

NF-kappaB Activity in Macrophages Determines Metastatic Potential of Breast Tumor Cells

DTIC Science & Technology

2011-08-01

Cheng DS, Chodosh LA, Blackwell TS, Yull FE: Activation of nuclear factor kappa B in mammary epithelium promotes milk loss during mammary... microbial products (15, 16). To date, the potential role of macrophages in the fetal lung innate immune response has not been closely examined. Studies...In this model, microbial products initially activate NF-kB in lung macrophages. The release of inflammatory mediators, particularly IL-1b and/or TNF-a

Altered GABAA receptor-mediated synaptic transmission disrupts the firing of gonadotropin-releasing hormone neurons in male mice under conditions that mimic steroid abuse

PubMed Central

Penatti, Carlos A A; Davis, Matthew C; Porter, Donna M; Henderson, Leslie P

2010-01-01

Gonadotropin–releasing hormone (GnRH) neurons are the central regulators of reproduction. GABAergic transmission plays a critical role in pubertal activation of pulsatile GnRH secretion. Self-administration of excessive doses of anabolic androgenic steroids (AAS) disrupts reproductive function and may have critical repercussions for pubertal onset in adolescent users. Here, we demonstrate that chronic treatment of adolescent male mice with the AAS, 17α-methyltestosterone (17αMT), significantly decreased action potential frequency in GnRH neurons, reduced the serum gonadotropin levels, and decreased testes mass. AAS treatment did not induce significant changes in GABAA receptor subunit mRNA levels or alter the amplitude or decay kinetics of GABAA receptor-mediated spontaneous postsynaptic currents (sPSC) or tonic currents in GnRH neurons. However, AAS treatment significantly increased action potential frequency in neighboring medial preoptic area (mPOA) neurons and GABAA receptor-mediated sPSC frequency in GnRH neurons. In addition, physical isolation of the more lateral aspects of the mPOA from the medially-localized GnRH neurons abrogated the AAS-induced increase in GABAA receptor-mediated sPSC frequency and the decrease in action potential firing in the GnRH cells. Our results indicate that AAS act predominantly on steroid-sensitive presynaptic neurons within the mPOA to impart significant increases in GABAA receptor-mediated inhibitory tone onto downstream GnRH neurons resulting in diminished activity of these pivotal mediators of reproductive function. These AAS-induced changes in central GABAergic circuits of the forebrain may significantly contribute to the disruptive actions of these drugs on pubertal maturation and the development of reproductive competence in male steroid abusers. PMID:20463213

Potential of acetylacetone as a mediator for Trametes versicolor laccase in enzymatic transformation of organic pollutants.

PubMed

Yang, Hua; Sun, Hongfei; Zhang, Shujuan; Wu, Bingdang; Pan, Bingcai

2015-07-01

Low-cost and environmentally friendly mediators could facilitate the application of laccase (EC 1.10.3.2) in variant biotechnological processes. Acetylacetone (AA) represents an inexpensive and low toxic small molecular diketone that has been proven as an effective mediator for laccase in free radical polymerization. However, the potential of AA as a mediator for laccase in pollutant detoxification and/or degradation is still unknown. In this work, the roles of AA in laccase-induced polymerization and transformation were investigated. AA was demonstrated to be a highly efficient mediator in the laccase-induced grafting copolymerization of acrylamide and chitosan. The efficacy of AA in the laccase-induced decoloration of malachite green (MG) was compared with that of the widely used 1-hydroxybenzotriazole (HBT). The laccase-AA system had the highest turnover number (TON, 39.1 μmol/U), followed by the laccase-only system (28.5 μmol/U), while the TON of the laccase-HBT system was the lowest (14.9 μmol/U). The pseudo-first-order transformation rate constant (k 1) of MG in the laccase-AA system was up to 0.283 h(-1) under the given conditions, while the k 1 of AA caused by laccase was only 0.008 h(-1). In the five-cycle run, the concentration of AA remained stable. The larger TON of the laccase-AA system and the stability of AA in the cycling runs demonstrate that AA was more recyclable than HBT in the LMS, leading to a prolonged serving life of laccase. These results suggest that AA might be a potential redox mediator for laccase.

Neutrophil-derived cytokines involved in physiological and pathological angiogenesis.

PubMed

Tecchio, Cristina; Cassatella, Marco Antonio

2014-01-01

Increasing data from the literature point to a neutrophil-mediated role via cytokine production in several aspects of mammalian biology, including angiogenesis. In such regard, neutrophils have been shown to synthetize and release a number of molecules able to promote, directly or indirectly, the growth and migration of endothelial cells, in turn inducing the formation of new blood vessels from preexisting ones. Interestingly, neutrophil-derived cytokines can be involved either in physiological or in pathological angiogenesis, depending on either the functioning or dysregulation of sophisticated interplays among different cell types, extracellular matrix and soluble mediators within the microenvironment. Our review resumes the most interesting studies elucidating the role of neutrophil-derived cytokines in human physiological and pathological angiogenesis. When appropriate, supporting observations generated in animal models will be also mentioned. Particular emphasis will be given to VEGF and PK2/Bv8, rather than CXCL8/IL-8 and OSM. We will also discuss the potential role of neutrophil-derived cytokines such as FGF2, Ang1 and IL-17, whose roles in angiogenesis - albeit anticipated - remain to be elucidated. Copyright © 2014 S. Karger AG, Basel.

B Cells and Humoral Immunity in Atherosclerosis

PubMed Central

Tsiantoulas, Dimitrios; Diehl, Cody J.; Witztum, Joseph L.; Binder, Christoph J.

2014-01-01

Insights into the important contribution of inflammation and immune functions in the development and progression of atherosclerosis have greatly improved our understanding of this disease. Although the role of T cells has been extensively studied for decades, only recently has the role of B cells gained more attention. Recent studies have identified differential effects of different B-cell subsets and helped to clarify the still poorly understood mechanisms by which these act. B1 cells have been shown to prevent lesion formation, whereas B2 cells have been suggested to promote it. Natural IgM antibodies, mainly derived from B1 cells, have been shown to mediate atheroprotective effects, but the functional role of other immunoglobulin classes, particularly IgG, still remains elusive. In this review, we will focus on recent insights on the role of B cells and various immunoglobulin classes and how these may mediate their effects in atherosclerotic lesion formation. Moreover, we will highlight potential therapeutic approaches focusing on B-cell depletion that could be used to translate experimental evidence to human disease. PMID:24855199

A dominant mutation in mediator of paramutation2, one of three second-largest subunits of a plant-specific RNA polymerase, disrupts multiple siRNA silencing processes.

PubMed

Sidorenko, Lyudmila; Dorweiler, Jane E; Cigan, A Mark; Arteaga-Vazquez, Mario; Vyas, Meenal; Kermicle, Jerry; Jurcin, Diane; Brzeski, Jan; Cai, Yu; Chandler, Vicki L

2009-11-01

Paramutation involves homologous sequence communication that leads to meiotically heritable transcriptional silencing. We demonstrate that mop2 (mediator of paramutation2), which alters paramutation at multiple loci, encodes a gene similar to Arabidopsis NRPD2/E2, the second-largest subunit of plant-specific RNA polymerases IV and V. In Arabidopsis, Pol-IV and Pol-V play major roles in RNA-mediated silencing and a single second-largest subunit is shared between Pol-IV and Pol-V. Maize encodes three second-largest subunit genes: all three genes potentially encode full length proteins with highly conserved polymerase domains, and each are expressed in multiple overlapping tissues. The isolation of a recessive paramutation mutation in mop2 from a forward genetic screen suggests limited or no functional redundancy of these three genes. Potential alternative Pol-IV/Pol-V-like complexes could provide maize with a greater diversification of RNA-mediated transcriptional silencing machinery relative to Arabidopsis. Mop2-1 disrupts paramutation at multiple loci when heterozygous, whereas previously silenced alleles are only up-regulated when Mop2-1 is homozygous. The dramatic reduction in b1 tandem repeat siRNAs, but no disruption of silencing in Mop2-1 heterozygotes, suggests the major role for tandem repeat siRNAs is not to maintain silencing. Instead, we hypothesize the tandem repeat siRNAs mediate the establishment of the heritable silent state-a process fully disrupted in Mop2-1 heterozygotes. The dominant Mop2-1 mutation, which has a single nucleotide change in a domain highly conserved among all polymerases (E. coli to eukaryotes), disrupts both siRNA biogenesis (Pol-IV-like) and potentially processes downstream (Pol-V-like). These results suggest either the wild-type protein is a subunit in both complexes or the dominant mutant protein disrupts both complexes. Dominant mutations in the same domain in E. coli RNA polymerase suggest a model for Mop2-1 dominance: complexes containing Mop2-1 subunits are non-functional and compete with wild-type complexes.

Association between social support and post-traumatic stress disorder symptoms among Chinese patients with ovarian cancer: A multiple mediation model

PubMed Central

Liu, Chunli; Zhang, Yi; Jiang, Hong; Wu, Hui

2017-01-01

Post-traumatic stress disorder (PTSD) symptoms can develop after person experiences one or more traumatic events. Little research, however, has been done on PTSD symptoms of patients with ovarian cancer. The present study aimed to estimate the prevalence of PTSD symptoms in patients with ovarian cancer in China; the effects of demographic and clinical variables on PTSD symptoms; multiple mediation roles in the association between social support and PTSD symptoms in patients with ovarian cancer in China. We collected demographic and clinical information of patients with ovarian cancer in the first and second hospitals of China Medical University between January 1, 2014 and December 31, 2015. Qualified patients were asked to complete the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C), Duke-UNC Functional Social Support Questionnaire, Herth Hope Index (HHI), and Resilience Scale-14 (RS-14). 201 patients provided responses. We performed hierarchical linear regression to assess the correlation between social support and PTSD symptoms and bootstrapping to test the mediating role of hope and resilience as potential mediators. After controlling demographic and clinical characteristics, social support negatively correlated with PTSD symptoms (β = -0.406, P < 0.01). Social support explained 14.7% of the variance in PTSD symptoms. Hope and resilience explained 17.0% of the variance in PTSD symptoms. The proportion of the hope mediating effect was 43.37% for social support and the proportion of the resilience mediating effect was 10.64% for social support. Hope and resilience partly mediated the correlation between social support and PTSD symptoms despite accounting for different proportions of the mediating effect. Future intervention plans should pay more attention to social support as well as hope and resilience to prevent, relieve and treat PTSD symptoms. PMID:28475593

Association between social support and post-traumatic stress disorder symptoms among Chinese patients with ovarian cancer: A multiple mediation model.

PubMed

Liu, Chunli; Zhang, Yi; Jiang, Hong; Wu, Hui

2017-01-01

Post-traumatic stress disorder (PTSD) symptoms can develop after person experiences one or more traumatic events. Little research, however, has been done on PTSD symptoms of patients with ovarian cancer. The present study aimed to estimate the prevalence of PTSD symptoms in patients with ovarian cancer in China; the effects of demographic and clinical variables on PTSD symptoms; multiple mediation roles in the association between social support and PTSD symptoms in patients with ovarian cancer in China. We collected demographic and clinical information of patients with ovarian cancer in the first and second hospitals of China Medical University between January 1, 2014 and December 31, 2015. Qualified patients were asked to complete the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C), Duke-UNC Functional Social Support Questionnaire, Herth Hope Index (HHI), and Resilience Scale-14 (RS-14). 201 patients provided responses. We performed hierarchical linear regression to assess the correlation between social support and PTSD symptoms and bootstrapping to test the mediating role of hope and resilience as potential mediators. After controlling demographic and clinical characteristics, social support negatively correlated with PTSD symptoms (β = -0.406, P < 0.01). Social support explained 14.7% of the variance in PTSD symptoms. Hope and resilience explained 17.0% of the variance in PTSD symptoms. The proportion of the hope mediating effect was 43.37% for social support and the proportion of the resilience mediating effect was 10.64% for social support. Hope and resilience partly mediated the correlation between social support and PTSD symptoms despite accounting for different proportions of the mediating effect. Future intervention plans should pay more attention to social support as well as hope and resilience to prevent, relieve and treat PTSD symptoms.

A Novel Mechanism of Estrogen Action in Breast Cancer Cells Mediated Through ER-FE65 Complex Formation

DTIC Science & Technology

2013-03-01

Deletion analyses mapped the ERα binding domain to the phosphotyrosine binding domain 2. Ectopic Fe65 increased the transcriptional activity of the...ERα in a PTB2 dependent manner in reporter assays. Fe65 knockdown decreased and its stable expression increased the activity of endogenous ERα in...Furthermore, Fe65 expression decreased the antagonistic activity of tamoxifen, suggesting a potential role for Fe65 in tamoxifen resistance. While a role of

Regulation of the endothelin-1 transmembrane signaling pathway: the potential role of agonist-induced desensitization in the coronary artery of the rapid ventricular pacing-overdrive dog model of heart failure.

PubMed

Calderone, A; Rouleau, J L; de Champlain, J; Bélichard, P; Stewart, D J

1993-08-01

This study examined the potential role of ET-1 and the contribution of protein kinase C (PKC) in the desensitization of the ET-1 transmembrane signaling pathway in the left circumflex coronary artery (CCA) of a dog model of congestive heart failure (CHF). In the CCA of the rapid ventricular pacing-overdrive dog model of CHF, elevated plasma endothelin levels were associated with a decrease in the basal accumulation of inositol phosphates and ET-1 mediated activation of phosphatidylinositol (PI) turnover (P < 0.05). To assess whether elevated plasma ET-1 levels may have contributed to the diminished ET-1 responsiveness in the heart failure dogs, ET-1 generation of inositol phosphates was measured following a one hour pretreatment of normal coronary artery rings with 0.1 nM ET-1. As compared to non-treated rings, ET-1 pretreatment resulted in a 33% decrease of ET-1 (10 nM) production of inositol phosphates. To evaluate the role of PKC in this process, normal coronary rings pretreated for a period of one hour with the phorbol ester, phorbol 12-myristate 13-acetate (PMA, 1 microM), resulted in a similar attenuation (36%) of ET-1 production of inositol phosphates. In the presence of the protein kinase C inhibitor staurosporine, both the agonist and phorbol ester induced decreases in ET-1 mediated PI turnover were reversed. Staurosporine even potentiated (75%) ET-1 induced PI turnover despite ET-1 and PMA pretreatments. These results suggest that agonist-induced desensitization of ET-1 mediated PI turnover can occur and is at least one of the possible mechanisms contributing to the desensitization of the ET-1 transmembrane signaling pathway in the pacing-overdrive model of heart failure in the dog.

Increasing verbal knowledge mediates development of multidimensional emotion representations

PubMed Central

Nook, Erik C.; Sasse, Stephanie F.; Lambert, Hilary K.; McLaughlin, Katie A.; Somerville, Leah H.

2017-01-01

How do people represent their own and others’ emotional experiences? Contemporary emotion theories and growing evidence suggest that the conceptual representation of emotion plays a central role in how people understand the emotions both they and other people feel.1–6 Although decades of research indicate that adults typically represent emotion concepts as multidimensional, with valence (positive—negative) and arousal (activating—deactivating) as two primary dimensions,7–10 little is known about how this bidimensional (or circumplex) representation arises.11 Here we show that emotion representations develop from a monodimensional focus on valence to a bidimensional focus on both valence and arousal from age 6 to age 25. We investigated potential mechanisms underlying this effect and found that increasing verbal knowledge mediated emotion representation development over and above three other potential mediators: (i) fluid reasoning, (ii) the general ability to represent non-emotional stimuli bidimensionally, and (iii) task-related behaviors (e.g., using extreme ends of rating scales). These results suggest that verbal development facilitates the expansion of emotion concept representations (and potentially emotional experiences) from a “positive or negative” dichotomy in childhood to a multidimensional organization in adulthood. PMID:29399639

Marital Processes Linking Gender Role Attitudes and Marital Satisfaction Among Mexican-Origin Couples: Application of an Actor-Partner Interdependence Mediation Model.

PubMed

Helms, Heather M; Supple, Andrew J; Hengstebeck, Natalie D; Wood, Claire A; Rodriguez, Yuliana

2018-01-24

Informed by dyadic approaches and culturally informed, ecological perspectives of marriage, we applied an actor-partner interdependence mediation model (APIMeM) in a sample of 120 Mexican-origin couples to examine (a) the associations linking Mexican immigrant husbands' and wives' gender role attitudes to marital satisfaction directly and indirectly through marital processes (i.e., warmth and negativity) and (b) whether the associations between spouses' gender role attitudes and marital processes were moderated by wives' employment. Although previous research has identified spouses' gender role attitudes as potential predictors of spouses' marital satisfaction, no study has examined these links in a dyadic model that elucidates how gender role attitudes may operate through processes to shape marital satisfaction and conditions under which associations may differ. We found that when spouses reported less sex-typed attitudes, their partners reported feeling more connected to them and more satisfied with the marriage, regardless of whether wives were employed. Our results suggest that marital satisfaction was highest for those Mexican-origin couples in which marital partners were less sex-typed in their attitudes about marital roles to the extent that partners' attitudinal role flexibility promoted spouses' feelings of warmth and connection to their partner. © 2018 Family Process Institute.

The Mediator Complex and Transcription Elongation

PubMed Central

Conaway, Ronald C.; Conaway, Joan Weliky

2013-01-01

Background Mediator is an evolutionarily conserved multisubunit RNA polymerase II (Pol II) coregulatory complex. Although Mediator was initially found to play a critical role in regulation of the initiation of Pol II transcription, recent studies have brought to light an expanded role for Mediator at post-initiation stages of transcription. Scope of review We provide a brief description of the structure of Mediator and its function in the regulation of Pol II transcription initiation, and we summarize recent findings implicating Mediator in the regulation of various stages of Pol II transcription elongation. Major conclusions Emerging evidence is revealing new roles for Mediator in nearly all stages of Pol II transcription, including initiation, promoter escape, elongation, pre-mRNA processing, and termination. General significance Mediator plays a central role in the regulation of gene expression by impacting nearly all stages of mRNA synthesis. PMID:22983086

The role of cGMP signalling in regulating life cycle progression of Plasmodium.

PubMed

Hopp, Christine S; Bowyer, Paul W; Baker, David A

2012-08-01

The 3'-5'-cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is the main mediator of cGMP signalling in the malaria parasite. This article reviews the role of PKG in Plasmodium falciparum during gametogenesis and blood stage schizont rupture, as well as the role of the Plasmodium berghei orthologue in ookinete differentiation and motility, and liver stage schizont development. The current views on potential effector proteins downstream of PKG and the mechanisms that may regulate cyclic nucleotide levels are presented. Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Dispositional Mindfulness and Memory Problems: The Role of Perceived Stress and Sleep Quality

PubMed Central

Brisbon, Nicholas M.; Lachman, Margie E.

2016-01-01

There is a growing body of evidence exploring the beneficial effects of mindfulness on stress, sleep quality, and memory, though the mechanisms involved are less certain. The present study explored the roles of perceived stress and sleep quality as potential mediators between dispositional mindfulness and subjective memory problems. Data were from a Boston area subsample of the Midlife in the United States study (MIDUS-II) assessed in 2004–2006, and again approximately one year later (N=299). As expected, higher dispositional mindfulness was associated with lower perceived stress and better sleep quality. There was no direct association found between mindfulness and subjective memory problems, however, there was a significant indirect effect through perceived stress, although not with sleep quality. The present findings suggest that perceived stress may play a mediating role between dispositional mindfulness and subjective memory problems, in that those with higher mindfulness generally report experiencing less stress than those with lower mindfulness, which may be protective of memory problems in everyday life. PMID:28344682

Taming dendritic cells with TIM-3: Another immunosuppressive strategy by tumors

PubMed Central

Patel, Jaina; Bozeman, Erica N.; Selvaraj, Periasamy

2013-01-01

The identification of TIM-3 expression on tumor associated dendritic cells (TADCs) provides insight into another aspect of tumor-mediated immunosuppression. The role of TIM-3 has been well characterized on tumor-infiltrating T cells, however its role on TADCs was not previously known. The current paper demonstrated that TIM-3 was predominantly expressed by TADCs and its interaction with the nuclear protein HMGB1 suppressed nucleic acid mediated activation of an effective antitumor immune response. The authors were able to show that TIM-3 interaction with HMGB1 prevented the localization of nucleic acids into endosomal vesicles. Furthermore, chemotherapy was found to be more effective in anti-TIM-3 mAb treated mice or mice depleted of all DCs which indicated that significant role played by TADCs inhibiting tumor regression. Taken together, these findings identify TIM-3 as a potential target for inducing antitumor immunity in conjunction with DNA vaccines and/or immunogenic chemotherapy in clinical settings. PMID:23240746

Dispositional Mindfulness and Memory Problems: The Role of Perceived Stress and Sleep Quality.

PubMed

Brisbon, Nicholas M; Lachman, Margie E

2017-04-01

There is a growing body of evidence exploring the beneficial effects of mindfulness on stress, sleep quality, and memory, though the mechanisms involved are less certain. The present study explored the roles of perceived stress and sleep quality as potential mediators between dispositional mindfulness and subjective memory problems. Data were from a Boston area subsample of the Midlife in the United States study (MIDUS-II) assessed in 2004-2006, and again approximately one year later (N=299). As expected, higher dispositional mindfulness was associated with lower perceived stress and better sleep quality. There was no direct association found between mindfulness and subjective memory problems, however, there was a significant indirect effect through perceived stress, although not with sleep quality. The present findings suggest that perceived stress may play a mediating role between dispositional mindfulness and subjective memory problems, in that those with higher mindfulness generally report experiencing less stress than those with lower mindfulness, which may be protective of memory problems in everyday life.

Houttuynia cordata modulates oral innate immune mediators: potential role of herbal plant on oral health.

PubMed

Satthakarn, S; Chung, W O; Promsong, A; Nittayananta, W

2015-05-01

Epithelial cells play an active role in oral innate immunity by producing various immune mediators. Houttuynia cordata Thunb (H. cordata), a herbal plant found in Asia, possesses many activities. However, its impacts on oral innate immunity have never been reported. The aim of this study was to determine the effects of H. cordata extract on the expression of innate immune mediators produced by oral epithelial cells. Primary gingival epithelial cells (GECs) were treated with various concentrations of the extract for 18 h. The gene expression of hBD2, SLPI, cytokines, and chemokines was measured using quantitative real-time RT-PCR. The secreted proteins in the culture supernatants were detected by ELISA or Luminex assay. Cytotoxicity of the extract was assessed using CellTiter-Blue Assay. H. cordata significantly induced the expression of hBD2, SLPI, IL-8, and CCL20 in a dose-dependent manner without cytotoxicity. The secreted hBD2 and SLPI proteins were modulated, and the levels of IL-2, IL-6, IL-8, and IFN-γ were significantly induced by the extract. Our data indicated that H. cordata can modulate oral innate immune mediators. These findings may lead to the development of new topical agents from H. cordata for the prevention and treatment of immune-mediated oral diseases. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dihydroartemisinin induces apoptosis preferentially via a Bim-mediated intrinsic pathway in hepatocarcinoma cells.

PubMed

Qin, Guiqi; Zhao, ChuBiao; Zhang, Lili; Liu, Hongyu; Quan, Yingyao; Chai, Liuying; Wu, Shengnan; Wang, Xiaoping; Chen, Tongsheng

2015-08-01

This report is designed to dissect the detail molecular mechanism by which dihydroartemisinin (DHA), a derivative of artemisinin, induces apoptosis in human hepatocellular carcinoma (HCC) cells. DHA induced a loss of the mitochondrial transmemberane potential (ΔΨm), release of cytochrome c, activation of caspases, and externalization of phosphatidylserine indicative of apoptosis induction. Compared with the modest inhibitory effects of silencing Bax, silencing Bak largely prevented DHA-induced ΔΨm collapse and apoptosis though DHA induced a commensurable activation of Bax and Bak, demonstrating a key role of the Bak-mediated intrinsic apoptosis pathway. DHA did not induce Bid cleavage and translocation from cytoplasm to mitochondria and had little effects on the expressions of Puma and Noxa, but did increase Bim and Bak expressions and decrease Mcl-1 expression. Furthermore, the cytotoxicity of DHA was remarkably reduced by silencing Bim, and modestly but significantly reduced by silencing Puma or Noxa. Silencing Bim or Noxa preferentially reduced DHA-induced Bak activation, while silencing Puma preferentially reduced DHA-induced Bax activation, demonstrating that Bim and to a lesser extent Noxa act as upstream mediators to trigger the Bak-mediated intrinsic apoptosis pathway. In addition, silencing Mcl-1 enhanced DHA-induced Bak activation and apoptosis. Taken together, our data demonstrate a crucial role of Bim in preferentially regulating the Bak/Mcl-1 rheostat to mediate DHA-induced apoptosis in HCC cells.

A Mediational Model Explaining the Connection Between Religiosity and Anti-Homosexual Attitudes in Italy: The Effects of Male Role Endorsement and Homosexual Stereotyping.

PubMed

Piumatti, Giovanni

2017-01-01

This study aimed to better understand the relationship between religiosity and anti-homosexual attitudes in Italy by examining the mediation effects of male role endorsement and homosexual stereotyping. A sample of 5,522 Italian residents (age range = 18-74) was drawn from a cross-sectional national representative survey carried out in 2011. Measures included general religiosity, male role endorsement, homosexual stereotyping, social acceptance of homosexuality, and homosexual rights endorsement. Structural equation modeling was used to test the mediational effects of male role endorsement and homosexual stereotyping on the relationship between general religiosity and attitudes toward lesbians and gay men. Results showed that both male role endorsement and homosexual stereotyping partially mediated the relationship. In a model where religiosity and both mediators positively explained anti-homosexual attitudes, male role endorsement was the strongest mediator. Endorsement of gender role beliefs and homosexual stereotyping may thus exacerbate the connection between religiosity and anti-homosexual attitudes among Italians.

Improving our chemistry: challenges and opportunities in the interdisciplinary study of floral volatiles.

PubMed

Raguso, R A; Thompson, J N; Campbell, D R

2015-07-01

The field of chemical ecology was established, in large part, through collaborative studies between biologists and chemists with common interests in the mechanisms that mediate chemical communication in ecological and evolutionary contexts. Pollination is one highly diverse and important category of such interactions, and there is growing evidence that floral volatiles play important roles in mediating pollinator behaviour and its consequences for plant reproductive ecology and evolution. Here we outline next-generation questions emerging in the study of plants and pollinators, and discuss the potential for strengthening collaboration between biologists and chemists in answering such questions.

MicroRNA-133 mediates cardiac diseases: Mechanisms and clinical implications.

PubMed

Liu, Yi; Liang, Yan; Zhang, Jin-Fang; Fu, Wei-Ming

2017-05-15

MicroRNAs (miRNAs) belong to the family of small non-coding RNAs that mediate gene expression by post-transcriptional regulation. Increasing evidence have demonstrated that miR-133 is enriched in muscle tissues and myogenic cells, and its aberrant expression could induce the occurrence and development of cardiac disorders, such as cardiac hypertrophy, heart failure, etc. In this review, we summarized the regulatory roles of miR-133 in cardiac disorders and the underlying mechanisms, which suggest that miR-133 may be a potential diagnostic and therapeutic tool for cardiac disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Membrane-targeted strategies for modulating APP and Aβ-mediated toxicity

PubMed Central

Price, Katherine A; Crouch, Peter J; Donnelly, Paul S; Masters, Colin L; White, Anthony R; Curtain, Cyril C

2009-01-01

Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by numerous pathological features including the accumulation of neurotoxic amyloid-β (Aβ) peptide. There is currently no effective therapy for AD, but the development of therapeutic strategies that target the cell membrane is gaining increased interest. The amyloid precursor protein (APP) from which Aβ is formed is a membrane-bound protein, and Aβ production and toxicity are both membrane mediated events. This review describes the critical role of cell membranes in AD with particular emphasis on how the composition and structure of the membrane and its specialized regions may influence toxic or benign Aβ/APP pathways in AD. The putative role of copper (Cu) in AD is also discussed, and we highlight how targeting the cell membrane with Cu complexes has therapeutic potential in AD. PMID:19278455

The role of household chaos in understanding relations between early poverty and children's academic achievement

PubMed Central

Mokrova, Irina; Vernon-Feagans, Lynne; Willoughby, Michael; Pan, Yi

2016-01-01

The following prospective longitudinal study used an epidemiological sample (N = 1,236) to consider the potential mediating role of early cumulative household chaos (6–58 months) on associations between early family income poverty (6 months) and children's academic achievement in kindergarten. Two dimensions of household chaos, disorganization and instability, were examined as mediators. Results revealed that, in the presence of household disorganization (but not instability) and relevant covariates, income poverty was no longer directly related to academic achievement. Income poverty was, however, positively related to household disorganization, which was, in turn, associated with lower academic achievement. Study results are consistent with previous research indicating that household chaos conveys some of the adverse longitudinal effects of income poverty on children's outcomes and extend previous findings specifically to academic achievement in early childhood. PMID:27330247

Non-ionotropic signaling by the NMDA receptor: controversy and opportunity.

PubMed

Gray, John A; Zito, Karen; Hell, Johannes W

2016-01-01

Provocative emerging evidence suggests that the N-methyl-d-aspartate (NMDA) receptor can signal in the absence of ion flux through the receptor. This non-ionotropic signaling is thought to be due to agonist-induced conformational changes in the receptor, independently of channel opening. Non-ionotropic NMDA receptor signaling has been proposed to be sufficient to induce synaptic long-term depression (LTD), directly challenging the decades-old model that prolonged low-level calcium influx is required to induce LTD. Here, we briefly review these recent findings, focusing primarily on the potential role of non-ionotropic signaling in NMDA receptor-mediated LTD. Further reports concerning additional roles of non-ionotropic NMDA receptor signaling are also discussed. If validated, this new view of NMDA receptor-mediated signaling will usher in an exciting new era of exploring synapse function and dysfunction.

Non-ionotropic signaling by the NMDA receptor: controversy and opportunity

PubMed Central

Gray, John A.; Zito, Karen; Hell, Johannes W.

2016-01-01

Provocative emerging evidence suggests that the N-methyl-d-aspartate (NMDA) receptor can signal in the absence of ion flux through the receptor. This non-ionotropic signaling is thought to be due to agonist-induced conformational changes in the receptor, independently of channel opening. Non-ionotropic NMDA receptor signaling has been proposed to be sufficient to induce synaptic long-term depression (LTD), directly challenging the decades-old model that prolonged low-level calcium influx is required to induce LTD. Here, we briefly review these recent findings, focusing primarily on the potential role of non-ionotropic signaling in NMDA receptor-mediated LTD. Further reports concerning additional roles of non-ionotropic NMDA receptor signaling are also discussed. If validated, this new view of NMDA receptor-mediated signaling will usher in an exciting new era of exploring synapse function and dysfunction. PMID:27303637

Neurological and Epigenetic Implications of Nutritional Deficiencies on Psychopathology: Conceptualization and Review of Evidence

PubMed Central

Liu, Jianghong; Zhao, Sophie R.; Reyes, Teresa

2015-01-01

In recent years, a role for epigenetic modifications in the pathophysiology of disease has received significant attention. Many studies are now beginning to explore the gene–environment interactions, which may mediate early-life exposure to risk factors, such as nutritional deficiencies and later development of behavioral problems in children and adults. In this paper, we review the current literature on the role of epigenetics in the development of psychopathology, with a specific focus on the potential for epigenetic modifications to link nutrition and brain development. We propose a conceptual framework whereby epigenetic modifications (e.g., DNA methylation) mediate the link between micro- and macro-nutrient deficiency early in life and brain dysfunction (e.g., structural aberration, neurotransmitter perturbation), which has been linked to development of behavior problems later on in life. PMID:26251900

Children's appraisals as mediators of the relationship between domestic violence and child adjustment.

PubMed

Fortin, Andrée; Doucet, Martin; Damant, Dominique

2011-01-01

This study examines the relationships among variables that were likely to mediate the effects of exposure to domestic violence on children's internalizing problems (i.e., children's appraisals of domestic violence and their perceptions of family relationships). The study was conducted with 79 children exposed to domestic violence, including 41 boys and 38 girls, aged between 9 and 12 years old. Indicators used for children's appraisals of violence were attribution of blame and perceived threat. Children's perceptions of family relationships were based on their levels of parentification and the degree of their loyalty conflicts. A path analysis was used to verify the predictive model's pathways and to test the multiple mediator effects. Findings confirm the contribution of mediating variables and also reflect the association between self-blame and children's parentification. The results stress the relevance of evaluating the combined role of different potential mediators to provide a better understanding of the impact of domestic violence on children.

The roles of special proresolving mediators in pain relief.

PubMed

Zhang, Lan-Yu; Jia, Ming-Rui; Sun, Tao

2018-02-08

The resolution of acute inflammation, once thought to be a passive process, is now recognized as an active one. The productions of endogenous special proresolving mediators (SPMs) are involved in this process. SPMs, including lipoxins, resolvins, protectins, and maresins, are endogenous lipid mediators generated from ω-6 arachidonic acid or ω-3 poly-unsaturated fatty acids during the resolution phase of acute inflammation. They have potent anti-inflammatory and proresolving actions in various inflammatory disorders. Due to the potent proresolving and anti-inflammatory effects, SPMs are also used for pain relief. This review focuses on the mechanisms by which SPMs act on their respective G-protein-coupled receptors in immune cells and nerve cells to normalize pain via regulating inflammatory mediators, transient receptor potential ion channels, and central sensitization. SPMs may offer novel therapeutic approaches for preventing and treating pain conditions associated with inflammation.

Public stigma and attitudes toward psychological help-seeking in the United Arab Emirates: The mediational role of self-stigma.

PubMed

Vally, Zahir; Cody, Brettjet L; Albloshi, Maryam A; Alsheraifi, Safeya N M

2018-04-17

Scholars argue that public stigma is predictive of self-stigma, and self-stigma is a primary predictor of attitudes toward seeking psychological help (ATPH). This assertion remains undetermined outside of the United States. This study examines a potential mediational model in which internalized stigma was hypothesized to mediate the relationship between public stigma and ATPH using a sample in the United Arab Emirates. Cross-sectional, correlational design; 114 students completed measures of public stigma, self-stigma, and ATPH. Full mediation occurred. The sample exhibited high levels of both public stigma and self-stigma. Psychology students manifested diminished levels of stigma and more favorable ATPH. Results are discussed in relation to the prevalent cultural and contextual factors. Stigma reduction campaigns in this locale should target internalized stigma and its associated socio-cultural nuances. © 2018 Wiley Periodicals, Inc.

Child Negative Emotionality and Parental Harsh Discipline in Chinese Preschoolers: The Different Mediating Roles of Maternal and Paternal Anxiety

PubMed Central

Xing, Xiaopei; Zhang, Hongli; Shao, Shuhui; Wang, Meifang

2017-01-01

Previous research has suggested that harsh discipline is still prevalent in modern Chinese families and it is necessary to explore the cause and the potential mechanisms of Chinese parental use of harsh discipline. This study examined the mediating effects of parental anxiety in the relations between child negative emotionality and parental harsh discipline in China. Using a sample of 328 Chinese father-mother dyads with their young children, findings revealed that maternal anxiety mediated the relations between child negative emotionality and maternal psychological aggression and corporal punishment, but the mediating effects of paternal anxiety on the relations between child negative emotionality and paternal harsh discipline was not significant. The findings provide an important supplement and extension to previous examinations of the factors associated with Chinese parental use of harsh discipline and its mechanisms. PMID:28326056

Types of prayer and depressive symptoms among cancer patients: the mediating role of rumination and social support.

PubMed

Pérez, John E; Rex Smith, Amy; Norris, Rebecca L; Canenguez, Katia M; Tracey, Elizabeth F; Decristofaro, Susan B

2011-12-01

We examined the association between different types of prayer and depressive symptoms--with rumination and social support as potential mediators--in a sample of predominantly White, Christian, and female ambulatory cancer patients. In a cross-sectional design, 179 adult cancer outpatients completed measures of prayer, rumination, social support, depressive symptoms, and demographic variables. Type and stage of cancer were collected from electronic medical charts. Depressive symptoms were negatively correlated with adoration prayer (r = -.15), reception prayer (r = -.17), thanksgiving prayer (r = -.29), and prayer for the well-being of others (r = -.26). In the path analysis, rumination fully mediated the link between thanksgiving prayer and depressive symptoms (β for indirect effect = -.05), whereas social support partially mediated the link between prayer for others and depressive symptoms (β for indirect effect = -.05). These findings suggest that unique mechanisms may link different prayer types to lower depressive symptoms among cancer patients.

Confidence mediates the sex difference in mental rotation performance.

PubMed

Estes, Zachary; Felker, Sydney

2012-06-01

On tasks that require the mental rotation of 3-dimensional figures, males typically exhibit higher accuracy than females. Using the most common measure of mental rotation (i.e., the Mental Rotations Test), we investigated whether individual variability in confidence mediates this sex difference in mental rotation performance. In each of four experiments, the sex difference was reliably elicited and eliminated by controlling or manipulating participants' confidence. Specifically, confidence predicted performance within and between sexes (Experiment 1), rendering confidence irrelevant to the task reliably eliminated the sex difference in performance (Experiments 2 and 3), and manipulating confidence significantly affected performance (Experiment 4). Thus, confidence mediates the sex difference in mental rotation performance and hence the sex difference appears to be a difference of performance rather than ability. Results are discussed in relation to other potential mediators and mechanisms, such as gender roles, sex stereotypes, spatial experience, rotation strategies, working memory, and spatial attention.

Child Negative Emotionality and Parental Harsh Discipline in Chinese Preschoolers: The Different Mediating Roles of Maternal and Paternal Anxiety.

PubMed

Xing, Xiaopei; Zhang, Hongli; Shao, Shuhui; Wang, Meifang

2017-01-01

Previous research has suggested that harsh discipline is still prevalent in modern Chinese families and it is necessary to explore the cause and the potential mechanisms of Chinese parental use of harsh discipline. This study examined the mediating effects of parental anxiety in the relations between child negative emotionality and parental harsh discipline in China. Using a sample of 328 Chinese father-mother dyads with their young children, findings revealed that maternal anxiety mediated the relations between child negative emotionality and maternal psychological aggression and corporal punishment, but the mediating effects of paternal anxiety on the relations between child negative emotionality and paternal harsh discipline was not significant. The findings provide an important supplement and extension to previous examinations of the factors associated with Chinese parental use of harsh discipline and its mechanisms.

[The perils of risk communication and the role of the mass media].

PubMed

Rossmann, C; Brosius, H-B

2013-01-01

Based on theories and empirical results from communication science, the present paper provides an overview of the role of mass media in risk communication. It is guided by the following questions: How do risk issues find their way into the media and how does the media depict them? How do mass-mediated risk messages affect people's perception of risks, knowledge, attitudes, and behavior? What potential does the media have in disseminating health risk information in campaigns? Hence, the present paper aims to provide a basis for the appropriate use of mass media in health risk communication so as to make use of the potential of mass media without neglecting its limits.

A novel trigger for cholesterol-dependent smooth muscle contraction mediated by the sphingosylphosphorylcholine-Rho-kinase pathway in the rat basilar artery: a mechanistic role for lipid rafts.

PubMed

Shirao, Satoshi; Yoneda, Hiroshi; Shinoyama, Mizuya; Sugimoto, Kazutaka; Koizumi, Hiroyasu; Ishihara, Hideyuki; Oka, Fumiaki; Sadahiro, Hirokazu; Nomura, Sadahiro; Fujii, Masami; Tamechika, Masakatsu; Kagawa, Yoshiteru; Owada, Yuji; Suzuki, Michiyasu

2015-05-01

Hyperlipidemia is a risk factor for abnormal cerebrovascular events. Rafts are cholesterol-enriched membrane microdomains that influence signal transduction. We previously showed that Rho-kinase-mediated Ca(2+) sensitization of vascular smooth muscle (VSM) induced by sphingosylphosphorylcholine (SPC) has a pivotal role in cerebral vasospasm. The goals of the study were to show SPC-Rho-kinase-mediated VSM contraction in vivo and to link this effect to cholesterol and rafts. The SPC-induced VSM contraction measured using a cranial window model was reversed by Y-27632, a Rho-kinase inhibitor, in rats fed a control diet. The extent of SPC-induced contraction correlated with serum total cholesterol. Total cholesterol levels in the internal carotid artery (ICA) were significantly higher in rats fed a cholesterol diet compared with a control diet or a β-cyclodextrin diet, which depletes VSM cholesterol. Western blotting and real-time PCR revealed increases in flotillin-1, a raft marker, and flotillin-1 mRNA in the ICA in rats fed a cholesterol diet, but not in rats fed the β-cyclodextrin diet. Depletion of cholesterol decreased rafts in VSM cells, and prevention of an increase in cholesterol by β-cyclodextrin inhibited SPC-induced contraction in a cranial window model. These results indicate that cholesterol potentiates SPC-Rho-kinase-mediated contractions of importance in cerebral vasospasm and are compatible with a role for rafts in this process.

Language proficiency and metacognition as predictors of spontaneous rehearsal in children.

PubMed

Bebko, James M; McMorris, Carly A; Metcalfe, Alisa; Ricciuti, Christina; Goldstein, Gayle

2014-03-01

Despite decades of research on fundamental memory strategies such as verbal rehearsal, the potential underlying skills associated with the emergence of rehearsal are still not fully understood. Two studies examined the relative roles of language proficiency and metamemory in predicting rehearsal use, as well as the prediction of metamemory performance by language proficiency. In Study 1, 59 children, 5 to 8 years old, were administered a serial recall task, 2 language measures, a nonverbal cognitive measure, and a rapid automatized naming (RAN) task. Language proficiency, RAN, and age were significant individual predictors of rehearsal use. In hierarchical regression analyses, language proficiency mediated almost completely the age → rehearsal use relation. In addition, automatized naming was a strong but partial mediator of the contribution of language proficiency to rehearsal use. In Study 2, 54 children were administered a metamemory test, a language measure, and a serial recall task. Metamemory skills and, again, language proficiency significantly predicted rehearsal use in the task. The predictive strength of metamemory skills was mediated by the children's language proficiency. The mutually supportive roles of automatized naming, language, and metamemory in the emergence of spontaneous cumulative verbal rehearsal are discussed in the context of the resulting model, along with the minimal roles of age and aspects of intelligence.

Interleukin-6 in the injured patient. Marker of injury or mediator of inflammation?

PubMed Central

Biffl, W L; Moore, E E; Moore, F A; Peterson, V M

1996-01-01

OBJECTIVE: The effects of interleukin (IL)-6 in the injured patient are examined in an attempt to clarify the potential pathophysiologic role of IL-6 in the response to injury. SUMMARY BACKGROUND DATA: Interleukin-6 is an integral cytokine mediator of the acute phase response to injury and infection. However, prolonged and excessive elevations of circulating IL-6 levels in patients after trauma, burns, and elective surgery have been associated with complications and mortality. The mechanistic role of IL-6 in mediating these effects is unclear. METHODS: A review of current literature is performed to summarize the origins, mechanisms of action, and biologic effects of IL-6 and to characterize the IL-6 response to injury. RESULTS: Interleukin-6 is a multifunctional cytokine expressed by a variety of cells after a multitude of stimuli, under complex regulatory control mechanisms. The IL-6 response to injury is uniquely consistent and related to the magnitude of the insult. Moreover, the early postinjury IL-6 response correlates with complications as well as mortality. CONCLUSIONS: Interleukin-6 appears to play an active role in the postinjury immune response, making it an attractive therapeutic target in attempts to control hyperinflammatory provoked organ injury. Images Figure 2. PMID:8916880

First evidence of bryophyte diaspores in the plumage of transequatorial migrant birds

PubMed Central

Behling, Emily; Gousse, Hannah; Qian, Emily; Elphick, Chris S.; Lamarre, Jean-François; Bêty, Joël; Liebezeit, Joe; Rozzi, Ricardo; Goffinet, Bernard

2014-01-01

Correlations between transequatorial migratory bird routes and bipolar biogeographic disjunctions in bryophytes suggest that disjunctions between northern and southern high latitude regions may result from bird-mediated dispersal; supporting evidence is, however, exclusively circumstantial. Birds disperse plant units (diaspores) internally via ingestion (endozoochory) or externally by the attachment of diaspores to the body (ectozoochory). Endozoochory is known to be the primary means of bird-mediated dispersal for seeds and invertebrates at local, regional, and continental scales. Data supporting the role of bird-mediated endozoochory or ectozoochory in the long distance dispersal of bryophytes remain sparse, however, despite the large number of bryophytes displaying bipolar disjunctions. To determine if transequatorial migrant shorebirds may play a role in the ectozoochory of bryophyte diaspores, we developed a method for screening feathers of wild birds. We provide the first evidence of microscopic bryophyte diaspores, as well as those from non-bryophyte lineages, embedded in the plumage of long distance transequatorial migrant birds captured in their arctic breeding grounds. The number of diaspores recovered suggests that entire migratory populations may be departing their northern breeding grounds laden with potentially viable plant parts and that they could thereby play significant roles in bipolar range expansions of lineages previously ignored in the migrant bird dispersal literature. PMID:24949241

The Role of Language Skill in Child Psychopathology: Implications for Intervention in the Early Years.

PubMed

Salmon, Karen; O'Kearney, Richard; Reese, Elaine; Fortune, Clare-Ann

2016-12-01

In this narrative review, we suggest that children's language skill should be targeted in clinical interventions for children with emotional and behavioral difficulties in the preschool years. We propose that language skill predicts childhood emotional and behavioral problems and this relationship may be mediated by children's self-regulation and emotion understanding skills. In the first sections, we review recent high-quality longitudinal studies which together demonstrate that that children's early language skill predicts: (1) emotional and behavioral problems, and this relationship is stronger than the reverse pattern; (2) self-regulation skill; this pattern may be stronger than the reverse pattern but moderated by child age. Findings also suggest that self-regulation skill mediates the relation between early language skill and children's emotional and behavioral problems. There is insufficient evidence regarding the mediating role of emotion understanding. In subsequent sections, we review evidence demonstrating that: (1) particular kinds of developmentally targeted parent-child conversations play a vital role in the development of language skill, and (2) some current clinical interventions, directly or indirectly, have a beneficial impact on children's vocabulary and narrative skills, but most approaches are ad hoc. Targeting language via parent-child conversation has the potential to improve the outcomes of current clinical interventions in the preschool years.

The Mediating Roles of Rejection Sensitivity and Proximal Stress in the Association Between Discrimination and Internalizing Symptoms Among Sexual Minority Women.

PubMed

Dyar, Christina; Feinstein, Brian A; Eaton, Nicholas R; London, Bonita

2018-01-01

The negative impact of discrimination on mental health among lesbian, gay, and bisexual populations has been well documented. However, the possible mediating roles of sexual orientation rejection sensitivity and rejection-based proximal stress in the association between discrimination and internalizing symptoms remain unclear. Rejection-based proximal stress is a subset of proximal stressors that are theorized to arise from concerns about and expectations of sexual orientation-based rejection and discrimination. Drawing on minority stress theory, we tested potential mediating effects using indirect effects structural equation modeling in a sample of 300 sexual minority women. Results indicated that the indirect effect of discrimination on internalizing symptoms (a latent variable indicated by depression and anxiety symptoms) through sexual orientation rejection sensitivity and rejection-based proximal stress (a latent variable indicated by preoccupation with stigma, concealment motivation, and difficulty developing a positive sexual identity) was significant. Additionally, the indirect effects of discrimination on rejection-based proximal stress through sexual orientation rejection sensitivity and of sexual orientation rejection sensitivity on internalizing symptoms through rejection-based proximal stress were also significant. These findings indicate that sexual orientation rejection sensitivity plays an important role in contributing to rejection-based proximal stress and internalizing symptoms among sexual minority women.

Dynamics of neuronal circuits in addiction: reward, antireward, and emotional memory.

PubMed

Koob, G F

2009-05-01

Drug addiction is conceptualized as chronic, relapsing compulsive use of drugs with significant dysregulation of brain hedonic systems. Compulsive drug use is accompanied by decreased function of brain substrates for drug positive reinforcement and recruitment of brain substrates mediating the negative reinforcement of motivational withdrawal. The neural substrates for motivational withdrawal ("dark side" of addiction) involve recruitment of elements of the extended amygdala and the brain stress systems, including corticotropin-releasing factor and norepinephrine. These changes, combined with decreased reward function, are hypothesized to persist in the form of an allostatic state that forms a powerful motivational background for relapse. Relapse also involves a key role for the basolateral amygdala in mediating the motivational effects of stimuli previously paired with drug seeking and drug motivational withdrawal. The basolateral amygdala has a key role in mediating emotional memories in general. The hypothesis argued here is that brain stress systems activated by the motivational consequences of drug withdrawal can not only form the basis for negative reinforcement that drives drug seeking, but also potentiate associative mechanisms that perpetuate the emotional state and help drive the allostatic state of addiction.

Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes.

PubMed

Verrier, Eloi R; Colpitts, Che C; Bach, Charlotte; Heydmann, Laura; Zona, Laetitia; Xiao, Fei; Thumann, Christine; Crouchet, Emilie; Gaudin, Raphaël; Sureau, Camille; Cosset, François-Loïc; McKeating, Jane A; Pessaux, Patrick; Hoshida, Yujin; Schuster, Catherine; Zeisel, Mirjam B; Baumert, Thomas F

2016-10-25

Chronic hepatitis B, C, and D virus (HBV, HCV, and HDV) infections are the leading causes of liver disease and cancer worldwide. Recently, the solute carrier and sodium taurocholate co-transporter NTCP has been identified as a receptor for HBV and HDV. Here, we uncover NTCP as a host factor regulating HCV infection. Using gain- and loss-of-function studies, we show that NTCP mediates HCV infection of hepatocytes and is relevant for cell-to-cell transmission. NTCP regulates HCV infection by augmenting the bile-acid-mediated repression of interferon-stimulated genes (ISGs), including IFITM3. In conclusion, our results uncover NTCP as a mediator of innate antiviral immune responses in the liver, and they establish a role for NTCP in the infection process of multiple viruses via distinct mechanisms. Collectively, our findings suggest a role for solute carriers in the regulation of innate antiviral responses, and they have potential implications for virus-host interactions and antiviral therapies. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

IL-17 in psoriasis: Implications for therapy and cardiovascular co-morbidities

PubMed Central

Golden, Jackelyn B.; McCormick, Thomas S.; Ward, Nicole L.

2013-01-01

Psoriasis is a prevalent, chronic inflammatory disease of the skin mediated by cross-talk occurring between epidermal keratinocytes, dermal vascular cells and immunocytes, including activated antigen presenting cells (APCs), monocytes/macrophages, and Th1 and Th17 cells. Increased proliferation of keratinocytes and endothelial cells in conjunction with immune cell infiltration leads to the distinct epidermal and vascular hyperplasia that is characteristic of lesional psoriatic skin. Interaction of activated T cells with monocytes/macrophages occurs via the Th17/IL-23 axis and is crucial for maintaining the chronic inflammation. Recent epidemiological evidence has demonstrated that psoriasis patients have an increased risk of developing and dying of cardiovascular disease. Similar pathology between psoriasis and cardiovascular disease, including involvement of key immunologic cell populations together with release of common inflammatory mediators such as IL-17A suggest a mechanistic link between the two diseases. This review will focus on concepts critical to psoriasis pathogenesis, systemic manifestations of psoriasis, the role of IL-17 in psoriasis and cardiovascular disease and the potential role for IL-17 in mediating cardiovascular co-morbidities in psoriasis patients. PMID:23562549

Complement in Non-Antibody-Mediated Kidney Diseases

PubMed Central

Angeletti, Andrea; Reyes-Bahamonde, Joselyn; Cravedi, Paolo; Campbell, Kirk N.

2017-01-01

The complement system is part of the innate immune response that plays important roles in protecting the host from foreign pathogens. The complement components and relative fragment deposition have long been recognized to be strongly involved also in the pathogenesis of autoantibody-related kidney glomerulopathies, leading to direct glomerular injury and recruitment of infiltrating inflammation pathways. More recently, unregulated complement activation has been shown to be associated with progression of non-antibody-mediated kidney diseases, including focal segmental glomerulosclerosis, C3 glomerular disease, thrombotic microangiopathies, or general fibrosis generation in progressive chronic kidney diseases. Some of the specific mechanisms associated with complement activation in these diseases were recently clarified, showing a dominant role of alternative activation pathway. Over the last decade, a growing number of anticomplement agents have been developed, and some of them are being approved for clinical use or already in use. Therefore, anticomplement therapies represent a realistic choice of therapeutic approaches for complement-related diseases. Herein, we review the complement system activation, regulatory mechanisms, their involvement in non-antibody-mediated glomerular diseases, and the recent advances in complement-targeting agents as potential therapeutic strategies. PMID:28748184

Advances in Discrete Dislocation Dynamics Modeling of Size-Affected Plasticity

NASA Astrophysics Data System (ADS)

El-Awady, Jaafar A.; Fan, Haidong; Hussein, Ahmed M.

In dislocation-mediated plasticity of crystalline materials, discrete dislocation dynamics (DDD) methods have been widely used to predict the plastic deformation in a number of technologically important problems. These simulations have led to significant improvement in the understanding of the different mechanism that controls the mechanical properties of crystalline materials, which can greatly accelerate the future development of materials with superior properties. This chapter provides an overview of different practical applications of both two-dimensional and three-dimensional DDD simulations in the field of size-affected dislocation-mediated plasticity. The chapter is divided into two major tracks. First, DDD simulations focusing on aspects of modeling size-dependent plasticity in single crystals in uniaxial micro-compression/tension, microtorsion, microbending, and nanoindentation are discussed. Special attention is directed towards the role of cross-slip and dislocation nucleation on the overall response. Second, DDD simulations focusing on the role of interfaces, including grain and twin boundaries, on dislocation-mediated plasticity are discussed. Finally, a number of challenges that are withholding DDD simulations from reaching their full potential are discussed.

A serial mediation model of message framing on intentions to receive the human papillomavirus (HPV) vaccine: revisiting the role of threat and efficacy perceptions.

PubMed

Krieger, Janice L; Sarge, Melanie A

2013-01-01

Previous research has yielded mixed findings regarding the potential for message framing to influence HPV vaccine-related intentions. Drawing on the Extended Parallel Process Model (EPPM), the current study focuses on the role of threat and efficacy as serial mediators linking message framing and HPV vaccine-related intentions. College-age females and their parents participated in a between-subjects, posttest only experiment to investigate whether behavioral intentions to talk to a doctor about the HPV vaccine differ as a function of framing messages in terms of disease prevention. For young women, framing messages as preventing genital warts (as compared to cancer prevention) significantly increased perceptions of self-efficacy, which enhanced response efficacy perceptions that, in turn, increased intentions to talk to a doctor about the HPV vaccine. There were no effects of message framing among parents. However, response efficacy was a significant mediator of self-efficacy and behavioral intentions for both the college-age females and their parents. The results of this study suggest new approaches for considering the relationship among EPPM constructs.

Predicting depressive symptoms among the mothers of children with leukaemia: a caregiver stress model perspective.

PubMed

Demirtepe-Saygılı, Dilek; Bozo, Ozlem

2011-05-01

The aim of this study was to find out the predictors of depressive symptoms of mothers of children with leukaemia. The potential predictors were chosen in the light of the caregiver stress model [Pearlin, Mullan, Semple, and Skaff, 1990. Caregiving and the stress process: An overview of concepts and their measures. The Gerontologist, 30(5), 583-594.], which examines the caregiver stress as composed of many factors such as the background variables, primary and secondary stressors, mediators and psychological health outcomes. This study included the caregiving tasks, basic needs of the caregivers and role strain as the stressors; coping strategies and perceived social support as mediators and depressive symptoms as the outcome variable. The participants of this study were 90 mothers of children with leukaemia. The results revealed that the satisfaction level of the basic needs and role strain were the predictors of the depressive symptoms. While emotion-focussed coping and perceived social support mediated the stressors and the depressive symptoms relationship, problem-focussed coping did not. The possible explanations of the results were explored and the implications were discussed.

The Mediating Roles of Upward Social Comparison and Self-esteem and the Moderating Role of Social Comparison Orientation in the Association between Social Networking Site Usage and Subjective Well-Being.

PubMed

Wang, Jin-Liang; Wang, Hai-Zhen; Gaskin, James; Hawk, Skyler

2017-01-01

The increased pervasiveness of social media use has raised questions about potential effects on users' subjective well-being, with studies reaching contrasting conclusions. To reconcile these discrepancies and shed new light on this phenomenon, the current study examined: (1) whether upward social comparison and self-esteem mediate the association between social networking site (SNS) usage and users' subjective well-being, and (2) whether the association between SNS usage and upward social comparison is moderated by users' social comparison orientation. Data from 696 participants were collected. Structural equation modeling revealed that upward social comparison and self-esteem mediated the relationship between SNS usage and users' subjective well-being. We found that social comparison orientation moderated the association between passive SNS usage and users' upward social comparison. Specifically, social comparison orientation strengthened the association between passive SNS usage and upward social comparison. The results might suggest a process through which passive SNS usage is related to subjective well-being, and identify a context under which these associations may differ.

The Mediating Roles of Upward Social Comparison and Self-esteem and the Moderating Role of Social Comparison Orientation in the Association between Social Networking Site Usage and Subjective Well-Being

PubMed Central

Wang, Jin-Liang; Wang, Hai-Zhen; Gaskin, James; Hawk, Skyler

2017-01-01

The increased pervasiveness of social media use has raised questions about potential effects on users’ subjective well-being, with studies reaching contrasting conclusions. To reconcile these discrepancies and shed new light on this phenomenon, the current study examined: (1) whether upward social comparison and self-esteem mediate the association between social networking site (SNS) usage and users’ subjective well-being, and (2) whether the association between SNS usage and upward social comparison is moderated by users’ social comparison orientation. Data from 696 participants were collected. Structural equation modeling revealed that upward social comparison and self-esteem mediated the relationship between SNS usage and users’ subjective well-being. We found that social comparison orientation moderated the association between passive SNS usage and users’ upward social comparison. Specifically, social comparison orientation strengthened the association between passive SNS usage and upward social comparison. The results might suggest a process through which passive SNS usage is related to subjective well-being, and identify a context under which these associations may differ. PMID:28553256

Regulation of necrotic cell death p53, PARP1 and Cyclophilin D -overlapping pathways of regulated necrosis?

PubMed Central

Ying, Yuan; Padanilam, Babu J.

2017-01-01

In contrast to apoptosis and autophagy, necrotic cell death was considered to be a random, passive cell death without definable mediators. However, this dogma has been challenged by recent developments suggesting that necrotic cell death can also be a regulated process. Regulated necrosis includes multiple cell death modalities such as necroptosis, parthanatos, ferroptosis, pyroptosis, and mitochondrial permeability transition pore (MPTP)-mediated necrosis. Several distinctive executive molecules, particularly residing on the mitochondrial inner and outer membrane, amalgamating to form the MPTP have been defined. The c-subunit of the F1F0ATP synthase on the inner membrane and Bax/Bak on the outer membrane are considered to be the long sought components that form the MPTP. Opening of the MPTP results in loss of mitochondrial inner membrane potential, disruption of ATP production, increased ROS production, organelle swelling, mitochondrial dysfunction and consequent necrosis. Cyclophilin D, along with adenine nucleotide translocator (ANT) and the phosphate carrier (PiC) are considered to be important regulators involved in the opening of MPTP. Increased production of ROS can further trigger other necrotic pathways mediated through molecules such as PARP1, leading to irreversible cell damage. This review examines the roles of PARP1 and cyclophilin D in necrotic cell death. The hierarchical role of p53 in regulation and integration of key components of signaling pathway to elicit MPTP-mediated necrosis and ferroptosis is explored. In the context of recent insights, the indistinct role of necroptosis signaling in tubular necrosis after ischemic kidney injury is scrutinized. We conclude by discussing the participation of p53, PARP1 and cyclophilin D and their overlapping pathways to elicit MPTP-mediated necrosis and ferroptosis in acute kidney injury. PMID:27048819

Regulation of necrotic cell death: p53, PARP1 and cyclophilin D-overlapping pathways of regulated necrosis?

PubMed

Ying, Yuan; Padanilam, Babu J

2016-06-01

In contrast to apoptosis and autophagy, necrotic cell death was considered to be a random, passive cell death without definable mediators. However, this dogma has been challenged by recent developments suggesting that necrotic cell death can also be a regulated process. Regulated necrosis includes multiple cell death modalities such as necroptosis, parthanatos, ferroptosis, pyroptosis, and mitochondrial permeability transition pore (MPTP)-mediated necrosis. Several distinctive executive molecules, particularly residing on the mitochondrial inner and outer membrane, amalgamating to form the MPTP have been defined. The c-subunit of the F1F0ATP synthase on the inner membrane and Bax/Bak on the outer membrane are considered to be the long sought components that form the MPTP. Opening of the MPTP results in loss of mitochondrial inner membrane potential, disruption of ATP production, increased ROS production, organelle swelling, mitochondrial dysfunction and consequent necrosis. Cyclophilin D, along with adenine nucleotide translocator and the phosphate carrier are considered to be important regulators involved in the opening of MPTP. Increased production of ROS can further trigger other necrotic pathways mediated through molecules such as PARP1, leading to irreversible cell damage. This review examines the roles of PARP1 and cyclophilin D in necrotic cell death. The hierarchical role of p53 in regulation and integration of key components of signaling pathway to elicit MPTP-mediated necrosis and ferroptosis is explored. In the context of recent insights, the indistinct role of necroptosis signaling in tubular necrosis after ischemic kidney injury is scrutinized. We conclude by discussing the participation of p53, PARP1 and cyclophilin D and their overlapping pathways to elicit MPTP-mediated necrosis and ferroptosis in acute kidney injury.

Negative life events and school adjustment among Chinese nursing students: The mediating role of psychological capital.

PubMed

Liu, Chunqin; Zhao, Yuanyuan; Tian, Xiaohong; Zou, Guiyuan; Li, Ping

2015-06-01

Adjustment difficulties of college students are common and their school adjustment has gained wide concern in recent years. Negative life events and psychological capital (PsyCap) have been associated with school adjustment. However, the potential impact of negative life events on PsyCap, and whether PsyCap mediates the relationship between negative life events and school adjustment among nursing students have not been studied. To investigate the relationship among negative life events, PsyCap, and school adjustment among five-year vocational high school nursing students in China and the mediating role of PsyCap between negative life events and school adjustment. A cross-sectional survey design was conducted. 643 five-year vocational high school nursing students were recruited from three public high vocational colleges in Shandong of China. Adolescent Self-Rating Life Event Checklist (ASLEC), the Psychological Capital Questionnaire for Adolescent Students scale (PCQAS), and the Chinese College Student Adjustment Scale (CCSAS) were used in this study. Hierarchical linear regression analyses were performed to explore the mediating role of PsyCap. Negative life events were negatively associated with the dimensions of school adjustment (interpersonal relationship adaptation, learning adaptation, campus life adaptation, career adaptation, emotional adaptation, self-adaptation, and degree of satisfaction). PsyCap was positively associated with the dimensions of school adjustment and negatively associated with negative life events. PsyCap partially mediated the relationship between negative life events and school adjustment. Negative life events may increase the risk of school maladjustment in individuals with low PsyCap. Interventions designed to increase nursing students' PsyCap might buffer the stress of adverse life events, and thereby, enhance students' positive adjustment to school. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cigarette smoke exposure inhibits contact hypersensitivity via the generation of platelet activating factor agonists

PubMed Central

Sahu, Ravi P.; Petrache, Irina; Van Demark, Mary J; Rashid, Badri M.; Ocana, Jesus A.; Tang, Yuxuan; Yi, Qiaofang; Turner, Matthew J.; Konger, Raymond L.; Travers, Jeffrey B.

2013-01-01

Previous studies have established that pro-oxidative stressors suppress host immunity due to their ability to generate oxidized lipids with PAF-receptor (PAF-R) agonist activity. Although exposure to the pro-oxidative stressor cigarette smoke (CS) is known to exert immunomodulatory effects, little is known regarding the role of platelet-activating factor (PAF) in these events. The current studies sought to determine the role of PAF-R signaling in CS-mediated immunomodulatory effects. We demonstrate that CS exposure induces the generation of a transient PAF-R agonistic activity in the blood of mice. CS exposure inhibits contact hypersensitivity in a PAF-R-dependent manner as PAF-R-deficient mice were resistant to these effects. Blocking PAF-R agonist production either by systemic antioxidants or treatment with serum PAF-acetyl hydrolase enzyme blocked both the CS-mediated generation of PAF-R-agonists and PAF-R dependent inhibition of CHS reactions, indicating a role for oxidized glycerophosphocholines with PAF-R agonistic activity in this process. In addition, cyclooxygenase-2 (COX-2) inhibition did not block PAF-R agonist production but prevented CS-induced inhibition of CHS. This suggests that COX-2 acts downstream of the PAF-R in mediating CS-induced systemic immunosuppression. Moreover, CS-exposure induced a significant increase in the expression of the regulatory T cell reporter gene in FoxP3EGFP mice but not in FoxP3EGFP mice on a PAF-R-deficient background. Finally, Treg depletion via anti-CD25 antibodies blocked CS-mediated inhibition of CHS, indicating the potential involvement of Tregs in CS-mediated systemic immunosuppression. These studies provide the first evidence that the pro-oxidative stressor CS can modulate cutaneous immunity via the generation of PAF-R agonists produced through lipid oxidation. PMID:23355733

Expression of membrane progesterone receptors (mPRs) in rat peripheral glial cell membranes and their potential role in the modulation of cell migration and protein expression.

PubMed

Castelnovo, Luca F; Magnaghi, Valerio; Thomas, Peter

2017-09-28

The role played by progestogens in modulating Schwann cell pathophysiology is well established. Progestogens exert their effects in these cells through both classical genomic and non-genomic mechanisms, the latter mediated by the GABA-A receptor. However, there is evidence that other receptors may be involved. Membrane progesterone receptors (mPRs) are novel 7-transmembrane receptors coupled to G proteins that have been characterized in different tissues and cells, including the central nervous system (CNS). The mPRs were shown to mediate some of progestogens' neuroprotective effects in the CNS, and to be upregulated in glial cells after traumatic brain injury. Based on this evidence, this paper investigated the possible involvement of mPRs in mediating progestogen actions in S42 Schwann cells. All five mPR isoforms and progesterone receptor membrane component 1 (PGRMC1) were detected in Schwann cells, and were present on the cell membrane. Progesterone and the mPR-specific agonist, Org-OD-02-0 (02) bound to these membranes, indicating the presence of functional mPRs. The mPR agonist 02 rapidly increased cell migration in an in vitro assay, suggesting a putative role of mPRs in the nerve regeneration process. Treatment with pertussis toxin and 8-Br-cAMP blocked 02-induced cell migration, suggesting this progestogen action is mediated by activation of an inhibitory G protein, leading to a decrease in intracellular cAMP levels. In contrast, long-term mPR activation led to increased expression levels of myelin associated glycoprotein (MAG). Taken together, these findings show that mPRs are present and active in Schwann cells and have a role in modulating their physiological processes. Copyright © 2017 Elsevier Inc. All rights reserved.

JNK signaling mediates EPHA2-dependent tumor cell proliferation, motility, and cancer stem cell-like properties in non-small cell lung cancer

PubMed Central

Song, Wenqiang; Ma, Yufang; Wang, Jialiang; Brantley-Sieders, Dana; Chen, Jin

2014-01-01

Recent genome-wide analyses in human lung cancer revealed that EPHA2 receptor tyrosine kinase is overexpressed in non-small cell lung cancer (NSCLC), and high levels of EPHA2 correlate with poor clinical outcome. However, the mechanistic basis for EPHA2-mediated tumor promotion in lung cancer remains poorly understood. Here we show that the JNK/c-JUN signaling mediates EPHA2-dependent tumor cell proliferation and motility. A screen of phospho-kinase arrays revealed a decrease in phospho-c-JUN levels in EPHA2 knockdown cells. Knockdown of EPHA2 inhibited p-JNK and p-c-JUN levels in approximately 50% of NSCLC lines tested. Treatment of parental cells with SP600125, a JNK inhibitor, recapitulated defects in EPHA2-deficient tumor cells; whereas constitutively activated JNK mutants were sufficient to rescue phenotypes. Knockdown of EPHA2 also inhibited tumor formation and progression in xenograft animal models in vivo. Furthermore, we investigated the role of EPHA2 in cancer stem-like cells. RNAi-mediated depletion of EPHA2 in multiple NSCLC lines decreased the ALDH positive cancer stem-like population and tumor spheroid formation in suspension. Depletion of EPHA2 in sorted ALDH positive populations markedly inhibited tumorigenicity in nude mice. Furthermore, analysis of a human lung cancer tissue microarray revealed a significant, positive association between EPHA2 and ALDH expression, indicating an important role for EPHA2 in human lung cancer stem-like cells. Collectively, these studies revealed a critical role of JNK signaling in EPHA2-dependent lung cancer cell proliferation and motility and a role for EPHA2 in cancer stem-like cell function, providing evidence for EPHA2 as a potential therapeutic target in NSCLC. PMID:24607842

The effect of albumin on podocytes: The role of the fatty acid moiety and the potential role of CD36 scavenger receptor

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

Pawluczyk, I.Z.A., E-mail: izap1@le.ac.uk; John Walls Renal Unit, Leicester General Hospital Leicester; Pervez, A.

Evidence is emerging that podocytes are able to endocytose proteins such as albumin using kinetics consistent with a receptor-mediated process. To date the role of the fatty acid moiety on albumin uptake kinetics has not been delineated and the receptor responsible for uptake is yet to be identified. Albumin uptake studies were carried out on cultured human podocytes exposed to FITC-labelled human serum albumin either carrying fatty acids (HSA{sub +FA}) or depleted of them (HSA{sub −FA}). Receptor-mediated endocytosis of FITC-HSA{sub +FA} over 60 min was 5 times greater than that of FITC-HSA{sub −FA}. 24 h exposure of podocytes to albuminmore » up-regulated nephrin expression and induced the activation of caspase-3. These effects were more pronounced in response to HSA{sub −FA.} Individually, anti-CD36 antibodies had no effect upon endocytosis of FITC-HSA. However, a cocktail of 2 antibodies reduced uptake by nearly 50%. Albumin endocytosis was enhanced in the presence of the CD36 specific inhibitor sulfo-N-succinimidyl oleate (SSO) while knock-down of CD36 using CD36siRNA had no effect on uptake. These data suggest that receptor-mediated endocytosis of albumin by podocytes is regulated by the fatty acid moiety, although, some of the detrimental effects are induced independently of it. CD36 does not play a direct role in the uptake of albumin. - Highlights: • The fatty acid moiety is essential for receptor mediated endocytosis of albumin. • Fatty acid depleted albumin is more pathogenic to podocytes. • CD36 is not directly involved in albumin uptake by podocytes.« less

Confounding and Statistical Significance of Indirect Effects: Childhood Adversity, Education, Smoking, and Anxious and Depressive Symptomatology.

PubMed

Sheikh, Mashhood Ahmed

2017-01-01

The life course perspective, the risky families model, and stress-and-coping models provide the rationale for assessing the role of smoking as a mediator in the association between childhood adversity and anxious and depressive symptomatology (ADS) in adulthood. However, no previous study has assessed the independent mediating role of smoking in the association between childhood adversity and ADS in adulthood. Moreover, the importance of mediator-response confounding variables has rarely been demonstrated empirically in social and psychiatric epidemiology. The aim of this paper was to (i) assess the mediating role of smoking in adulthood in the association between childhood adversity and ADS in adulthood, and (ii) assess the change in estimates due to different mediator-response confounding factors (education, alcohol intake, and social support). The present analysis used data collected from 1994 to 2008 within the framework of the Tromsø Study ( N = 4,530), a representative prospective cohort study of men and women. Seven childhood adversities (low mother's education, low father's education, low financial conditions, exposure to passive smoke, psychological abuse, physical abuse, and substance abuse distress) were used to create a childhood adversity score. Smoking status was measured at a mean age of 54.7 years (Tromsø IV), and ADS in adulthood was measured at a mean age of 61.7 years (Tromsø V). Mediation analysis was used to assess the indirect effect and the proportion of mediated effect (%) of childhood adversity on ADS in adulthood via smoking in adulthood. The test-retest reliability of smoking was good (Kappa: 0.67, 95% CI: 0.63; 0.71) in this sample. Childhood adversity was associated with a 10% increased risk of smoking in adulthood (Relative risk: 1.10, 95% CI: 1.03; 1.18), and both childhood adversity and smoking in adulthood were associated with greater levels of ADS in adulthood ( p < 0.001). Smoking in adulthood did not significantly mediate the association between childhood adversity and ADS in adulthood. However, when education was excluded as a mediator-response confounding variable, the indirect effect of childhood adversity on ADS in adulthood was statistically significant ( p < 0.05). This study shows that a careful inclusion of potential confounding variables is important when assessing mediation.

Confounding and Statistical Significance of Indirect Effects: Childhood Adversity, Education, Smoking, and Anxious and Depressive Symptomatology

PubMed Central

Sheikh, Mashhood Ahmed

2017-01-01

The life course perspective, the risky families model, and stress-and-coping models provide the rationale for assessing the role of smoking as a mediator in the association between childhood adversity and anxious and depressive symptomatology (ADS) in adulthood. However, no previous study has assessed the independent mediating role of smoking in the association between childhood adversity and ADS in adulthood. Moreover, the importance of mediator-response confounding variables has rarely been demonstrated empirically in social and psychiatric epidemiology. The aim of this paper was to (i) assess the mediating role of smoking in adulthood in the association between childhood adversity and ADS in adulthood, and (ii) assess the change in estimates due to different mediator-response confounding factors (education, alcohol intake, and social support). The present analysis used data collected from 1994 to 2008 within the framework of the Tromsø Study (N = 4,530), a representative prospective cohort study of men and women. Seven childhood adversities (low mother's education, low father's education, low financial conditions, exposure to passive smoke, psychological abuse, physical abuse, and substance abuse distress) were used to create a childhood adversity score. Smoking status was measured at a mean age of 54.7 years (Tromsø IV), and ADS in adulthood was measured at a mean age of 61.7 years (Tromsø V). Mediation analysis was used to assess the indirect effect and the proportion of mediated effect (%) of childhood adversity on ADS in adulthood via smoking in adulthood. The test-retest reliability of smoking was good (Kappa: 0.67, 95% CI: 0.63; 0.71) in this sample. Childhood adversity was associated with a 10% increased risk of smoking in adulthood (Relative risk: 1.10, 95% CI: 1.03; 1.18), and both childhood adversity and smoking in adulthood were associated with greater levels of ADS in adulthood (p < 0.001). Smoking in adulthood did not significantly mediate the association between childhood adversity and ADS in adulthood. However, when education was excluded as a mediator-response confounding variable, the indirect effect of childhood adversity on ADS in adulthood was statistically significant (p < 0.05). This study shows that a careful inclusion of potential confounding variables is important when assessing mediation. PMID:28824498

Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel.

PubMed

Sarmiento, Daniela; Montorfano, Ignacio; Cerda, Oscar; Cáceres, Mónica; Becerra, Alvaro; Cabello-Verrugio, Claudio; Elorza, Alvaro A; Riedel, Claudia; Tapia, Pablo; Velásquez, Luis A; Varela, Diego; Simon, Felipe

2015-03-01

A hallmark of severe inflammation is reactive oxygen species (ROS) overproduction induced by increased inflammatory mediators secretion. During systemic inflammation, inflammation mediators circulating in the bloodstream interact with endothelial cells (ECs) raising intracellular oxidative stress at the endothelial monolayer. Oxidative stress mediates several pathological functions, including an exacerbated EC migration. Because cell migration critically depends on calcium channel-mediated Ca(2+) influx, the molecular identification of the calcium channel involved in oxidative stress-modulated EC migration has been the subject of intense investigation. The transient receptor potential melastatin 4 (TRPM4) protein is a ROS-modulated non-selective cationic channel that performs several cell functions, including regulating intracellular Ca(2+) overload and Ca(2+) oscillation. This channel is expressed in multiple tissues, including ECs, and contributes to the migration of certain immune cells. However, whether the TRPM4 ion channel participates in oxidative stress-mediated EC migration is not known. Herein, we investigate whether oxidative stress initiates or enhances EC migration and study the role played by the ROS-modulated TRPM4 ion channel in oxidative stress-mediated EC migration. We demonstrate that oxidative stress enhances, but does not initiate, EC migration in a dose-dependent manner. Notably, we demonstrate that the TRPM4 ion channel is critical in promoting H2O2-enhanced EC migration. These results show that TRPM4 is a novel pharmacological target for the possible treatment of severe inflammation and other oxidative stress-mediated inflammatory diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Shyness and Vocabulary: The Roles of Executive Functioning and Home Environmental Stimulation

ERIC Educational Resources Information Center

Blankson, A. Nayena; O'Brien, Marion; Leerkes, Esther M.; Marcovitch, Stuart; Calkins, Susan D.

2011-01-01

Although shyness has often been found to be negatively related to vocabulary, few studies have examined the processes that produce or modify this relation. The present study examined executive functioning skills and home environmental stimulation as potential mediating and moderating mechanisms. A sample of 3 1/2-year-old children (N = 254) was…

Cognitive Biases and the Link between Shyness and Social Anxiety in Early Adolescence

ERIC Educational Resources Information Center

Weeks, Murray; Ooi, Laura L.; Coplan, Robert J.

2016-01-01

Shy children display wariness in unfamiliar social situations and often experience feelings of social anxiety. This study explored the potential mediating role of cognitive biases in the link between shyness and social anxiety in early adolescence. In particular, we focused on judgments of the probability and cost of negative social situations…

Maturation, Peer Context, and Indigenous Girls' Early-Onset Substance Use

ERIC Educational Resources Information Center

Walls, Melissa L.; Whitbeck, Les B.

2011-01-01

This article examines a biosocial model of the impact of puberty on indigenous girls' early-onset substance use by considering the potential mediating role of peer context (i.e., mixed-sex peer groups and substance use prototypes) on the puberty and substance use relationship. Data include responses from 360 girls of a common indigenous cultural…

Unresolved Attachment Status and Trauma-Related Symptomatology in Maltreated Adolescents: An Examination of Cognitive Mediators

ERIC Educational Resources Information Center

Joubert, David; Webster, Linda; Hackett, Rachelle Kisst

2012-01-01

Attachment Theory has received increasing interest as a framework allowing for a more refined understanding of the potential consequences of early relational trauma on psychological and social adjustment. Research has provided support for the role of disorganized attachment, both as a sequela of traumatic experiences and as a risk factor for…

Maternal Experiences of Childhood Abuse and Intimate Partner Violence: Psychopathology and Functional Impairment in Clinical Children and Adolescents

ERIC Educational Resources Information Center

Miranda, Jenniffer K.; de la Osa, Nuria; Granero, Roser; Ezpeleta, Lourdes

2011-01-01

Objectives: The current study examined the independent effects of mothers' childhood abuse (CA) and intimate partner violence (IPV) on psychopathology and functional impairment in children; and the potential moderating and mediating role of individual and family factors in these relationships. Additionally, this study explored the potential…

Spatial Ability Mediates the Gender Difference in Middle School Students' Science Performance

ERIC Educational Resources Information Center

Ganley, Colleen M.; Vasilyeva, Marina; Dulaney, Alana

2014-01-01

Prior research has demonstrated a male advantage in spatial skills and science achievement. The present research integrated these findings by testing the potential role of spatial skills in gender differences in the science performance of eighth-grade students (13-15 years old). In "Study 1" (N = 113), the findings showed that mental…

The Role of Anxiety and Working Memory in Gender Differences in Mathematics

ERIC Educational Resources Information Center

Ganley, Colleen M.; Vasilyeva, Marina

2014-01-01

This research examined a potential mechanism underlying gender differences in math performance by testing a mediation model in which women's higher anxiety taxes their working memory resources, leading to underperformance on a mathematics test. Participants for the 2 studies were college students (N = 87, N = 118) who completed an anxiety measure,…

Examining the Link between Infant Attachment and Child Conduct Problems in Grade 1

ERIC Educational Resources Information Center

Vando, Jessica; Rhule-Louie, Dana M.; McMahon, Robert J.; Spieker, Susan J.

2008-01-01

We examined the extent to which infant attachment status is directly related to child conduct problems 6 years later, and assessed the potential mediating roles of hostile parenting and maternal depression. The sample included 84 adolescent mothers and their children (45 girls, 39 boys). Infant attachment status was assessed using the Strange…

Effects of Inbound Marketing Communications on HEIs' Brand Equity: The Mediating Role of the Student's Decision-Making Process. An Exploratory Research

ERIC Educational Resources Information Center

Royo-Vela, Marcelo; Hünermund, Ute

2016-01-01

A context of increased competition between higher education institutions (HEIs) for attracting potential national and international students has led universities to implement marketing communication strategies. Those strategies which are used to some extent include, among others, interactive inbound marketing. The purpose of the present…

Satellite Cell Functional Alterations Following Cutaneous Burn in rats Include an Increase in Their Osteogenic Potential

DTIC Science & Technology

2013-10-07

response to local injury [3]. They have also been recognized as having a role in diseases, including cachexia and sarcopenia, where muscle mass may be...1961;9:493. [4] Dasarathy S. Consilience in sarcopenia of cirrhosis. J Cachexia Sarcopenia Muscle 2012;3:225. [5] Glass DJ. Signaling pathways that mediate

Body Image as a Mediator of Non-Suicidal Self-Injury in Adolescents

ERIC Educational Resources Information Center

Muehlenkamp, Jennifer J.; Brausch, Amy M.

2012-01-01

Attitudes towards the body have been largely overlooked as a potential risk factor for adolescent non-suicidal self-injury (NSSI) despite theorizing that a negative body image may play a critical role in the development of this behavior. The current study used structural equation modeling to evaluate the fit of a theoretical model specifying body…

Survival, dispersal, and potential soil-mediated suppression of Phytophthora ramorum in a California redwood-tanoak forest

Treesearch

E. J. Fichtner; S. C. Lynch; D. M. Rizzo

2009-01-01

Because the role of soil inoculum of Phytophthora ramorum in the sudden oak death disease cycle is not well understood, this work addresses survival, chlamydospore production, pathogen suppression, and splash dispersal of the pathogen in infested forest soils. Colonized rhododendron and bay laurel leaf disks were placed in mesh sachets before...

Drawing, Visualisation and Young Children's Exploration of "Big Ideas"

ERIC Educational Resources Information Center

Brooks, Margaret

2009-01-01

It is in the visualisation of ideas, and the expression or representation of our ideas, that we can bring something more clearly into consciousness. A drawing might be seen as an externalisation of a concept or idea. Drawing has the potential to play a mediating role in the visualisation of ideas and concepts in relation to young children…

Relation of Adolescent Mothers' History of Antisocial Behavior to Child Conduct Problems and Social Competence

ERIC Educational Resources Information Center

Rhule, Dana M.; McMahon, Robert J.; Spieker, Susan J.

2004-01-01

We examined the extent to which maternal antisocial behavior (ASB) is directly related to child conduct problems and social competence and assessed the potential mediating role of negative parenting. The sample included 93 adolescent mothers and their children (44 boys, 49 girls). Mothers retrospectively reported about their ASB since the child's…

Cystic Fibrosis Transmembrane Conductance Regulator Regulates Epithelial Cell Response to Aspergillus and Resultant Pulmonary Inflammation

PubMed Central

Chaudhary, Neelkamal; Datta, Kausik; Askin, Frederic B.; Staab, Janet F.

2012-01-01

Rationale: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) alter epithelial cell (EC) interactions with multiple microbes, such that dysregulated inflammation and injury occur with airway colonization in people with cystic fibrosis (CF). Aspergillus fumigatus frequently colonizes CF airways, but it has been assumed to be an innocent saprophyte; its potential role as a cause of lung disease is controversial. Objectives: To study the interactions between Aspergillus and EC, and the role of the fungus in evoking inflammatory responses. Methods: A. fumigatus expressing green fluorescent protein was developed for in vitro and in vivo models, which used cell lines and mouse tracheal EC. Measurements and Main Results: Fungal spores (conidia) are rapidly ingested by ECs derived from bronchial cell lines and murine tracheas, supporting a role for EC in early airway clearance. Bronchial ECs harboring CFTR mutations (ΔF508) or deletion demonstrate impaired uptake and killing of conidia, and ECs with CFTR mutation undergo more conidial-induced apoptosis. Germinated (hyphal) forms of the fungus evoke secretion of inflammatory mediators, with CFTR mutation resulting in increased airway levels of macrophage inflammatory protein 2 and KC, and higher lung monocyte chemotactic protein-1. After A. fumigatus inhalation, CFTR−/− mice develop exaggerated lymphocytic inflammation, mucin accumulation, and lung injury. Conclusions: Data demonstrate a critical role for CFTR in mediating EC responses to A. fumigatus. Results suggest that the fungus elicits aberrant pulmonary inflammation in the setting of CFTR mutation, supporting the potential role of antifungals to halt progressive CF lung disease. PMID:22135344

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

PubMed

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

2016-06-01

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

The Association Between Self-Management Barriers and Self-Efficacy in Chinese Patients with Type 2 Diabetes: The Mediating Role of Appraisal.

PubMed

Cheng, Li; Sit, Janet W H; Leung, Doris Y P; Li, Xiaomei

2016-10-01

Patients with higher levels of self-management barriers are more likely to exhibit a lower level of self-efficacy. However, the theoretically meaningful mechanisms underlying the association between the two variables have not yet been established. Informed by the Transactional Model of Stress and Coping, this study aimed to examine the potential role of diabetes appraisal on the association of self-management barriers and self-efficacy in patients with type 2 diabetes mellitus. This article presents the secondary data analyses of a multicenter, cross-sectional study. A sample of 346 adults with type 2 diabetes was interviewed, using the Personal Diabetes Questionnaire, the Appraisal of Diabetes scale, the Diabetes Empowerment Scale-Short Form, and the Summary of Diabetes Self-Care Activities. Structure equation modeling was performed with 10,000 bootstrap samples using Mplus 7. The hypothesized model provided a good fit to the data (χ 2 = 22.975, df = 33; p = .1144; CFI = 0.989; SRMR = 0.036; RMSEA = 0.042). The mediating effect of diabetes appraisal on the association of self-management barriers and self-efficacy was significant (β = -0.521; 95% CI: -0.865, -0.283), explaining 44.82% of the total effect of barriers on self-efficacy. Significant associations were also detected between diet knowledge and diabetes appraisal (β = 0.148, p = .047). Diabetes appraisal plays a mediating role in the association between self-management barriers and self-efficacy in patients with type 2 diabetes. Reflecting on patients' appraisal of diabetes can help to develop evidence-based and patient-centered interventions. Interventions that enhance individuals' positive appraisal of diabetes have the potential to buffer the negative effects of self-management barriers on self-efficacy. © 2016 Sigma Theta Tau International.

Evidence for Multiple Mediator Complexes in Yeast Independently Recruited by Activated Heat Shock Factor

PubMed Central

Anandhakumar, Jayamani; Moustafa, Yara W.; Chowdhary, Surabhi; Kainth, Amoldeep S.

2016-01-01

Mediator is an evolutionarily conserved coactivator complex essential for RNA polymerase II transcription. Although it has been generally assumed that in Saccharomyces cerevisiae, Mediator is a stable trimodular complex, its structural state in vivo remains unclear. Using the “anchor away” (AA) technique to conditionally deplete select subunits within Mediator and its reversibly associated Cdk8 kinase module (CKM), we provide evidence that Mediator's tail module is highly dynamic and that a subcomplex consisting of Med2, Med3, and Med15 can be independently recruited to the regulatory regions of heat shock factor 1 (Hsf1)-activated genes. Fluorescence microscopy of a scaffold subunit (Med14)-anchored strain confirmed parallel cytoplasmic sequestration of core subunits located outside the tail triad. In addition, and contrary to current models, we provide evidence that Hsf1 can recruit the CKM independently of core Mediator and that core Mediator has a role in regulating postinitiation events. Collectively, our results suggest that yeast Mediator is not monolithic but potentially has a dynamic complexity heretofore unappreciated. Multiple species, including CKM-Mediator, the 21-subunit core complex, the Med2-Med3-Med15 tail triad, and the four-subunit CKM, can be independently recruited by activated Hsf1 to its target genes in AA strains. PMID:27185874

Tumor necrosis factor-α in Guillain-Barré syndrome, friend or foe?

PubMed

Wang, Ying; Zhang, Jingdian; Luo, Peijuan; Zhu, Jie; Feng, Jiachun; Zhang, Hong-Liang

2017-01-01

Guillain-Barré syndrome (GBS) is an immune-mediated disorder in the peripheral nervous system (PNS), and experimental autoimmune neuritis (EAN) serves as an animal model of GBS. TNF-α plays an important role in the pathogenesis of GBS and is a potential therapeutic target of GBS. Areas covered: 'TNF-α' and 'Guillain-Barré syndrome' were the keywords used to search for related publications on Pubmed. By binding to different TNF receptors, TNF-α bears distinct immune properties. TNF-α gene polymorphisms are associated with the features of GBS. The major role of TNF-α in GBS/EAN is to aggravate inflammation; however, data from several studies indicated a protective role of TNF-α. Multiple lines of evidence point to TNF-α as a potential therapeutic target for GBS. However, such clinical trials are scarce in that GBS per se is a probable side effect of anti-TNF-α treatment. Expert opinion: TNF-α plays a dual role in GBS and EAN, and is a potential therapeutic target on GBS/EAN.

Maternal childhood trauma, postpartum depression, and infant outcomes: Avoidant affective processing as a potential mechanism.

PubMed

Choi, Karmel W; Sikkema, Kathleen J; Vythilingum, Bavi; Geerts, Lut; Faure, Sheila C; Watt, Melissa H; Roos, Annerine; Stein, Dan J

2017-03-15

Women who have experienced childhood trauma may be at risk for postpartum depression, increasing the likelihood of negative outcomes among their children. Predictive pathways from maternal childhood trauma to child outcomes, as mediated by postpartum depression, require investigation. A longitudinal sample of South African women (N=150) was followed through pregnancy and postpartum. Measures included maternal trauma history reported during pregnancy; postpartum depression through six months; and maternal-infant bonding, infant development, and infant physical growth at one year. Structural equation models tested postpartum depression as a mediator between maternal experiences of childhood trauma and children's outcomes. A subset of women (N=33) also participated in a lab-based emotional Stroop paradigm, and their responses to fearful stimuli at six weeks were explored as a potential mechanism linking maternal childhood trauma, postpartum depression, and child outcomes. Women with childhood trauma experienced greater depressive symptoms through six months postpartum, which then predicted negative child outcomes at one year. Mediating effects of postpartum depression were significant, and persisted for maternal-infant bonding and infant growth after controlling for covariates and antenatal distress. Maternal avoidance of fearful stimuli emerged as a potential affective mechanism. Limitations included modest sample size, self-report measures, and unmeasured potential confounders. Findings suggest a mediating role of postpartum depression in the intergenerational transmission of negative outcomes. Perinatal interventions that address maternal trauma histories and depression, as well as underlying affective mechanisms, may help interrupt cycles of disadvantage, particularly in high-trauma settings such as South Africa. Copyright © 2017. Published by Elsevier B.V.

Baclofen, a GABABR Agonist, Ameliorates Immune-Complex Mediated Acute Lung Injury by Modulating Pro-Inflammatory Mediators

PubMed Central

Jin, Shunying; Merchant, Michael L.; Ritzenthaler, Jeffrey D.; McLeish, Kenneth R.; Lederer, Eleanor D.; Torres-Gonzalez, Edilson; Fraig, Mostafa; Barati, Michelle T.; Lentsch, Alex B.; Roman, Jesse; Klein, Jon B.; Rane, Madhavi J.

2015-01-01

Immune-complexes play an important role in the inflammatory diseases of the lung. Neutrophil activation mediates immune-complex (IC) deposition-induced acute lung injury (ALI). Components of gamma amino butyric acid (GABA) signaling, including GABA B receptor 2 (GABABR2), GAD65/67 and the GABA transporter, are present in the lungs and in the neutrophils. However, the role of pulmonary GABABR activation in the context of neutrophil-mediated ALI has not been determined. Thus, the objective of the current study was to determine whether administration of a GABABR agonist, baclofen would ameliorate or exacerbate ALI. We hypothesized that baclofen would regulate IC-induced ALI by preserving pulmonary GABABR expression. Rats were subjected to sham injury or IC-induced ALI and two hours later rats were treated intratracheally with saline or 1 mg/kg baclofen for 2 additional hours and sacrificed. ALI was assessed by vascular leakage, histology, TUNEL, and lung caspase-3 cleavage. ALI increased total protein, tumor necrosis factor α (TNF-α and interleukin-1 receptor associated protein (IL-1R AcP), in the bronchoalveolar lavage fluid (BALF). Moreover, ALI decreased lung GABABR2 expression, increased phospho-p38 MAPK, promoted IκB degradation and increased neutrophil influx in the lung. Administration of baclofen, after initiation of ALI, restored GABABR expression, which was inhibited in the presence of a GABABR antagonist, CGP52432. Baclofen administration activated pulmonary phospho-ERK and inhibited p38 MAPK phosphorylation and IκB degradation. Additionally, baclofen significantly inhibited pro-inflammatory TNF-α and IL-1βAcP release and promoted BAL neutrophil apoptosis. Protective effects of baclofen treatment on ALI were possibly mediated by inhibition of TNF-α- and IL-1β-mediated inflammatory signaling. Interestingly, GABABR2 expression was regulated in the type II pneumocytes in lung tissue sections from lung injured patients, further suggesting a physiological role for GABABR2 in the repair process of lung damage. GABABR2 agonists may play a potential therapeutic role in ALI. PMID:25848767

Housing mobility and adolescent mental health: The role of substance use, social networks, and family mental health in the Moving to Opportunity Study.

PubMed

Schmidt, Nicole M; Glymour, M Maria; Osypuk, Theresa L

2017-12-01

The Moving to Opportunity (MTO) experiment was a housing mobility program begun in the mid-nineties that relocated volunteer low income families from public housing to rental units in higher opportunity neighborhoods in 5 US cities, using the Section 8 affordable housing voucher program. Compared to the control group who stayed behind in public housing, the MTO voucher group exhibited a harmful main effect for boys' mental health, and a beneficial main effect for girls' mental health. But no studies have examined how this social experiment caused these puzzling, opposite gender effects. The present study tests potential mediating mechanisms of the MTO voucher experiment on adolescent mental health (n=2829, aged 12-19 in 2001-2002). Using Inverse Odds Ratio Weighting causal mediation, we tested whether adolescent substance use comorbidity, social networks, or family mental health acted as potential mediators. Our results document that comorbid substance use (e.g. past 30 day alcohol use, cigarette use, and number of substances used) significantly partially mediated the effect of MTO on boys' behavior problems, resulting in -13% to -18% percent change in the total effect. The social connectedness domain was a marginally significant mediator for boys' psychological distress. Yet no tested variables mediated MTO's beneficial effects on girls' psychological distress. Confounding sensitivity analyses suggest that the indirect effect of substance use for mediating boys' behavior problems was robust, but social connectedness for mediating boys' psychological distress was not robust. Understanding how housing mobility policies achieve their effects may inform etiology of neighborhoods as upstream causes of health, and inform enhancement of future affordable housing programs.

A prospective examination of the path from child abuse and neglect to illicit drug use in middle adulthood: the potential mediating role of four risk factors.

PubMed

Wilson, Helen W; Widom, Cathy Spatz

2009-03-01

This study examines prostitution, homelessness, delinquency and crime, and school problems as potential mediators of the relationship between childhood abuse and neglect (CAN) and illicit drug use in middle adulthood. Children with documented cases of physical and sexual abuse and neglect (ages 0-11) during 1967-1971 were matched with non-maltreated children and followed into middle adulthood (approximate age 39). Mediators were assessed in young adulthood (approximate age 29) through in-person interviews between 1989 and 1995 and official arrest records through 1994 (N = 1,196). Drug use was assessed via self-reports of past year use of marijuana, psychedelics, cocaine, and/or heroin during 2000-2002 (N = 896). Latent variable structural equation modeling (SEM) was used to test: (1) a four-factor model with separate pathways from CAN to illicit drug use through each of the mediating risk factors and (2) a second-order model with a single mediating risk factor comprised of prostitution, homelessness, delinquency and crime, and poor school performance. Analyses were performed separately for women and men, controlling for race/ethnicity and early drug use. In the four-factor model for both men and women, CAN was significantly related to each of the mediators, but no paths from the mediators to drug use were significant. For women, the second-order risk factor mediated the relationship between CAN and illicit drug use in middle adulthood. For men, neither child abuse and neglect nor the second-order risk factor predicted drug use in middle adulthood. These results suggest that for women, the path from CAN to middle adulthood drug use is part of a general "problem behavior syndrome" evident earlier in life.

Socioeconomic indices as independent correlates of C-reactive protein in the National Longitudinal Study of Adolescent Health.

PubMed

Brummett, Beverly H; Babyak, Michael A; Singh, Abanish; Jiang, Rong; Williams, Redford B; Harris, Kathleen Mullan; Siegler, Ilene C

2013-01-01

To examine the association between socioeconomic status (SES) and C-reactive protein (CRP) to understand how SES may increase the risk of cardiovascular disease and thus identify targets for prevention measures. Path models were used to examine direct and indirect associations of four indices of SES (objective early life built environment ratings, parental and participant education, and income) with CRP measured during early adulthood using data from the National Longitudinal Adolescent Health Study (n = 11,371; mean age = 29 years, range = 24-32 years; 53.8% women, 28.0% black participants). The present study examined potential mediation of the association of SES with CRP by way of body mass index (BMI), smoking, and alcohol consumption within white and black men and women. BMI was a mediator of the relation between parent education and CRP for white men (path coefficient [γ] = -0.05, p < .001) and women (γ = -0.05, p < .001). Smoking mediated the income-CRP (γ = -0.01, p < .01) and the education-CRP (γ = -0.07, p < .001) relation for white men. BMI mediated the relation between all measures of SES and CRP for white women (γ values between -0.02 and -0.05; p values < .01). None of the risk factors mediated the SES-CRP relation in black participants. These findings indicate that the association of SES with CRP is influenced by both the timing and type of SES measure examined. In addition, race and sex play a role in how potential mediators are involved with the SES-CRP relationship, such that BMI and smoking were mediators in white men, whereas BMI was the sole mediator in white women.

PTSD, food addiction, and disordered eating in a sample of primarily older veterans: The mediating role of emotion regulation

PubMed Central

Mitchell, Karen S.; Wolf, Erika J.

2016-01-01

Posttraumatic stress disorder (PTSD) has been associated with eating disorders (EDs) and addictive behaviors, including the relatively new construct food addiction. However, few studies have investigated mechanisms that account for these associations, and men are underrepresented in studies of EDs and food addiction. We examined whether lifetime PTSD symptoms were associated with current food addiction and ED symptoms, and whether emotion regulation (expressive suppression and cognitive reappraisal), which has been associated with both PTSD and EDs, mediated these relations, in a sample of trauma-exposed, male (n = 642) and female (n = 55) veterans. Participants were recruited from the Knowledge Networks-GfK Research Panel and completed an online questionnaire. Structural equation modeling revealed that PTSD was directly associated with ED symptoms, food addiction, expressive suppression, and cognitive reappraisal in the full sample and with all constructs except cognitive reappraisal in the male subsample. Expressive suppression was significantly associated with ED symptoms and mediated the PTSD—ED relation. These results highlight the importance of investigating PTSD as a risk factor for food addiction and ED symptoms and the potential mediating role of emotion regulation in the development of PTSD and EDs in order to identify targets for treatments. PMID:27344589

PTSD, food addiction, and disordered eating in a sample of primarily older veterans: The mediating role of emotion regulation.

PubMed

Mitchell, Karen S; Wolf, Erika J

2016-09-30

Posttraumatic stress disorder (PTSD) has been associated with eating disorders (EDs) and addictive behaviors, including the relatively new construct food addiction. However, few studies have investigated mechanisms that account for these associations, and men are underrepresented in studies of EDs and food addiction. We examined whether lifetime PTSD symptoms were associated with current food addiction and ED symptoms, and whether emotion regulation (expressive suppression and cognitive reappraisal), which has been associated with both PTSD and EDs, mediated these relations, in a sample of trauma-exposed, male (n=642) and female (n=55) veterans. Participants were recruited from the Knowledge Networks-GfK Research Panel and completed an online questionnaire. Structural equation modeling revealed that PTSD was directly associated with ED symptoms, food addiction, expressive suppression, and cognitive reappraisal in the full sample and with all constructs except cognitive reappraisal in the male subsample. Expressive suppression was significantly associated with ED symptoms and mediated the PTSD-ED relation. These results highlight the importance of investigating PTSD as a risk factor for food addiction and ED symptoms and the potential mediating role of emotion regulation in the development of PTSD and EDs in order to identify targets for treatments. Published by Elsevier Ireland Ltd.

Labeling of sexual assault and its relationship with sexual functioning: the mediating role of coping.

PubMed

Kelley, Erika L; Gidycz, Christine A

2015-01-01

Little research has examined the relationship between women's labeling of their sexual assault experiences and sexual functioning, as well as identification of variables that may mediate the labeling-trauma outcome relationship. The purpose of this study was to fill this gap in the literature, by examining the potential mediating role of coping strategies in response to sexual assault in the relationship between labeling and sexual functioning. The sample included 135 college women with a history of adolescent/early adulthood sexual assault. Labeling was not bivariately related to sexual functioning outcomes; however, anxious coping mediated the relationships between labeling and both sexual lubrication and sexual satisfaction. This suggests that correlational analyses between labeling and trauma outcomes may not capture the complexity of this relationship, as it may be more indirect. Furthermore, results suggest that labeling is part of the coping process in response to sexual assault; some women who consider their experience to be sexual assault may engage in anxious coping efforts, contributing to difficulties with sexual lubrication and sexual dissatisfaction. Victims actively working to integrate their sexual assault experience with prior beliefs and self-concept may benefit from treatment focused on decreasing anxious coping, especially as it relates to sexual functioning. © The Author(s) 2014.

Microbial mitigation-exacerbation continuum: a novel framework for microbiome effects on hosts in the face of stress.

PubMed

David, Aaron S; Thapa-Magar, Khum B; Afkhami, Michelle E

2018-03-01

A key challenge to understanding microbiomes and their role in ecological processes is contextualizing their effects on host organisms, particularly when faced with environmental stress. One influential theory, the Stress Gradient Hypothesis, might predict that the frequency of positive interactions increases with stressful conditions such that microbial taxa would mitigate harmful effects on host performance. Yet, equally plausible is that microbial taxa could exacerbate these effects. Here, we introduce the Mitigation-Exacerbation Continuum as a novel framework to conceptualize microbial mediation of stress. We (1) use this continuum to quantify microbial mediation of stress for six plant species and (2) test the association between these continuum values and natural species' abundance. We factorially manipulated a common stress (allelopathy) and the presence of soil microbes to quantify microbial effects in benign and stressed environments for two critical early life-history metrics, seed germination and seedling biomass. Although we found evidence of both mitigation and exacerbation among the six species, exacerbation was more common. Across species, the degree of microbial-mediated effects on germination explained >80% of the variation of natural field abundances. Our results suggest a critical role of soil microbes in mediating plant stress responses, and a potential microbial mechanism underlying species abundance. © 2018 by the Ecological Society of America.

Why are people with high self-control happier? The effect of trait self-control on happiness as mediated by regulatory focus

PubMed Central

Cheung, Tracy T. L.; Gillebaart, Marleen; Kroese, Floor; De Ridder, Denise

2014-01-01

Background: While self-control has often been related to positive outcomes in life such as higher academic achievements and better health, recent insights reveal that people with high trait self-control (TSC) may even experience greater life satisfaction or happiness. Objective: The current study further scrutinizes this potential association between TSC and happiness, and examines how regulatory focus, defined as the way people frame and direct their goal pursuit strategies, plays a role in this relationship. Accordingly, the present study examines the mediating role of regulatory-focus (promotion and prevention focus) on the relationship between TSC and happiness. Method: Data was collected from 545 individuals (65.9% female, Mage = 27.52 years) regarding their TSC, regulatory focus, and happiness. Results: Mediation analyses demonstrate that TSC positively predicts happiness, while this effect was partially mediated by relatively more promotion focus and less prevention focus. Conclusion: Results suggest that people with higher TSC are happier possibly because they are: (1) more promotion-focused on acquiring positive gains thereby facilitating more approach-oriented behaviors, and (2) less prevention-focused on avoiding losses thereby reducing avoidance-oriented behaviors. These findings are relevant for topical scientific debates regarding the underlying mechanisms of self-control regarding initiatory and inhibitory behaviors. PMID:25071683

The association between negative affect and prescription opioid misuse in patients with chronic pain: The mediating role of opioid craving

PubMed Central

Martel, MO; Dolman, AJ; Edwards, RR; Jamison, RN; Wasan, AD

2013-01-01

Over the past decade, considerable research has accumulated showing that chronic pain patients experiencing high levels of negative affect (i.e., anxiety, depression) are at increased risk for prescription opioid misuse. The primary objective of the present study was to examine the factors that underlie the association between negative affect (NA) and prescription opioid misuse among patients with chronic pain. In this study, 82 patients with chronic musculoskeletal pain being prescribed opioid medication completed the Current Opioid Misuse Measure (COMM), a well-validated self-report questionnaire designed to assess prescription opioid misuse. Patients were also asked to complete self-report measures of pain intensity, NA, and opioid craving. A bootstrapped multiple mediation analysis was used to examine the mediating role of patients’ pain intensity and opioid craving in the association between NA and prescription opioid misuse. Consistent with previous research, we found a significant association between NA and prescription opioid misuse. Interestingly, results revealed that opioid craving, but not pain intensity, mediated the association between NA and opioid misuse. Discussion addresses the potential psychological and neurobiological factors that might contribute to the inter-relationships between NA, opioid craving, and prescription opioid misuse in patients with pain. The clinical implications of our findings are also discussed. PMID:24295876

Linking organizational resources and work engagement to employee performance and customer loyalty: the mediation of service climate.

PubMed

Salanova, Marisa; Agut, Sonia; Peiró, José María

2005-11-01

This study examined the mediating role of service climate in the prediction of employee performance and customer loyalty. Contact employees (N=342) from 114 service units (58 hotel front desks and 56 restaurants) provided information about organizational resources, engagement, and service climate. Furthermore, customers (N=1,140) from these units provided information on employee performance and customer loyalty. Structural equation modeling analyses were consistent with a full mediation model in which organizational resources and work engagement predict service climate, which in turn predicts employee performance and then customer loyalty. Further analyses revealed a potential reciprocal effect between service climate and customer loyalty. Implications of the study are discussed, together with limitations and suggestions for future research. ((c) 2005 APA, all rights reserved).

25 CFR 291.10 - What is the role of the mediator appointed by the Secretary?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false What is the role of the mediator appointed by the... ENTERPRISES CLASS III GAMING PROCEDURES § 291.10 What is the role of the mediator appointed by the Secretary? (a) The mediator must ask the Indian tribe and the State to submit their last best proposal for Class...

The Relationship between Psychological Contract Breach and Organizational Commitment: Exchange Imbalance as a Moderator of the Mediating Role of Violation

ERIC Educational Resources Information Center

Cassar, Vincent; Briner, Rob B.

2011-01-01

This study tested the mediating role of violation in the relationship between breach and both affective and continuance commitment and the extent to which this mediating role is moderated by exchange imbalance amongst a sample of 103 sales personnel. Results suggest that violation mediated the relationship between breach and commitment. Also,…

Sleep problems as a mediator of the association between parental education levels, perceived family economy and poor mental health in children.

PubMed

Bøe, Tormod; Hysing, Mari; Stormark, Kjell Morten; Lundervold, Astri J; Sivertsen, Børge

2012-12-01

The aim of this study was to investigate the association between familial socioeconomic status (SES) and children's sleep problems, and the role of sleep problems as a mediator between familial SES and childhood mental health problems. Participants were 5781 11-13 year old children from the Bergen Child Study. Data were collected on family economy, parental education, and children's difficulties initiating and/or maintaining sleep (DIMS), time in bed (TIB) and self-reported mental health problems using the Strengths and Difficulties Questionnaire (SDQ). Sleep problems were significantly more common in children from lower SES families. Children from families with poor and average perceived family economy had significantly higher odds of reporting DIMS compared to children from families with very good economy (ORs=3.5 and 1.7, respectively). The odds were reduced by 12-36% adjusting for poor parental health and single parenting, but remained significant. Children from families with a poor economy had increased odds of a short TIB, both in the crude model (OR=1.9) and adjusted for parental characteristics (OR=2.2). Maternal education level was significantly associated with short TIB. Path analysis was conducted to investigate the potential mediating role of DIMS in the relationship between SES and mental health. The significant direct association between perceived family economy and SDQ total problems score was partially mediated by a significant indirect effect of sleep problems. Sleep problems are common among children from families with a lower SES and may be a potential mechanism through which low SES is translated into mental health problems. Copyright © 2012 Elsevier Inc. All rights reserved.

RAG-induced DNA lesions activate proapoptotic BIM to suppress lymphomagenesis in p53-deficient mice

PubMed Central

Herold, Marco J.

2016-01-01

Neoplastic transformation is driven by oncogenic lesions that facilitate unrestrained cell expansion and resistance to antiproliferative signals. These oncogenic DNA lesions, acquired through errors in DNA replication, gene recombination, or extrinsically imposed damage, are thought to activate multiple tumor suppressive pathways, particularly apoptotic cell death. DNA damage induces apoptosis through well-described p53-mediated induction of PUMA and NOXA. However, loss of both these mediators (even together with defects in p53-mediated induction of cell cycle arrest and cell senescence) does not recapitulate the tumor susceptibility observed in p53−/− mice. Thus, potentially oncogenic DNA lesions are likely to also trigger apoptosis through additional, p53-independent processes. We found that loss of the BH3-only protein BIM accelerated lymphoma development in p53-deficient mice. This process was negated by concomitant loss of RAG1/2-mediated antigen receptor gene rearrangement. This demonstrates that BIM is critical for the induction of apoptosis caused by potentially oncogenic DNA lesions elicited by RAG1/2-induced gene rearrangement. Furthermore, this highlights the role of a BIM-mediated tumor suppressor pathway that acts in parallel to the p53 pathway and remains active even in the absence of wild-type p53 function, suggesting this may be exploited in the treatment of p53-deficient cancers. PMID:27621418

Adolescent impulsivity and soft drink consumption: The role of parental regulation.

PubMed

Melbye, Elisabeth L; Bergh, Ingunn H; Hausken, Solveig E S; Sleddens, Ester F C; Glavin, Kari; Lien, Nanna; Bjelland, Mona

2016-01-01

The present study aimed to explore the process in which impulsivity might influence soft drink consumption in adolescents, addressing potential mediating effects of perceived parental regulation regarding unhealthy eating. A cross-sectional survey was performed among 440 13-15-year-olds in Eastern Norway. The survey questionnaire included measures of impulsivity, six types of maternal and paternal regulation (as perceived by the adolescents), and consumption of sugar-sweetened beverages (SSB). Parallel multiple-mediator analyses were performed to reveal potential mediating effects of perceived parental regulatory behaviors on the association between adolescent impulsivity and SSB consumption. Separate models were run for maternal and paternal regulation. Results from our model analyses (both maternal and paternal models) indicated that all the six measured parental regulatory behaviors jointly acted as mediators on the association between adolescent impulsivity and SSB consumption. However, only perceived maternal and paternal legitimacy of regulation showed a unique contribution to the mediated effect. This finding suggests that adolescents' perception of parental legitimate authority is of particular importance in explaining the relationship between impulsivity and unhealthy eating behaviors in adolescents. Future nutrition interventions targeting adolescents and their parents should take personal factors such as adolescents' level of impulsivity into account. Ultimately; what may be an appropriate approach to impulsive individuals and their parents may diverge from what may be an appropriate approach to less impulsive individuals and their parents. Copyright © 2015 Elsevier Ltd. All rights reserved.

Potential Role of Extracellular Vesicles in the Pathophysiology of Drug Addiction.

PubMed

Rao, P S S; O'Connell, Kelly; Finnerty, Thomas Kyle

2018-01-23

Extracellular vesicles (EVs) are small vesicles secreted by cells and are known to carry sub-cellular components including microRNA, proteins, and lipids. Due to their ability to transport cargo between cells, EVs have been identified as important regulators of various pathophysiological conditions and can therefore influence treatment outcomes. In particular, the significance of microRNAs in EV-mediated cell-cell communication is well-documented. While the influence of EVs and the cargo delivered by EVs has been extensively reviewed in other neurological disorders, the available literature on the potential role of EVs in the pathophysiology of drug addiction has not been reviewed. Hence, in this article, the known effects of commonly abused drugs (ethanol, nicotine, opiates, cocaine, and cannabinoids) on EV secretion have been reviewed. In addition, the potential role of drugs of abuse in affecting the delivery of EV-packaged microRNAs, and the subsequent impact on neuronal health and continued drug dependence, has been discussed.

Systematic identification of phosphorylation-mediated protein interaction switches

PubMed Central

Wichmann, Oliver; Utz, Mathias; Andre, Timon; Minguez, Pablo; Parca, Luca; Roth, Frederick P.; Gavin, Anne-Claude; Bork, Peer; Russell, Robert B.

2017-01-01

Proteomics techniques can identify thousands of phosphorylation sites in a single experiment, the majority of which are new and lack precise information about function or molecular mechanism. Here we present a fast method to predict potential phosphorylation switches by mapping phosphorylation sites to protein-protein interactions of known structure and analysing the properties of the protein interface. We predict 1024 sites that could potentially enable or disable particular interactions. We tested a selection of these switches and showed that phosphomimetic mutations indeed affect interactions. We estimate that there are likely thousands of phosphorylation mediated switches yet to be uncovered, even among existing phosphorylation datasets. The results suggest that phosphorylation sites on globular, as distinct from disordered, parts of the proteome frequently function as switches, which might be one of the ancient roles for kinase phosphorylation. PMID:28346509

Anxiety and Decision-Making

PubMed Central

Hartley, Catherine A.; Phelps, Elizabeth A.

2013-01-01

While the everyday decision-making of clinically anxious individuals is clearly influenced by their excessive fear and worry, the relationship between anxiety and decision-making remains relatively unexplored in neuroeconomic studies. In this review, we attempt to explore the role of anxiety in decision-making using a neuroeconomic approach. We first review the neural systems mediating fear and anxiety, which overlap with a network of brain regions implicated in studies of economic decision-making. We then discuss the potential influence of cognitive biases associated with anxiety upon economic choice, focusing on a set of decision-making biases involving choice in the face of potential aversive outcomes. We propose that the neural circuitry supporting fear learning and regulation may mediate the influence of anxiety upon choice, and suggest that techniques for altering fear and anxiety may also change decisions. PMID:22325982

Advances in the role of oxytocin receptors in human parturition.

PubMed

Kim, Sung Hye; Bennett, Phillip R; Terzidou, Vasso

2017-07-05

Oxytocin (OT) is a neurohypophysial hormone which has been found to play a central role in the regulation of human parturition. The most established role of oxytocin/oxytocin receptor (OT/OTR) system in human parturition is the initiation of uterine contractions, however, recent evidence have demonstrated that it may have a more complex role including initiation of inflammation, regulation of miRNA expression, as well as mediation of other non-classical oxytocin actions via receptor crosstalk with other G protein-coupled receptors (GPCRs). In this review we highlight both established and newly emerging roles of OT/OTR system in human parturition and discuss the expanding potential for OTRs as pharmacological targets in the management of preterm labour. Copyright © 2017. Published by Elsevier B.V.

Dynamic synchronization of ongoing neuronal activity across spinal segments regulates sensory information flow

PubMed Central

Contreras-Hernández, E; Chávez, D; Rudomin, P

2015-01-01

Previous studies on the correlation between spontaneous cord dorsum potentials recorded in the lumbar spinal segments of anaesthetized cats suggested the operation of a population of dorsal horn neurones that modulates, in a differential manner, transmission along pathways mediating Ib non-reciprocal postsynaptic inhibition and pathways mediating primary afferent depolarization and presynaptic inhibition. In order to gain further insight into the possible neuronal mechanisms that underlie this process, we have measured changes in the correlation between the spontaneous activity of individual dorsal horn neurones and the cord dorsum potentials associated with intermittent activation of these inhibitory pathways. We found that high levels of neuronal synchronization within the dorsal horn are associated with states of incremented activity along the pathways mediating presynaptic inhibition relative to pathways mediating Ib postsynaptic inhibition. It is suggested that ongoing changes in the patterns of functional connectivity within a distributed ensemble of dorsal horn neurones play a relevant role in the state-dependent modulation of impulse transmission along inhibitory pathways, among them those involved in the central control of sensory information. This feature would allow the same neuronal network to be involved in different functional tasks. Key points We have examined, in the spinal cord of the anaesthetized cat, the relationship between ongoing correlated fluctuations of dorsal horn neuronal activity and state-dependent activation of inhibitory reflex pathways. We found that high levels of synchronization between the spontaneous activity of dorsal horn neurones occur in association with the preferential activation of spinal pathways leading to primary afferent depolarization and presynaptic inhibition relative to activation of pathways mediating Ib postsynaptic inhibition. It is suggested that changes in synchronization of ongoing activity within a distributed network of dorsal horn neurones play a relevant role in the configuration of structured (non-random) patterns of functional connectivity that shape the interaction of sensory inputs with spinal reflex pathways subserving different functional tasks. PMID:25653206

[The role of VEGF, HSP-70 and protein S-100B in the potentiation effect of the neuroprotective effect of hypercapnic hypoxia].

PubMed

Bespalov, A G; Tregub, P P; Kulikov, V P; Pijanzin, A I; Belousov, A A

2014-01-01

Studied the role of VEGF, HSP-70 and S-100B in potentiating hypercapnia neuroprotective effect of hypoxia. Demonstrated that neuroprotective effects when exposed hypercapnic hypoxia-mediated protein synthesis increased S-100B, mainly due to the action of carbon dioxide, and not oxygen deficiency. Neuroprotective effects of HSP-70 due to hypoxia, but the combined effect of hypoxia and hypercapnia gives a significant increase in the synthesis of HSP-70 in comparison with the isolated effect of hypoxia. Vascularization activated equally as hypoxia and hypercapnia, without adding significant effects in combination. This suggests dominant effect hypercapnia, hypoxia compared in neuroprotection mechanisms related to protein S-100B, but not the protein VEGF, hypercapnia and potentiate the neuroprotective efficacy of hypoxia-related protein HSP-70.

VIP1 and Its Homologs Are Not Required for Agrobacterium-Mediated Transformation, but Play a Role in Botrytis and Salt Stress Responses

PubMed Central

Lapham, Rachelle; Lee, Lan-Ying; Tsugama, Daisuke; Lee, Sanghun; Mengiste, Tesfaye; Gelvin, Stanton B.

2018-01-01

The bZIP transcription factor VIP1 interacts with the Agrobacterium virulence protein VirE2, but the role of VIP1 in Agrobacterium-mediated transformation remains controversial. Previously tested vip1-1 mutant plants produce a truncated protein containing the crucial bZIP DNA-binding domain. We generated the CRISPR/Cas mutant vip1-2 that lacks this domain. The transformation susceptibility of vip1-2 and wild-type plants is similar. Because of potential functional redundancy among VIP1 homologs, we tested transgenic lines expressing VIP1 fused to a SRDX repression domain. All VIP1-SRDX transgenic lines showed wild-type levels of transformation, indicating that neither VIP1 nor its homologs are required for Agrobacterium-mediated transformation. Because VIP1 is involved in innate immune response signaling, we tested the susceptibility of vip1 mutant and VIP1-SRDX plants to Pseudomonas syringae and Botrytis cinerea. vip1 mutant and VIP1-SRDX plants show increased susceptibility to B. cinerea but not to P. syringae infection, suggesting a role for VIP1 in B. cinerea, but not in P. syringae, defense signaling. B. cinerea susceptibility is dependent on abscisic acid (ABA) which is also important for abiotic stress responses. The germination of vip1 mutant and VIP1-SRDX seeds is sensitive to exogenous ABA, suggesting a role for VIP1 in response to ABA. vip1 mutant and VIP1-SRDX plants show increased tolerance to growth in salt, indicating a role for VIP1 in response to salt stress. PMID:29946325

The intergenerational transmission of problem gambling: The mediating role of parental psychopathology.

PubMed

Dowling, N A; Shandley, K; Oldenhof, E; Youssef, G J; Thomas, S A; Frydenberg, E; Jackson, A C

2016-08-01

The present study investigated the intergenerational transmission of problem gambling and the potential mediating role of parental psychopathology (problem drinking, drug use problems, and mental health issues). The study comprised 3953 participants (1938 males, 2015 females) recruited from a large-scale Australian community telephone survey of adults retrospectively reporting on parental problem gambling and psychopathology during their childhood. Overall, 4.0% [95%CI 3.0, 5.0] (n=157) of participants reported paternal problem gambling and 1.7% [95%CI 1.0, 2.0] (n=68) reported maternal problem gambling. Compared to their peers, participants reporting paternal problem gambling were 5.1 times more likely to be moderate risk gamblers and 10.7 times more likely to be problem gamblers. Participants reporting maternal problem gambling were 1.7 times more likely to be moderate risk gamblers and 10.6 times more likely to be problem gamblers. The results revealed that the relationships between paternal-and-participant and maternal-and-participant problem gambling were significant, but that only the relationship between paternal-and-participant problem gambling remained statistically significant after controlling for maternal problem gambling and sociodemographic factors. Paternal problem drinking and maternal drug use problems partially mediated the relationship between paternal-and-participant problem gambling, and fully mediated the relationship between maternal-and-participant problem gambling. In contrast, parental mental health issues failed to significantly mediate the transmission of gambling problems by either parent. When parental problem gambling was the mediator, there was full mediation of the effect between parental psychopathology and offspring problem gambling for fathers but not mothers. Overall, the study highlights the vulnerability of children from problem gambling households and suggests that it would be of value to target prevention and intervention efforts towards this cohort. Copyright © 2016 Elsevier Ltd. All rights reserved.

PUMA mediates ER stress-induced apoptosis in portal hypertensive gastropathy

PubMed Central

Tan, S; Wei, X; Song, M; Tao, J; Yang, Y; Khatoon, S; Liu, H; Jiang, J; Wu, B

2014-01-01

Mucosal apoptosis has been demonstrated to be an essential pathological feature in portal hypertensive gastropathy (PHG). p53-upregulated modulator of apoptosis (PUMA) was identified as a BH3-only Bcl-2 family protein that has an essential role in apoptosis induced by a variety of stimuli, including endoplasmic reticulum (ER) stress. However, whether PUMA is involved in mucosal apoptosis in PHG remains unclear, and whether PUMA induces PHG by mediating ER stress remains unknown. The aim of the study is to investigate whether PUMA is involved in PHG by mediating ER stress apoptotic signaling. To identify whether PUMA is involved in PHG by mediating ER stress, gastric mucosal injury and apoptosis were studied in both PHG patients and PHG animal models using PUMA knockout (PUMA-KO) and PUMA wild-type (PUMA-WT) mice. The induction of PUMA expression and ER stress signaling were investigated, and the mechanisms of PUMA-mediated apoptosis were analyzed. GES-1 and SGC7901 cell lines were used to further identify whether PUMA-mediated apoptosis was induced by ER stress in vitro. Epithelial apoptosis and PUMA were markedly induced in the gastric mucosa of PHG patients and mouse PHG models. ER stress had a potent role in the induction of PUMA and apoptosis in PHG models, and the apoptosis was obviously attenuated in PUMA-KO mice. Although the targeted deletion of PUMA did not affect ER stress, mitochondrial apoptotic signaling was downregulated in mice. Meanwhile, PUMA knockdown significantly ameliorated ER stress-induced mitochondria-dependent apoptosis in vitro. These results indicate that PUMA mediates ER stress-induced mucosal epithelial apoptosis through the mitochondrial apoptotic pathway in PHG, and that PUMA is a potentially therapeutic target for PHG. PMID:24625987

Understanding the Links Between Self-Report Emotional Intelligence and Suicide Risk: Does Psychological Distress Mediate This Relationship Across Time and Samples?

PubMed Central

Mérida-López, Sergio; Extremera, Natalio; Rey, Lourdes

2018-01-01

Objective: In the last decades, increasing attention has been paid to examining psychological resources that might contribute to our understanding of suicide risk. Although Emotional Intelligence (EI) is one dimension that has been linked with decreased suicidal ideation and behaviors, we detected several gaps in the literature in this area regarding the research designs and samples involved. In this research, we aimed to test a mediator model considering self-report EI, psychological distress and suicide risk across samples adopting both cross-sectional and prospective designs in two independent studies. Method: In Study 1, our purpose was to examine the potential role of psychological distress as a mediator in the relationship between self-report EI and suicide risk in a community sample comprised of 438 adults (270 women; mean age: 33.21 years). In Study 2, we sought to examine the proposed mediator model considering a 2-month prospective design in a sample of college students (n = 330 in T1; n = 311 in T2; 264 women; mean age: 22.22 years). Results: In Study 1, we found that psychological distress partially mediated the effect of self-report EI on suicide risk. More interestingly, findings from Study 2 showed that psychological distress fully mediated the relationship between self-report EI and suicide risk at Time 2. Conclusion: These results point out the role of psychological distress as a mediator in the association between self-report EI and suicide risk. These findings suggest an underlying process by which self-report EI may act as a protective factor against suicidal ideation and behaviors. In line with the limitations of our work, plausible avenues for future research and interventions are discussed. PMID:29867607

Transmission to interneurons is via slow excitatory synaptic potentials mediated by P2Y(1) receptors during descending inhibition in guinea-pig ileum.

PubMed

Thornton, Peter D J; Gwynne, Rachel M; McMillan, Darren J; Bornstein, Joel C

2013-01-01

The nature of synaptic transmission at functionally distinct synapses in intestinal reflex pathways has not been fully identified. In this study, we investigated whether transmission between interneurons in the descending inhibitory pathway is mediated by a purine acting at P2Y receptors to produce slow excitatory synaptic potentials (EPSPs). Myenteric neurons from guinea-pig ileum in vitro were impaled with intracellular microelectrodes. Responses to distension 15 mm oral to the recording site, in a separately perfused stimulation chamber and to electrical stimulation of local nerve trunks were recorded. A subset of neurons, previously identified as nitric oxide synthase immunoreactive descending interneurons, responded to both stimuli with slow EPSPs that were reversibly abolished by a high concentration of PPADS (30 μM, P2 receptor antagonist). When added to the central chamber of a three chambered organ bath, PPADS concentration-dependently depressed transmission through that chamber of descending inhibitory reflexes, measured as inhibitory junction potentials in the circular muscle of the anal chamber. Reflexes evoked by distension in the central chamber were unaffected. A similar depression of transmission was seen when the specific P2Y(1) receptor antagonist MRS 2179 (10 μM) was in the central chamber. Blocking either nicotinic receptors (hexamethonium 200 μM) or 5-HT(3) receptors (granisetron 1 μM) together with P2 receptors had no greater effect than blocking P2 receptors alone. Slow EPSPs mediated by P2Y(1) receptors, play a primary role in transmission between descending interneurons of the inhibitory reflexes in the guinea-pig ileum. This is the first demonstration for a primary role of excitatory metabotropic receptors in physiological transmission at a functionally identified synapse.

Bioaccumulation and glutathione-mediated detoxification of copper and cadmium in Sphagnum squarrosum Crome Samml.

PubMed

Saxena, Anuj; Saxena, Anjali

2012-07-01

Physiological and biochemical responses, metal bioaccumulation and tolerance potential of Sphagnum squarrosum Crome Samml. to Cu and Cd were studied to determine its bioindication and bioremediation potential. Results suggest that glutathione treatment increases the metal accumulation potential and plays a definite role in heavy metal scavenging. High abundance of Sphagnum in metal-rich sites strongly suggests its high metal tolerance capabilities. This experiment demonstrates that S. squarrosum is able to accumulate and tolerate a high amount of metals and feasibility of its application as bioindicator and remediator test species of metal-contaminated environment.

The Effects of Anti-Vaccine Conspiracy Theories on Vaccination Intentions

PubMed Central

Jolley, Daniel; Douglas, Karen M.

2014-01-01

The current studies investigated the potential impact of anti-vaccine conspiracy beliefs, and exposure to anti-vaccine conspiracy theories, on vaccination intentions. In Study 1, British parents completed a questionnaire measuring beliefs in anti-vaccine conspiracy theories and the likelihood that they would have a fictitious child vaccinated. Results revealed a significant negative relationship between anti-vaccine conspiracy beliefs and vaccination intentions. This effect was mediated by the perceived dangers of vaccines, and feelings of powerlessness, disillusionment and mistrust in authorities. In Study 2, participants were exposed to information that either supported or refuted anti-vaccine conspiracy theories, or a control condition. Results revealed that participants who had been exposed to material supporting anti-vaccine conspiracy theories showed less intention to vaccinate than those in the anti-conspiracy condition or controls. This effect was mediated by the same variables as in Study 1. These findings point to the potentially detrimental consequences of anti-vaccine conspiracy theories, and highlight their potential role in shaping health-related behaviors. PMID:24586574

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

PubMed

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

2001-12-01

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

The effects of anti-vaccine conspiracy theories on vaccination intentions.

PubMed

Jolley, Daniel; Douglas, Karen M

2014-01-01

The current studies investigated the potential impact of anti-vaccine conspiracy beliefs, and exposure to anti-vaccine conspiracy theories, on vaccination intentions. In Study 1, British parents completed a questionnaire measuring beliefs in anti-vaccine conspiracy theories and the likelihood that they would have a fictitious child vaccinated. Results revealed a significant negative relationship between anti-vaccine conspiracy beliefs and vaccination intentions. This effect was mediated by the perceived dangers of vaccines, and feelings of powerlessness, disillusionment and mistrust in authorities. In Study 2, participants were exposed to information that either supported or refuted anti-vaccine conspiracy theories, or a control condition. Results revealed that participants who had been exposed to material supporting anti-vaccine conspiracy theories showed less intention to vaccinate than those in the anti-conspiracy condition or controls. This effect was mediated by the same variables as in Study 1. These findings point to the potentially detrimental consequences of anti-vaccine conspiracy theories, and highlight their potential role in shaping health-related behaviors.

N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor.

PubMed

Stamler, J; Mendelsohn, M E; Amarante, P; Smick, D; Andon, N; Davies, P F; Cooke, J P; Loscalzo, J

1989-09-01

Recent evidence suggests that endothelium-derived relaxing factor exhibits properties of nitric oxide. Like nitric oxide, it inhibits platelet function and mediates its effects by elevating intracellular cyclic GMP. In this study we have investigated the role of reduced thiol in the mechanism of action of endothelium-derived relaxing factor on platelets. Bovine aortic endothelial cells were grown on microcarrier beads and pretreated with aspirin before use. Endothelial cells stimulated with bradykinin or exposed to stirred medium expressed a dose-dependent inhibition of platelet aggregation that was potentiated by the reduced thiol, N-acetylcysteine. Endothelial cell-mediated platelet inhibition was attenuated by methylene blue. Inhibition of platelet aggregation by endothelial cells was associated with a rise in platelet intracellular cyclic GMP, an effect that was enhanced by N-acetylcysteine. These data show that 1) the reduced thiol N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor and 2) this effect is associated with increasing intracellular platelet cyclic GMP levels.

LPS induces direct death of IFN-gamma primed murine embryonic hepatocyte, BNL CL2 cells in a TNF-alpha independent manner.

PubMed

So, H S; Jung, B H; Yeum, S S; Park, J S; Kim, M S; Lee, J H; Chung, S Y; Choi, S; Chae, H J; Kim, H R; Ko, C B; Chung, H T; Park, R

2000-11-01

Although it has been well known that the role of LPS on liver damage is mediated through TNF-alpha, the mechanism by which LPS modulates the cytotoxicity of IFN-gamma on hepatocytes has not yet been clearly demonstrated. Here, we demonstrate that IFN-gamma mediated apoptosis in murine embryonic hepatocyte BNL CL2 cells is potentiated by the addition of LPS (0.5 microg/ml). Consistently, LPS markedly increases the catalytic activity of caspase 3-like protease but not caspase 1-like protease in IFN-gamma treated cells. In addition, TNF-alpha alone does not affect cell viability but rather it potentiates the cytotoxic effect of IFN-gamma on BNL CL2 cells. However, the cell viability of IFN-gamma/LPS treated cells is affected by the addition of polymyxin B but not by TNF binding protein I (TNF-BPI). These data suggest that the lipid moiety of LPS may mediate direct cytotoxicity of BNL CL2 cells in a TNF-alpha independent manner.

ER Stress-Mediated Signaling: Action Potential and Ca(2+) as Key Players.

PubMed

Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

2016-09-15

The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca(2+)) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca(2+) regulates cell death both at the early and late stages of apoptosis. Severe Ca(2+) dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca(2+) (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca(2+) and action potential in ER stress-mediated apoptosis.

Shyness and Vocabulary: The Roles of Executive Functioning and Home Environmental Stimulation

PubMed Central

Nayena Blankson, A.; O’Brien, Marion; Leerkes, Esther M.; Marcovitch, Stuart; Calkins, Susan D.

2010-01-01

Although shyness has often been found to be negatively related to vocabulary, few studies have examined the processes that produce or modify this relation. The present study examined executive functioning skills and home environmental stimulation as potential mediating and moderating mechanisms. A sample of 3.5-year-old children (N=254) were administered executive functioning tasks and a vocabulary test during a laboratory visit. Mothers completed questionnaires assessing child shyness and home environmental stimulation. Our primary hypothesis was that executive functioning mediates the association between shyness and vocabulary, and home environmental stimulation moderates the relation between executive functioning and vocabulary. Alternative hypotheses were also tested. Results indicated that children with better executive functioning skills developed stronger vocabularies when reared in more, versus less, stimulating environments. Implications of these results are discussed in terms of the role of shyness, executive functioning, and home environmental stimulation in early vocabulary development. PMID:22096267

An Analysis of Pathological Activities of CCN Proteins in Joint Disorders: Mechanical Stretch-Mediated CCN2 Expression in Cultured Meniscus Cells.

PubMed

Furumatsu, Takayuki; Ozaki, Toshifumi

2017-01-01

The multifunctional growth factor CYR61/CTGF/NOV (CCN) 2, also known as connective tissue growth factor, regulates cellular proliferation, differentiation, and tissue regeneration. Recent literatures have described important roles of CCN2 in the meniscus metabolism. However, the mechanical stress-mediated transcriptional regulation of CCN2 in the meniscus remains unclear. The meniscus is a fibrocartilaginous tissue that controls complex biomechanics of the knee joint. Therefore, the injured unstable meniscus has a poor healing potential especially in the avascular inner region. In addition, dysfunction of the meniscus correlates with the progression of degenerative knee joint disorders and joint space narrowing. Here, we describe an experimental approach that investigates the distinct cellular behavior of inner and outer meniscus cells in response to mechanical stretch. Our experimental model can analyze the relationships between stretch-induced CCN2 expression and its functional role in the meniscus homeostasis.

[Free radicals and hepatic ischemia-reperfusion].

PubMed

Szijártó, Attila

2015-11-22

The critical importance of the ischemic-reperfusive injury is well documented with regards to numerous organs and clinical conditions. Oxygen free radicals play a central role in the mediation of the injury, which dominantly influences the prevalence of postoperative complications, (long term) organ damage, and the potential manifestation of systemic reactions. The both anatomically and pathophysiologically unique ischemic-reperfusive injury of the liver, which is expressively vulnerable to free radicals, is of utmost importance in liver surgery. Several techniques (adaptive maneuvers, chemical agents) are known to ameliorate the reperfusive injury. Based on the prior research of the workgroup of the author, the aim of the current article is to overview the set of measures capable of attenuating ischemic-reperfusive injury (ischemic preconditioning, -perconditioning, administration of adenosine, -inosine, -levosimendan, and -poly-ADP-ribose-polymerase inhibitor), with special attention to the ischemic-reperfusive injury of the liver, as well as the special pathophysiological role of free radicals in mediating hepatic damage.

Is cohesin required for spindle-pole-body/centrosome cohesion?

PubMed Central

Jin, Hui; Avey, Martin

2012-01-01

Centrosomes are microtubule-organizing centers that nucleate spindle microtubules during cell division. In budding yeast, the centrosome, often referred to as the spindle pole body, shares structural components with the centriole, the central core of the animal centrosome. The parental centrosome is duplicated when DNA replication takes place. Like sister chromatids tethered together by cohesin, duplicated centrosomes are linked and then separate to form the bipolar spindle necessary for chromosome segregation. Recent studies have shown that cohesin is also localized to the animal centrosome and is perhaps directly involved in engaging paired centrioles. Here we discuss the potential role of cohesin in mediating spindle-pole-body cohesion in the context of yeast meiosis. We propose that the coordination of chromosome segregation with centrosome cohesion and duplication is mediated by the antagonistic interaction between the Aurora kinase and the Polo kinase and that the role of cohesin in centrosome regulation appears to be indirect in budding yeast. PMID:22482005

The Role of Neighborhood Context and School Climate in School-Level Academic Achievement.

PubMed

Ruiz, Linda D; McMahon, Susan D; Jason, Leonard A

2018-06-01

In recent years, the quality of education available to children has become increasingly dependent on the social and economic demographics of neighborhoods in which the children live. This study assesses the role of community violence in explaining the relation between socio-economic status (SES) and academic outcomes and the potential of positive school climate to promote academic achievement. With a sample of 297 Chicago public elementary schools, we examine community-level and school-level data and use Geographic Information Systems (GIS) mapping to illustrate how school academic achievement coincides with neighborhood economics and crime statistics. Results support the hypothesized mediation, such that lower SES was associated with lower academic achievement, and violent crime partially mediated this relation. School climate was positively associated with academic achievement, and student safety significantly moderated the relation between SES and academic achievement. Implications for theory, research, and intervention are discussed. © Society for Community Research and Action 2018.

Glutathione S-transferase mediates an ageing response to mitochondrial dysfunction

PubMed Central

Dancy, Beverley M.; Brockway, Nicole; Ramadasan-Nair, Renjini; Yang, Yoing; Sedensky, Margaret M.; Morgan, Philip G.

2016-01-01

To understand primary mitochondrial disease, we utilized a complex I-deficient Caenorhabditis elegans mutant, gas-1. These animals strongly upregulate the expression of gst-14 (encoding a glutathione S-transferase). Knockdown of gst-14 dramatically extends the lifespan of gas-1 and increases hydroxynonenal (HNE) modified mitochondrial proteins without improving complex I function. We observed no change in reactive oxygen species levels as measured by Mitosox staining, consistent with a potential role of GST-14 in HNE clearance. The upregulation of gst-14 in gas-1 animals is specific to the pharynx. These data suggest that an HNE-mediated response in the pharynx could be beneficial for lifespan extension in the context of complex I dysfunction in C. elegans. Thus, whereas HNE is typically considered damaging, our work is consistent with recent reports of its role in signaling, and that in this case, the signal is pro-longevity in a model of mitochondrial dysfunction. PMID:26704446

Adolescent insecure attachment as a predictor of maladaptive coping and externalizing behaviors in emerging adulthood

PubMed Central

Dawson, Anne E.; Allen, Joseph P.; Marston, Emily G.; Hafen, Christopher A.; Schad, Megan M.

2014-01-01

This study investigated whether insecure adolescent attachment organization (i.e., preoccupied and dismissing) longitudinally predicted self- and peer-reported externalizing behavior in emerging adulthood. Secondarily, maladaptive coping strategies were examined for their potential role in mediating the relationship between insecure attachment and future externalizing behaviors. Target participants (N = 184) were given the Adult Attachment Interview (AAI) at age 14 and re-interviewed seven and eight years later with their closest peer. Qualities of both preoccupied and dismissing attachment organization predicted self-reported externalizing behaviors in emerging adulthood eight years later, but only preoccupation was predictive of close-peer reports of emerging adult externalizing behavior. Maladaptive coping strategies only mediated the relationship between a dismissing stance toward attachment and future self-reported externalizing behaviors. Understanding the role of coping and emotional regulation in attachment may help us to understand the unique aspects of both dismissing and preoccupied stances toward attachment. PMID:24995478

EVIDENCE FOR BASE EXCISION REPAIR PROCESSING OF DNA INTERSTRAND CROSSLINKS

PubMed Central

Kothandapani, Anbarasi; Patrick, Steve M

2013-01-01

Many bifunctional alkylating agents and anticancer drugs exert their cytotoxicity by producing cross links between the two complementary strands of DNA, termed interstrand crosslinks (ICLs). This blocks the strand separating processes during DNA replication and transcription, which can lead to cell cycle arrest and apoptosis. Cells use multiple DNA repair systems to eliminate the ICLs. Concerted action of repair proteins involved in Nucleotide Excision Repair and Homologous Recombination pathways are suggested to play a key role in the ICL repair. However, recent studies indicate a possible role for Base Excision Repair (BER) in mediating the cytotoxicity of ICL inducing agents in mammalian cells. Elucidating the mechanism of BER mediated modulation of ICL repair would help in understanding the recognition and removal of ICLs and aid in the development of potential therapeutic agents. In this review, the influence of BER proteins on ICL DNA repair and the possible mechanisms of action are discussed. PMID:23219605

MicroRNA-132 regulates recognition memory and synaptic plasticity in the perirhinal cortex

PubMed Central

Scott, Helen L; Tamagnini, Francesco; Narduzzo, Katherine E; Howarth, Joanna L; Lee, Youn-Bok; Wong, Liang-Fong; Brown, Malcolm W; Warburton, Elizabeth C; Bashir, Zafar I; Uney, James B

2012-01-01

Evidence suggests that the acquisition of recognition memory depends upon CREB-dependent long-lasting changes in synaptic plasticity in the perirhinal cortex. The CREB-responsive microRNA miR-132 has been shown to regulate synaptic transmission and we set out to investigate a role for this microRNA in recognition memory and its underlying plasticity mechanisms. To this end we mediated the specific overexpression of miR-132 selectively in the rat perirhinal cortex and demonstrated impairment in short-term recognition memory. This functional deficit was associated with a reduction in both long-term depression and long-term potentiation. These results confirm that microRNAs are key coordinators of the intracellular pathways that mediate experience-dependent changes in the brain. In addition, these results demonstrate a role for miR-132 in the neuronal mechanisms underlying the formation of short-term recognition memory. PMID:22845676

The role of Drosophila Piezo in mechanical nociception.

PubMed

Kim, Sung Eun; Coste, Bertrand; Chadha, Abhishek; Cook, Boaz; Patapoutian, Ardem

2012-02-19

Transduction of mechanical stimuli by receptor cells is essential for senses such as hearing, touch and pain. Ion channels have a role in neuronal mechanotransduction in invertebrates; however, functional conservation of these ion channels in mammalian mechanotransduction is not observed. For example, no mechanoreceptor potential C (NOMPC), a member of transient receptor potential (TRP) ion channel family, acts as a mechanotransducer in Drosophila melanogaster and Caenorhabditis elegans; however, it has no orthologues in mammals. Degenerin/epithelial sodium channel (DEG/ENaC) family members are mechanotransducers in C. elegans and potentially in D. melanogaster; however, a direct role of its mammalian homologues in sensing mechanical force has not been shown. Recently, Piezo1 (also known as Fam38a) and Piezo2 (also known as Fam38b) were identified as components of mechanically activated channels in mammals. The Piezo family are evolutionarily conserved transmembrane proteins. It is unknown whether they function in mechanical sensing in vivo and, if they do, which mechanosensory modalities they mediate. Here we study the physiological role of the single Piezo member in D. melanogaster (Dmpiezo; also known as CG8486). Dmpiezo expression in human cells induces mechanically activated currents, similar to its mammalian counterparts. Behavioural responses to noxious mechanical stimuli were severely reduced in Dmpiezo knockout larvae, whereas responses to another noxious stimulus or touch were not affected. Knocking down Dmpiezo in sensory neurons that mediate nociception and express the DEG/ENaC ion channel pickpocket (ppk) was sufficient to impair responses to noxious mechanical stimuli. Furthermore, expression of Dmpiezo in these same neurons rescued the phenotype of the constitutive Dmpiezo knockout larvae. Accordingly, electrophysiological recordings from ppk-positive neurons revealed a Dmpiezo-dependent, mechanically activated current. Finally, we found that Dmpiezo and ppk function in parallel pathways in ppk-positive cells, and that mechanical nociception is abolished in the absence of both channels. These data demonstrate the physiological relevance of the Piezo family in mechanotransduction in vivo, supporting a role of Piezo proteins in mechanosensory nociception.

Reactive Oxygen Species/Hypoxia-Inducible Factor-1α/Platelet-Derived Growth Factor-BB Autocrine Loop Contributes to Cocaine-Mediated Alveolar Epithelial Barrier Damage

PubMed Central

Yang, Lu; Chen, Xufeng; Simet, Samantha M.; Hu, Guoku; Cai, Yu; Niu, Fang; Kook, Yeonhee

2016-01-01

Abuse of psychostimulants, such as cocaine, has been shown to be closely associated with complications of the lung, such as pulmonary hypertension, edema, increased inflammation, and infection. However, the mechanism by which cocaine mediates impairment of alveolar epithelial barrier integrity that underlies various pulmonary complications has not been well determined. Herein, we investigate the role of cocaine in disrupting the alveolar epithelial barrier function and the associated signaling cascade. Using the combinatorial electric cell–substrate impedance sensing and FITC-dextran permeability assays, we demonstrated cocaine-mediated disruption of the alveolar epithelial barrier, as evidenced by increased epithelial monolayer permeability with a concomitant loss of the tight junction protein zonula occludens-1 (Zo-1) in both mouse primary alveolar epithelial cells and the alveolar epithelial cell line, L2 cells. To dissect the signaling pathways involved in this process, we demonstrated that cocaine-mediated induction of permeability factors, platelet-derived growth factor (PDGF-BB) and vascular endothelial growth factor, involved reactive oxygen species (ROS)-dependent induction of hypoxia-inducible factor (HIF)-1α. Interestingly, we demonstrated that ROS-dependent induction of another transcription factor, nuclear factor erythroid-2–related factor-2, that did not play a role in cocaine-mediated barrier dysfunction. Importantly, this study identifies, for the first time, that ROS/HIF-1α/PDGF-BB autocrine loop contributes to cocaine-mediated barrier disruption via amplification of oxidative stress and downstream signaling. Corroboration of these cell culture findings in vivo demonstrated increased permeability of the alveolar epithelial barrier, loss of expression of Zo-1, and a concomitantly increased expression of both HIF-1α and PDGF-BB. Pharmacological blocking of HIF-1α significantly abrogated cocaine-mediated loss of Zo-1. Understanding the mechanism(s) by which cocaine mediates barrier dysfunction could provide insights into the development of potential therapeutic targets for cocaine-mediated pulmonary hypertension. PMID:27391108

Mucosal-associated invariant T cells in autoimmunity, immune-mediated diseases and airways disease.

PubMed

Hinks, Timothy S C

2016-05-01

Mucosal-associated invariant T (MAIT) cells are a novel class of innate-like T cells, expressing a semi-invariant T-cell receptor (TCR) and able to recognize small molecules presented on the non-polymorphic MHC-related protein 1. Their intrinsic effector-memory phenotype, enabling secretion of pro-inflammatory cytokines, and their relative abundance in humans imply a significant potential to contribute to autoimmune processes. However, as MAIT cells were unknown until recently and specific immunological tools were unavailable, little is known of their roles in disease. Here I review observations from clinical studies and animal models of autoimmune and immune-mediated diseases including the roles of MAIT cells in systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and airways diseases. MAIT cell deficiencies are frequently observed in peripheral blood, and at sites of disease such as the airways in asthma. However, MAIT cells have a specific sensitivity to suppression by therapeutic corticosteroids that may confound many of these observations, as may the tendency of the surface marker CD161 to activation-induced down-regulation. Nonetheless, the dependence on bacteria for the development of MAIT cells suggests a potentially important protective role linking the influences of early life microbial exposures and subsequent development of autoimmunity. Conversely, MAIT cells could contribute to chronic inflammation either through TCR-independent activation, or potentially by TCR recognition of as yet undiscovered ligands. Future research will be greatly facilitated by the immunological tools that are now available, including murine genetic models and human and murine specific tetramers. © 2016 The Authors. Immunology published by John Wiley & Sons Ltd.

The mediational role of identification in the relationship between experience mode and self-efficacy: Enactive role-playing versus passive observation.

PubMed

Peng, Wei

2008-12-01

Abstract Based on Social Cognitive Theory, this study proposes a new concept-mediated enactive experience to understand game playing effects on self-efficacy in the context of a health promotion role-playing game. An experiment demonstrated that a mediated enactive experience afforded by game playing was more effective than a mediated observational experience provided by game watching in influencing self-efficacy. It was found that identification with the game character partially mediated the relationship between experience mode and self-efficacy.

Melanopsin mediates light-dependent relaxation in blood vessels

PubMed Central

Sikka, Gautam; Hussmann, G. Patrick; Pandey, Deepesh; Cao, Suyi; Hori, Daijiro; Park, Jong Taek; Steppan, Jochen; Kim, Jae Hyung; Barodka, Viachaslau; Myers, Allen C.; Santhanam, Lakshmi; Nyhan, Daniel; Halushka, Marc K.; Koehler, Raymond C.; Snyder, Solomon H.; Shimoda, Larissa A.; Berkowitz, Dan E.

2014-01-01

Melanopsin (opsin4; Opn4), a non-image-forming opsin, has been linked to a number of behavioral responses to light, including circadian photo-entrainment, light suppression of activity in nocturnal animals, and alertness in diurnal animals. We report a physiological role for Opn4 in regulating blood vessel function, particularly in the context of photorelaxation. Using PCR, we demonstrate that Opn4 (a classic G protein-coupled receptor) is expressed in blood vessels. Force-tension myography demonstrates that vessels from Opn4−/− mice fail to display photorelaxation, which is also inhibited by an Opn4-specific small-molecule inhibitor. The vasorelaxation is wavelength-specific, with a maximal response at ∼430–460 nm. Photorelaxation does not involve endothelial-, nitric oxide-, carbon monoxide-, or cytochrome p450-derived vasoactive prostanoid signaling but is associated with vascular hyperpolarization, as shown by intracellular membrane potential measurements. Signaling is both soluble guanylyl cyclase- and phosphodiesterase 6-dependent but protein kinase G-independent. β-Adrenergic receptor kinase 1 (βARK 1 or GRK2) mediates desensitization of photorelaxation, which is greatly reduced by GRK2 inhibitors. Blue light (455 nM) regulates tail artery vasoreactivity ex vivo and tail blood blood flow in vivo, supporting a potential physiological role for this signaling system. This endogenous opsin-mediated, light-activated molecular switch for vasorelaxation might be harnessed for therapy in diseases in which altered vasoreactivity is a significant pathophysiologic contributor. PMID:25404319

Underlying spirituality and mental health: the role of burnout.

PubMed

Ho, Rainbow Tin Hung; Sing, Cheuk Yan; Fong, Ted Chun Tat; Au-Yeung, Friendly So Wah; Law, Kit Ying; Lee, Lai Fan; Ng, Siu Man

2016-01-01

This study investigated the effects of burnout on the relationship between spirituality and mental health among healthcare workers in Hong Kong. Using a cross-sectional design, 312 healthcare workers (mean age=38.6, SD=9.9; 77.7% females) in a mental rehabilitation institution completed a self-administered questionnaire on anxiety, depression, burnout, and daily spiritual experiences. Multivariate regressions were used to test the effects of burnout on the relationships between daily spiritual experiences and anxiety and depression. After adjusting for age, education level, marital status, and staff ranking, higher levels of daily spiritual experience were associated with lower levels of burnout (β=-0.22, p<0.01), depression (β=-0.68, p<0.01), and anxiety (β=-0.05, p<0.01). Burnout was found to have a significant partial mediating effect on the relationship between daily spiritual experiences and depression (z=-2.99, p<0.01), accounting for 37.8% of the variation in depression. Burnout also completely mediated the relationship between daily spiritual experiences and anxiety (z=-3.06, p<0.01), accounting for 73.9% of the variation in anxiety. The results suggested that the association between spirituality and mental health is influenced by the level of burnout, thereby supporting the role of burnout as a potential mediator. Moreover, day-to-day spiritual practice was found to be potentially protective against burnout and mental health problems. Future interventions could incorporate spirituality training to reduce burnout so as to improve the well-being of healthcare workers.

The Potential Link between Gut Microbiota and IgE-Mediated Food Allergy in Early Life

PubMed Central

Molloy, John; Allen, Katrina; Collier, Fiona; Tang, Mimi L. K.; Ward, Alister C.; Vuillermin, Peter

2013-01-01

There has been a dramatic rise in the prevalence of IgE-mediated food allergy over recent decades, particularly among infants and young children. The cause of this increase is unknown but one putative factor is a change in the composition, richness and balance of the microbiota that colonize the human gut during early infancy. The coevolution of the human gastrointestinal tract and commensal microbiota has resulted in a symbiotic relationship in which gut microbiota play a vital role in early life immune development and function, as well as maintenance of gut wall epithelial integrity. Since IgE mediated food allergy is associated with immune dysregulation and impaired gut epithelial integrity there is substantial interest in the potential link between gut microbiota and food allergy. Although the exact link between gut microbiota and food allergy is yet to be established in humans, recent experimental evidence suggests that specific patterns of gut microbiota colonization may influence the risk and manifestations of food allergy. An understanding of the relationship between gut microbiota and food allergy has the potential to inform both the prevention and treatment of food allergy. In this paper we review the theory and evidence linking gut microbiota and IgE-mediated food allergy in early life. We then consider the implications and challenges for future research, including the techniques of measuring and analyzing gut microbiota, and the types of studies required to advance knowledge in the field. PMID:24351744

Delusions and the Right Hemisphere: A Review of the Case for the Right Hemisphere as a Mediator of Reality-Based Belief.

PubMed

Gurin, Lindsey; Blum, Sonja

2017-01-01

Delusions are beliefs that remain fixed despite evidence that they are incorrect. Although the precise neural mechanism of delusional belief remains to be elucidated, there is a predominance of right-hemisphere lesions among patients with delusional syndromes accompanied by structural pathology, suggesting that right-hemisphere lesions, or networks with key nodes in the right hemisphere, may be playing a role. The authors discuss the potential theoretical basis and empiric support for a specific right-hemisphere role in delusion production, drawing on its roles in pragmatic communication; perceptual integration; attentional surveillance and anomaly/novelty detection; and belief updating.

The Role of Glia in Sleep Regulation and Function.

PubMed

Frank, Marcos G

2018-01-28

The cellular mechanisms governing the expression, regulation, and function of sleep are not entirely understood. The traditional view is that these mechanisms are neuronal. An alternative view is that glial brain cells may play important roles in these processes. Their ubiquity in the central nervous system makes them well positioned to modulate neuronal circuits that gate sleep and wake. Their ability to respond to chemical neuronal signals suggests that they form feedback loops with neurons that may globally regulate neuronal activity. Their potential role in detoxifying the brain, regulating neuronal metabolism, and promoting synaptic plasticity raises the intriguing possibility that glia mediate important functions ascribed to sleep.

To NFκB or not to NFκB: The Dilemma on How to Inhibit a Cancer Cell Fate Regulator

PubMed Central

Sorriento, Daniela; Illario, Maddalena; Finelli, Rosa; Iaccarino, Guido

2012-01-01

Nuclear factor κB (NFκB) is a transcription factor that plays an important role in carcinogenesis as well as in the regulation of inflammatory response. NFκB is constitutively expressed in tumours where it induces the expression of genes which promote cell proliferation, apoptotic events, angiogenesis, invasion and metastasis. Furthermore, many cancer cells show aberrant or constitutive NFκB activation that mediates resistance to chemo- and radio-therapy. Therefore, the inhibition of NFκB activity appears a potential therapeutic strategy for cancer treatment. In this review, we focus on the role of NFκB in carcinogenesis and summarize actual inhibitors of NFκB that could be potential therapeutic target in cancer therapy. PMID:23905066

FBI-1 enhances ETS-1 signaling activity and promotes proliferation of human colorectal carcinoma cells.

PubMed

Zhu, Min; Li, Mingyang; Zhang, Fan; Feng, Fan; Chen, Weihao; Yang, Yutao; Cui, Jiajun; Zhang, Dong; Linghu, Enqiang

2014-01-01

In this study, we investigated a potential regulatory role of FBI-1 in transcription factor activity of ETS-1. The protein interaction was identified between ETS-1 and FBI-1 in lovo cells. The accumulating data showed that FBI-1 promoted the recruitment of ETS-1 to endogenous promoter of its target genes and increase ETS-1 accumulation in the nuclear. Our work also indicated that the FBI-1 enhances ETS-1 transcription factor activity via down-regulating p53-mediated inhibition on ETS-1. Further, FBI-1 plays a role in regulation of colorectal carcinoma cells proliferation. These findings supported that FBI-1 might be a potential molecule target for treating colorectal carcinoma.

FBI-1 Enhances ETS-1 Signaling Activity and Promotes Proliferation of Human Colorectal Carcinoma Cells

PubMed Central

Chen, Weihao; Yang, Yutao; Cui, Jiajun; Zhang, Dong; Linghu, Enqiang

2014-01-01

In this study, we investigated a potential regulatory role of FBI-1 in transcription factor activity of ETS-1. The protein interaction was identified between ETS-1 and FBI-1 in lovo cells. The accumulating data showed that FBI-1 promoted the recruitment of ETS-1 to endogenous promoter of its target genes and increase ETS-1 accumulation in the nuclear. Our work also indicated that the FBI-1 enhances ETS-1 transcription factor activity via down-regulating p53-mediated inhibition on ETS-1. Further, FBI-1 plays a role in regulation of colorectal carcinoma cells proliferation. These findings supported that FBI-1 might be a potential molecule target for treating colorectal carcinoma. PMID:24857950

Targeting BET bromodomain proteins in solid tumors

PubMed Central

Sahai, Vaibhav; Redig, Amanda J.; Collier, Katharine A.; Eckerdt, Frank D.; Munshi, Hidayatullah G.

2016-01-01

There is increasing interest in inhibitors targeting BET (bromodomain and extra-terminal) proteins because of the association between this family of proteins and cancer progression. BET inhibitors were initially shown to have efficacy in hematologic malignancies; however, a number of studies have now shown that BET inhibitors can also block progression of non-hematologic malignancies. In this Review, we summarize the efficacy of BET inhibitors in select solid tumors; evaluate the role of BET proteins in mediating resistance to current targeted therapies; and consider potential toxicities of BET inhibitors. We also evaluate recently characterized mechanisms of resistance to BET inhibitors; summarize ongoing clinical trials with these inhibitors; and discuss potential future roles of BET inhibitors in patients with solid tumors. PMID:27283767

Mediator: A key regulator of plant development.

PubMed

Buendía-Monreal, Manuel; Gillmor, C Stewart

2016-11-01

Mediator is a multiprotein complex that regulates transcription at the level of RNA pol II assembly, as well as through regulation of chromatin architecture, RNA processing and recruitment of epigenetic marks. Though its modular structure is conserved in eukaryotes, its subunit composition has diverged during evolution and varies in response to environmental and tissue-specific inputs, suggesting different functions for each subunit and/or Mediator conformation. In animals, Mediator has been implicated in the control of differentiation and morphogenesis through modulation of numerous signaling pathways. In plants, studies have revealed roles for Mediator in regulation of cell division, cell fate and organogenesis, as well as developmental timing and hormone responses. We begin this review with an overview of biochemical mechanisms of yeast and animal Mediator that are likely to be conserved in all eukaryotes, as well as a brief discussion of the role of Mediator in animal development. We then present a comprehensive review of studies of the role of Mediator in plant development. Finally, we point to important questions for future research on the role of Mediator as a master coordinator of development. Copyright © 2016 Elsevier Inc. All rights reserved.

Calcium Currents of Olfactory Bulb Juxtaglomerular Cells: Profile and Multiple Conductance Plateau Potential Simulation

PubMed Central

Masurkar, Arjun V.; Chen, Wei R.

2011-01-01

The olfactory glomerulus is the locus of information transfer between olfactory sensory neurons and output neurons of the olfactory bulb. Juxtaglomerular cells (JGCs) may influence intraglomerular processing by firing plateau potentials that support multiple spikes. It is unclear what inward currents mediate this firing pattern. In previous work, we characterized potassium currents of JGCs. We focus here on the inward currents using whole cell current clamp and voltage recording in a rat in vitro slice preparation, as well as computer simulation. We first showed that sodium current was not required to mediate plateau potentials. Voltage clamp characterization of calcium current (ICa) determined that ICa consisted of a slow activating, rapidly inactivating (τ10%–90% rise 6–8ms, τinactivation 38–77ms) component Icat1, similar to T-type currents, and a sustained (τinactivation≫500ms) component Icat2, likely composed of L-type and P/Q-type currents. We used computer simulation to test their roles in plateau potential firing. We robustly modeled Icat1 and Icat2 to Hodgkin-Huxley schemes (m3h and m2, respectively) and simulated a JGC plateau potential with 6 conductances: calcium currents as above, potassium currents from our prior study (A-type Ikt1, D-type Ikt2, delayed rectifier Ikt3), and a fast sodium current (INa). We demonstrated that Icat1 was required for mediating the plateau potential, unlike INa and Icat2, and its τinactivation determined plateau duration. We also found that Ikt1 dictated plateau potential shape more than Ikt2 and Ikt3. The influence of these two transient and opposing conductances suggests a unique mechanism of plateau potential physiology. PMID:21704681

Over-expression of Thioredoxin-1 mediates growth, survival, and chemoresistance and is a druggable target in diffuse large B-cell lymphoma

PubMed Central

Li, Changping; Thompson, Michael A.; Tamayo, Archito T.; Zuo, Zhuang; Lee, John; Vega, Francisco; Ford, Richard J.; Pham, Lan V.

2012-01-01

Diffuse Large B cell lymphomas (DLBCL) are the most prevalent of the non-Hodgkin lymphomas and are currently initially treated fairly successfully, but frequently relapse as refractory disease, resulting in poor salvage therapy options and short survival. The greatest challenge in improving survival of DLBCL patients is overcoming chemo-resistance, whose basis is poorly understood. Among the potential mediators of DLBCL chemo-resistance is the thioredxoin (Trx) family, primarily because Trx family members play critical roles in the regulation of cellular redox homeostasis, and recent studies have indicated that dysregulated redox homeostasis also plays a key role in chemoresistance. In this study, we showed that most of the DLBCL-derived cell lines and primary DLBCL cells express higher basal levels of Trx-1 than normal B cells and that Trx-1 expression level is associated with decreased patients survival. Our functional studies showed that inhibition of Trx-1 by small interfering RNA or a Trx-1 inhibitor (PX-12) inhibited DLBCL cell growth, clonogenicity, and also sensitized DLBCL cells to doxorubicin-induced cell growth inhibition in vitro. These results indicate that Trx-1 plays a key role in cell growth and survival, as well as chemoresistance, and is a potential target to overcome drug resistance in relapsed/refractory DLBCL. PMID:22447839

The Relationship of Instructor Self-Disclosure, Nonverbal Immediacy, and Credibility to Student Incivility in the College Classroom

ERIC Educational Resources Information Center

Miller, Ann Neville; Katt, James A.; Brown, Tim; Sivo, Stephen A.

2014-01-01

In this study, we examined the potential mediating role of instructor credibility in the relationship of instructor self-disclosure and nonverbal immediacy to student incivility in the college classroom. Four hundred thirty-eight students completed online questionnaires regarding the instructor of the class they attended prior to the one in which…

Moderator and Mediator Effects of Scuba Diving Specialization on Marine-Based Environmental Knowledge-Behavior Contingency

ERIC Educational Resources Information Center

Thapa, Brijesh; Graefe, Alan R.; Meyer, Louisa A.

2005-01-01

Given the growth in scuba diving activities and the importance of environmental education programs to alleviate the potential impacts on coral reef ecosystems, there is a need to better understand the diving community, its environmental knowledge, and subsequent behavioral actions. The purpose of this study was to explore the role or influence of…

A Partial Exploration of the Potential Energy Surfaces of SCN and HSCN: Implications for the Enzyme-Mediated Detoxification of Cyanide

DTIC Science & Technology

2009-01-01

its role in toxicology , Tox. Sci. 78 (2004) 185–188. [6] (a) B.H. Sorbo, Crystalline rhodanese. I. Purification and physicochemical exam- ination, Acta...the devel- opment of quantitative structure–activity relationships ( QSARs ). pKa-values of phenols and aromatic and aliphatic carboxylic acids, Chemosphere 19 (1989) 1595.

Social Anxiety and Socioemotional Functioning during Early Adolescence: The Mediating Role of Best Friend Emotion Socialization

ERIC Educational Resources Information Center

Borowski, Sarah K.; Zeman, Janice; Braunstein, Kara

2018-01-01

Best friend expected emotion socialization responses were examined as a potential explanation for the link between social anxiety and youths' friendship quality and dysfunctional emotion regulation (ER). A community sample of 202 young adolescents ([X-bar][subscript age] = 12.66; 52.5% girls, 75.7% White) within 101 same-sex, reciprocated best…

Effects of Child Psychopathology on Maternal Depression: The Mediating Role of Child-Related Acute and Chronic Stressors

ERIC Educational Resources Information Center

Raposa, Elizabeth B.; Hammen, Constance L.; Brennan, Patricia A.

2011-01-01

In light of recent research highlighting the potential effects of children's behavior on mothers' mental health, the current study examined 679 mothers and their adolescent children from a community-based sample to determine the effects of youth psychopathology on maternal depression and levels of child-related stress in mothers' lives. It was…

Students' Attitudes and Intentions toward Higher Education as Determinants for Grade Performance

ERIC Educational Resources Information Center

Malmström, Malin; Öqvist, Anna

2018-01-01

Little empirical evidence is available on what drives young people to engage in higher education. Such knowledge is crucial in order to motivate students to make the most of their potential. This study surveyed a total of 294 Swedish high school students. The result shows that intentions play a mediating role between students' attitudes and the…

Developmental Pathways to Depressive Symptoms in Adolescence: A Multi-Wave Prospective Study of Negative Emotionality, Stressors, and Anxiety

ERIC Educational Resources Information Center

Barrocas, Andrea L.; Hankin, Benjamin L.

2011-01-01

This study examined two potential developmental pathways through which the temperament risk factor of negative emotionality (NE) leads to prospective increases in depressive symptoms through the mediating role of stressors and anxious symptoms in a sample of early to middle adolescents (N = 350, 6th-10th graders). The primary hypothesized model…

Disentangling the Relationship between Working Memory and Language: The Roles of Short-Term Storage and Cognitive Control

ERIC Educational Resources Information Center

Engel de Abreu, Pascale Marguerite Josiane; Gathercole, Susan Elizabeth; Martin, Romain

2011-01-01

This study investigates the relationship between working memory and language in young children growing up in a multilingual environment. The aim is to explore whether mechanisms of short-term storage and cognitive control hold similar relations to emerging language skills and to investigate if potential links are mediated by related cognitive…

New ADCY3 Variants Dance in Obesity Etiology.

PubMed

Tian, Yan; Peng, Boqiang; Fu, Xianghui

2018-02-14

The genetic etiology for obesity-related traits remains elusive. Recent studies link novel ADCY3 variants to obesity and diabetes, and identify an important role of ADCY3-mediated signaling at neuronal primary cilia in the predisposition of obesity. These findings provide new information on obesity etiology and suggest potential anti-obesity therapeutic strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Association of Age, Sense of Control, Optimism, and Self-Esteem with Emotional Distress

ERIC Educational Resources Information Center

Jiménez, M. Guadalupe; Montorio, Ignacio; Izal, María

2017-01-01

The aim of this study was to test a model of emotional distress, which incorporates the potential mediator role of positive resources (sense of control, self-esteem, and optimism) in the association of age with emotional distress. The study used a cross-sectional design with intentional sampling and the voluntary participation of 325 adults…

Prostaglandins and Inflammation

PubMed Central

Ricciotti, Emanuela; FitzGerald, Garret A.

2011-01-01

Prostaglandins are lipid autacoids derived from arachidonic acid. They both sustain homeostatic functions and mediate pathogenic mechanisms, including the inflammatory response. They are generated from arachidonate by the action of cyclooxygenase (COX) isoenzymes and their biosynthesis is blocked by nonsteroidal anti-inflammatory drugs (NSAIDs), including those selective for inhibition of COX-2. Despite the clinical efficacy of NSAIDs, prostaglandins may function in both the promotion and resolution of inflammation. This review summarizes insights into the mechanisms of prostaglandin generation and the roles of individual mediators and their receptors in modulating the inflammatory response. Prostaglandin biology has potential clinical relevance for atherosclerosis, the response to vascular injury and aortic aneurysm. PMID:21508345

The mediating role of dietary factors and leisure time physical activity on socioeconomic inequalities in body mass index among Australian adults.

PubMed

Gearon, Emma; Backholer, Kathryn; Hodge, Allison; Peeters, Anna

2013-12-21

The relationship between socioeconomic position and obesity has been clearly established, however, the extent to which specific behavioural factors mediate this relationship is less clear. This study aimed to ascertain the contribution of specific dietary elements and leisure-time physical activity (LTPA) to variations in obesity with education in the baseline (1990-1994) Melbourne Collaborative Cohort Study (MCCS). 18, 489 women and 12, 141 men were included in this cross-sectional analysis. A series of linear regression models were used in accordance with the products of coefficients method to examine the mediating role of alcohol, soft drink (regular and diet), snacks (healthy and sweet), savoury items (healthy and unhealthy), meeting fruit and vegetable guidelines and LTPA on the relationship between education and body mass index (BMI). Compared to those with lowest educational attainment, those with the highest educational attainment had a 1 kg/m2 lower BMI. Among men and women, 27% and 48%, respectively, of this disparity was attributable to differences in LTPA and diet. Unhealthy savoury item consumption and LTPA contributed most to the mediated effects for men and women. Alcohol and diet soft drink were additionally important mediators for women. Diet and LTPA are potentially modifiable behavioural risk factors for the development of obesity that contribute substantially to inequalities in BMI. Our findings highlight the importance of specific behaviours which may be useful to the implementation of effective, targeted public policy to reduce socioeconomic inequalities in obesity.

Asy2/Mer2: an evolutionarily conserved mediator of meiotic recombination, pairing, and global chromosome compaction

PubMed Central

Tessé, Sophie; Bourbon, Henri-Marc; Debuchy, Robert; Budin, Karine; Dubois, Emeline; Liangran, Zhang; Antoine, Romain; Piolot, Tristan; Kleckner, Nancy; Zickler, Denise; Espagne, Eric

2017-01-01

Meiosis is the cellular program by which a diploid cell gives rise to haploid gametes for sexual reproduction. Meiotic progression depends on tight physical and functional coupling of recombination steps at the DNA level with specific organizational features of meiotic-prophase chromosomes. The present study reveals that every step of this coupling is mediated by a single molecule: Asy2/Mer2. We show that Mer2, identified so far only in budding and fission yeasts, is in fact evolutionarily conserved from fungi (Mer2/Rec15/Asy2/Bad42) to plants (PRD3/PAIR1) and mammals (IHO1). In yeasts, Mer2 mediates assembly of recombination–initiation complexes and double-strand breaks (DSBs). This role is conserved in the fungus Sordaria. However, functional analysis of 13 mer2 mutants and successive localization of Mer2 to axis, synaptonemal complex (SC), and chromatin revealed, in addition, three further important functions. First, after DSB formation, Mer2 is required for pairing by mediating homolog spatial juxtaposition, with implications for crossover (CO) patterning/interference. Second, Mer2 participates in the transfer/maintenance and release of recombination complexes to/from the SC central region. Third, after completion of recombination, potentially dependent on SUMOylation, Mer2 mediates global chromosome compaction and post-recombination chiasma development. Thus, beyond its role as a recombinosome–axis/SC linker molecule, Mer2 has important functions in relation to basic chromosome structure. PMID:29021238

Crying in Middle Childhood: A Report on Gender Differences.

PubMed

Jellesma, Francine C; Vingerhoets, Ad J J M

2012-10-01

The aims of this study were (1) to confirm gender differences in crying in middle childhood and (2) to identify factors that may explain why girls cry more than boys in a Dutch sample (North Holland and Utrecht). We examined 186 children's (age: 9-13 years) self-reports on crying, catharsis, seeking support for feelings, and internalizing feelings. Girls reported a greater crying frequency and crying proneness, and more emotional and physical catharsis after crying. In addition, they more frequently sought support for feelings and more often experienced sadness and somatic complaints than boys. Seeking help for negative feelings and the experience of sadness and somatic complaints were positively associated with crying frequency and crying proneness. Emotional catharsis was positively linked to crying proneness. Support was found for the potential mediating role of sadness and somatic complaints with respect to the gender difference in crying frequency and for the potential mediating role of emotional catharsis and somatic complaints for crying proneness. This study demonstrates that gender differences in crying frequency already exist in middle childhood and the findings suggest a linkage between these gender differences in crying and psychosocial factors.

Role of Platelet-Derived Microvesicles As Crosstalk Mediators in Atherothrombosis and Future Pharmacology Targets: A Link between Inflammation, Atherosclerosis, and Thrombosis

PubMed Central

Badimon, Lina; Suades, Rosa; Fuentes, Eduardo; Palomo, Iván; Padró, Teresa

2016-01-01

Reports in the last decade have suggested that the role of platelets in atherosclerosis and its thrombotic complications may be mediated, in part, by local secretion of platelet-derived microvesicles (pMVs), small cell blebs released during the platelet activation process. MVs are the most abundant cell-derived microvesicle subtype in the circulation. High concentrations of circulating MVs have been reported in patients with atherosclerosis, acute vascular syndromes, and/or diabetes mellitus, suggesting a potential correlation between the quantity of microvesicles and the clinical severity of the atherosclerotic disease. pMVs are considered to be biomarkers of disease but new information indicates that pMVs are also involved in signaling functions. pMVs evoke or promote haemostatic and inflammatory responses, neovascularization, cell survival, and apoptosis, processes involved in the pathophysiology of cardiovascular disease. This review is focused on the complex cross-talk between platelet-derived microvesicles, inflammatory cells and vascular elements and their relevance in the development of the atherosclerotic disease and its clinical outcomes, providing an updated state-of-the art of pMV involvement in atherothrombosis and pMV potential use as therapeutic agent influencing cardiovascular biomedicine in the future. PMID:27630570

Dissociable Effects of Subthalamic Stimulation in Obsessive Compulsive Disorder on Risky Reward and Loss Prospects.

PubMed

Voon, Valerie; Droux, Fabien; Chabardes, Stephan; Bougerol, Thierry; Kohl, Sina; David, Olivier; Krack, Paul; Polosan, Mircea

2018-07-01

Our daily decisions involve an element of risk, a behavioral process that is potentially modifiable. Here we assess the role of the associative-limbic subthalamic nucleus (STN) in obsessive compulsive disorder (OCD) testing on and off deep-brain stimulation (DBS) on anticipatory risk taking to obtain rewards and avoid losses. We assessed 12 OCD STN DBS in a randomized double-blind within-subject cross-over design. STN DBS decreased risk taking to rewards (p = 0.02) and greater risk taking to rewards was positively correlated with OCD severity (p = 0.01) and disease duration (p = 0.01). STN DBS was also associated with impaired subjective discrimination of loss magnitude (p < 0.05), an effect mediated by acute DBS rather than chronic DBS. We highlight a role for the STN in mediating dissociable valence prospects on risk seeking. STN stimulation decreases risk taking to rewards and impairs discrimination of loss magnitude. These findings may have implications for behavioral symptoms related to STN DBS and the potential for STN DBS for the treatment of psychiatric disorders. Copyright © 2018. Published by Elsevier Ltd.

Metabolic control of female puberty: potential therapeutic targets.

PubMed

Castellano, Juan M; Tena-Sempere, Manuel

2016-10-01

The onset of puberty in females is highly sensitive to the nutritional status and the amount of energy reserves of the organism. This metabolic information is sensed and transmitted to hypothalamic GnRH neurons, considered to be ultimately responsible for triggering puberty through the coordinated action of different peripheral hormones, central neurotransmitters, and molecular mediators. This article will review and discuss (i) the relevant actions of the adipose hormone leptin, as a stimulatory/permissive signal, and the gut hormone ghrelin, as an inhibitory factor, in the metabolic control of female puberty; (ii) the crucial role of the hypothalamic kisspeptin neurons, recently emerged as essential gatekeepers of puberty, in transmitting this metabolic information to GnRH neurons; and (iii) the potential involvement of key cellular energy sensors, such as mTOR, as molecular mediators in this setting. The thorough characterization of the physiological roles of the above elements in the metabolic control of female puberty, along with the discovery of novel factors, pathways, and mechanisms involved, will promote our understanding of the complex networks connecting metabolism and puberty and, ultimately, will aid in the design of target-specific treatments for female pubertal disorders linked to conditions of metabolic stress.

The effects of gender discrimination on refugee torture survivors: a cross-cultural traumatology perspective.

PubMed

Kira, Ibrahim A; Smith, Iris; Lewandowski, Linda; Templin, Thomas

2010-09-01

Trauma developmental theory identifies gender discrimination (GD) as a type of persistent, ongoing trauma that has the potential for serious, negative effects on mental health. This study was conducted to examine the potential role of GD in the development of cumulative trauma disorders (CTD) and symptoms of posttraumatic stress disorder (PTSD) as well as the role of GD in mediating the effects of other traumas on these disorders. The sample included 160 female torture survivors from more than 30 countries. Measures of PTSD, CTD, and types of trauma exposure were acquired as part of a larger study on refugee torture survivors. Structural equation modeling was used to test several plausible models for the direct and indirect effects of GD on PTSD and CTD, within the context of other trauma exposure. Results suggest that GD mediates the effects of identity traumas on CTD and PTSD. GD also had direct effects on CTD, including relationships with dissociation, suicidality, and deficits in executive function. GD did not appear to directly influence the development of PTSD. The implications of these results for assessment and treatment of women's trauma-related disorders as well as strategies for their prevention are discussed.

Caregiver mental health and potentially harmful caregiving behavior: the central role of caregiver anger.

PubMed

Macneil, Gordon; Kosberg, Jordan I; Durkin, Daniel W; Dooley, W Keith; Decoster, Jamie; Williamson, Gail M

2010-02-01

Caregivers feeling stress and experiencing mental health problems can be at risk for engaging in abusive acts against elderly care recipients. Potentially harmful behavior (PHB) was used as a measure of caregivers' engagement in, or fear of engagement in, behavior that places dependent care recipients at risk of physical and/or psychological maltreatment and may be seen as an antecedent of, or a proxy for, identifiably abusive behavior. The study examined the ability of anger to mediate and moderate the relations of depression, resentment, and anxiety with PBH. Data are from the first wave of the second Family Relationships in Late Life study of caregivers of community-dwelling elderly care recipients with whom they coreside. Caregivers (N = 417) completed face-to-face interviews. Anger was found to mediate the relation between anxiety and PHB. Anger both mediates and moderates the relations of both depression and resentment with PHB in a dynamic way such that the mediating effect of anger increases substantially with increased scores on both depression and resentment. Identifying anger levels among caregivers who report symptoms of depression is warranted. Reducing depression in caregivers who report high levels of anger may result in reductions of PHB. Screening for resentment is warranted, as the relation between resentment and anger is similar to that between depression and anger.

The role of strain hardening in the transition from dislocation-mediated to frictional deformation of marbles within the Karakoram Fault Zone, NW India

NASA Astrophysics Data System (ADS)

Wallis, David; Lloyd, Geoffrey E.; Hansen, Lars N.

2018-02-01

The onset of frictional failure and potentially seismogenic deformation in carbonate rocks undergoing exhumation within fault zones depends on hardening processes that reduce the efficiency of aseismic dislocation-mediated deformation as temperature decreases. However, few techniques are available for quantitative analysis of dislocation slip system activity and hardening in natural tectonites. Electron backscatter diffraction maps of crystal orientations offer one such approach via determination of Schmid factors, if the palaeostress conditions can be inferred and the critical resolved shear stresses of slip systems are constrained. We analyse calcite marbles deformed in simple shear within the Karakoram Fault Zone, NW India, to quantify changes in slip system activity as the rocks cooled during exhumation. Microstructural evidence demonstrates that between ∼300 °C and 200-250 °C the dominant deformation mechanisms transitioned from dislocation-mediated flow to twinning and frictional failure. However, Schmid factor analysis, considering critical resolved shear stresses for yield of undeformed single crystals, indicates that the fraction of grains with sufficient resolved shear stress for glide apparently increased with decreasing temperature. Misorientation analysis and previous experimental data indicate that strain-dependent work hardening is responsible for this apparent inconsistency and promoted the transition from dislocation-mediated flow to frictional, and potentially seismogenic, deformation.

TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival

PubMed Central

Raphaël, Maylis; Lehen’kyi, V’yacheslav; Vandenberghe, Matthieu; Beck, Benjamin; Khalimonchyk, Sergiy; Vanden Abeele, Fabien; Farsetti, Leonardo; Germain, Emmanuelle; Bokhobza, Alexandre; Mihalache, Adriana; Gosset, Pierre; Romanin, Christoph; Clézardin, Philippe; Skryma, Roman; Prevarskaya, Natalia

2014-01-01

Transient receptor potential vanilloid subfamily member 6 (TRPV6) is a highly selective calcium channel that has been considered as a part of store-operated calcium entry (SOCE). Despite its first discovery in the early 2000s, the role of this channel in prostate cancer (PCa) remained, until now, obscure. Here we show that TRPV6 mediates calcium entry, which is highly increased in PCa due to the remodeling mechanism involving the translocation of the TRPV6 channel to the plasma membrane via the Orai1/TRPC1-mediated Ca2+/Annexin I/S100A11 pathway, partially contributing to SOCE. The TRPV6 calcium channel is expressed de novo by the PCa cell to increase its survival by enhancing proliferation and conferring apoptosis resistance. Xenografts in nude mice and bone metastasis models confirmed the remarkable aggressiveness of TRPV6-overexpressing tumors. Immunohistochemical analysis of these demonstrated the increased expression of clinical markers such as Ki-67, prostate specific antigen, synaptophysin, CD31, and CD56, which are strongly associated with a poor prognosis. Thus, the TRPV6 channel acquires its oncogenic potential in PCa due to the remodeling mechanism via the Orai1-mediated Ca2+/Annexin I/S100A11 pathway. PMID:25172921

The role of sleep problems in the relationship between peer victimization and antisocial behavior: A five-year longitudinal study.

PubMed

Chang, Ling-Yin; Wu, Wen-Chi; Wu, Chi-Chen; Lin, Linen Nymphas; Yen, Lee-Lan; Chang, Hsing-Yi

2017-01-01

Peer victimization in children and adolescents is a serious public health concern. Growing evidence exists for negative consequences of peer victimization, but research has mostly been short term and little is known about the mechanisms that moderate and mediate the impacts of peer victimization on subsequent antisocial behavior. The current study intended to examine the longitudinal relationship between peer victimization in adolescence and antisocial behavior in young adulthood and to determine whether sleep problems influence this relationship. In total, 2006 adolescents participated in a prospective study from 2009 to 2013. The moderating role of sleep problems was examined by testing the significance of the interaction between peer victimization and sleep problems. The mediating role of sleep problems was tested by using bootstrapping mediational analyses. All analyses were conducted using SAS 9.3 software. We found that peer victimization during adolescence was positively and significantly associated with antisocial behavior in young adulthood (β = 0.10, p < 0.0001). This association was mediated, but not moderated by sleep problems. Specifically, peer victimization first increased levels of sleep problems, which in turn elevated the risk of antisocial behavior (indirect effect: 0.01, 95% bootstrap confidence interval: 0.004, 0.021). These findings imply that sleep problems may operate as a potential mechanism through which peer victimization during adolescence leads to increases in antisocial behavior in young adulthood. Prevention and intervention programs that target sleep problems may yield benefits for decreasing antisocial behavior in adolescents who have been victimized by peers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mast cells and their mediators in cutaneous wound healing--active participants or innocent bystanders?

PubMed

Artuc, M; Hermes, B; Steckelings, U M; Grützkau, A; Henz, B M

1999-02-01

Mast cells are traditionally viewed as effector cells of immediate type hypersensitivity reactions. There is, however, a growing body of evidence that the cells might play an important role in the maintenance of tissue homeostasis and repair. We here present our own data and those from the literature elucidating the possible role of mast cells during wound healing. Studies on the fate of mast cells in scars of varying ages suggest that these cells degranulate during wounding, with a marked decrease of chymase-positive cells, although the total number of cells does not decrease, based on SCF-receptor staining. Mast cells contain a plethora of preformed mediators like heparin, histamine, tryptase, chymase, VEGF and TNF-alpha which, on release during the initial stages of wound healing, affect bleeding and subsequent coagulation and acute inflammation. Various additional vasoactive and chemotactic, rapidly generated mediators (C3a, C5a, LTB4, LTC4, PAF) will contribute to these processes, whereas mast cell-derived proinflammatory and growth promoting peptide mediators (VEGF, FGF-2, PDGF, TGF-beta, NGF, IL-4, IL-8) contribute to neoangiogenesis, fibrinogenesis or re-epithelization during the repair process. The increasing number of tryptase-positive mast cells in older scars suggest that these cells continue to be exposed to specific chemotactic, growth- and differentiation-promoting factors throughout the process of tissue remodelling. All these data indicate that mast cells contribute in a major way to wound healing. their role as potential initiators of or as contributors to this process, compared to other cell types, will however have to be further elucidated.

p75 neurotrophin receptor cleavage by α- and γ-secretases is required for neurotrophin-mediated proliferation of brain tumor-initiating cells.

PubMed

Forsyth, Peter A; Krishna, Niveditha; Lawn, Samuel; Valadez, J Gerardo; Qu, Xiaotao; Fenstermacher, David A; Fournier, Michelle; Potthast, Lisa; Chinnaiyan, Prakash; Gibney, Geoffrey T; Zeinieh, Michele; Barker, Philip A; Carter, Bruce D; Cooper, Michael K; Kenchappa, Rajappa S

2014-03-21

Malignant gliomas are highly invasive, proliferative, and resistant to treatment. Previously, we have shown that p75 neurotrophin receptor (p75NTR) is a novel mediator of invasion of human glioma cells. However, the role of p75NTR in glioma proliferation is unknown. Here we used brain tumor-initiating cells (BTICs) and show that BTICs express neurotrophin receptors (p75NTR, TrkA, TrkB, and TrkC) and their ligands (NGF, brain-derived neurotrophic factor, and neurotrophin 3) and secrete NGF. Down-regulation of p75NTR significantly decreased proliferation of BTICs. Conversely, exogenouous NGF stimulated BTIC proliferation through α- and γ-secretase-mediated p75NTR cleavage and release of its intracellular domain (ICD). In contrast, overexpression of the p75NTR ICD induced proliferation. Interestingly, inhibition of Trk signaling blocked NGF-stimulated BTIC proliferation and p75NTR cleavage, indicating a role of Trk in p75NTR signaling. Further, blocking p75NTR cleavage attenuated Akt activation in BTICs, suggesting role of Akt in p75NTR-mediated proliferation. We also found that p75NTR, α-secretases, and the four subunits of the γ-secretase enzyme were elevated in glioblastoma multiformes patients. Importantly, the ICD of p75NTR was commonly found in malignant glioma patient specimens, suggesting that the receptor is activated and cleaved in patient tumors. These results suggest that p75NTR proteolysis is required for BTIC proliferation and is a novel potential clinical target.

p75 Neurotrophin Receptor Cleavage by α- and γ-Secretases Is Required for Neurotrophin-mediated Proliferation of Brain Tumor-initiating Cells*

PubMed Central

Forsyth, Peter A.; Krishna, Niveditha; Lawn, Samuel; Valadez, J. Gerardo; Qu, Xiaotao; Fenstermacher, David A.; Fournier, Michelle; Potthast, Lisa; Chinnaiyan, Prakash; Gibney, Geoffrey T.; Zeinieh, Michele; Barker, Philip A.; Carter, Bruce D.; Cooper, Michael K.; Kenchappa, Rajappa S.

2014-01-01

Malignant gliomas are highly invasive, proliferative, and resistant to treatment. Previously, we have shown that p75 neurotrophin receptor (p75NTR) is a novel mediator of invasion of human glioma cells. However, the role of p75NTR in glioma proliferation is unknown. Here we used brain tumor-initiating cells (BTICs) and show that BTICs express neurotrophin receptors (p75NTR, TrkA, TrkB, and TrkC) and their ligands (NGF, brain-derived neurotrophic factor, and neurotrophin 3) and secrete NGF. Down-regulation of p75NTR significantly decreased proliferation of BTICs. Conversely, exogenouous NGF stimulated BTIC proliferation through α- and γ-secretase-mediated p75NTR cleavage and release of its intracellular domain (ICD). In contrast, overexpression of the p75NTR ICD induced proliferation. Interestingly, inhibition of Trk signaling blocked NGF-stimulated BTIC proliferation and p75NTR cleavage, indicating a role of Trk in p75NTR signaling. Further, blocking p75NTR cleavage attenuated Akt activation in BTICs, suggesting role of Akt in p75NTR-mediated proliferation. We also found that p75NTR, α-secretases, and the four subunits of the γ-secretase enzyme were elevated in glioblastoma multiformes patients. Importantly, the ICD of p75NTR was commonly found in malignant glioma patient specimens, suggesting that the receptor is activated and cleaved in patient tumors. These results suggest that p75NTR proteolysis is required for BTIC proliferation and is a novel potential clinical target. PMID:24519935

The gender gap in student engagement: The role of teachers' autonomy support, structure, and involvement.

PubMed

Lietaert, Sofie; Roorda, Debora; Laevers, Ferre; Verschueren, Karine; De Fraine, Bieke

2015-12-01

The gender gap in education in favour of girls is a widely known phenomenon. Boys generally have higher dropout rates, obtain lower grades, and show lower engagement. Insight into factors related to these academic outcomes could help to address the gender gap. This study investigated, for Dutch language classes, (1) how boys and girls differ in behavioural engagement, (2) which teacher support dimensions (autonomy support, structure, involvement) may explain gender differences in engagement (mediation hypothesis), and (3) whether and which of these teacher support dimensions matter more for boys' as opposed to girls' engagement (moderation or differential effects hypothesis). A total of 385 Grade 7 students and their 15 language teachers participated in this study. Teacher support was assessed through student reports. Student engagement was measured using student, teacher, and observer reports. By means of structural equation modelling, the mediating role of the teacher support dimensions for gender differences in behavioural engagement was tested. The potential differential role of the teacher support dimensions for boys' and girls' engagement was investigated through multigroup analysis. Boys were less engaged than girls and reported lower support from their teacher. Autonomy support and involvement partially mediated the relationship between gender and behavioural engagement. Autonomy support was demonstrated to be a protective factor for boys' engagement but not for girls'. Structure and involvement contributed equally to engagement for both sexes. Although involvement and autonomy support partly explained the gender gap in engagement (mediation hypothesis), more support was found for differential effects of autonomy support on boys' versus girls' engagement (differential effects hypothesis). © 2015 The British Psychological Society.

Self-perceived provision of patient centered care by healthcare professionals: The role of emotional intelligence and general self-efficacy.

PubMed

Sommaruga, Marinella; Casu, Giulia; Giaquinto, Francesco; Gremigni, Paola

2017-05-01

This study aimed to investigate whether healthcare professionals' emotional intelligence (EI) is associated with self-perceived provision of patient-centered care (PCC), taking into account the potential mediating effect of general self-efficacy (GSE). A sample of 318 healthcare professionals, recruited in 2015 among four hospitals in Italy, completed the Provider-Patient Relationship Questionnaire, the Emotional Intelligence Scale, and the General Self-Efficacy scale. A structural equation model was tested with GSE mediating the relationship between EI and self-perceived provision of PCC. Groups of participants based on gender, profession, and work setting were also compared on the study variables. EI had direct effects on the self-perceived provision of PCC dimensions. GSE partially mediated only the relationship between EI and involving the patient in care. Healthcare professionals in rehabilitation units showed higher self-perceived provision of PCC than those in acute care or ambulatory services. Self-perceived provision of PCC seems to have the potential to be improved by EI and to be distinguishable from GSE. Since EI can be developed, findings of this study have potential implications for improving PCC through continuing education interventions for healthcare professionals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Mental health consequences of international migration for Vietnamese Americans and the mediating effects of physical health and social networks: results from a natural experiment approach.

PubMed

Fu, Hongyun; VanLandingham, Mark J

2012-05-01

Although the existing literature on immigrant mental health is extensive, major substantive and methodological gaps remain. Substantively, there is little population-based research that focuses on the mental health consequences of migration for Vietnamese Americans. More generally, although a wide range of mental health problems among immigrants has been identified, the potential causal or mediating mechanisms underlying these problems remain elusive. This latter substantive shortcoming is related to a key methodological challenge involving the potentially confounding effects of selection on migration-related outcomes. This article addresses these challenges by employing a "natural experiment" design, involving comparisons among three population-based samples of Vietnamese immigrants, never-leavers, and returnees (N=709). Data were collected in Ho Chi Minh City and in New Orleans between 2003 and 2005. The study investigates the long-term impact of international migration on Vietnamese mental health, and the potential mediating effects of social networks and physical health on these migration-related outcomes. The results reveal both mental health advantages and disadvantages among Vietnamese immigrants relative to the two groups of Vietnamese nationals. Selection can be ruled out for some of these differences, and both social networks and physical health are found to play important explanatory roles.

Longitudinal study of diet quality and change in asthma symptoms in adults, according to smoking status.

PubMed

Li, Zhen; Kesse-Guyot, Emmanuelle; Dumas, Orianne; Garcia-Aymerich, Judith; Leynaert, Bénédicte; Pison, Christophe; Le Moual, Nicole; Romieu, Isabelle; Siroux, Valérie; Camargo, Carlos A; Nadif, Rachel; Varraso, Raphaëlle

2017-02-01

It has been hypothesised that increased asthma prevalence in westernised countries is associated with changes in lifestyle factors, including a poorer diet. However, little is known regarding the association between diet quality and asthma. In the diet-asthma association, the role of BMI as a potential mediator needs clarification; moreover, potential effect modification by non-diet sources of oxidants, such as smoking, merits investigation. We investigated the association between diet quality and change in asthma symptoms, as well as assessed effect modification by smoking, while accounting for BMI as a potential mediator. Using data from the French prospective Epidemiological study on the Genetics and Environment of Asthma study, we assessed diet quality using the Alternate Healthy Eating Index 2010 (AHEI-2010) at baseline and change in asthma symptoms (stable (reference), worsening, improved; mean follow-up time: 7 years). Mediation analysis was used to disentangle total and direct effects and the indirect effect mediated by BMI. The analyses included 969 adults (mean age 43 years; 49 % men; 42 % ever asthma). We observed a significant interaction between smoking and AHEI-2010 on change in asthma symptoms (P for interaction=0·04). Among never smokers (n 499), we observed a positive total effect (multivariable OR 1·39; 95 % CI 1·07, 1·80) and a positive direct effect (OR 1·41; 95 % CI 1·09, 1·80) of the AHEI-2010 (per ten-point increment) on improved symptoms. No indirect effect mediated through BMI was observed (OR 0·99; 95 % CI 0·91, 1·07). Among former and current smokers, all effects were statistically non-significant. Better diet quality was associated with improved asthma symptoms over time in never smokers, independently of BMI.

Macrophages: contributors to allograft dysfunction, repair, or innocent bystanders?

PubMed

Mannon, Roslyn B

2012-02-01

Macrophages are members of the innate immune response. However, their role in the adaptive immune response is not known. The purpose of this review is to highlight our current understanding of macrophage structure and function and how they may participate in allograft injury. Studies in acute kidney injury models identify macrophages as key mediators of inflammatory injury, while more recent studies indicate that they may play a reparative role, depending on phenotype - M1 or M2 type macrophages. Mregs, generated in vitro, appear to have immune suppressive abilities and a unique phenotype. In solid-organ transplant, the emphasis of studies has been on acute or chronic injury. These data are derived from animal models using depletion of macrophages or antagonizing their activation and inflammatory responses. The relative contribution of macrophage phenotype in transplantation has not been explored. These studies suggest that macrophages play an injurious role in acute cellular allograft rejection, as well as in chronic injury. Infiltration of an allograft with macrophages is also associated with worse graft function and poor prognosis. Further studies are needed to understand the mechanisms of macrophage-mediated injury, explore their potential reparative role, and determine if they or their functional products are biomarkers of poor graft outcomes.

Role of Matricellular Proteins in Disorders of the Central Nervous System.

PubMed

Jayakumar, A R; Apeksha, A; Norenberg, M D

2017-03-01

Matricellular proteins (MCPs) are actively expressed non-structural proteins present in the extracellular matrix, which rapidly turnover and possess regulatory roles, as well as mediate cell-cell interactions. MCPs characteristically contain binding sites for other extracellular proteins, cell surface receptors, growth factors, cytokines and proteases, that provide structural support for surrounding cells. MCPs are present in most organs, including brain, and play a major role in cell-cell interactions and tissue repair. Among the MCPs found in brain include thrombospondin-1/2, secreted protein acidic and rich in cysteine family (SPARC), including Hevin/SC1, Tenascin C and CYR61/Connective Tissue Growth Factor/Nov family of proteins, glypicans, galectins, plasminogen activator inhibitor (PAI-1), autotaxin, fibulin and perisostin. This review summarizes the potential role of MCPs in the pathogenesis of major neurological disorders, including Alzheimer's disease, amyotrophic lateral sclerosis, ischemia, trauma, hepatic encephalopathy, Down's syndrome, autism, multiple sclerosis, brain neoplasms, Parkinson's disease and epilepsy. Potential therapeutic opportunities of MCP's for these disorders are also considered in this review.

[Friend or Foe in the Pocket? - The Role of the Individual, Peergroup and Parents for (dys)functional Mobile Phone Use].

PubMed

Knop, Karin; Hefner, Dorothée

2018-02-01

Friend or Foe in the Pocket? - The Role of the Individual, Peergroup and Parents for (dys)functional Mobile Phone Use In order to provide consultative support to parents as well as to children and young people, background knowledge regarding the motives of mobile phone use, functions of usage, comprehension of the attraction of this all-round medium also as knowledge about potential hazards are essential. This study offers empirical results about potentials and risks. The peergroup plays an important role for riskful and problematic mobile phone involvement. Parents function as a role model and the explicit parental mediation practices and their impact on the child are in focus. Data was acquired from a quota-sample survey with 500 children between the age of 8 and 14 years and one of their parents, qualitative interviews (20 children and their parents) and eight peergroup-discussions (52 participants). The present paper illuminates the above mentioned aspects and derives implications for guidance practice.

Mediation analysis of relationships between chronic inflammation and quality of life in older adults.

PubMed

Nowakowski, Alexandra C H; Graves, Katelyn Y; Sumerau, J E

2016-03-22

This article summarizes exploratory analyses of relationships between chronic inflammation, its physical consequences, and quality of life (QoL). It summarizes key findings from preliminary analyses, and contextualizes these results with extant sociomedical literature to recommend directions for future research. Cross-sectional data from the National Social Life, Health, and Aging Project (NSHAP) were used to explore these relationships. Inflammation was assessed via the biomarker C-reactive protein (CRP). We examined associations between CRP levels and two different domains of QoL: happiness with life in general and happiness with intimate relationships. We used ordinal logistic regression with companion OLS models and Sobel-Goodman tests to assess potential mediation, and also conducted a variety of sensitivity analyses. Findings suggest that mediation pathways for the overall association between chronic inflammation and QoL may differ markedly across particular outcome constructs. Specifically, it shows mediation potential for the clinical sequelae of chronic inflammation in frameworks using happiness as an outcome measure, but not in those using relationship satisfaction. Disability appears to mediate the effect of inflammation by 27 %; chronic pain appears to exert a similar mediation effect of 21 %. Pain and disability linked to chronic inflammation appear to play a small but significant mediating role in the overall reduction in QoL observed among older adults with biomarker evidence of chronic inflammation. We note that these patterns are best framed as dynamic elements of a complex causal fabric, rather than powerful determinants that override other factors contributing to QoL. Hypotheses for further exploration using longitudinal data from the NSHAP are thus offered, pending availability of Wave III data in future years.

A systems approach for discovering linoleic acid derivatives that potentially mediate pain and itch

PubMed Central

Ramsden, Christopher E.; Domenichiello, Anthony F.; Yuan, Zhi-Xin; Sapio, Matthew R.; Keyes, Gregory S.; Mishra, Santosh K.; Gross, Jacklyn R.; Majchrzak-Hong, Sharon; Zamora, Daisy; Horowitz, Mark S.; Davis, John M.; Sorokin, Alexander V.; Dey, Amit; LaPaglia, Danielle M.; Wheeler, Joshua J.; Vasko, Michael R.; Mehta, Nehal N.; Mannes, Andrew J.; Iadarola, Michael J.

2018-01-01

Chronic pain and itch are common hypersensitivity syndromes that are affected by endogenous mediators. We applied a systems-based, translational approach to predict, discover, and characterize mediators of pain and itch that are regulated by diet and inflammation. Profiling of tissue-specific precursor abundance and biosynthetic gene expression predicted that inflamed skin would be abundant in four previously unknown 11-hydroxy-epoxy-or 11-keto-epoxy-octadecenoate linoleic acid derivatives and four previously identified 9- or 13-hydroxy-epoxy- or 9- or 13-keto-epoxy-octadecenoate linoleic acid derivatives. All of these mediators were confirmed to be abundant in rat and human skin by mass spectrometry. However, only the two 11-hydroxy-epoxy-octadecenoates sensitized rat dorsal root ganglion neurons to release more calcitonin gene–related peptide (CGRP), which is involved in pain transmission, in response to low pH (which mimics an inflammatory state) or capsaicin (which activates ion channels involved in nociception). The two 11-hydroxy-epoxy-octadecenoates share a 3-hydroxy-Z-pentenyl-E-epoxide moiety, thus suggesting that this substructure could mediate nociceptor sensitization. In rats, intradermal hind paw injection of 11-hydroxy-12,13-trans-epoxy-(9Z)-octadecenoate elicited C-fiber–mediated sensitivity to thermal pain. In a randomized trial testing adjunctive strategies to manage refractory chronic headaches, reducing the dietary intake of linoleic acid was associated with decreases in plasma 11-hydroxy-12,13-trans-epoxy-(9Z)-octadecenoate, which correlated with clinical pain reduction. Human psoriatic skin had 30-fold higher 9-keto-12,13-trans-epoxy-(10E)-octadecenoate compared to control skin, and intradermal injection of this compound induced itch-related scratching behavior in mice. Collectively, these findings define a family of endogenous mediators with potential roles in pain and itch. PMID:28831021

[The Relationship Between Marital Adjustment and Psychological Symptoms in Women: The Mediator Roles of Coping Strategies and Gender Role Attitudes].

PubMed

Yüksel, Özge; Dağ, İhsan

2015-01-01

The aim of this study were to investigate the mediator role of coping strategies and gender roles attitudes on the relationship between women's marital adjustment and psychological symptoms. 248 married women participated in the study. Participants completed Marital Adjustment Scale, Ways of Coping Questionnaire, Brief Symptom Inventory, Gender Role Attitudes Scale and Demographic Information Form. Regression analyses revealed that Submissive (Sobel z= -2.47, p<.01) and Helpless Coping Approach (Sobel z=-2.95, p<.001) have partial mediator role on the relationship between marital relationship score and psychological symptom level. Also, having Egalitarian Gender Role Attitude effects the psychological symptoms in relation with the marital relationship, but it is seen that this effect is not higher enough to play a mediator role (Sobel z =-1.21, p>.05). Regression analysis showed that there is a statistically significant correlation between women's marital adjustment and their psychological symptoms, indicating that the marital adjustment decreases as the psychological symptoms increases. It is also found out that submissive and helpless coping approach have mediator roles in this relationship. Also, contrary to expectations, having egalitarian gender role attitude effects the psychological symptoms in relation with the marital relationship, but this effect does not seem to play a mediator role. It is thought that the effects of marriage and couple therapy approaches considering couples’s problem solving and coping styles should be examined in further studies.

Thioredoxin 1 mediates TGF-β-induced epithelial-mesenchymal transition in salivary adenoid cystic carcinoma.

PubMed

Jiang, Yang; Feng, Xin; Zheng, Lei; Li, Sheng-Lin; Ge, Xi-Yuan; Zhang, Jian-Guo

2015-09-22

Epithelial-mesenchymal transition (EMT) plays an important role in the invasion and metastasis of salivary adenoid cystic carcinoma (SACC) which is characterized by wide local infiltration, perineural spread, a propensity to local recurrence and late distant metastasis. Our recent studies have disclosed that TGF-β is a crucial factor for EMT in metastatic SACC. In this study, we further uncovered small redox protein thioredoxin 1 (TXN) as a critical mediator of TGF-β induced EMT. Immunohistochemistry analysis revealed significantly higher expressions of TXN, thioredoxin reductase 1 (TXNRD1) and N-cadherin, and lower expression of E-cadherin in human metastatic SACC compared to non-metastatic SACC tissues. Consistently, cultured SACC cells with stable TXN overexpression had decreased E-cadherin and increased N-cadherin as well as Snail and Slug expressions. The enhanced migration and invasion potential of these cells was abrogated by Akt or TXNRD1 inhibitors. Expression of N-cadherin and Akt p-Akt decreased, whereas E-cadherin expression increased in a BBSKE (TXNRD1 inhibitor)-dose-dependent manner. In a xenograft mouse model, TXN overexpression facilitated the metastatic potential of SACC-83 cells to the lung. Our results indicate that TXN plays a key role in SACC invasion and metastasis through the modulation of TGF-β-Akt/GSK-3β on EMT. TXN could be a potential therapeutic target for SACC.

Curcumin and treatment of melanoma: The potential role of microRNAs.

PubMed

Lelli, Diana; Pedone, Claudio; Sahebkar, Amirhosssein

2017-04-01

Melanoma is the most aggressive type of skin cancer and is characterized by poor prognosis in its advanced stages because treatments are poorly effective and burdened with severe adverse effects. MicroRNAs (miRNAs) are small non-coding RNAs that are implicated in several cellular processes; they are categorized as oncogenic and tumor suppressor miRNAs. Several miRNAs are implicated in the pathogenesis and progression of melanoma, such as the tumor suppressor miR-let7b that targets cyclin D and regulates cell cycle. Curcumin is a natural compound derived from Curcuma longa L. (turmeric) with anti-cancer properties, documented also in melanoma, and is well tolerated in humans. Pharmacological activity of curcumin is mediated by modulation of several pathways, such as JAK-2/STAT3, thus inhibiting melanoma cell migration and invasion and enhancing apoptosis of these cells. The low oral bioavailability of curcumin has led to the development of curcumin analogues, such as EF24, with greater anti-tumor efficacy and metabolic stability. Potential anti-cancer activity of curcumin and its analogues is also mediated by modulation of miRNAs such as miR21, that is implicated in cell cycle regulation and apoptosis through down-regulation of PTEN and PDCD4 proteins. Curcumin has a potential role in the treatment of melanoma, though further studies are necessary to explore its clinical efficacy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-κB-mediated inflammation

PubMed Central

Leus, Niek G.J.; Zwinderman, Martijn R.H.; Dekker, Frank J.

2016-01-01

Activation of inflammatory gene expression is regulated, among other factors, by post-translational modifications of histone proteins. The most investigated type of histone modifications are lysine acetylations. Histone deacetylases (HDACs) remove acetylations from lysines, thereby influencing (inflammatory) gene expression. Intriguingly, apart from histones, HDACs also target non-histone proteins. The nuclear factor κB (NF-κB) pathway is an important regulator in the expression of numerous inflammatory genes, and acetylation plays a crucial role in regulating its responses. Several studies have shed more light on the role of HDAC 1-3 in inflammation with a particular pro-inflammatory role for HDAC 3. Nevertheless, the HDAC-NF-κB interactions in inflammatory signalling have not been fully understood. An important challenge in targeting the regulatory role of HDACs in the NF-κB pathway is the development of highly potent small molecules that selectively target HDAC iso-enzymes. This review focuses on the role of HDAC 3 in (NF-κB-mediated) inflammation and NF-κB lysine acetylation. In addition, we address the application of frequently used small molecule HDAC inhibitors as an approach to attenuate inflammatory responses, and their potential as novel therapeutics. Finally, recent progress and future directions in medicinal chemistry efforts aimed at HDAC 3-selective inhibitors are discussed. PMID:27371876

Neutrophil-derived 5′-Adenosine Monophosphate Promotes Endothelial Barrier Function via CD73-mediated Conversion to Adenosine and Endothelial A2B Receptor Activation

PubMed Central

Lennon, Paul F.; Taylor, Cormac T.; Stahl, Gregory L.; Colgan, Sean P.

1998-01-01

During episodes of inflammation, polymorphonuclear leukocyte (PMN) transendothelial migration has the potential to disturb vascular barrier function and give rise to intravascular fluid extravasation and edema. However, little is known regarding innate mechanisms that dampen fluid loss during PMN-endothelial interactions. Using an in vitro endothelial paracellular permeability model, we observed a PMN-mediated decrease in endothelial paracellular permeability. A similar decrease was elicited by cell-free supernatants from activated PMN (FMLP 10−6 M), suggesting the presence of a PMN-derived soluble mediator(s). Biophysical and biochemical analysis of PMN supernatants revealed a role for PMN-derived 5′-adenosine monophosphate (AMP) and its metabolite, adenosine, in modulation of endothelial paracellular permeability. Supernatants from activated PMN contained micromolar concentrations of bioactive 5′-AMP and adenosine. Furthermore, exposure of endothelial monolayers to authentic 5′-AMP and adenosine increased endothelial barrier function more than twofold in both human umbilical vein endothelial cells and human microvascular endothelial cells. 5′-AMP bioactivity required endothelial CD73-mediated conversion of 5′-AMP to adenosine via its 5′-ectonucleotidase activity. Decreased endothelial paracellular permeability occurred through adenosine A2B receptor activation and was accompanied by a parallel increase in intracellular cAMP. We conclude that activated PMN release soluble mediators, such as 5′-AMP and adenosine, that promote endothelial barrier function. During inflammation, this pathway may limit potentially deleterious increases in endothelial paracellular permeability and could serve as a basic mechanism of endothelial resealing during PMN transendothelial migration. PMID:9782120

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

PubMed

Smith, Dale L; Gozal, David; Hunter, Scott J; Kheirandish-Gozal, Leila

2017-01-01

Numerous 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. This 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. Indirect 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. Potential 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.

Internalized weight bias mediates the relationship between depressive symptoms and disordered eating behavior among women who think they are overweight.

PubMed

Sienko, Rachel M; Saules, Karen K; Carr, Meagan M

2016-08-01

This study tested the potential mediating role of Internalized Weight Bias (IWB) in the relationship between depressive symptoms (DEP-SX) and disordered eating behavior. In particular, we hypothesized that IWB may be an intervening variable in the well documented association between depression and disordered eating. College women (N=172) who were taking undergraduate psychology courses and who endorsed thinking they were overweight completed the Patient Health Questionnaire depression screener (PHQ-9), the Weight Bias Internalization Scale (WBIS), and the Eating Disorder Examination Questionnaire (EDE-Q). Bootstrapping mediation analyses were conducted to explore the relationships between these variables. IWB was significantly correlated with eating disorder symptoms and DEP-SX, but not Body Mass Index. Mediation analyses supported a model in which IWB mediated the relationship between DEP-SX and disordered eating behavior. Results indicate that individuals with elevated DEP-SX may be likely to internalize weight bias, which may in turn lead to maladaptive approaches to eating and weight control, regardless of one's actual weight status. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adolescent survivors of childhood sexual abuse: the mediating role of attachment style and coping in psychological and interpersonal functioning.

PubMed

Shapiro, D L; Levendosky, A A

1999-11-01

To examine attachment style and coping strategies as potential mediating variables between childhood sexual abuse (CSA) and psychological and interpersonal functioning in an attempt to explain variability in extent of disorder and level of functioning. Eighty adolescent females, aged 14-16 years, answered questions regarding abuse history, attachment style, coping with an interpersonal stressor, depression and trauma symptomatology, and conflict with a best friend. Structural equation modeling analyses indicated that attachment style mediates the effects of CSA and child abuse and neglect on coping and psychological distress. The indirect effects of CSA and other abuse through attachment accounted for most of the effects on coping and psychological distress. Avoidant and cognitive coping strategies also served as mediators in the models, accounting for most of the effects of the other variables on interpersonal conflict. The findings indicate that attachment style and coping strategies influence psychological and interpersonal functioning, mediating the direct effects of CSA and other types of child abuse and neglect. These results have implications for therapeutic intervention with children and adolescents who have experienced child abuse.

RAS in the central nervous system: Potential role in neuropsychiatric disorders.

PubMed

Rocha, Natalia Pessoa; Simões e Silva, Ana Cristina; Prestes, Thiago Ruiz Rodrigues; Feracin, Victor; Machado, Caroline Amaral; Ferreira, Rodrigo Novaes; Teixeira, Antonio Lucio; de Miranda, Aline Silva

2018-02-25

The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders of the modulation of RAS. We carried out an extensive literature search in PubMed central. Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and haemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Evidence for Multiple Mediator Complexes in Yeast Independently Recruited by Activated Heat Shock Factor.

PubMed

Anandhakumar, Jayamani; Moustafa, Yara W; Chowdhary, Surabhi; Kainth, Amoldeep S; Gross, David S

2016-07-15

Mediator is an evolutionarily conserved coactivator complex essential for RNA polymerase II transcription. Although it has been generally assumed that in Saccharomyces cerevisiae, Mediator is a stable trimodular complex, its structural state in vivo remains unclear. Using the "anchor away" (AA) technique to conditionally deplete select subunits within Mediator and its reversibly associated Cdk8 kinase module (CKM), we provide evidence that Mediator's tail module is highly dynamic and that a subcomplex consisting of Med2, Med3, and Med15 can be independently recruited to the regulatory regions of heat shock factor 1 (Hsf1)-activated genes. Fluorescence microscopy of a scaffold subunit (Med14)-anchored strain confirmed parallel cytoplasmic sequestration of core subunits located outside the tail triad. In addition, and contrary to current models, we provide evidence that Hsf1 can recruit the CKM independently of core Mediator and that core Mediator has a role in regulating postinitiation events. Collectively, our results suggest that yeast Mediator is not monolithic but potentially has a dynamic complexity heretofore unappreciated. Multiple species, including CKM-Mediator, the 21-subunit core complex, the Med2-Med3-Med15 tail triad, and the four-subunit CKM, can be independently recruited by activated Hsf1 to its target genes in AA strains. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Tryptase potentiates enteric nerve activation by histamine and serotonin: Relevance for the effects of mucosal biopsy supernatants from irritable bowel syndrome patients.

PubMed

Ostertag, D; Annahazi, A; Krueger, D; Michel, K; Demir, I E; Ceyhan, G O; Zeller, F; Schemann, M

2017-09-01

We previously showed that mucosal biopsy supernatants from irritable bowel syndrome patients activated neurons despite low concentrations of tryptase, histamine, and serotonin which individually would not cause spike discharge. We studied the potentiating responses between these mediators on excitability of enteric neurons. Calcium-imaging was performed using the calcium-sensitive dye Fluo-4 AM in human submucous plexus preparations from 45 individuals. Histamine, serotonin, and tryptase were applied alone and in combinations to evaluate nerve activation which was assessed by analyzing increase in intracellular Ca 2+ ([Ca 2+ ] i ), the proportion of responding neurons and the product of both defined as Ca-neuroindex (NI). Protease activated receptor (PAR) 2 activating peptide, PAR2 antagonist and the serine protease-inhibitor FUT-175 were used to particularly investigate the role of proteases. Histamine or serotonin (1 μmol/L each) evoked only few small responses (median NI [25%/75%]: 0 [0/148]; 85 [0/705] respectively). Their combined application evoked statistically similar responses (216 [21/651]). Addition of the PAR2 activator tryptase induced a significantly higher Ca-NI (1401 [867/4075]) compared to individual application of tryptase or to coapplied histamine and serotonin. This synergistic potentiation was neither mimicked by PAR2 activating peptide nor reversed by the PAR2 antagonist GB83, but abolished by FUT-175. We observed synergistic potentiation between histamine, serotonin, and tryptase in enteric neurons, which is mediated by proteolytic activity rather than PAR2 activation. This explained neuronal activation by a cocktail of these mediators despite their low concentrations and despite a relatively small PAR2-mediated response in human submucous neurons. © 2017 John Wiley & Sons Ltd.