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Sample records for mediation analyses revealed

  1. Mediation Analyses in the Real World

    DEFF Research Database (Denmark)

    Lange, Theis; Starkopf, Liis

    2016-01-01

    The paper by Nguyen et al.1 published in this issue of Epidemiology presents a comparison of the recently suggested inverse odds ratio approach for addressing mediation and a more conventional Baron and Kenny-inspired method. Interestingly, the comparison is not done through a discussion of restr......The paper by Nguyen et al.1 published in this issue of Epidemiology presents a comparison of the recently suggested inverse odds ratio approach for addressing mediation and a more conventional Baron and Kenny-inspired method. Interestingly, the comparison is not done through a discussion...... it simultaneously ensures that the comparison is based on properties, which matter in actual applications, and makes the comparison accessible for a broader audience. In a wider context, the choice to stay close to real-life problems mirrors a general trend within the literature on mediation analysis namely to put...... applications using the inverse odds ration approach, as it simply has not had enough time to move from theoretical concept to published applied paper, we do expect to be able to judge the willingness of authors and journals to employ the causal inference-based approach to mediation analyses. Our hope...

  2. Self-esteem as a mediator between personality traits and body esteem: path analyses across gender and race/ethnicity.

    Science.gov (United States)

    Skorek, Małgorzata; Song, Anna V; Dunham, Yarrow

    2014-01-01

    Prior literature examines the direct relationship between personality traits and body esteem. This article explores the possibility that self-esteem mediates this relationship. 165 undergraduate women and 133 men (age 18-21; 42.6% Hispanic, 28.9% Asian, 28.5% Caucasian) completed items measuring personality traits (Big Five), self-esteem, and body esteem. Path analyses were used to test for mediation. The analyses confirmed that in both men and women self-esteem mediated the relationship between three personality traits and body esteem: higher levels of conscientiousness, emotional stability, and extraversion were associated with higher self-esteem and consequently higher body esteem. Once self-esteem was included in the model the relationships between personality traits and body esteem were not significant, suggesting full mediation. In addition, the analyses revealed several racial/ethnic differences. In Asian American participants, self-esteem mediated the relationship between conscientiousness and body esteem and between emotional stability and body esteem. In Hispanic Americans, self-esteem mediated the relationship between conscientiousness and body esteem and between extraversion and body esteem. And in Caucasian Americans, self-esteem mediated the relationship between emotional stability and body esteem and between extraversion and body esteem. The most important contribution of this study is evidence for an indirect relationship between personality traits and body esteem, with this relationship being mediated by self-esteem. This has important implications for the study of personality and eating disorders in young adults, most particularly implying a need for more emphasis on self-esteem as a predictor of body image problems.

  3. Self-esteem as a mediator between personality traits and body esteem: path analyses across gender and race/ethnicity.

    Directory of Open Access Journals (Sweden)

    Małgorzata Skorek

    Full Text Available Prior literature examines the direct relationship between personality traits and body esteem. This article explores the possibility that self-esteem mediates this relationship. 165 undergraduate women and 133 men (age 18-21; 42.6% Hispanic, 28.9% Asian, 28.5% Caucasian completed items measuring personality traits (Big Five, self-esteem, and body esteem. Path analyses were used to test for mediation. The analyses confirmed that in both men and women self-esteem mediated the relationship between three personality traits and body esteem: higher levels of conscientiousness, emotional stability, and extraversion were associated with higher self-esteem and consequently higher body esteem. Once self-esteem was included in the model the relationships between personality traits and body esteem were not significant, suggesting full mediation. In addition, the analyses revealed several racial/ethnic differences. In Asian American participants, self-esteem mediated the relationship between conscientiousness and body esteem and between emotional stability and body esteem. In Hispanic Americans, self-esteem mediated the relationship between conscientiousness and body esteem and between extraversion and body esteem. And in Caucasian Americans, self-esteem mediated the relationship between emotional stability and body esteem and between extraversion and body esteem. The most important contribution of this study is evidence for an indirect relationship between personality traits and body esteem, with this relationship being mediated by self-esteem. This has important implications for the study of personality and eating disorders in young adults, most particularly implying a need for more emphasis on self-esteem as a predictor of body image problems.

  4. Self-Esteem as a Mediator between Personality Traits and Body Esteem: Path Analyses across Gender and Race/Ethnicity

    Science.gov (United States)

    Skorek, Małgorzata; Song, Anna V.; Dunham, Yarrow

    2014-01-01

    Prior literature examines the direct relationship between personality traits and body esteem. This article explores the possibility that self-esteem mediates this relationship. 165 undergraduate women and 133 men (age 18–21; 42.6% Hispanic, 28.9% Asian, 28.5% Caucasian) completed items measuring personality traits (Big Five), self-esteem, and body esteem. Path analyses were used to test for mediation. The analyses confirmed that in both men and women self-esteem mediated the relationship between three personality traits and body esteem: higher levels of conscientiousness, emotional stability, and extraversion were associated with higher self-esteem and consequently higher body esteem. Once self-esteem was included in the model the relationships between personality traits and body esteem were not significant, suggesting full mediation. In addition, the analyses revealed several racial/ethnic differences. In Asian American participants, self-esteem mediated the relationship between conscientiousness and body esteem and between emotional stability and body esteem. In Hispanic Americans, self-esteem mediated the relationship between conscientiousness and body esteem and between extraversion and body esteem. And in Caucasian Americans, self-esteem mediated the relationship between emotional stability and body esteem and between extraversion and body esteem. The most important contribution of this study is evidence for an indirect relationship between personality traits and body esteem, with this relationship being mediated by self-esteem. This has important implications for the study of personality and eating disorders in young adults, most particularly implying a need for more emphasis on self-esteem as a predictor of body image problems. PMID:25375238

  5. Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer.

    Science.gov (United States)

    Du, Zhou; Sun, Tong; Hacisuleyman, Ezgi; Fei, Teng; Wang, Xiaodong; Brown, Myles; Rinn, John L; Lee, Mary Gwo-Shu; Chen, Yiwen; Kantoff, Philip W; Liu, X Shirley

    2016-03-15

    Mounting evidence suggests that long noncoding RNAs (lncRNAs) can function as microRNA sponges and compete for microRNA binding to protein-coding transcripts. However, the prevalence, functional significance and targets of lncRNA-mediated sponge regulation of cancer are mostly unknown. Here we identify a lncRNA-mediated sponge regulatory network that affects the expression of many protein-coding prostate cancer driver genes, by integrating analysis of sequence features and gene expression profiles of both lncRNAs and protein-coding genes in tumours. We confirm the tumour-suppressive function of two lncRNAs (TUG1 and CTB-89H12.4) and their regulation of PTEN expression in prostate cancer. Surprisingly, one of the two lncRNAs, TUG1, was previously known for its function in polycomb repressive complex 2 (PRC2)-mediated transcriptional regulation, suggesting its sub-cellular localization-dependent function. Our findings not only suggest an important role of lncRNA-mediated sponge regulation in cancer, but also underscore the critical influence of cytoplasmic localization on the efficacy of a sponge lncRNA.

  6. Applied mediation analyses

    DEFF Research Database (Denmark)

    Lange, Theis; Hansen, Kim Wadt; Sørensen, Rikke

    2017-01-01

    In recent years, mediation analysis has emerged as a powerful tool to disentangle causal pathways from an exposure/treatment to clinically relevant outcomes. Mediation analysis has been applied in scientific fields as diverse as labour market relations and randomized clinical trials of heart...... disease treatments. In parallel to these applications, the underlying mathematical theory and computer tools have been refined. This combined review and tutorial will introduce the reader to modern mediation analysis including: the mathematical framework; required assumptions; and software implementation...

  7. Comparative proteomic analyses reveal that FlbA down-regulates gliT expression and SOD activity in Aspergillus fumigatus.

    Science.gov (United States)

    Shin, Kwang-Soo; Park, Hee-Soo; Kim, Young-Hwan; Yu, Jae-Hyuk

    2013-07-11

    FlbA is a regulator of G-protein signaling protein that plays a central role in attenuating heterotrimeric G-protein mediated vegetative growth signaling in Aspergillus. The deletion of flbA (∆flbA) in the opportunistic human pathogen Aspergillus fumigatus results in accelerated cell death and autolysis in submerged culture. To further investigate the effects of ∆flbA on intracellular protein levels we carried out 2-D proteome analyses of 2-day old submerged cultures of ∆flbA and wild type (WT) strains and observed 160 differentially expressed proteins. Via nano-LC-ESI-MS/MS analyses, we revealed the identity of 10 and 2 proteins exhibiting high and low level accumulation, respectively, in ∆flbA strain. Notably, the GliT protein is accumulated at about 1800-fold higher levels in ∆flbA than WT. Moreover, GliT is secreted at high levels from ∆flbA strain, whereas Sod1 (superoxide dismutase) is secreted at a higher level in WT. Northern blot analyses reveal that ∆flbA results in elevated accumulation of gliT mRNA. Consequently, ∆flbA strain exhibits enhanced tolerance to gliotoxin toxicity. Finally, ∆flbA strain displayed enhanced SOD activity and elevated resistance to menadione and paraquat. In summary, FlbA-mediated signaling control negatively affects cellular responses associated with detoxification of reactive oxygen species and of exogenous gliotoxin in A. fumigatus. Regulator of G protein Signaling (RGS) proteins play crucial roles in fundamental biological processes in filamentous fungi. FlbA is the first studied filamentous fungal RGS protein, yet much remains to be understood about its roles in the opportunistic human pathogen Aspergillus fumigatus. In the present study, we examined the effects of the deletion of flbA using comprehensive analyses of the intra- and extracellular proteomes of A. fumigatus wild type and the flbA deletion mutant. Via MS analyses, we identified 10 proteins exhibiting high level accumulation in the flbA deletion

  8. Conserved regulators of nucleolar size revealed by global phenotypic analyses.

    Science.gov (United States)

    Neumüller, Ralph A; Gross, Thomas; Samsonova, Anastasia A; Vinayagam, Arunachalam; Buckner, Michael; Founk, Karen; Hu, Yanhui; Sharifpoor, Sara; Rosebrock, Adam P; Andrews, Brenda; Winston, Fred; Perrimon, Norbert

    2013-08-20

    Regulation of cell growth is a fundamental process in development and disease that integrates a vast array of extra- and intracellular information. A central player in this process is RNA polymerase I (Pol I), which transcribes ribosomal RNA (rRNA) genes in the nucleolus. Rapidly growing cancer cells are characterized by increased Pol I-mediated transcription and, consequently, nucleolar hypertrophy. To map the genetic network underlying the regulation of nucleolar size and of Pol I-mediated transcription, we performed comparative, genome-wide loss-of-function analyses of nucleolar size in Saccharomyces cerevisiae and Drosophila melanogaster coupled with mass spectrometry-based analyses of the ribosomal DNA (rDNA) promoter. With this approach, we identified a set of conserved and nonconserved molecular complexes that control nucleolar size. Furthermore, we characterized a direct role of the histone information regulator (HIR) complex in repressing rRNA transcription in yeast. Our study provides a full-genome, cross-species analysis of a nuclear subcompartment and shows that this approach can identify conserved molecular modules.

  9. Conserved Regulators of Nucleolar Size Revealed by Global Phenotypic Analyses

    Science.gov (United States)

    Neumüller, Ralph A.; Gross, Thomas; Samsonova, Anastasia A.; Vinayagam, Arunachalam; Buckner, Michael; Founk, Karen; Hu, Yanhui; Sharifpoor, Sara; Rosebrock, Adam P.; Andrews, Brenda; Winston, Fred; Perrimon, Norbert

    2014-01-01

    Regulation of cell growth is a fundamental process in development and disease that integrates a vast array of extra- and intracellular information. A central player in this process is RNA polymerase I (Pol I), which transcribes ribosomal RNA (rRNA) genes in the nucleolus. Rapidly growing cancer cells are characterized by increased Pol I–mediated transcription and, consequently, nucleolar hypertrophy. To map the genetic network underlying the regulation of nucleolar size and of Pol I–mediated transcription, we performed comparative, genome-wide loss-of-function analyses of nucleolar size in Saccharomyces cerevisiae and Drosophila melanogaster coupled with mass spectrometry–based analyses of the ribosomal DNA (rDNA) promoter. With this approach, we identified a set of conserved and nonconserved molecular complexes that control nucleolar size. Furthermore, we characterized a direct role of the histone information regulator (HIR) complex in repressing rRNA transcription in yeast. Our study provides a full-genome, cross-species analysis of a nuclear subcompartment and shows that this approach can identify conserved molecular modules. PMID:23962978

  10. Mediational Analyses of the Effects of Responsive Teaching on the Developmental Functioning of Preschool Children with Disabilities

    Science.gov (United States)

    Karaaslan, Ozcan; Mahoney, Gerald

    2015-01-01

    Mediational analyses were conducted with data from two small randomized control trials of the Responsive Teaching (RT) parent-mediated developmental intervention which used nearly identical intervention and control procedures. The purpose of these analyses was to determine whether or how the changes in maternal responsiveness and children's…

  11. Self-Esteem as a Mediator between Personality Traits and Body Esteem: Path Analyses across Gender and Race/Ethnicity

    OpenAIRE

    Skorek, Małgorzata; Song, Anna V.; Dunham, Yarrow

    2014-01-01

    Prior literature examines the direct relationship between personality traits and body esteem. This article explores the possibility that self-esteem mediates this relationship. 165 undergraduate women and 133 men (age 18-21; 42.6% Hispanic, 28.9% Asian, 28.5% Caucasian) completed items measuring personality traits (Big Five), self-esteem, and body esteem. Path analyses were used to test for mediation. The analyses confirmed that in both men and women self-esteem mediated the relationship betw...

  12. Structure and Sequence Analyses of Clustered Protocadherins Reveal Antiparallel Interactions that Mediate Homophilic Specificity.

    Science.gov (United States)

    Nicoludis, John M; Lau, Sze-Yi; Schärfe, Charlotta P I; Marks, Debora S; Weihofen, Wilhelm A; Gaudet, Rachelle

    2015-11-03

    Clustered protocadherin (Pcdh) proteins mediate dendritic self-avoidance in neurons via specific homophilic interactions in their extracellular cadherin (EC) domains. We determined crystal structures of EC1-EC3, containing the homophilic specificity-determining region, of two mouse clustered Pcdh isoforms (PcdhγA1 and PcdhγC3) to investigate the nature of the homophilic interaction. Within the crystal lattices, we observe antiparallel interfaces consistent with a role in trans cell-cell contact. Antiparallel dimerization is supported by evolutionary correlations. Two interfaces, located primarily on EC2-EC3, involve distinctive clustered Pcdh structure and sequence motifs, lack predicted glycosylation sites, and contain residues highly conserved in orthologs but not paralogs, pointing toward their biological significance as homophilic interaction interfaces. These two interfaces are similar yet distinct, reflecting a possible difference in interaction architecture between clustered Pcdh subfamilies. These structures initiate a molecular understanding of clustered Pcdh assemblies that are required to produce functional neuronal networks. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Vesicular trafficking of immune mediators in human eosinophils revealed by immunoelectron microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Melo, Rossana C.N., E-mail: rossana.melo@ufjf.edu.br [Laboratory of Cellular Biology, Department of Biology, ICB, Federal University of Juiz de Fora, UFJF, Rua José Lourenço Kelmer, Juiz de Fora, MG 36036-900 (Brazil); Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 943, Boston, MA 02215 (United States); Weller, Peter F. [Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 943, Boston, MA 02215 (United States)

    2016-10-01

    Electron microscopy (EM)-based techniques are mostly responsible for our current view of cell morphology at the subcellular level and continue to play an essential role in biological research. In cells from the immune system, such as eosinophils, EM has helped to understand how cells package and release mediators involved in immune responses. Ultrastructural investigations of human eosinophils enabled visualization of secretory processes in detail and identification of a robust, vesicular trafficking essential for the secretion of immune mediators via a non-classical secretory pathway associated with secretory (specific) granules. This vesicular system is mainly organized as large tubular-vesicular carriers (Eosinophil Sombrero Vesicles – EoSVs) actively formed in response to cell activation and provides a sophisticated structural mechanism for delivery of granule-stored mediators. In this review, we highlight the application of EM techniques to recognize pools of immune mediators at vesicular compartments and to understand the complex secretory pathway within human eosinophils involved in inflammatory and allergic responses. - Highlights: • Application of EM to understand the complex secretory pathway in human eosinophils. • EM techniques reveal an active vesicular system associated with secretory granules. • Tubular vesicles are involved in the transport of granule-derived immune mediators.

  14. Vesicular trafficking of immune mediators in human eosinophils revealed by immunoelectron microscopy

    International Nuclear Information System (INIS)

    Melo, Rossana C.N.; Weller, Peter F.

    2016-01-01

    Electron microscopy (EM)-based techniques are mostly responsible for our current view of cell morphology at the subcellular level and continue to play an essential role in biological research. In cells from the immune system, such as eosinophils, EM has helped to understand how cells package and release mediators involved in immune responses. Ultrastructural investigations of human eosinophils enabled visualization of secretory processes in detail and identification of a robust, vesicular trafficking essential for the secretion of immune mediators via a non-classical secretory pathway associated with secretory (specific) granules. This vesicular system is mainly organized as large tubular-vesicular carriers (Eosinophil Sombrero Vesicles – EoSVs) actively formed in response to cell activation and provides a sophisticated structural mechanism for delivery of granule-stored mediators. In this review, we highlight the application of EM techniques to recognize pools of immune mediators at vesicular compartments and to understand the complex secretory pathway within human eosinophils involved in inflammatory and allergic responses. - Highlights: • Application of EM to understand the complex secretory pathway in human eosinophils. • EM techniques reveal an active vesicular system associated with secretory granules. • Tubular vesicles are involved in the transport of granule-derived immune mediators.

  15. Protein expression profiling of inflammatory mediators in human temporal lobe epilepsy reveals co-activation of multiple chemokines and cytokines

    Directory of Open Access Journals (Sweden)

    Kan Anne A

    2012-08-01

    Full Text Available Abstract Mesial temporal lobe epilepsy (mTLE is a chronic and often treatment-refractory brain disorder characterized by recurrent seizures originating from the hippocampus. The pathogenic mechanisms underlying mTLE remain largely unknown. Recent clinical and experimental evidence supports a role of various inflammatory mediators in mTLE. Here, we performed protein expression profiling of 40 inflammatory mediators in surgical resection material from mTLE patients with and without hippocampal sclerosis, and autopsy controls using a multiplex bead-based immunoassay. In mTLE patients we identified 21 upregulated inflammatory mediators, including 10 cytokines and 7 chemokines. Many of these upregulated mediators have not previously been implicated in mTLE (for example, CCL22, IL-7 and IL-25. Comparing the three patient groups, two main hippocampal expression patterns could be distinguished, pattern I (for example, IL-10 and IL-25 showing increased expression in mTLE + HS patients compared to mTLE-HS and controls, and pattern II (for example, CCL4 and IL-7 showing increased expression in both mTLE groups compared to controls. Upregulation of a subset of inflammatory mediators (for example, IL-25 and IL-7 could not only be detected in the hippocampus of mTLE patients, but also in the neocortex. Principle component analysis was used to cluster the inflammatory mediators into several components. Follow-up analyses of the identified components revealed that the three patient groups could be discriminated based on their unique expression profiles. Immunocytochemistry showed that IL-25 IR (pattern I and CCL4 IR (pattern II were localized in astrocytes and microglia, whereas IL-25 IR was also detected in neurons. Our data shows co-activation of multiple inflammatory mediators in hippocampus and neocortex of mTLE patients, indicating activation of multiple pro- and anti-epileptogenic immune pathways in this disease.

  16. Analysis of Schizosaccharomyces pombe mediator reveals a set of essential subunits conserved between yeast and metazoan cells

    DEFF Research Database (Denmark)

    Spåhr, H; Samuelsen, C O; Baraznenok, V

    2001-01-01

    . cerevisiae share an essential protein module, which associates with nonessential speciesspecific subunits. In support of this view, sequence analysis of the conserved yeast Mediator components Med4 and Med8 reveals sequence homology to the metazoan Mediator components Trap36 and Arc32. Therefore, 8 of 10...... essential genes conserved between S. pombe and S. cerevisiae also have a metazoan homolog, indicating that an evolutionary conserved Mediator core is present in all eukaryotic cells. Our data suggest a closer functional relationship between yeast and metazoan Mediator than previously anticipated....

  17. Reconstitution of active human core Mediator complex reveals a critical role of the MED14 subunit.

    Science.gov (United States)

    Cevher, Murat A; Shi, Yi; Li, Dan; Chait, Brian T; Malik, Sohail; Roeder, Robert G

    2014-12-01

    The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to MS (CX-MS). Whereas the reconstituted head and middle modules can stably associate, basal and coactivator functions are acquired only after incorporation of MED14 into the bimodular complex. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematic dissection of the multiple layers of functionality associated with the Mediator complex.

  18. How and for whom does web-based acceptance and commitment therapy work? Mediation and moderation analyses of web-based ACT for depressive symptoms.

    Science.gov (United States)

    Pots, Wendy T M; Trompetter, Hester R; Schreurs, Karlein M G; Bohlmeijer, Ernst T

    2016-05-23

    Acceptance and Commitment Therapy (ACT) has been demonstrated to be effective in reducing depressive symptoms. However, little is known how and for whom therapeutic change occurs, specifically in web-based interventions. This study focuses on the mediators, moderators and predictors of change during a web-based ACT intervention. Data from 236 adults from the general population with mild to moderate depressive symptoms, randomized to either web-based ACT (n = 82) or one of two control conditions (web-based Expressive Writing (EW; n = 67) and a waiting list (n = 87)), were analysed. Single and multiple mediation analyses, and exploratory linear regression analyses were performed using PROCESS and linear regression analyses, to examine mediators, moderators and predictors on pre- to post- and follow-up treatment change of depressive symptoms. The treatment effect of ACT versus the waiting list was mediated by psychological flexibility and two mindfulness facets. The treatment effect of ACT versus EW was not significantly mediated. The moderator analyses demonstrated that the effects of web-based ACT did not vary according to baseline patient characteristics when compared to both control groups. However, higher baseline depressive symptoms and positive mental health and lower baseline anxiety were identified as predictors of outcome across all conditions. Similar results are found for follow-up. The findings of this study corroborate the evidence that psychological flexibility and mindfulness are distinct process mechanisms that mediate the effects of web-based ACT intervention. The results indicate that there are no restrictions to the allocation of web-based ACT intervention and that web-based ACT can work for different subpopulations. Netherlands Trial Register NTR2736 . Registered 6 February 2011.

  19. Reconstitution of active human core Mediator complex reveals a pivotal role of the MED14 subunit

    Science.gov (United States)

    Cevher, Murat A.; Shi, Yi; Li, Dan; Chait, Brian T.; Malik, Sohail; Roeder, Robert G.

    2014-01-01

    The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here, we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to mass spectrometry (CX-MS). Whereas the reconstituted head and middle modules can stably associate, only with incorporation of MED14 into the bi-modular complex does it acquire basal and coactivator functions. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematically dissecting the multiple layers of functionalities associated with the Mediator complex. PMID:25383669

  20. Transcriptomic and Hormonal Analyses Reveal that YUC-Mediated Auxin Biogenesis Is Involved in Shoot Regeneration from Rhizome in Cymbidium.

    Science.gov (United States)

    Liu, Yang; Zhang, Hai-Liang; Guo, He-Rong; Xie, Li; Zeng, Rui-Zhen; Zhang, Xiang-Qian; Zhang, Zhi-Sheng

    2017-01-01

    Cymbidium , one of the most important orchid genera in horticulture, can be classified into epiphytic and terrestrial species. Generally, epiphytic Cymbidium seedlings can be easily propagated by tissue culture, but terrestrial seedlings are difficult to propagate. To date, the molecular mechanisms underlying the differences in the ease with which terrestrial and epiphytic cymbidiums can be propagated are largely unknown. Using RNA-sequencing, quantitative reverse transcription PCR and enzyme-linked immunosorbent assay, Cymbidium 'Xiaofeng' (CXF), which can be efficiently micropropagated, and terrestrial Cymbidium sinense 'Qijianbaimo' (CSQ), which has a low regeneration ability, were used to explore the molecular mechanisms underlying the micropropagation ability of Cymbidium species. To this end, 447 million clean short reads were generated, and 31,264 annotated unigenes were obtained from 10 cDNA libraries. A total of 1,290 differentially expressed genes (DEGs) were identified between CXF and CSQ during shoot induction. Gene ontology (GO) enrichment analysis indicated that the DEGs were significantly enriched in auxin pathway-related GO terms. Further analysis demonstrated that YUC and GH3 family genes, which play crucial roles in the regulation of auxin/IAA (indole-3-acetic acid) metabolism, acted quickly in response to shoot induction culture in vitro and were closely correlated with variation in shoot regeneration between CXF and CSQ. In addition, the study showed that IAA accumulated rapidly and significantly during shoot induction in CXF compared to that in CSQ; in contrast, no significant changes in other hormones were observed between CXF and CSQ. Furthermore, shoot regeneration in CXF was inhibited by a yucasin-auxin biosynthesis inhibitor, indicating that increased IAA level is required for high-frequency shoot regeneration in CXF. In conclusion, our study revealed that YUC-mediated auxin biogenesis is involved in shoot regeneration from rhizome in

  1. Transcriptomic and Hormonal Analyses Reveal that YUC-Mediated Auxin Biogenesis Is Involved in Shoot Regeneration from Rhizome in Cymbidium

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2017-10-01

    Full Text Available Cymbidium, one of the most important orchid genera in horticulture, can be classified into epiphytic and terrestrial species. Generally, epiphytic Cymbidium seedlings can be easily propagated by tissue culture, but terrestrial seedlings are difficult to propagate. To date, the molecular mechanisms underlying the differences in the ease with which terrestrial and epiphytic cymbidiums can be propagated are largely unknown. Using RNA-sequencing, quantitative reverse transcription PCR and enzyme-linked immunosorbent assay, Cymbidium ‘Xiaofeng’ (CXF, which can be efficiently micropropagated, and terrestrial Cymbidium sinense ‘Qijianbaimo’ (CSQ, which has a low regeneration ability, were used to explore the molecular mechanisms underlying the micropropagation ability of Cymbidium species. To this end, 447 million clean short reads were generated, and 31,264 annotated unigenes were obtained from 10 cDNA libraries. A total of 1,290 differentially expressed genes (DEGs were identified between CXF and CSQ during shoot induction. Gene ontology (GO enrichment analysis indicated that the DEGs were significantly enriched in auxin pathway-related GO terms. Further analysis demonstrated that YUC and GH3 family genes, which play crucial roles in the regulation of auxin/IAA (indole-3-acetic acid metabolism, acted quickly in response to shoot induction culture in vitro and were closely correlated with variation in shoot regeneration between CXF and CSQ. In addition, the study showed that IAA accumulated rapidly and significantly during shoot induction in CXF compared to that in CSQ; in contrast, no significant changes in other hormones were observed between CXF and CSQ. Furthermore, shoot regeneration in CXF was inhibited by a yucasin-auxin biosynthesis inhibitor, indicating that increased IAA level is required for high-frequency shoot regeneration in CXF. In conclusion, our study revealed that YUC-mediated auxin biogenesis is involved in shoot

  2. Causal mediation analysis with multiple causally non-ordered mediators.

    Science.gov (United States)

    Taguri, Masataka; Featherstone, John; Cheng, Jing

    2018-01-01

    In many health studies, researchers are interested in estimating the treatment effects on the outcome around and through an intermediate variable. Such causal mediation analyses aim to understand the mechanisms that explain the treatment effect. Although multiple mediators are often involved in real studies, most of the literature considered mediation analyses with one mediator at a time. In this article, we consider mediation analyses when there are causally non-ordered multiple mediators. Even if the mediators do not affect each other, the sum of two indirect effects through the two mediators considered separately may diverge from the joint natural indirect effect when there are additive interactions between the effects of the two mediators on the outcome. Therefore, we derive an equation for the joint natural indirect effect based on the individual mediation effects and their interactive effect, which helps us understand how the mediation effect works through the two mediators and relative contributions of the mediators and their interaction. We also discuss an extension for three mediators. The proposed method is illustrated using data from a randomized trial on the prevention of dental caries.

  3. Causal Mediation Analysis of Survival Outcome with Multiple Mediators.

    Science.gov (United States)

    Huang, Yen-Tsung; Yang, Hwai-I

    2017-05-01

    Mediation analyses have been a popular approach to investigate the effect of an exposure on an outcome through a mediator. Mediation models with multiple mediators have been proposed for continuous and dichotomous outcomes. However, development of multimediator models for survival outcomes is still limited. We present methods for multimediator analyses using three survival models: Aalen additive hazard models, Cox proportional hazard models, and semiparametric probit models. Effects through mediators can be characterized by path-specific effects, for which definitions and identifiability assumptions are provided. We derive closed-form expressions for path-specific effects for the three models, which are intuitively interpreted using a causal diagram. Mediation analyses using Cox models under the rare-outcome assumption and Aalen additive hazard models consider effects on log hazard ratio and hazard difference, respectively; analyses using semiparametric probit models consider effects on difference in transformed survival time and survival probability. The three models were applied to a hepatitis study where we investigated effects of hepatitis C on liver cancer incidence mediated through baseline and/or follow-up hepatitis B viral load. The three methods show consistent results on respective effect scales, which suggest an adverse estimated effect of hepatitis C on liver cancer not mediated through hepatitis B, and a protective estimated effect mediated through the baseline (and possibly follow-up) of hepatitis B viral load. Causal mediation analyses of survival outcome with multiple mediators are developed for additive hazard and proportional hazard and probit models with utility demonstrated in a hepatitis study.

  4. Genomic Analyses Reveal the Influence of Geographic Origin, Migration, and Hybridization on Modern Dog Breed Development

    Directory of Open Access Journals (Sweden)

    Heidi G. Parker

    2017-04-01

    Full Text Available There are nearly 400 modern domestic dog breeds with a unique histories and genetic profiles. To track the genetic signatures of breed development, we have assembled the most diverse dataset of dog breeds, reflecting their extensive phenotypic variation and heritage. Combining genetic distance, migration, and genome-wide haplotype sharing analyses, we uncover geographic patterns of development and independent origins of common traits. Our analyses reveal the hybrid history of breeds and elucidate the effects of immigration, revealing for the first time a suggestion of New World dog within some modern breeds. Finally, we used cladistics and haplotype sharing to show that some common traits have arisen more than once in the history of the dog. These analyses characterize the complexities of breed development, resolving longstanding questions regarding individual breed origination, the effect of migration on geographically distinct breeds, and, by inference, transfer of trait and disease alleles among dog breeds.

  5. Parental mediation and cyberbullying - a longitudinal study.

    Science.gov (United States)

    Chng, Grace S; Liau, Albert; Khoo, Angeline; Li, Dongdong

    2014-01-01

    Parents use active and restrictive mediation strategies to guide and regulate children's online participation and the online risks they encounter. However, changes in parental mediation do occur over time and the effectiveness of these strategies on cyberbullying demands for further empirical investigation. The current study addresses these issues with a sample of 1084 students (49% girls) in a longitudinal, three-wave design. Gender differences were tested via multi-group analyses. Longitudinal growth models showed that parental use of both active and restrictive mediation decreased over time. For both types of mediation, the mean rate of change had a significant effect on boys' engagement in cyberbullying, but not for girls. Initial levels of restrictive mediation, but not active mediation, were found to be significantly predictive of cyberbullying in both genders. Girls had higher initial levels of both parental mediation types in comparison to boys. The results reveal that the effectiveness of active and restrictive mediation in relation to students' cyberbullying differs and informs us on gender differences. The implications of these results for parental education in online mediation are discussed.

  6. Comparative genomics analyses revealed two virulent Listeria monocytogenes strains isolated from ready-to-eat food.

    Science.gov (United States)

    Lim, Shu Yong; Yap, Kien-Pong; Thong, Kwai Lin

    2016-01-01

    Listeria monocytogenes is an important foodborne pathogen that causes considerable morbidity in humans with high mortality rates. In this study, we have sequenced the genomes and performed comparative genomics analyses on two strains, LM115 and LM41, isolated from ready-to-eat food in Malaysia. The genome size of LM115 and LM41 was 2,959,041 and 2,963,111 bp, respectively. These two strains shared approximately 90% homologous genes. Comparative genomics and phylogenomic analyses revealed that LM115 and LM41 were more closely related to the reference strains F2365 and EGD-e, respectively. Our virulence profiling indicated a total of 31 virulence genes shared by both analysed strains. These shared genes included those that encode for internalins and L. monocytogenes pathogenicity island 1 (LIPI-1). Both the Malaysian L. monocytogenes strains also harboured several genes associated with stress tolerance to counter the adverse conditions. Seven antibiotic and efflux pump related genes which may confer resistance against lincomycin, erythromycin, fosfomycin, quinolone, tetracycline, and penicillin, and macrolides were identified in the genomes of both strains. Whole genome sequencing and comparative genomics analyses revealed two virulent L. monocytogenes strains isolated from ready-to-eat foods in Malaysia. The identification of strains with pathogenic, persistent, and antibiotic resistant potentials from minimally processed food warrant close attention from both healthcare and food industry.

  7. Comparative Transcriptomic and Proteomic Analyses Reveal a FluG-Mediated Signaling Pathway Relating to Asexual Sporulation of Antrodia camphorata.

    Science.gov (United States)

    Li, Hua-Xiang; Lu, Zhen-Ming; Zhu, Qing; Gong, Jin-Song; Geng, Yan; Shi, Jin-Song; Xu, Zheng-Hong; Ma, Yan-He

    2017-09-01

    Medicinal mushroom Antrodia camphorata sporulate large numbers of arthroconidia in submerged fermentation, which is rarely reported in basidiomycetous fungi. Nevertheless, the molecular mechanisms underlying this asexual sporulation (conidiation) remain unclear. Here, we used comparative transcriptomic and proteomic approaches to elucidate possible signaling pathway relating to the asexual sporulation of A. camphorata. First, 104 differentially expressed proteins and 2586 differential cDNA sequences during the culture process of A. camphorata were identified by 2DE and RNA-seq, respectively. By applying bioinformatics analysis, a total of 67 genes which might play roles in the sporulation were obtained, and 18 of these genes, including fluG, sfgA, SfaD, flbA, flbB, flbC, flbD, nsdD, brlA, abaA, wetA, ganB, fadA, PkaA, veA, velB, vosA, and stuA might be involved in a potential FluG-mediated signaling pathway. Furthermore, the mRNA expression levels of the 18 genes in the proposed FluG-mediated signaling pathway were analyzed by quantitative real-time PCR. In summary, our study helps elucidate the molecular mechanisms underlying the asexual sporulation of A. camphorata, and provides also useful transcripts and proteome for further bioinformatics study of this valuable medicinal mushroom. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. A genomewide screen for suppressors of Alu-mediated rearrangements reveals a role for PIF1.

    Directory of Open Access Journals (Sweden)

    Karen M Chisholm

    Full Text Available Alu-mediated rearrangement of tumor suppressor genes occurs frequently during carcinogenesis. In breast cancer, this mechanism contributes to loss of the wild-type BRCA1 allele in inherited disease and to loss of heterozygosity in sporadic cancer. To identify genes required for suppression of Alu-mediated recombination we performed a genomewide screen of a collection of 4672 yeast gene deletion mutants using a direct repeat recombination assay. The primary screen and subsequent analysis identified 12 candidate genes including TSA, ELG1, and RRM3, which are known to play a significant role in maintaining genomic stability. Genetic analysis of the corresponding human homologs was performed in sporadic breast tumors and in inherited BRCA1-associated carcinomas. Sequencing of these genes in high risk breast cancer families revealed a potential role for the helicase PIF1 in cancer predisposition. PIF1 variant L319P was identified in three breast cancer families; importantly, this variant, which is predicted to be functionally damaging, was not identified in a large series of controls nor has it been reported in either dbSNP or the 1000 Genomes Project. In Schizosaccharomyces pombe, Pfh1 is required to maintain both mitochondrial and nuclear genomic integrity. Functional studies in yeast of human PIF1 L319P revealed that this variant cannot complement the essential functions of Pfh1 in either the nucleus or mitochondria. Our results provide a global view of nonessential genes involved in suppressing Alu-mediated recombination and implicate variation in PIF1 in breast cancer predisposition.

  9. Proteomic and physiological analyses reveal the role of exogenous spermidine on cucumber roots in response to Ca(NO3)2 stress.

    Science.gov (United States)

    Du, Jing; Guo, Shirong; Sun, Jin; Shu, Sheng

    2018-05-01

    The mechanism of exogenous Spd-induced Ca(NO 3 ) 2 stress tolerance in cucumber was studied by proteomics and physiological analyses. Protein-protein interaction network revealed 13 key proteins involved in Spd-induced Ca(NO 3 ) 2 stress resistance. Ca(NO 3 ) 2 stress is one of the major reasons for secondary salinization that limits cucumber plant development in greenhouse. The conferred protective role of exogenous Spd on cucumber in response to Ca(NO 3 ) 2 stress cues involves changes at the cellular and physiological levels. To investigate the molecular foundation of exogenous Spd in Ca(NO 3 ) 2 stress tolerance, a proteomic approach was performed in our work. After a 9 days period of Ca(NO 3 ) 2 stress and/or exogenous Spd, 71 differential protein spots were confidently identified. The resulting proteins were enriched in seven different categories of biological processes, including protein metabolism, carbohydrate and energy metabolism, ROS homeostasis and stress defense, cell wall related, transcription, others and unknown. Protein metabolism (31.2%), carbohydrate and energy metabolism (15.6%), ROS homeostasis and stress defense (32.5%) were the three largest functional categories in cucumber root and most of them were significantly increased by exogenous Spd. The Spd-responsive protein interaction network revealed 13 key proteins, whose accumulation changes could be critical for Spd-induced resistance; all 13 proteins were upregulated by Spd at transcriptional and protein levels in response to Ca(NO 3 ) 2 stress. Furthermore, accumulation of antioxidant enzymes, non-enzymatic antioxidant and polyamines, along with reduction of H 2 O 2 and MDA, were detected after exogenous Spd application during Ca(NO 3 ) 2 stress. The results of these proteomic and physiological analyses in cucumber root may facilitate a better understanding of the underlying mechanism of Ca(NO 3 ) 2 stress tolerance mediated by exogenous Spd.

  10. Harm mediates the disgust-immorality link.

    Science.gov (United States)

    Schein, Chelsea; Ritter, Ryan S; Gray, Kurt

    2016-09-01

    Many acts are disgusting, but only some of these acts are immoral. Dyadic morality predicts that disgusting acts should be judged as immoral to the extent that they seem harmful. Consistent with this prediction, 3 studies reveal that perceived harm mediates the link between feelings of disgust and moral condemnation-even for ostensibly harmless "purity" violations. In many cases, accounting for perceived harm completely eliminates the link between disgust and moral condemnation. Analyses also reveal the predictive power of anger and typicality/weirdness in moral judgments of disgusting acts. The mediation of disgust by harm holds across diverse acts including gay marriage, sex acts, and religious blasphemy. Revealing the endogenous presence and moral relevance of harm within disgusting-but-ostensibly harmless acts argues against modular accounts of moral cognition such as moral foundations theory. Instead, these data support pluralistic conceptions of harm and constructionist accounts of morality and emotion. Implications for moral cognition and the concept of "purity" are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  11. Single-Cell Analyses of ESCs Reveal Alternative Pluripotent Cell States and Molecular Mechanisms that Control Self-Renewal

    Directory of Open Access Journals (Sweden)

    Dmitri Papatsenko

    2015-08-01

    Full Text Available Analyses of gene expression in single mouse embryonic stem cells (mESCs cultured in serum and LIF revealed the presence of two distinct cell subpopulations with individual gene expression signatures. Comparisons with published data revealed that cells in the first subpopulation are phenotypically similar to cells isolated from the inner cell mass (ICM. In contrast, cells in the second subpopulation appear to be more mature. Pluripotency Gene Regulatory Network (PGRN reconstruction based on single-cell data and published data suggested antagonistic roles for Oct4 and Nanog in the maintenance of pluripotency states. Integrated analyses of published genomic binding (ChIP data strongly supported this observation. Certain target genes alternatively regulated by OCT4 and NANOG, such as Sall4 and Zscan10, feed back into the top hierarchical regulator Oct4. Analyses of such incoherent feedforward loops with feedback (iFFL-FB suggest a dynamic model for the maintenance of mESC pluripotency and self-renewal.

  12. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses

    DEFF Research Database (Denmark)

    Brok, J.; Thorlund, K.; Gluud, C.

    2008-01-01

    in 80% (insufficient information size). TSA(15%) and TSA(LBHIS) found that 95% and 91% had absence of evidence. The remaining nonsignificant meta-analyses had evidence of lack of effect. CONCLUSION: TSA reveals insufficient information size and potentially false positive results in many meta......OBJECTIVES: To evaluate meta-analyses with trial sequential analysis (TSA). TSA adjusts for random error risk and provides the required number of participants (information size) in a meta-analysis. Meta-analyses not reaching information size are analyzed with trial sequential monitoring boundaries...... analogous to interim monitoring boundaries in a single trial. STUDY DESIGN AND SETTING: We applied TSA on meta-analyses performed in Cochrane Neonatal reviews. We calculated information sizes and monitoring boundaries with three different anticipated intervention effects of 30% relative risk reduction (TSA...

  13. Time-Series Analyses of Transcriptomes and Proteomes Reveal Molecular Networks Underlying Oil Accumulation in Canola.

    Science.gov (United States)

    Wan, Huafang; Cui, Yixin; Ding, Yijuan; Mei, Jiaqin; Dong, Hongli; Zhang, Wenxin; Wu, Shiqi; Liang, Ying; Zhang, Chunyu; Li, Jiana; Xiong, Qing; Qian, Wei

    2016-01-01

    Understanding the regulation of lipid metabolism is vital for genetic engineering of canola ( Brassica napus L.) to increase oil yield or modify oil composition. We conducted time-series analyses of transcriptomes and proteomes to uncover the molecular networks associated with oil accumulation and dynamic changes in these networks in canola. The expression levels of genes and proteins were measured at 2, 4, 6, and 8 weeks after pollination (WAP). Our results show that the biosynthesis of fatty acids is a dominant cellular process from 2 to 6 WAP, while the degradation mainly happens after 6 WAP. We found that genes in almost every node of fatty acid synthesis pathway were significantly up-regulated during oil accumulation. Moreover, significant expression changes of two genes, acetyl-CoA carboxylase and acyl-ACP desaturase, were detected on both transcriptomic and proteomic levels. We confirmed the temporal expression patterns revealed by the transcriptomic analyses using quantitative real-time PCR experiments. The gene set association analysis show that the biosynthesis of fatty acids and unsaturated fatty acids are the most significant biological processes from 2-4 WAP and 4-6 WAP, respectively, which is consistent with the results of time-series analyses. These results not only provide insight into the mechanisms underlying lipid metabolism, but also reveal novel candidate genes that are worth further investigation for their values in the genetic engineering of canola.

  14. Single-cell analysis reveals a link between CD3- and CD59-mediated signaling pathways in Jurkat T cells

    International Nuclear Information System (INIS)

    Lipp, A. M.

    2012-01-01

    Elevation of intracellular free calcium concentration ([Ca2+]i) is a key signal during T cell activation and is commonly used as a read-out parameter for stimulation of T cell signaling. Upon T cell stimulation a variety of calcium signals is produced by individual cells of the T cell population and the type of calcium signal strongly influences cell fate decisions. The heterogeneous nature of T cells is masked in ensemble measurements, which highlights the need for single-cell measurements. In this study we used single-cell calcium measurements in Jurkat cells to investigate signaling pathways, which are triggered by different proteins, namely CD3 and CD59. By application of an automated cluster algorithm the presented assay provides unbiased analysis of a large data set of individual calcium time traces generated by the whole cell population. By using this method we could demonstrate that the Jurkat population generates heterogeneous calcium signals in a stimulus-dependent manner. Furthermore, our data revealed the existence of a link between CD3- and CD59-mediated signaling pathways. Single-cell calcium measurements in Jurkat cells expressing different levels of the T cell receptor (TCR) complex indicated that CD59-mediated calcium signaling is critically dependent on TCR surface expression levels. In addition, triggering CD59-mediated calcium signaling resulted in down-regulation of TCR surface expression levels, which is known to happen upon direct TCR triggering too. Moreover, by using siRNA-mediated protein knock-downs and protein knock-out Jurkat mutants we could show that CD3- and CD59-mediated calcium signaling require identical key proteins. We therefore explored by which mechanism CD59-mediated signaling couples into TCR-mediated signaling. Fluorescence recovery after photobleaching (FRAP) experiments and live-cell protein-protein interaction assays provided no evidence of a direct physical interaction between CD3- and CD59-mediated signaling pathways

  15. Metabolomic Analyses of Leishmania Reveal Multiple Species Differences and Large Differences in Amino Acid Metabolism.

    Directory of Open Access Journals (Sweden)

    Gareth D Westrop

    Full Text Available Comparative genomic analyses of Leishmania species have revealed relatively minor heterogeneity amongst recognised housekeeping genes and yet the species cause distinct infections and pathogenesis in their mammalian hosts. To gain greater information on the biochemical variation between species, and insights into possible metabolic mechanisms underpinning visceral and cutaneous leishmaniasis, we have undertaken in this study a comparative analysis of the metabolomes of promastigotes of L. donovani, L. major and L. mexicana. The analysis revealed 64 metabolites with confirmed identity differing 3-fold or more between the cell extracts of species, with 161 putatively identified metabolites differing similarly. Analysis of the media from cultures revealed an at least 3-fold difference in use or excretion of 43 metabolites of confirmed identity and 87 putatively identified metabolites that differed to a similar extent. Strikingly large differences were detected in their extent of amino acid use and metabolism, especially for tryptophan, aspartate, arginine and proline. Major pathways of tryptophan and arginine catabolism were shown to be to indole-3-lactate and arginic acid, respectively, which were excreted. The data presented provide clear evidence on the value of global metabolomic analyses in detecting species-specific metabolic features, thus application of this technology should be a major contributor to gaining greater understanding of how pathogens are adapted to infecting their hosts.

  16. Individual-based analyses reveal limited functional overlap in a coral reef fish community.

    Science.gov (United States)

    Brandl, Simon J; Bellwood, David R

    2014-05-01

    Detailed knowledge of a species' functional niche is crucial for the study of ecological communities and processes. The extent of niche overlap, functional redundancy and functional complementarity is of particular importance if we are to understand ecosystem processes and their vulnerability to disturbances. Coral reefs are among the most threatened marine systems, and anthropogenic activity is changing the functional composition of reefs. The loss of herbivorous fishes is particularly concerning as the removal of algae is crucial for the growth and survival of corals. Yet, the foraging patterns of the various herbivorous fish species are poorly understood. Using a multidimensional framework, we present novel individual-based analyses of species' realized functional niches, which we apply to a herbivorous coral reef fish community. In calculating niche volumes for 21 species, based on their microhabitat utilization patterns during foraging, and computing functional overlaps, we provide a measurement of functional redundancy or complementarity. Complementarity is the inverse of redundancy and is defined as less than 50% overlap in niche volumes. The analyses reveal extensive complementarity with an average functional overlap of just 15.2%. Furthermore, the analyses divide herbivorous reef fishes into two broad groups. The first group (predominantly surgeonfishes and parrotfishes) comprises species feeding on exposed surfaces and predominantly open reef matrix or sandy substrata, resulting in small niche volumes and extensive complementarity. In contrast, the second group consists of species (predominantly rabbitfishes) that feed over a wider range of microhabitats, penetrating the reef matrix to exploit concealed surfaces of various substratum types. These species show high variation among individuals, leading to large niche volumes, more overlap and less complementarity. These results may have crucial consequences for our understanding of herbivorous processes on

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

    Directory of Open Access Journals (Sweden)

    Walid Briki

    2016-10-01

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

  18. Combined Metabonomic and Quantitative RT-PCR Analyses Revealed Metabolic Reprogramming Associated with Fusarium graminearum Resistance in Transgenic Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Fangfang Chen

    2018-01-01

    Full Text Available Fusarium head blight disease resulting from Fusarium graminearum (FG infection causes huge losses in global production of cereals and development of FG-resistant plants is urgently needed. To understand biochemistry mechanisms for FG resistance, here, we have systematically investigated the plant metabolomic phenotypes associated with FG resistance for transgenic Arabidopsis thaliana expressing a class-I chitinase (Chi, a Fusarium-specific recombinant antibody gene (CWP2 and fused Chi-CWP2. Plant disease indices, mycotoxin levels, metabonomic characteristics, and expression levels of several key genes were measured together with their correlations. We found that A. thaliana expressing Chi-CWP2 showed higher FG resistance with much lower disease indices and mycotoxin levels than the wild-type and the plants expressing Chi or CWP2 alone. The combined metabonomic and quantitative RT-PCR analyses revealed that such FG-resistance was closely associated with the promoted biosynthesis of secondary metabolites (phenylpropanoids, alkanoids and organic osmolytes (proline, betaine, glucose, myo-inositol together with enhanced TCA cycle and GABA shunt. These suggest that the concurrently enhanced biosyntheses of the shikimate-mediated secondary metabolites and organic osmolytes be an important strategy for A. thaliana to develop and improve FG resistance. These findings provide essential biochemical information related to FG resistance which is important for developing FG-resistant cereals.

  19. DNA sequence analyses reveal abundant diversity, endemism and evidence for Asian origin of the porcini mushrooms.

    Directory of Open Access Journals (Sweden)

    Bang Feng

    Full Text Available The wild gourmet mushroom Boletus edulis and its close allies are of significant ecological and economic importance. They are found throughout the Northern Hemisphere, but despite their ubiquity there are still many unresolved issues with regard to the taxonomy, systematics and biogeography of this group of mushrooms. Most phylogenetic studies of Boletus so far have characterized samples from North America and Europe and little information is available on samples from other areas, including the ecologically and geographically diverse regions of China. Here we analyzed DNA sequence variation in three gene markers from samples of these mushrooms from across China and compared our findings with those from other representative regions. Our results revealed fifteen novel phylogenetic species (about one-third of the known species and a newly identified lineage represented by Boletus sp. HKAS71346 from tropical Asia. The phylogenetic analyses support eastern Asia as the center of diversity for the porcini sensu stricto clade. Within this clade, B. edulis is the only known holarctic species. The majority of the other phylogenetic species are geographically restricted in their distributions. Furthermore, molecular dating and geological evidence suggest that this group of mushrooms originated during the Eocene in eastern Asia, followed by dispersal to and subsequent speciation in other parts of Asia, Europe, and the Americas from the middle Miocene through the early Pliocene. In contrast to the ancient dispersal of porcini in the strict sense in the Northern Hemisphere, the occurrence of B. reticulatus and B. edulis sensu lato in the Southern Hemisphere was probably due to recent human-mediated introductions.

  20. DNA Sequence Analyses Reveal Abundant Diversity, Endemism and Evidence for Asian Origin of the Porcini Mushrooms

    Science.gov (United States)

    Feng, Bang; Xu, Jianping; Wu, Gang; Zeng, Nian-Kai; Li, Yan-Chun; Tolgor, Bau; Kost, Gerhard W.; Yang, Zhu L.

    2012-01-01

    The wild gourmet mushroom Boletus edulis and its close allies are of significant ecological and economic importance. They are found throughout the Northern Hemisphere, but despite their ubiquity there are still many unresolved issues with regard to the taxonomy, systematics and biogeography of this group of mushrooms. Most phylogenetic studies of Boletus so far have characterized samples from North America and Europe and little information is available on samples from other areas, including the ecologically and geographically diverse regions of China. Here we analyzed DNA sequence variation in three gene markers from samples of these mushrooms from across China and compared our findings with those from other representative regions. Our results revealed fifteen novel phylogenetic species (about one-third of the known species) and a newly identified lineage represented by Boletus sp. HKAS71346 from tropical Asia. The phylogenetic analyses support eastern Asia as the center of diversity for the porcini sensu stricto clade. Within this clade, B. edulis is the only known holarctic species. The majority of the other phylogenetic species are geographically restricted in their distributions. Furthermore, molecular dating and geological evidence suggest that this group of mushrooms originated during the Eocene in eastern Asia, followed by dispersal to and subsequent speciation in other parts of Asia, Europe, and the Americas from the middle Miocene through the early Pliocene. In contrast to the ancient dispersal of porcini in the strict sense in the Northern Hemisphere, the occurrence of B. reticulatus and B. edulis sensu lato in the Southern Hemisphere was probably due to recent human-mediated introductions. PMID:22629418

  1. Mediation of Changes in Anxiety and Depression During Treatment of Social Phobia

    Science.gov (United States)

    Moscovitch, David A.; Stefan G. Hofmann, Michael K.; Suvak, Michael K.; In-Albon, Tina

    2005-01-01

    To investigate the interactive process of changes in social anxiety and depression during treatment, the authors assessed weekly symptoms in 66 adult outpatients with social phobia (social anxiety disorder) who participated in cognitive- behavioral group therapy. Multilevel mediational analyses revealed that improvements in social anxiety mediated…

  2. Why do perfectionists have a higher burnout risk than others? The mediational effect of workaholism

    Directory of Open Access Journals (Sweden)

    van Beek, Ilona

    2010-04-01

    Full Text Available Previous research has revealed that perfectionists have a higher burnout risk than others, but the mechanisms accounting for this association have rarely been examined. The present study proposes that workaholism mediates this relation, as previous research revealed that (a perfectionists are more likely to be workaholics than others, and (b workaholics have a higher burnout risk than others. Using cross-sectional data from 199 Dutch managers, regression analyses revealed that holding high standards towards oneself (a self-directed indicator of perfectionism was unrelated to any of the three dimensions of the Maslach Burnout Inventory. However, high concern over making mistakes in the face of others (representing socially prescribed perfectionism was systematically associated with high levels of burnout and workaholism. Moreover, workaholism was positively associated with high levels of exhaustion. Subsequent mediation analysis revealed that the association between (the socially prescribed aspect of perfectionism and burnout (emotional exhaustion was mediated by workaholism.

  3. Relationships among race, education, criminal thinking, and recidivism: moderator and mediator effects.

    Science.gov (United States)

    Walters, Glenn D

    2014-02-01

    Moderator and mediator relationships linking variables from three different theoretical traditions-race (subcultural theory), education (life-course theory), and criminal thinking (social learning theory)-and recidivism were examined in 1,101 released male federal prison inmates. Preliminary regression analyses indicated that racial status (White, Black, Hispanic) moderated the relationship between criminal thinking, as measured by the General Criminal Thinking (GCT) score of the Psychological Inventory of Criminal Thinking Styles (PICTS), and recidivism. Further analysis, however, revealed that it was not racial status, per se, that moderated the relationship between the PICTS and recidivism, but educational attainment. Whereas the PICTS was largely effective in predicting recidivism in inmates with 12 or more years of education, it was largely ineffective in predicting recidivism in inmates with fewer than 12 years of education. When education and the GCT score were compared as possible mediators of the race-recidivism relationship only the GCT successfully mediated this relationship. Sensitivity testing showed that the GCT mediating effect was moderately robust to violations of the sequential ignorability assumption on which causal mediation analysis rests. Moderator and mediator analyses are potentially important avenues through which theoretical constructs can be integrated and assessment strategies devised.

  4. Special analyses reveal coke-deposit structure

    International Nuclear Information System (INIS)

    Albright, L.F.

    1988-01-01

    A scanning electron microscope (SEM) and an energy dispersive X-ray analyzer (EDAX) have been used to obtain information that clarifies the three mechanisms of coke formation in ethylene furnaces, and to analyze the metal condition at the exit of furnace. The results can be used to examine furnace operations and develop improved ethylene plant practices. In this first of four articles on the analyses of coke and metal samples, the coking mechanisms and coke deposits in a section of tube from an actual ethylene furnace (Furnace A) from a plant on the Texas Gulf Coast are discussed. The second articles in the series will analyze the condition of the tube metal in the same furnace. To show how coke deposition and metal condition dependent on the operating parameters of an ethylene furnace, the third article in the series will show the coke deposition in a Texas Gulf Coast furnace tube (Furnace B) that operated at shorter residence time. The fourth article discusses the metal condition in that furnace. Some recommendations, based on the analyses and findings, are offered in the fourth article that could help extend the life of ethylene furnace tubes, and also improve overall ethylene plant operations

  5. Estimation of Causal Mediation Effects for a Dichotomous Outcome in Multiple-Mediator Models using the Mediation Formula

    OpenAIRE

    Wang, Wei; Nelson, Suchitra; Albert, Jeffrey M.

    2013-01-01

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets ...

  6. Depression as a mediator between family factors and peer-bullying victimization in Latino adolescents.

    Science.gov (United States)

    Yabko, Brandon A; Hokoda, Audrey; Ulloa, Emilio C

    2008-01-01

    The purpose of this study was to assess the mediating role of depression in three different relationships: (a) sibling bullying and peer victimization, (b) mothers' power-assertive parenting and peer victimization, and (c) fathers' power-assertive parenting and peer victimization. Results from 242 Latino middle school adolescents from a large southwestern city bordering Mexico revealed that both boys' and girls' peer victimization were related to familial factors and depression. Regression analyses for boys revealed that depression mediated three relationships: (a) sibling bullying and peer victimization, (b) mothers' power-assertive parenting and peer victimization, and (c) fathers' power-assertive parenting and peer victimization. Depression also mediated the relationship between fathers' power-assertive parenting and girls' victimization by peers. The findings support the development of family-based interventions for peer victimization that include curriculum addressing depression.

  7. Imaging an optogenetic pH sensor reveals that protons mediate lateral inhibition in the retina.

    Science.gov (United States)

    Wang, Tzu-Ming; Holzhausen, Lars C; Kramer, Richard H

    2014-02-01

    The reciprocal synapse between photoreceptors and horizontal cells underlies lateral inhibition and establishes the antagonistic center-surround receptive fields of retinal neurons to enhance visual contrast. Despite decades of study, the signal mediating the negative feedback from horizontal cells to cones has remained under debate because the small, invaginated synaptic cleft has precluded measurement. Using zebrafish retinas, we show that light elicits a change in synaptic proton concentration with the correct magnitude, kinetics and spatial dependence to account for lateral inhibition. Light, which hyperpolarizes horizontal cells, causes synaptic alkalinization, whereas activating an exogenously expressed ligand-gated Na(+) channel, which depolarizes horizontal cells, causes synaptic acidification. Whereas acidification was prevented by blocking a proton pump, re-alkalinization was prevented by blocking proton-permeant ion channels, suggesting that distinct mechanisms underlie proton efflux and influx. These findings reveal that protons mediate lateral inhibition in the retina, raising the possibility that protons are unrecognized retrograde messengers elsewhere in the nervous system.

  8. Silver (I) as DNA glue: Ag+-mediated guanine pairing revealed by removing Watson-Crick constraints

    Science.gov (United States)

    Swasey, Steven M.; Leal, Leonardo Espinosa; Lopez-Acevedo, Olga; Pavlovich, James; Gwinn, Elisabeth G.

    2015-01-01

    Metal ion interactions with DNA have far-reaching implications in biochemistry and DNA nanotechnology. Ag+ is uniquely interesting because it binds exclusively to the bases rather than the backbone of DNA, without the toxicity of Hg2+. In contrast to prior studies of Ag+ incorporation into double-stranded DNA, we remove the constraints of Watson-Crick pairing by focusing on homo-base DNA oligomers of the canonical bases. High resolution electro-spray ionization mass spectrometry reveals an unanticipated Ag+-mediated pairing of guanine homo-base strands, with higher stability than canonical guanine-cytosine pairing. By exploring unrestricted binding geometries, quantum chemical calculations find that Ag+ bridges between non-canonical sites on guanine bases. Circular dichroism spectroscopy shows that the Ag+-mediated structuring of guanine homobase strands persists to at least 90 °C under conditions for which canonical guanine-cytosine duplexes melt below 20 °C. These findings are promising for DNA nanotechnology and metal-ion based biomedical science. PMID:25973536

  9. Silver (I) as DNA glue: Ag(+)-mediated guanine pairing revealed by removing Watson-Crick constraints.

    Science.gov (United States)

    Swasey, Steven M; Leal, Leonardo Espinosa; Lopez-Acevedo, Olga; Pavlovich, James; Gwinn, Elisabeth G

    2015-05-14

    Metal ion interactions with DNA have far-reaching implications in biochemistry and DNA nanotechnology. Ag(+) is uniquely interesting because it binds exclusively to the bases rather than the backbone of DNA, without the toxicity of Hg(2+). In contrast to prior studies of Ag(+) incorporation into double-stranded DNA, we remove the constraints of Watson-Crick pairing by focusing on homo-base DNA oligomers of the canonical bases. High resolution electro-spray ionization mass spectrometry reveals an unanticipated Ag(+)-mediated pairing of guanine homo-base strands, with higher stability than canonical guanine-cytosine pairing. By exploring unrestricted binding geometries, quantum chemical calculations find that Ag(+) bridges between non-canonical sites on guanine bases. Circular dichroism spectroscopy shows that the Ag(+)-mediated structuring of guanine homobase strands persists to at least 90 °C under conditions for which canonical guanine-cytosine duplexes melt below 20 °C. These findings are promising for DNA nanotechnology and metal-ion based biomedical science.

  10. Silver (I) as DNA glue: Ag+-mediated guanine pairing revealed by removing Watson-Crick constraints

    Science.gov (United States)

    Swasey, Steven M.; Leal, Leonardo Espinosa; Lopez-Acevedo, Olga; Pavlovich, James; Gwinn, Elisabeth G.

    2015-05-01

    Metal ion interactions with DNA have far-reaching implications in biochemistry and DNA nanotechnology. Ag+ is uniquely interesting because it binds exclusively to the bases rather than the backbone of DNA, without the toxicity of Hg2+. In contrast to prior studies of Ag+ incorporation into double-stranded DNA, we remove the constraints of Watson-Crick pairing by focusing on homo-base DNA oligomers of the canonical bases. High resolution electro-spray ionization mass spectrometry reveals an unanticipated Ag+-mediated pairing of guanine homo-base strands, with higher stability than canonical guanine-cytosine pairing. By exploring unrestricted binding geometries, quantum chemical calculations find that Ag+ bridges between non-canonical sites on guanine bases. Circular dichroism spectroscopy shows that the Ag+-mediated structuring of guanine homobase strands persists to at least 90 °C under conditions for which canonical guanine-cytosine duplexes melt below 20 °C. These findings are promising for DNA nanotechnology and metal-ion based biomedical science.

  11. Why do perfectionists have a higher burnout risk than others? The mediational effect of workaholism

    OpenAIRE

    van Beek, Ilona; Schaufeli, Wilmar B.; Taris, Toon W.

    2010-01-01

    Previous research has revealed that perfectionists have a higher burnout risk than others, but the mechanisms accounting for this association have rarely been examined. The present study proposes that workaholism mediates this relation, as previous research revealed that (a) perfectionists are more likely to be workaholics than others, and (b) workaholics have a higher burnout risk than others. Using cross-sectional data from 199 Dutch managers, regression analyses revealed that holding high ...

  12. Genome-wide analyses reveal a role for peptide hormones in planarian germline development.

    Directory of Open Access Journals (Sweden)

    James J Collins

    Full Text Available Bioactive peptides (i.e., neuropeptides or peptide hormones represent the largest class of cell-cell signaling molecules in metazoans and are potent regulators of neural and physiological function. In vertebrates, peptide hormones play an integral role in endocrine signaling between the brain and the gonads that controls reproductive development, yet few of these molecules have been shown to influence reproductive development in invertebrates. Here, we define a role for peptide hormones in controlling reproductive physiology of the model flatworm, the planarian Schmidtea mediterranea. Based on our observation that defective neuropeptide processing results in defects in reproductive system development, we employed peptidomic and functional genomic approaches to characterize the planarian peptide hormone complement, identifying 51 prohormone genes and validating 142 peptides biochemically. Comprehensive in situ hybridization analyses of prohormone gene expression revealed the unanticipated complexity of the flatworm nervous system and identified a prohormone specifically expressed in the nervous system of sexually reproducing planarians. We show that this member of the neuropeptide Y superfamily is required for the maintenance of mature reproductive organs and differentiated germ cells in the testes. Additionally, comparative analyses of our biochemically validated prohormones with the genomes of the parasitic flatworms Schistosoma mansoni and Schistosoma japonicum identified new schistosome prohormones and validated half of all predicted peptide-encoding genes in these parasites. These studies describe the peptide hormone complement of a flatworm on a genome-wide scale and reveal a previously uncharacterized role for peptide hormones in flatworm reproduction. Furthermore, they suggest new opportunities for using planarians as free-living models for understanding the reproductive biology of flatworm parasites.

  13. Comparative Genomics and Transcriptomics Analyses Reveal Divergent Lifestyle Features of Nematode Endoparasitic Fungus Hirsutella minnesotensis

    Science.gov (United States)

    Lai, Yiling; Liu, Keke; Zhang, Xinyu; Zhang, Xiaoling; Li, Kuan; Wang, Niuniu; Shu, Chi; Wu, Yunpeng; Wang, Chengshu; Bushley, Kathryn E.; Xiang, Meichun; Liu, Xingzhong

    2014-01-01

    Hirsutella minnesotensis [Ophiocordycipitaceae (Hypocreales, Ascomycota)] is a dominant endoparasitic fungus by using conidia that adhere to and penetrate the secondary stage juveniles of soybean cyst nematode. Its genome was de novo sequenced and compared with five entomopathogenic fungi in the Hypocreales and three nematode-trapping fungi in the Orbiliales (Ascomycota). The genome of H. minnesotensis is 51.4 Mb and encodes 12,702 genes enriched with transposable elements up to 32%. Phylogenomic analysis revealed that H. minnesotensis was diverged from entomopathogenic fungi in Hypocreales. Genome of H. minnesotensis is similar to those of entomopathogenic fungi to have fewer genes encoding lectins for adhesion and glycoside hydrolases for cellulose degradation, but is different from those of nematode-trapping fungi to possess more genes for protein degradation, signal transduction, and secondary metabolism. Those results indicate that H. minnesotensis has evolved different mechanism for nematode endoparasitism compared with nematode-trapping fungi. Transcriptomics analyses for the time-scale parasitism revealed the upregulations of lectins, secreted proteases and the genes for biosynthesis of secondary metabolites that could be putatively involved in host surface adhesion, cuticle degradation, and host manipulation. Genome and transcriptome analyses provided comprehensive understanding of the evolution and lifestyle of nematode endoparasitism. PMID:25359922

  14. Phylogeographic analyses of the pampas cat (Leopardus colocola; Carnivora, Felidae) reveal a complex demographic history

    Science.gov (United States)

    da Silva Santos, Anelisie; Trigo, Tatiane Campos; de Oliveira, Tadeu Gomes; Silveira, Leandro

    2018-01-01

    Abstract The pampas cat is a small felid that occurs in open habitats throughout much of South America. Previous studies have revealed intriguing patterns of morphological differentiation and genetic structure among its populations, as well as molecular evidence for hybridization with the closely related L. tigrinus. Here we report phylogeographic analyses encompassing most of its distribution (focusing particularly on Brazilian specimens, which had been poorly sampled in previous studies), using a novel dataset comprising 2,143 bp of the mitogenome, along with previously reported mtDNA sequences. Our data revealed strong population strutucture and supported a west-to-east colonization process in this species’ history. We detected two population expansion events, one older (ca. 200 thousand years ago [kya]) in western South America and another more recent (ca. 60-50 kya) in eastern areas, coinciding with the expansion of savanna environments in Brazil. Analyses including L. tigrinus individuals bearing introgressed mtDNA from L. colocola showed a complete lack of shared haplotypes between species, indicating that their hybridization was ancient. Finally, we observed a close relationship between Brazilian/Uruguayan L. colocola haplotypes and those sampled in L. tigrinus, indicating that their hybridization was likely related to the demographic expansion of L. colocola into eastern South America. PMID:29668017

  15. The effect of computer-mediated administration on self-disclosure of problems on the addiction severity index.

    Science.gov (United States)

    Butler, Stephen F; Villapiano, Albert; Malinow, Andrew

    2009-12-01

    People tend to disclose more personal information when communication is mediated through the use of a computer. This study was conducted to examine the impact of this phenomenon on the way respondents answer questions during computer-mediated, self-administration of the Addiction Severity Index (ASI) called the Addiction Severity Index-Multimedia Version((R)) (ASI-MV((R))). A sample of 142 clients in substance abuse treatment was administered the ASI via an interviewer and the computerized ASI-MV((R)), three to five days apart in a counterbalanced order. Seven composite scores were compared between the two test administrations using paired t-tests. Post hoc analyses examined interviewer effects. Comparisons of composite scores for each of the domains between the face-to-face administered and computer-mediated, self-administered ASI revealed that significantly greater problem severity was reported by clients in five of the seven domains during administration of the computer-mediated, self-administered version compared to the trained interviewer version. Item analyses identified certain items as responsible for significant differences, especially those asking clients to rate need for treatment. All items that were significantly different between the two modes of administration revealed greater problem severity reported on the ASI-MV((R)) as compared to the interview administered assessment. Post hoc analyses yielded significant interviewer effects on four of the five domains where differences were observed. These data support a growing literature documenting a tendency for respondents to be more self-disclosing in a computer-mediated format over a face-to-face interview. Differences in interviewer skill in establishing rapport may account for these observations.

  16. [Mediator effect of resilience between burnout and health in nursing staff].

    Science.gov (United States)

    Arrogante, Óscar

    2014-01-01

    To determine the relationships between 3 burnout dimensions (Emotional Exhaustion, Depersonalization, and Reduced Personal Accomplishment), health (physical and mental health), and resilience, as well as to analyse the mediator role of resilience in relationships between burnout and health in a sample of Nursing staff. A correlational and cross-sectional study with probabilistic sampling was conducted on a sample of 194 Nursing staff of University Hospital of Fuenlabrada (Madrid), and composed of nurses (n=133) and nursing assistants (n=61). MBI-HSS (burnout syndrome), SF-12v1 (physical and mental components of health), 10-Item CD-RISC (resilience), and sociodemographic variables. Correlational analyses showed that mental health was negatively related with 3 burnout dimensions and positively with resilience. Furthermore, physical health was only negatively related with Emotional Exhaustion, and positively with resilience. Mediational analyses revealed that resilience mediated, on one hand, the relationship between Emotional Exhaustion and Depersonalization with mental health (partial mediation) and, on the other hand, the relationship between Reduced Personal Accomplishment and mental health (total mediation). Resilience is not only important to improve the mental health of Nursing staff, but also to buffer and minimize the negative consequences of the occupational stress to which they are at risk, with its most adverse result being signs of burnout. Therefore, resilience training should be promoted to improve nursing clinical practice. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

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

    Science.gov (United States)

    Briki, Walid

    2017-01-01

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

  18. Interventional effects for mediation analysis with multiple mediators

    OpenAIRE

    Vansteelandt, Stijn; Daniel, Rhian M.

    2017-01-01

    The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator–outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that...

  19. Forms of Mediation: The Case of Interpreter-Mediated Interactions in Medical Systems

    Science.gov (United States)

    Baraldi, Claudio

    2009-01-01

    This paper analyses the forms of mediation in interlinguistic interactions performed in Italian healthcare services and in contexts of migration. The literature encourages dialogic transformative mediation, empowering participants' voices and changing cultural presuppositions in social systems. It may be doubtful, however, whether mediation can…

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

    Science.gov (United States)

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

    2017-04-01

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

  1. Mediator links transcription and DNA repair by facilitating Rad2/XPG recruitment.

    Science.gov (United States)

    Eyboulet, Fanny; Cibot, Camille; Eychenne, Thomas; Neil, Helen; Alibert, Olivier; Werner, Michel; Soutourina, Julie

    2013-12-01

    Mediator is a large multiprotein complex conserved in all eukaryotes. The crucial function of Mediator in transcription is now largely established. However, we found that this complex also plays an important role by connecting transcription with DNA repair. We identified a functional contact between the Med17 Mediator subunit and Rad2/XPG, the 3' endonuclease involved in nucleotide excision DNA repair. Genome-wide location analyses revealed that Rad2 is associated with RNA polymerase II (Pol II)- and Pol III-transcribed genes and telomeric regions in the absence of exogenous genotoxic stress. Rad2 occupancy of Pol II-transcribed genes is transcription-dependent. Genome-wide Rad2 occupancy of class II gene promoters is well correlated with that of Mediator. Furthermore, UV sensitivity of med17 mutants is correlated with reduced Rad2 occupancy of class II genes and concomitant decrease of Mediator interaction with Rad2 protein. Our results suggest that Mediator is involved in DNA repair by facilitating Rad2 recruitment to transcribed genes.

  2. Causal Models for Mediation Analysis: An Introduction to Structural Mean Models.

    Science.gov (United States)

    Zheng, Cheng; Atkins, David C; Zhou, Xiao-Hua; Rhew, Isaac C

    2015-01-01

    Mediation analyses are critical to understanding why behavioral interventions work. To yield a causal interpretation, common mediation approaches must make an assumption of "sequential ignorability." The current article describes an alternative approach to causal mediation called structural mean models (SMMs). A specific SMM called a rank-preserving model (RPM) is introduced in the context of an applied example. Particular attention is given to the assumptions of both approaches to mediation. Applying both mediation approaches to the college student drinking data yield notable differences in the magnitude of effects. Simulated examples reveal instances in which the traditional approach can yield strongly biased results, whereas the RPM approach remains unbiased in these cases. At the same time, the RPM approach has its own assumptions that must be met for correct inference, such as the existence of a covariate that strongly moderates the effect of the intervention on the mediator and no unmeasured confounders that also serve as a moderator of the effect of the intervention or the mediator on the outcome. The RPM approach to mediation offers an alternative way to perform mediation analysis when there may be unmeasured confounders.

  3. Burnout and health among critical care professionals: The mediational role of resilience.

    Science.gov (United States)

    Arrogante, Oscar; Aparicio-Zaldivar, Eva

    2017-10-01

    To analyse the mediational role of resilience in relationships between burnout and health in critical care professionals; to determine relationships among resilience level, three burnout dimensions, and physical/mental health; and to establish demographic differences in psychological variables evaluated. Cross-sectional study. A total of 52 critical care professionals, mainly nurses, were recruited from an intensive care unit of Madrid (Spain). All participants were assessed with the questionnaires 10-item Connor-Davidson Resilience Scale, Maslach Burnout Inventory-Human Services Survey, and Short Form-12 Health Survey. No demographic differences were found. Three burnout dimensions were negatively associated with mental health and resilience. Mediational analyses revealed resilience mediated 1) the relationships between emotional exhaustion and depersonalisation with mental health (partial mediations) and 2) the relationship between personal accomplishment and mental health (total mediation). Resilience minimises and buffers the impact of negative outcomes of workplace stress on mental health of critical care professionals. As a result, resilience prevents the occurrence of burnout syndrome. Resilience improves not only their mental health, but also their ability to practice effectively. It is therefore imperative to develop resilience programs for critical care nurses in nursing schools, universities and health centres. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Mitochondrial DNA analyses reveal low genetic diversity in Culex quinquefasciatus from residential areas in Malaysia.

    Science.gov (United States)

    Low, V L; Lim, P E; Chen, C D; Lim, Y A L; Tan, T K; Norma-Rashid, Y; Lee, H L; Sofian-Azirun, M

    2014-06-01

    The present study explored the intraspecific genetic diversity, dispersal patterns and phylogeographic relationships of Culex quinquefasciatus Say (Diptera: Culicidae) in Malaysia using reference data available in GenBank in order to reveal this species' phylogenetic relationships. A statistical parsimony network of 70 taxa aligned as 624 characters of the cytochrome c oxidase subunit I (COI) gene and 685 characters of the cytochrome c oxidase subunit II (COII) gene revealed three haplotypes (A1-A3) and four haplotypes (B1-B4), respectively. The concatenated sequences of both COI and COII genes with a total of 1309 characters revealed seven haplotypes (AB1-AB7). Analysis using tcs indicated that haplotype AB1 was the common ancestor and the most widespread haplotype in Malaysia. The genetic distance based on concatenated sequences of both COI and COII genes ranged from 0.00076 to 0.00229. Sequence alignment of Cx. quinquefasciatus from Malaysia and other countries revealed four haplotypes (AA1-AA4) by the COI gene and nine haplotypes (BB1-BB9) by the COII gene. Phylogenetic analyses demonstrated that Malaysian Cx. quinquefasciatus share the same genetic lineage as East African and Asian Cx. quinquefasciatus. This study has inferred the genetic lineages, dispersal patterns and hypothetical ancestral genotypes of Cx. quinquefasciatus. © 2013 The Royal Entomological Society.

  5. Molecular Analyses Reveal Inflammatory Mediators in the Solid Component and Cyst Fluid of Human Adamantinomatous Craniopharyngioma.

    Science.gov (United States)

    Donson, Andrew M; Apps, John; Griesinger, Andrea M; Amani, Vladimir; Witt, Davis A; Anderson, Richard C E; Niazi, Toba N; Grant, Gerald; Souweidane, Mark; Johnston, James M; Jackson, Eric M; Kleinschmidt-DeMasters, Bette K; Handler, Michael H; Tan, Aik-Choon; Gore, Lia; Virasami, Alex; Gonzalez-Meljem, Jose Mario; Jacques, Thomas S; Martinez-Barbera, Juan Pedro; Foreman, Nicholas K; Hankinson, Todd C

    2017-09-01

    Pediatric adamantinomatous craniopharyngioma (ACP) is a highly solid and cystic tumor, often causing substantial damage to critical neuroendocrine structures such as the hypothalamus, pituitary gland, and optic apparatus. Paracrine signaling mechanisms driving tumor behavior have been hypothesized, with IL-6R overexpression identified as a potential therapeutic target. To identify potential novel therapies, we characterized inflammatory and immunomodulatory factors in ACP cyst fluid and solid tumor components. Cytometric bead analysis revealed a highly pro-inflammatory cytokine pattern in fluid from ACP compared to fluids from another cystic pediatric brain tumor, pilocytic astrocytoma. Cytokines and chemokines with particularly elevated concentrations in ACPs were IL-6, CXCL1 (GRO), CXCL8 (IL-8) and the immunosuppressive cytokine IL-10. These data were concordant with solid tumor compartment transcriptomic data from a larger cohort of ACPs, other pediatric brain tumors and normal brain. The majority of receptors for these cytokines and chemokines were also over-expressed in ACPs. In addition to IL-10, the established immunosuppressive factor IDO-1 was overexpressed by ACPs at the mRNA and protein levels. These data indicate that ACP cyst fluids and solid tumor components are characterized by an inflammatory cytokine and chemokine expression pattern. Further study regarding selective cytokine blockade may inform novel therapeutic interventions. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  6. Evaluative beliefs as mediators of the relationship between parental bonding and symptoms of paranoia and depression.

    Science.gov (United States)

    Valiente, Carmen; Romero, Nuria; Hervas, Gonzalo; Espinosa, Regina

    2014-01-30

    This study was aimed to explore the distinct pathways that lead to depression and paranoia. We first examined the association of dysfunctional parenting experiences and negative self-evaluations in depression and paranoia. Furthermore, we also examined whether different self-evaluative beliefs could mediate the relationships between dysfunctional parenting experiences (i.e. parental overprotection or lack of care) and the development of depression and paranoia. A sample composed of 55 paranoid patients, 38 depressed patients and 44 healthy controls completed the Parental Bonding Instrument (PBI), the Evaluative Beliefs Scale (EBS) and some clinical scales. Our analyses revealed that lack of parental care and negative self-self evaluations were associated with depression symptoms. Analyses also revealed that parental overprotection and negative other-self evaluations were associated with paranoid symptoms. Furthermore, negative self-self and other-self evaluations fully mediated the relationship of parental overprotection and paranoia, whereas negative self-self evaluations partially mediated the relationship between lack of parental care and depression. These findings suggest that distinct patterns of parental practices may contribute to the development of different dysfunctional schemas which in turn may lead to either depression or paranoia. © 2013 Published by Elsevier Ireland Ltd.

  7. Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue.

    Directory of Open Access Journals (Sweden)

    Monique Ramos de Oliveira Trugilho

    2017-05-01

    Full Text Available Dengue is the most prevalent human arbovirus disease worldwide. Dengue virus (DENV infection causes syndromes varying from self-limiting febrile illness to severe dengue. Although dengue pathophysiology is not completely understood, it is widely accepted that increased inflammation plays important roles in dengue pathogenesis. Platelets are blood cells classically known as effectors of hemostasis which have been increasingly recognized to have major immune and inflammatory activities. Nevertheless, the phenotype and effector functions of platelets in dengue pathogenesis are not completely understood. Here we used quantitative proteomics to investigate the protein content of platelets in clinical samples from patients with dengue compared to platelets from healthy donors. Our assays revealed a set of 252 differentially abundant proteins. In silico analyses associated these proteins with key molecular events including platelet activation and inflammatory responses, and with events not previously attributed to platelets during dengue infection including antigen processing and presentation, proteasome activity, and expression of histones. From these results, we conducted functional assays using samples from a larger cohort of patients and demonstrated evidence for platelet activation indicated by P-selectin (CD62P translocation and secretion of granule-stored chemokines by platelets. In addition, we found evidence that DENV infection triggers HLA class I synthesis and surface expression by a mechanism depending on functional proteasome activity. Furthermore, we demonstrate that cell-free histone H2A released during dengue infection binds to platelets, increasing platelet activation. These findings are consistent with functional importance of HLA class I, proteasome subunits, and histones that we found exclusively in proteome analysis of platelets in samples from dengue patients. Our study provides the first in-depth characterization of the platelet

  8. Coping strategies as mediators and moderators between stress and quality of life among parents of children with autistic disorder.

    Science.gov (United States)

    Dardas, Latefa A; Ahmad, Muayyad M

    2015-02-01

    The purpose of this cross-sectional study was to examine coping strategies as mediators and moderators between stress and quality of life (QoL) among parents of children with autistic disorder. The convenience sample of the study consisted of 184 parents of children with autistic disorder. Advanced statistical methods for analyses of mediator and moderator effects of coping strategies were used. The results revealed that 'accepting responsibility' was the only mediator strategy in the relationship between stress and QoL. The results also revealed that only 'seeking social support' and 'escape avoidance' were moderator strategies in the relationship between stress and QoL. This study is perhaps the first to investigate the mediating and moderating effects of coping on QoL of parents of children with autistic disorder. Recommendations for practice and future research are presented. © 2013 John Wiley & Sons, Ltd.

  9. PIC Activation through Functional Interplay between Mediator and TFIIH.

    Science.gov (United States)

    Malik, Sohail; Molina, Henrik; Xue, Zhu

    2017-01-06

    The multiprotein Mediator coactivator complex functions in large part by controlling the formation and function of the promoter-bound preinitiation complex (PIC), which consists of RNA polymerase II and general transcription factors. However, precisely how Mediator impacts the PIC, especially post-recruitment, has remained unclear. Here, we have studied Mediator effects on basal transcription in an in vitro transcription system reconstituted from purified components. Our results reveal a close functional interplay between Mediator and TFIIH in the early stages of PIC development. We find that under conditions when TFIIH is not normally required for transcription, Mediator actually represses transcription. TFIIH, whose recruitment to the PIC is known to be facilitated by the Mediator, then acts to relieve Mediator-induced repression to generate an active form of the PIC. Gel mobility shift analyses of PICs and characterization of TFIIH preparations carrying mutant XPB translocase subunit further indicate that this relief of repression is achieved through expending energy via ATP hydrolysis, suggesting that it is coupled to TFIIH's established promoter melting activity. Our interpretation of these results is that Mediator functions as an assembly factor that facilitates PIC maturation through its various stages. Whereas the overall effect of the Mediator is to stimulate basal transcription, its initial engagement with the PIC generates a transcriptionally inert PIC intermediate, which necessitates energy expenditure to complete the process. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Service climate as a mediator of organizational empowerment in customer-service employees.

    Science.gov (United States)

    Mendoza-Sierra, Maria Isabel; Orgambídez-Ramos, Alejandro; Carrasco-González, Ana María; León-Jariego, José Carlos

    2014-01-01

    The aim of this study is to examine the mediating role of the service climate between organizational empowerment (i.e., dynamic structural framework, control of workplace decisions, fluidity in information sharing) and service quality (functional and relational). 428 contact employees from 46 hotels participated in the survey. Correlations demonstrated that dynamic structural framework, control decisions, and fluidity in information sharing are related to both functional and relational service quality. Regression analyses and Sobel tests revealed that service climate totally mediated the relationship between all three dimensions of organizational empowerment and relational service quality. Implications for practice and future research are discussed.

  11. Fossil-based comparative analyses reveal ancient marine ancestry erased by extinction in ray-finned fishes.

    Science.gov (United States)

    Betancur-R, Ricardo; Ortí, Guillermo; Pyron, Robert Alexander

    2015-05-01

    The marine-freshwater boundary is a major biodiversity gradient and few groups have colonised both systems successfully. Fishes have transitioned between habitats repeatedly, diversifying in rivers, lakes and oceans over evolutionary time. However, their history of habitat colonisation and diversification is unclear based on available fossil and phylogenetic data. We estimate ancestral habitats and diversification and transition rates using a large-scale phylogeny of extant fish taxa and one containing a massive number of extinct species. Extant-only phylogenetic analyses indicate freshwater ancestry, but inclusion of fossils reveal strong evidence of marine ancestry in lineages now restricted to freshwaters. Diversification and colonisation dynamics vary asymmetrically between habitats, as marine lineages colonise and flourish in rivers more frequently than the reverse. Our study highlights the importance of including fossils in comparative analyses, showing that freshwaters have played a role as refuges for ancient fish lineages, a signal erased by extinction in extant-only phylogenies. © 2015 John Wiley & Sons Ltd/CNRS.

  12. Cross-Sectional Analysis of Longitudinal Mediation Processes.

    Science.gov (United States)

    O'Laughlin, Kristine D; Martin, Monica J; Ferrer, Emilio

    2018-01-01

    Statistical mediation analysis can help to identify and explain the mechanisms behind psychological processes. Examining a set of variables for mediation effects is a ubiquitous process in the social sciences literature; however, despite evidence suggesting that cross-sectional data can misrepresent the mediation of longitudinal processes, cross-sectional analyses continue to be used in this manner. Alternative longitudinal mediation models, including those rooted in a structural equation modeling framework (cross-lagged panel, latent growth curve, and latent difference score models) are currently available and may provide a better representation of mediation processes for longitudinal data. The purpose of this paper is twofold: first, we provide a comparison of cross-sectional and longitudinal mediation models; second, we advocate using models to evaluate mediation effects that capture the temporal sequence of the process under study. Two separate empirical examples are presented to illustrate differences in the conclusions drawn from cross-sectional and longitudinal mediation analyses. Findings from these examples yielded substantial differences in interpretations between the cross-sectional and longitudinal mediation models considered here. Based on these observations, researchers should use caution when attempting to use cross-sectional data in place of longitudinal data for mediation analyses.

  13. Aspergillus fumigatus spore proteomics and genetics reveal that VeA represses DefA-mediated DNA damage response.

    Science.gov (United States)

    Shin, Kwang-Soo; Park, Hee-Soo; Kim, Young; Heo, In-Beom; Kim, Young Hwan; Yu, Jae-Hyuk

    2016-10-04

    Aspergillus fumigatus reproduces and infects host by forming a high number of small asexual spores (conidia). The velvet proteins are global transcriptional regulators governing the complex process of conidiogenesis in this fungus. Here, to further understand the velvet-mediated regulation, we carried out comparative proteomic analyses of conidia of wild type (WT) and three velvet mutants (ΔveA, ΔvelB and ΔvosA). Cluster analysis of 184 protein spots showing at least 1.5-fold differential accumulation between WT and mutants reveal the clustering of WT- ΔveA and ΔvelB-ΔvosA. Among 43 proteins identified by Nano-LC-ESI-MS/MS, 23 including several heat shock proteins showed more than two-fold reduction in both the ∆velB and ∆vosA conidia. On the contrary, three proteins exhibited more than five-fold increase in ∆veA only, including the putative RNA polymerase II degradation factor DefA. The deletion of defA resulted in a reduced number of conidia and restricted colony growth. In addition, the defA deletion mutant conidia showed hypersensitivity against the DNA damaging agents NQO and MMS, while the ΔveA mutant conidia were more resistant against to NQO. Taken together, we propose that VeA controls protein level of DefA in conidia, which are dormant and equipped with multiple layers of protection against environmental cues. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Perceived Interpersonal Burdensomeness as a Mediator between Nightmare Distress and Suicidal ideation in Nightmare Sufferers

    Directory of Open Access Journals (Sweden)

    Sooyeon Suh

    2016-11-01

    Full Text Available Previous studies have supported the significant association between nightmares and suicidal ideation, but the underlying mechanisms are largely unknown. The purpose of the present study was to investigate perceived burdensomeness and thwarted belongingness as mediators in the relationship between nightmare distress and suicidal ideation. This sample consisted of 301 undergraduate students who endorsed experiencing nightmares (mean age 21.87 ± 2.17, 78.1% female. All participants completed questionnaires on nightmare distress (Nightmare Distress Questionnaire, unmet interpersonal needs (Interpersonal Needs Questionnaire, and suicidal ideation (Depressive Symptom Inventory - Suicidality Subscale. Analyses were performed using multiple mediation regression. Results indicated that nightmare distress was associated with perceived burdensomeness (r = .17, p < .001 and suicidal ideation (r = .24, p < .001, but was not related to thwarted belongingness (r = .10, p = .06. Multiple mediation analyses revealed that perceived burdensomeness partially mediated the relationship between nightmares and suicidal ideation, but thwarted belongingness did not. Additionally, this mediating relationship for perceived burdensomeness was moderated by gender, being significant only for females. These findings highlight the important role of interpersonal factors in the relationship between nightmares and suicidal ideation.

  15. Interventional Effects for Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    Vansteelandt, Stijn; Daniel, Rhian M

    2017-03-01

    The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator-outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that involve repeatedly measured mediators, or multiple correlated mediators. VanderWeele, Vansteelandt, and Robins introduced so-called interventional (in)direct effects. These can be identified under much weaker conditions than natural (in)direct effects, but have the drawback of not adding up to the total effect. In this article, we adapt their proposal to achieve an exact decomposition of the total effect, and extend it to the multiple mediator setting. Interestingly, the proposed effects capture the path-specific effects of an exposure on an outcome that are mediated by distinct mediators, even when-as often-the structural dependence between the multiple mediators is unknown, for instance, when the direction of the causal effects between the mediators is unknown, or there may be unmeasured common causes of the mediators.

  16. Women, Physical Activity, and Quality of Life: Self-concept as a Mediator.

    Science.gov (United States)

    Gonzalo Silvestre, Tamara; Ubillos Landa, Silvia

    2016-02-22

    The objectives of this research are: (a) analyze the incremental validity of physical activity's (PA) influence on perceived quality of life (PQL); (b) determine if PA's predictive power is mediated by self-concept; and (c) study if results vary according to a unidimensional or multidimensional approach to self-concept measurement. The sample comprised 160 women from Burgos, Spain aged 18 to 45 years old. Non-probability sampling was used. Two three-step hierarchical regression analyses were applied to forecast PQL. The hedonic quality-of-life indicators, self-concept, self-esteem, and PA were included as independent variables. The first regression analysis included global self-concept as predictor variable, while the second included its five dimensions. Two mediation analyses were conducted to see if PA's ability to predict PQL was mediated by global and physical self-concept. Results from the first regression shows that self-concept, satisfaction with life, and PA were significant predictors. PA slightly but significantly increased explained variance in PQL (2.1%). In the second regression, substituting global self-concept with its five constituent factors, only the physical dimension and satisfaction with life predicted PQL, while PA ceased to be a significant predictor. Mediation analysis revealed that only physical self-concept mediates the relationship between PA and PQL (z = 1.97, p relationship between PQL, PA, and self-concept.

  17. Relationships between cohesion, collective efficacy and performance in professional basketball teams: an examination of mediating effects.

    Science.gov (United States)

    Heuzé, Jean-Philippe; Raimbault, Nicolas; Fontayne, Paul

    2006-01-01

    The main aim of this study was to examine mediating effects in the relationships between cohesion, collective efficacy and performance in professional basketball teams. A secondary aim was to examine the correlates of collective efficacy in a professional sport. A total of 154 French and foreign professional players completed French or English versions of questionnaires about cohesion and collective efficacy. Two composite measures of individual performance were used (pre- and post-performance). Individual-level analyses were performed. Regression analyses supported two mediating relationships with collective efficacy as a mediator of the pre-performance - Group integration-task relationship, and Group integration-task as a mediator of the pre-performance - collective efficacy relationship. Statistical analyses indicated that neither Group integration-task nor collective efficacy was a better mediator in the relationship between pre-performance and the other group variables. Results also revealed positive relationships between three dimensions of cohesion (i.e. Individual attractions to the group-task, Group integration-task, Group integration-social) and collective efficacy. These findings suggest that in professional basketball teams, staff members should look after athletes who perform at a lower or below their usual level because their performances might lead them into a downward cohesion - collective efficacy spiral. Staff members should also develop a high quality of group functioning, both on and off the basketball court, given its relationship with collective efficacy.

  18. Proteomic analysis of cAMP-mediated signaling during differentiation of 3 T3-L1 preadipocytes

    DEFF Research Database (Denmark)

    Borkowski, Kamil; Wrzesinski, Krzysztow; Rogowska-Wrzesinska, Adelina

    2014-01-01

    Initiation of adipocyte differentiation is promoted by the synergistic action of insulin/insulin-like growth factor, glucocorticoids, and agents activating cAMP-dependent signaling. The action of cAMP is mediated via PKA and Epac, where at least part of the PKA function relates to strong repression...... a comprehensive evaluation of Epac-mediated processes and their interplay with PKA during the initiation of 3 T3-L1 preadipocyte differentiation using a combination of proteomics, molecular approaches, and bioinformatics. Proteomic analyses revealed 7 proteins specifically regulated in response to Epac activation......-dependent signaling thereby adding a novel facet to our understanding of cAMP-mediated potentiation of adipocyte differentiation....

  19. Mediator and moderator effects in developmental and behavioral pediatric research.

    Science.gov (United States)

    Rose, Brigid M; Holmbeck, Grayson N; Coakley, Rachael Millstein; Franks, Elizabeth A

    2004-02-01

    The terms mediation and moderation are defined and clarified with particular emphasis on the role of mediational and moderational analyses in developmental and behavioral pediatric research. The article highlights the applicability of mediational and moderational analyses to longitudinal, intervention, and risk and protective factor research, and it provides basic information about how these analyses might be conducted. Also included is a discussion of various ways that both mediator and moderator variables can be incorporated into a single model. The article concludes with extended examples of both types of analyses using a longitudinal pediatric study for illustration. The article provides recommendations for applying mediational and moderational research in clinical practice.

  20. Integrated analyses resolve conflicts over squamate reptile phylogeny and reveal unexpected placements for fossil taxa.

    Directory of Open Access Journals (Sweden)

    Tod W Reeder

    Full Text Available Squamate reptiles (lizards and snakes are a pivotal group whose relationships have become increasingly controversial. Squamates include >9000 species, making them the second largest group of terrestrial vertebrates. They are important medicinally and as model systems for ecological and evolutionary research. However, studies of squamate biology are hindered by uncertainty over their relationships, and some consider squamate phylogeny unresolved, given recent conflicts between molecular and morphological results. To resolve these conflicts, we expand existing morphological and molecular datasets for squamates (691 morphological characters and 46 genes, for 161 living and 49 fossil taxa, including a new set of 81 morphological characters and adding two genes from published studies and perform integrated analyses. Our results resolve higher-level relationships as indicated by molecular analyses, and reveal hidden morphological support for the molecular hypothesis (but not vice-versa. Furthermore, we find that integrating molecular, morphological, and paleontological data leads to surprising placements for two major fossil clades (Mosasauria and Polyglyphanodontia. These results further demonstrate the importance of combining fossil and molecular information, and the potential problems of estimating the placement of fossil taxa from morphological data alone. Thus, our results caution against estimating fossil relationships without considering relevant molecular data, and against placing fossils into molecular trees (e.g. for dating analyses without considering the possible impact of molecular data on their placement.

  1. Integrated analyses resolve conflicts over squamate reptile phylogeny and reveal unexpected placements for fossil taxa.

    Science.gov (United States)

    Reeder, Tod W; Townsend, Ted M; Mulcahy, Daniel G; Noonan, Brice P; Wood, Perry L; Sites, Jack W; Wiens, John J

    2015-01-01

    Squamate reptiles (lizards and snakes) are a pivotal group whose relationships have become increasingly controversial. Squamates include >9000 species, making them the second largest group of terrestrial vertebrates. They are important medicinally and as model systems for ecological and evolutionary research. However, studies of squamate biology are hindered by uncertainty over their relationships, and some consider squamate phylogeny unresolved, given recent conflicts between molecular and morphological results. To resolve these conflicts, we expand existing morphological and molecular datasets for squamates (691 morphological characters and 46 genes, for 161 living and 49 fossil taxa, including a new set of 81 morphological characters and adding two genes from published studies) and perform integrated analyses. Our results resolve higher-level relationships as indicated by molecular analyses, and reveal hidden morphological support for the molecular hypothesis (but not vice-versa). Furthermore, we find that integrating molecular, morphological, and paleontological data leads to surprising placements for two major fossil clades (Mosasauria and Polyglyphanodontia). These results further demonstrate the importance of combining fossil and molecular information, and the potential problems of estimating the placement of fossil taxa from morphological data alone. Thus, our results caution against estimating fossil relationships without considering relevant molecular data, and against placing fossils into molecular trees (e.g. for dating analyses) without considering the possible impact of molecular data on their placement.

  2. Integrated Analyses Resolve Conflicts over Squamate Reptile Phylogeny and Reveal Unexpected Placements for Fossil Taxa

    Science.gov (United States)

    Reeder, Tod W.; Townsend, Ted M.; Mulcahy, Daniel G.; Noonan, Brice P.; Wood, Perry L.; Sites, Jack W.; Wiens, John J.

    2015-01-01

    Squamate reptiles (lizards and snakes) are a pivotal group whose relationships have become increasingly controversial. Squamates include >9000 species, making them the second largest group of terrestrial vertebrates. They are important medicinally and as model systems for ecological and evolutionary research. However, studies of squamate biology are hindered by uncertainty over their relationships, and some consider squamate phylogeny unresolved, given recent conflicts between molecular and morphological results. To resolve these conflicts, we expand existing morphological and molecular datasets for squamates (691 morphological characters and 46 genes, for 161 living and 49 fossil taxa, including a new set of 81 morphological characters and adding two genes from published studies) and perform integrated analyses. Our results resolve higher-level relationships as indicated by molecular analyses, and reveal hidden morphological support for the molecular hypothesis (but not vice-versa). Furthermore, we find that integrating molecular, morphological, and paleontological data leads to surprising placements for two major fossil clades (Mosasauria and Polyglyphanodontia). These results further demonstrate the importance of combining fossil and molecular information, and the potential problems of estimating the placement of fossil taxa from morphological data alone. Thus, our results caution against estimating fossil relationships without considering relevant molecular data, and against placing fossils into molecular trees (e.g. for dating analyses) without considering the possible impact of molecular data on their placement. PMID:25803280

  3. Profession of mediator as the professional provider of the mediation process

    Directory of Open Access Journals (Sweden)

    Jernej Šoštar

    2017-03-01

    Full Text Available The civil mediation programme, which is a court-connected programme, established as a form of alternative dispute resolution, is increasingly gaining ground as a field with its own theoretical and practical knowledge, principles and basic rules. Mediation has already set up its own body of knowledge, based on studies, classification of cases and the analyses of the results. In this article, we examine whether in the context of the development of mediation in Slovenia we might already talk about the profession of the mediator, defined as a provider of the mediation process. We examine the court-connected civil mediation and mediators who mediate at the court-connected civil mediation, and define them theoretically. By interviewing the mediation experts and mediators we examine their opinions about mediators and the court mediation. We examine the legal basis for the court-connected mediation programmes in Slovenia as well as in the European Union. Proceeding from our findings we conclude that the legal regulation of the court mediation in Slovenia is well established, and that the mediators of the court-connected civil mediation programmes can be accepted as the professional providers of the mediation process.

  4. The Mediated Transparent Society

    DEFF Research Database (Denmark)

    Backer, Lise

    2001-01-01

    in the mediated transparent society. The paper concludes that, based on these analyses, the mediated panopticism working on the business segment is not an effective disciplinary apparatus, which can guarantee that business corporations are carrying out important ecological or ethical improvements....

  5. A classical regression framework for mediation analysis: fitting one model to estimate mediation effects.

    Science.gov (United States)

    Saunders, Christina T; Blume, Jeffrey D

    2017-10-26

    Mediation analysis explores the degree to which an exposure's effect on an outcome is diverted through a mediating variable. We describe a classical regression framework for conducting mediation analyses in which estimates of causal mediation effects and their variance are obtained from the fit of a single regression model. The vector of changes in exposure pathway coefficients, which we named the essential mediation components (EMCs), is used to estimate standard causal mediation effects. Because these effects are often simple functions of the EMCs, an analytical expression for their model-based variance follows directly. Given this formula, it is instructive to revisit the performance of routinely used variance approximations (e.g., delta method and resampling methods). Requiring the fit of only one model reduces the computation time required for complex mediation analyses and permits the use of a rich suite of regression tools that are not easily implemented on a system of three equations, as would be required in the Baron-Kenny framework. Using data from the BRAIN-ICU study, we provide examples to illustrate the advantages of this framework and compare it with the existing approaches. © The Author 2017. Published by Oxford University Press.

  6. Phosphoproteomics Reveals Regulatory T Cell-Mediated DEF6 Dephosphorylation That Affects Cytokine Expression in Human Conventional T Cells

    KAUST Repository

    Joshi, Rubin N.

    2017-09-25

    Regulatory T cells (Tregs) control key events of immune tolerance, primarily by suppression of effector T cells. We previously revealed that Tregs rapidly suppress T cell receptor (TCR)-induced calcium store depletion in conventional CD4CD25 T cells (Tcons) independently of IP levels, consequently inhibiting NFAT signaling and effector cytokine expression. Here, we study Treg suppression mechanisms through unbiased phosphoproteomics of primary human Tcons upon TCR stimulation and Treg-mediated suppression, respectively. Tregs induced a state of overall decreased phosphorylation as opposed to TCR stimulation. We discovered novel phosphosites (T595_S597) in the DEF6 (SLAT) protein that were phosphorylated upon TCR stimulation and conversely dephosphorylated upon coculture with Tregs. Mutation of these DEF6 phosphosites abrogated interaction of DEF6 with the IP receptor and affected NFAT activation and cytokine transcription in primary Tcons. This novel mechanism and phosphoproteomics data resource may aid in modifying sensitivity of Tcons to Treg-mediated suppression in autoimmune disease or cancer.

  7. Emotion dysregulation mediates the relationship between child maltreatment and psychopathology: A structural equation model.

    Science.gov (United States)

    Jennissen, Simone; Holl, Julia; Mai, Hannah; Wolff, Sebastian; Barnow, Sven

    2016-12-01

    The present study investigated the mediating effects of emotion dysregulation on the relationship between child maltreatment and psychopathology. An adult sample (N=701) from diverse backgrounds of psychopathology completed the Childhood Trauma Questionnaire (CTQ), the Difficulties in Emotion Regulation Scale (DERS), the Brief Symptom Inventory (BSI), and the negative affect subscale of the Positive and Negative Affect Schedule (PANAS) in a cross-sectional online survey. Correlational analyses showed that all types of child maltreatment were uniformly associated with emotion dysregulation, and dimensions of emotion dysregulation were strongly related to psychopathology. Limited access to strategies for emotion regulation emerged as the most powerful predictor. Structural equation modeling analyses revealed that emotion dysregulation partially mediated the relationship between child maltreatment and psychopathology, even after controlling for shared variance with negative affect. These findings emphasize the importance of emotion dysregulation as a possible mediating mechanism in the association between child maltreatment and later psychopathology. Additionally, interventions targeting specific emotion regulation strategies may be effective to reduce psychopathology in victims of child maltreatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Linking organizational resources and work engagement to employee performance and customer loyalty: the mediation of service climate.

    Science.gov (United States)

    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).

  9. ETHICAL LEADERSHIP AND EMPLOYEE VOICE: EMPLOYEE SELF-EFFICACY AND SELF-IMPACT AS MEDIATORS.

    Science.gov (United States)

    Wang, Duanxu; Gan, Chenjing; Wu, Chaoyan; Wang, Danqi

    2015-06-01

    Previous studies have used social learning theory to explain the influence of ethical leadership. This study continues the previous research by using social learning theory to explain the mediating effect of self-efficacy on the relationship between ethical leadership and employee voice. In addition, this study extends previous studies by introducing expectancy theory to explore whether self-impact also mediates the relationship between ethical leadership and employee voice. Ethical leadership, self-efficacy, self-impact, and employee voice were assessed using paired surveys among 59 supervisors and 295 subordinates employed at nine firms in the People's Republic of China. Using HLM and SEM analyses, the results revealed that ethical leadership was positively related to employee voice and that this relationship was partially mediated by both self-efficacy and self-impact.

  10. Distinct signaling roles of ceramide species in yeast revealed through systematic perturbation and systems biology analyses.

    Science.gov (United States)

    Montefusco, David J; Chen, Lujia; Matmati, Nabil; Lu, Songjian; Newcomb, Benjamin; Cooper, Gregory F; Hannun, Yusuf A; Lu, Xinghua

    2013-10-29

    Ceramide, the central molecule of sphingolipid metabolism, is an important bioactive molecule that participates in various cellular regulatory events and that has been implicated in disease. Deciphering ceramide signaling is challenging because multiple ceramide species exist, and many of them may have distinct functions. We applied systems biology and molecular approaches to perturb ceramide metabolism in the yeast Saccharomyces cerevisiae and inferred causal relationships between ceramide species and their potential targets by combining lipidomic, genomic, and transcriptomic analyses. We found that during heat stress, distinct metabolic mechanisms controlled the abundance of different groups of ceramide species and provided experimental support for the importance of the dihydroceramidase Ydc1 in mediating the decrease in dihydroceramides during heat stress. Additionally, distinct groups of ceramide species, with different N-acyl chains and hydroxylations, regulated different sets of functionally related genes, indicating that the structural complexity of these lipids produces functional diversity. The transcriptional modules that we identified provide a resource to begin to dissect the specific functions of ceramides.

  11. Adult attachment, perceived social support, cultural orientation, and depressive symptoms: A moderated mediation model.

    Science.gov (United States)

    Zhu, Wenzhen; Wang, Chiachih Dc; Chong, Chu Chian

    2016-11-01

    In the current study, we tested a moderated mediation model in which cultural orientation moderated the mediation model of adult attachment-perceived social support-depressive symptoms, using 2 comparable cross-cultural samples of college students recruited from China and the U.S. (n = 363 for each group). Results indicated that perceived social support mediated the effect of attachment anxiety on depressive symptoms as well as the link between attachment avoidance and depression in both samples. Moderated mediation analyses using PROCESS revealed that interdependent self-construal significantly buffered the indirect effect of attachment avoidance (via perceived social support) on depressive symptoms. The findings indicated significant differences in the mediation models between the U.S. and China groups and interdependent self-construal accounted for the between-country differences. Limitations, implications of the findings, and future research directions are discussed from the perspectives of cross-cultural variation of adult attachment functioning. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  12. Testing Mediation Using Multiple Regression and Structural Equation Modeling Analyses in Secondary Data

    Science.gov (United States)

    Li, Spencer D.

    2011-01-01

    Mediation analysis in child and adolescent development research is possible using large secondary data sets. This article provides an overview of two statistical methods commonly used to test mediated effects in secondary analysis: multiple regression and structural equation modeling (SEM). Two empirical studies are presented to illustrate the…

  13. Genome Wide Transcriptome Analysis reveals ABA mediated response in Arabidopsis during Gold (AuCl4- treatment

    Directory of Open Access Journals (Sweden)

    Devesh eShukla

    2014-11-01

    Full Text Available The unique physico-chemical properties of gold nanoparticles (AuNPs find manifold applications in diagnostics, medicine and catalysis. Chemical synthesis produces reactive AuNPs and generates hazardous by-products. Alternatively, plants can be utilized to produce AuNPs in an eco-friendly manner. To better control the biosynthesis of AuNPs, we need to first understand the detailed molecular response induced by AuCl4- In this study, we carried out global transcriptome analysis in root tissue of Arabidopsis grown for 12- hours in presence of gold solution (HAuCl4 using the novel unbiased Affymetrix exon array. Transcriptomics analysis revealed differential regulation of a total of 704 genes and 4900 exons. Of these, 492 and 212 genes were up- and downregulated, respectively. The validation of the expressed key genes, such as glutathione-S-transferases, auxin responsive genes, cytochrome P450 82C2, methyl transferases, transducin (G protein beta subunit, ERF transcription factor, ABC, and MATE transporters, was carried out through quantitative RT-PCR. These key genes demonstrated specific induction under AuCl4- treatment relative to other heavy metals, suggesting a unique plant-gold interaction. GO enrichment analysis reveals the upregulation of processes like oxidative stress, glutathione binding, metal binding, transport, and plant hormonal responses. Changes predicted in biochemical pathways indicated major modulation in glutathione mediated detoxification, flavones and derivatives, and plant hormone biosynthesis. Motif search analysis identified a highly significant enriched motif, ACGT, which is an abscisic acid responsive core element (ABRE, suggesting the possibility of ABA- mediated signaling. Identification of abscisic acid response element (ABRE points to the operation of a predominant signaling mechanism in response to AuCl4- exposure. Overall, this study presents a useful picture of plant-gold interaction with an identification of

  14. Does parental mediation of media influence child outcomes? A meta-analysis on media time, aggression, substance use, and sexual behavior.

    Science.gov (United States)

    Collier, Kevin M; Coyne, Sarah M; Rasmussen, Eric E; Hawkins, Alan J; Padilla-Walker, Laura M; Erickson, Sage E; Memmott-Elison, Madison K

    2016-05-01

    The current study examined how parental mediation of media (restrictive mediation, active mediation, and coviewing) influenced child outcomes. Three meta-analyses, 1 for each type of mediation, were conducted on a total of 57 studies. Each analysis assessed the effectiveness of parental mediation on 4 pertinent child outcomes: media use, aggression, substance use, and sexual behavior. The overall results indicated small, but significant relationships between child outcomes and restrictive mediation (r+ = -.06), and coviewing (r+ = .09). Overall active mediation was nonsignificant, though active mediation was individually related to lower levels of aggression (r+ = -.08), sexual behavior (r+ = -.06), and substance use (r+ = -.11). This analysis revealed that parents may have the ability to mitigate some of the adverse effects of the media by using certain mediation strategies. Overall, a cooperative effort from the communication and parenting fields is necessary for a comprehensive analysis of parental mediation as well as a disentanglement of the various parental mediation measures. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  15. Functional assays and metagenomic analyses reveals differences between the microbial communities inhabiting the soil horizons of a Norway spruce plantation.

    Directory of Open Access Journals (Sweden)

    Stéphane Uroz

    Full Text Available In temperate ecosystems, acidic forest soils are among the most nutrient-poor terrestrial environments. In this context, the long-term differentiation of the forest soils into horizons may impact the assembly and the functions of the soil microbial communities. To gain a more comprehensive understanding of the ecology and functional potentials of these microbial communities, a suite of analyses including comparative metagenomics was applied on independent soil samples from a spruce plantation (Breuil-Chenue, France. The objectives were to assess whether the decreasing nutrient bioavailability and pH variations that naturally occurs between the organic and mineral horizons affects the soil microbial functional biodiversity. The 14 Gbp of pyrosequencing and Illumina sequences generated in this study revealed complex microbial communities dominated by bacteria. Detailed analyses showed that the organic soil horizon was significantly enriched in sequences related to Bacteria, Chordata, Arthropoda and Ascomycota. On the contrary the mineral horizon was significantly enriched in sequences related to Archaea. Our analyses also highlighted that the microbial communities inhabiting the two soil horizons differed significantly in their functional potentials according to functional assays and MG-RAST analyses, suggesting a functional specialisation of these microbial communities. Consistent with this specialisation, our shotgun metagenomic approach revealed a significant increase in the relative abundance of sequences related glycoside hydrolases in the organic horizon compared to the mineral horizon that was significantly enriched in glycoside transferases. This functional stratification according to the soil horizon was also confirmed by a significant correlation between the functional assays performed in this study and the functional metagenomic analyses. Together, our results suggest that the soil stratification and particularly the soil resource

  16. Estimation of causal mediation effects for a dichotomous outcome in multiple-mediator models using the mediation formula.

    Science.gov (United States)

    Wang, Wei; Nelson, Suchitra; Albert, Jeffrey M

    2013-10-30

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit-normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two-mediator models with various combinations of mediator types. The results also show that the power to detect a nonzero total mediation effect increases as the correlation coefficient between two mediators increases, whereas power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator-outcome confounders is violated. Copyright © 2013 John Wiley & Sons, Ltd.

  17. Estimation of Causal Mediation Effects for a Dichotomous Outcome in Multiple-Mediator Models using the Mediation Formula

    Science.gov (United States)

    Nelson, Suchitra; Albert, Jeffrey M.

    2013-01-01

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit-normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two-mediator models with various combinations of mediator types. The results also show that the power to detect a non-zero total mediation effect increases as the correlation coefficient between two mediators increases, while power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator-outcome confounders is violated. PMID:23650048

  18. Identification of Mediator Kinase Substrates in Human Cells using Cortistatin A and Quantitative Phosphoproteomics.

    Science.gov (United States)

    Poss, Zachary C; Ebmeier, Christopher C; Odell, Aaron T; Tangpeerachaikul, Anupong; Lee, Thomas; Pelish, Henry E; Shair, Matthew D; Dowell, Robin D; Old, William M; Taatjes, Dylan J

    2016-04-12

    Cortistatin A (CA) is a highly selective inhibitor of the Mediator kinases CDK8 and CDK19. Using CA, we now report a large-scale identification of Mediator kinase substrates in human cells (HCT116). We identified over 16,000 quantified phosphosites including 78 high-confidence Mediator kinase targets within 64 proteins, including DNA-binding transcription factors and proteins associated with chromatin, DNA repair, and RNA polymerase II. Although RNA-seq data correlated with Mediator kinase targets, the effects of CA on gene expression were limited and distinct from CDK8 or CDK19 knockdown. Quantitative proteome analyses, tracking around 7,000 proteins across six time points (0-24 hr), revealed that CA selectively affected pathways implicated in inflammation, growth, and metabolic regulation. Contrary to expectations, increased turnover of Mediator kinase targets was not generally observed. Collectively, these data support Mediator kinases as regulators of chromatin and RNA polymerase II activity and suggest their roles extend beyond transcription to metabolism and DNA repair. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Transcription Profiles Reveal Sugar and Hormone Signaling Pathways Mediating Flower Induction in Apple (Malus domestica Borkh.).

    Science.gov (United States)

    Xing, Li-Bo; Zhang, Dong; Li, You-Mei; Shen, Ya-Wen; Zhao, Cai-Ping; Ma, Juan-Juan; An, Na; Han, Ming-Yu

    2015-10-01

    Flower induction in apple (Malus domestica Borkh.) is regulated by complex gene networks that involve multiple signal pathways to ensure flower bud formation in the next year, but the molecular determinants of apple flower induction are still unknown. In this research, transcriptomic profiles from differentiating buds allowed us to identify genes potentially involved in signaling pathways that mediate the regulatory mechanisms of flower induction. A hypothetical model for this regulatory mechanism was obtained by analysis of the available transcriptomic data, suggesting that sugar-, hormone- and flowering-related genes, as well as those involved in cell-cycle induction, participated in the apple flower induction process. Sugar levels and metabolism-related gene expression profiles revealed that sucrose is the initiation signal in flower induction. Complex hormone regulatory networks involved in cytokinin (CK), abscisic acid (ABA) and gibberellic acid pathways also induce apple flower formation. CK plays a key role in the regulation of cell formation and differentiation, and in affecting flowering-related gene expression levels during these processes. Meanwhile, ABA levels and ABA-related gene expression levels gradually increased, as did those of sugar metabolism-related genes, in developing buds, indicating that ABA signals regulate apple flower induction by participating in the sugar-mediated flowering pathway. Furthermore, changes in sugar and starch deposition levels in buds can be affected by ABA content and the expression of the genes involved in the ABA signaling pathway. Thus, multiple pathways, which are mainly mediated by crosstalk between sugar and hormone signals, regulate the molecular network involved in bud growth and flower induction in apple trees. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.

  20. Transcriptomic profiling-based mutant screen reveals three new transcription factors mediating menadione resistance in Neurospora crassa.

    Science.gov (United States)

    Zhu, Jufen; Yu, Xinxu; Xie, Baogui; Gu, Xiaokui; Zhang, Zhenying; Li, Shaojie

    2013-06-01

    To gain insight into the regulatory mechanisms of oxidative stress responses in filamentous fungi, the genome-wide transcriptional response of Neurospora crassa to menadione was analysed by digital gene expression (DGE) profiling, which identified 779 upregulated genes and 576 downregulated genes. Knockout mutants affecting 130 highly-upregulated genes were tested for menadione sensitivity, which revealed that loss of the transcription factor siderophore regulation (SRE) (a transcriptional repressor for siderophore biosynthesis), catatase-3, cytochrome c peroxidase or superoxide dismutase 1 copper chaperone causes hypersensitivity to menadione. Deletion of sre dramatically increased transcription of the siderophore biosynthesis gene ono and the siderophore iron transporter gene sit during menadione stress, suggesting that SRE is required for repression of iron uptake under oxidative stress conditions. Contrary to its phenotype, the sre deletion mutant showed higher transcriptional levels of genes encoding reactive oxygen species (ROS) scavengers than wild type during menadione stress, which implies that the mutant suffers a higher level of oxidative stress than wild type. Uncontrolled iron uptake in the sre mutant might exacerbate cellular oxidative stress. This is the first report of a negative regulator of iron assimilation participating in the fungal oxidative stress response. In addition to SRE, eight other transcription factor genes were also menadione-responsive but their single gene knockout mutants showed wild-type menadione sensitivity. Two of them, named as mit-2 (menadione induced transcription factor-2) and mit-4 (menadione induced transcription factor-4), were selected for double mutant analysis. The double mutant was hypersensitive to menadione. Similarly, the double mutation of mit-2 and sre also had additive effects on menadione sensitivity, suggesting multiple transcription factors mediate oxidative stress resistance in an additive manner

  1. Are mediation clauses binding and mandatory?

    Directory of Open Access Journals (Sweden)

    Constantinescu Miruna

    2017-06-01

    Full Text Available This study analyses the legal force of mediation clauses in the common law systems and civil law systems with a main focus on the Romanian approach. First, the introductory section illustrates the paradox between the concept of binding and mandatory effect and the mediation mechanism, a voluntary manner to settle disputes. Notwithstanding, the possibility to coerce the parties to engage into a mediation, the voluntary character of the process is illustrated by the parties’ freedom to decide whether they settle or not. Second, the role of mediation clause is analysed and its advantages are briefly described. Third, the non-compliance of the prior mediation mechanism is presented, the starting point of the discussion being represented by the manner in which the parties drafted the mediation clause. A carefully drafted mediation clause, reflecting the parties’ consent, can determine a court or an arbitral tribunal to enforce such clause. Fourth, the study ends by mentioning the approach adopted by different national courts, emphasizing the Romanian legal perspective.

  2. HIV-1 adaptation studies reveal a novel Env-mediated homeostasis mechanism for evading lethal hypermutation by APOBEC3G.

    Directory of Open Access Journals (Sweden)

    Terumasa Ikeda

    2018-04-01

    Full Text Available HIV-1 replication normally requires Vif-mediated neutralization of APOBEC3 antiviral enzymes. Viruses lacking Vif succumb to deamination-dependent and -independent restriction processes. Here, HIV-1 adaptation studies were leveraged to ask whether viruses with an irreparable vif deletion could develop resistance to restrictive levels of APOBEC3G. Several resistant viruses were recovered with multiple amino acid substitutions in Env, and these changes alone are sufficient to protect Vif-null viruses from APOBEC3G-dependent restriction in T cell lines. Env adaptations cause decreased fusogenicity, which results in higher levels of Gag-Pol packaging. Increased concentrations of packaged Pol in turn enable faster virus DNA replication and protection from APOBEC3G-mediated hypermutation of viral replication intermediates. Taken together, these studies reveal that a moderate decrease in one essential viral activity, namely Env-mediated fusogenicity, enables the virus to change other activities, here, Gag-Pol packaging during particle production, and thereby escape restriction by the antiviral factor APOBEC3G. We propose a new paradigm in which alterations in viral homeostasis, through compensatory small changes, constitute a general mechanism used by HIV-1 and other viral pathogens to escape innate antiviral responses and other inhibitions including antiviral drugs.

  3. The mediating effects of self-esteem and delinquency on the relationship between family social capital and adolescents’ educational achievement

    Directory of Open Access Journals (Sweden)

    Omolola Abiola Adedokun

    2008-07-01

    Full Text Available Using a nationally representative data of rural adolescent boys and girls in 10th grade through 12th grade, this study explored the mediating effects of self-esteem and delinquency on the educational achievement of rural adolescents. Structural equation modeling analyses reveal that the combination of self-esteem and delinquency completely mediates the influence of family social capital on educational achievement. The findings of the models make a compelling case that the impact of family processes on educational achievement is indirect rather than direct.

  4. Mediation Analysis of the Efficacy of the Eban HIV/STD Risk-Reduction Intervention for African American HIV Serodiscordant Couples.

    Science.gov (United States)

    El-Bassel, Nabila; Jemmott, John B; Bellamy, Scarlett L; Pequegnat, Willo; Wingood, Gina M; Wyatt, Gail E; Landis, J Richard; Remien, Robert H

    2016-06-01

    Targeting couples is a promising behavioral HIV risk-reduction strategy, but the mechanisms underlying the effects of such interventions are unknown. We report secondary analyses testing whether Social-Cognitive-Theory variables mediated the Eban HIV-risk-reduction intervention's effects on condom-use outcomes. In a multisite randomized controlled trial conducted in four US cities, 535 African American HIV-serodiscordant couples were randomized to the Eban HIV risk-reduction intervention or attention-matched control intervention. Outcomes were proportion condom-protected sex, consistent condom use, and frequency of unprotected sex measured pre-, immediately post-, and 6 and 12 months post-intervention. Potential mediators included Social-Cognitive-Theory variables: outcome expectancies and self-efficacy. Mediation analyses using the product-of-coefficients approach in a generalized-estimating-equations framework revealed that condom-use outcome expectancy, partner-reaction outcome expectancy, intention, self-efficacy, and safer-sex communication improved post-intervention and mediated intervention-induced improvements in condom-use outcomes. These findings underscore the importance of targeting outcome expectancies, self-efficacy, and safer-sex communication in couples-level HIV risk-reduction interventions.

  5. Single-Level and Multilevel Mediation Analysis

    Science.gov (United States)

    Tofighi, Davood; Thoemmes, Felix

    2014-01-01

    Mediation analysis is a statistical approach used to examine how the effect of an independent variable on an outcome is transmitted through an intervening variable (mediator). In this article, we provide a gentle introduction to single-level and multilevel mediation analyses. Using single-level data, we demonstrate an application of structural…

  6. Cytoskeletal dynamics in interphase, mitosis and cytokinesis analysed through Agrobacterium-mediated transient transformation of tobacco BY-2 cells.

    Science.gov (United States)

    Buschmann, H; Green, P; Sambade, A; Doonan, J H; Lloyd, C W

    2011-04-01

    Transient transformation with Agrobacterium is a widespread tool allowing rapid expression analyses in plants. However, the available methods generate expression in interphase and do not allow the routine analysis of dividing cells. Here, we present a transient transformation method (termed 'TAMBY2') to enable cell biological studies in interphase and cell division. Agrobacterium-mediated transient gene expression in tobacco BY-2 was analysed by Western blotting and quantitative fluorescence microscopy. Time-lapse microscopy of cytoskeletal markers was employed to monitor cell division. Double-labelling in interphase and mitosis enabled localization studies. We found that the transient transformation efficiency was highest when BY-2/Agrobacterium co-cultivation was performed on solid medium. Transformants produced in this way divided at high frequency. We demonstrated the utility of the method by defining the behaviour of a previously uncharacterized microtubule motor, KinG, throughout the cell cycle. Our analyses demonstrated that TAMBY2 provides a flexible tool for the transient transformation of BY-2 with Agrobacterium. Fluorescence double-labelling showed that KinG localizes to microtubules and to F-actin. In interphase, KinG accumulates on microtubule lagging ends, suggesting a minus-end-directed function in vivo. Time-lapse studies of cell division showed that GFP-KinG strongly labels preprophase band and phragmoplast, but not the metaphase spindle. © 2010 The Authors. New Phytologist © 2010 New Phytologist Trust.

  7. Molecular analyses reveal high species diversity of trematodes in a sub-Arctic lake

    Science.gov (United States)

    Soldánová, Miroslava; Georgieva, Simona; Roháčováa, Jana; Knudsen, Rune; Kuhn, Jesper A.; Henriksen, Eirik H.; Siwertsson, Anna; Shaw, Jenny C.; Kuris, Armand M.; Amundsen, Per-Arne; Scholz, Tomáš; Lafferty, Kevin D.; Kostadinova, Aneta

    2017-01-01

    To identify trematode diversity and life-cycles in the sub-Arctic Lake Takvatn, Norway, we characterised 120 trematode isolates from mollusc first intermediate hosts, metacercariae from second intermediate host fishes and invertebrates, and adults from fish and invertebrate definitive hosts, using molecular techniques. Phylogenies based on nuclear and/or mtDNA revealed high species richness (24 species or species-level genetic lineages), and uncovered trematode diversity (16 putative new species) from five families typical in lake ecosystems (Allocreadiidae, Diplostomidae, Plagiorchiidae, Schistosomatidae and Strigeidae). Sampling potential invertebrate hosts allowed matching of sequence data for different stages, thus achieving molecular elucidation of trematode life-cycles and exploration of host-parasite interactions. Phylogenetic analyses also helped identify three major mollusc intermediate hosts (Radix balthica, Pisidium casertanum and Sphaerium sp.) in the lake. Our findings increase the known trematode diversity at the sub-Arctic Lake Takvatn, showing that digenean diversity is high in this otherwise depauperate sub-Arctic freshwater ecosystem, and indicating that sub-Arctic and Arctic ecosystems may be characterised by unique trematode assemblages.

  8. Self-centeredness and selflessness: happiness correlates and mediating psychological processes.

    Science.gov (United States)

    Dambrun, Michael

    2017-01-01

    The main objective of this research was to test central assumptions from the Self-centeredness/Selflessness Happiness Model. According to this model, while self-centered psychological functioning induces fluctuating happiness, authentic-durable happiness results from selflessness. Distinct mediating processes are supposed to account for these relationships: afflictive affects (e.g., anger, fear, jealousy, frustration) in the case of the former, and both emotional stability and feelings of harmony in the case of the latter. We tested these hypotheses in two studies based on heterogeneous samples of citizens ( n  = 547). Factor analyses revealed that self-centeredness (assessed through egocentrism and materialism) and selflessness (assessed through self-transcendence and connectedness to other) were two distinct psychological constructs. Second, while self-centeredness was positively and significantly related to fluctuating happiness, selflessness was positively and significantly related to authentic-durable happiness. Finally, distinct psychological processes mediated these relationships (study 2). On one hand, the relationship between self-centeredness and fluctuating happiness was fully mediated by afflictive affects. On the other hand, emotional stability and the feeling of being in harmony partially mediated the relation between selflessness and authentic-durable happiness.

  9. Self-centeredness and selflessness: happiness correlates and mediating psychological processes

    Science.gov (United States)

    2017-01-01

    The main objective of this research was to test central assumptions from the Self-centeredness/Selflessness Happiness Model. According to this model, while self-centered psychological functioning induces fluctuating happiness, authentic–durable happiness results from selflessness. Distinct mediating processes are supposed to account for these relationships: afflictive affects (e.g., anger, fear, jealousy, frustration) in the case of the former, and both emotional stability and feelings of harmony in the case of the latter. We tested these hypotheses in two studies based on heterogeneous samples of citizens (n = 547). Factor analyses revealed that self-centeredness (assessed through egocentrism and materialism) and selflessness (assessed through self-transcendence and connectedness to other) were two distinct psychological constructs. Second, while self-centeredness was positively and significantly related to fluctuating happiness, selflessness was positively and significantly related to authentic–durable happiness. Finally, distinct psychological processes mediated these relationships (study 2). On one hand, the relationship between self-centeredness and fluctuating happiness was fully mediated by afflictive affects. On the other hand, emotional stability and the feeling of being in harmony partially mediated the relation between selflessness and authentic–durable happiness. PMID:28507820

  10. Genetic Diversity among Rhizobium leguminosarum bv. Trifolii Strains Revealed by Allozyme and Restriction Fragment Length Polymorphism Analyses

    Science.gov (United States)

    Demezas, David H.; Reardon, Terry B.; Watson, John M.; Gibson, Alan H.

    1991-01-01

    Allozyme electrophoresis and restriction fragment length polymorphism (RFLP) analyses were used to examine the genetic diversity of a collection of 18 Rhizobium leguminosarum bv. trifolii, 1 R. leguminosarum bv. viciae, and 2 R. meliloti strains. Allozyme analysis at 28 loci revealed 16 electrophoretic types. The mean genetic distance between electrophoretic types of R. leguminosarum and R. meliloti was 0.83. Within R. leguminosarum, the single strain of bv. viciae differed at an average of 0.65 from strains of bv. trifolii, while electrophoretic types of bv. trifolii differed at a range of 0.23 to 0.62. Analysis of RFLPs around two chromosomal DNA probes also delineated 16 unique RFLP patterns and yielded genetic diversity similar to that revealed by the allozyme data. Analysis of RFLPs around three Sym (symbiotic) plasmid-derived probes demonstrated that the Sym plasmids reflect genetic divergence similar to that of their bacterial hosts. The large genetic distances between many strains precluded reliable estimates of their genetic relationships. PMID:16348600

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

    Science.gov (United States)

    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.

  12. The Merits of Using Longitudinal Mediation

    Science.gov (United States)

    Jose, Paul E.

    2016-01-01

    Many of the mediation analyses reported in the literature are based on concurrent or single-occasion data sets. The 2 overarching themes of the present article are: Results of concurrent mediations are inherently ambiguous, and researchers would be wise to conduct mediations on longitudinal data sets instead. An example included here demonstrates…

  13. The Influence of Orthographic Neighborhood Density and Word Frequency on Visual Word Recognition: Insights from RT Distributional Analyses

    Directory of Open Access Journals (Sweden)

    Stephen Wee Hun eLim

    2016-03-01

    Full Text Available The effects of orthographic neighborhood density and word frequency in visual word recognition were investigated using distributional analyses of response latencies in visual lexical decision. Main effects of density and frequency were observed in mean latencies. Distributional analyses, in addition, revealed a density x frequency interaction: for low-frequency words, density effects were mediated predominantly by distributional shifting whereas for high-frequency words, density effects were absent except at the slower RTs, implicating distributional skewing. The present findings suggest that density effects in low-frequency words reflect processes involved in early lexical access, while the effects observed in high-frequency words reflect late postlexical checking processes.

  14. Transcription regulation by the Mediator complex.

    Science.gov (United States)

    Soutourina, Julie

    2018-04-01

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

  15. Dynamic Analyses of Alternative Polyadenylation from RNA-Seq Reveal 3′-UTR Landscape Across 7 Tumor Types

    Science.gov (United States)

    Xia, Zheng; Donehower, Lawrence A; Cooper, Thomas A.; Neilson, Joel R.; Wheeler, David A.; Wagner, Eric J.; Li, Wei

    2015-01-01

    Alternative polyadenylation (APA) is a pervasive mechanism in the regulation of most human genes, and its implication in diseases including cancer is only beginning to be appreciated. Since conventional APA profiling has not been widely adopted, global cancer APA studies are very limited. Here we develop a novel bioinformatics algorithm (DaPars) for the de novo identification of dynamic APAs from standard RNA-seq. When applied to 358 TCGA Pan-Cancer tumor/normal pairs across 7 tumor types, DaPars reveals 1,346 genes with recurrent and tumor-specific APAs. Most APA genes (91%) have shorter 3′ UTRs in tumors that can avoid miRNA-mediated repression, including glutaminase (GLS), a key metabolic enzyme for tumor proliferation. Interestingly, selected APA events add strong prognostic power beyond common clinical and molecular variables, suggesting their potential as novel prognostic biomarkers. Finally, our results implicate CstF64, an essential polyadenylation factor, as a master regulator of 3′ UTR shortening across multiple tumor types. PMID:25409906

  16. Personality and job performance: test of the mediating effects of motivation among sales representatives.

    Science.gov (United States)

    Barrick, Murray R; Stewart, Greg L; Piotrowski, Mike

    2002-02-01

    Research shows consistent relations between personality and job performance. In this study the authors develop and test a model of job performance that examines the mediating effects of cognitive-motivational work orientations on the relationships between personality traits and performance in a sales job (N = 164). Covariance structural analyses revealed proximal motivational variables to be influential mechanisms through which distal personality traits affect job performance. Specifically, striving for status and accomplishment mediate the effects of Extraversion and Conscientiousness on ratings of sales performance. Although Agreeableness was related to striving for communion, neither Agreeableness nor communion striving was related to success in this sales job. The importance of the proposed motivational orientations model is discussed.

  17. Counterproductive work behaviours in response to emotional exhaustion: a moderated mediational approach.

    Science.gov (United States)

    Bolton, LaMarcus R; Harvey, Richard D; Grawitch, Matthew J; Barber, Larissa K

    2012-08-01

    Drawing from the conservation of resources framework and self-control principles, we proposed a moderated mediational model through which emotional exhaustion may be linked to counterproductive work behaviours (CWBs). Analyses conducted with 175 Midwestern government workers revealed that both depersonalization (i.e. detachment from one's work, customers or co-workers) and organizational disidentification (i.e. cognitive opposition to an organization) were viable predictors of deviancy. Further, depersonalization and disidentification mediated the relationship between emotional exhaustion and CWBs, although disidentification drove these findings. Lastly, trait self-control moderated most variations of this relationship, in that this mediational model only applied to individuals with low and moderate self-control but not high self-control. Consistent with the conservation of resources framework, this study suggests that in a state of depleted emotional resources, heightened depersonalization and disidentification together provide the necessary levels of psychological/emotional withdrawal and justification for CWBs to emerge. Copyright © 2011 John Wiley & Sons, Ltd.

  18. The Schizosaccharomyces pombe Mediator

    DEFF Research Database (Denmark)

    Venturi, Michela

    , Schizosaccharomyces pombe and mammalian Mediator. In our study, we have taken the S. pombe Mediator into consideration and characterized genetically and biochemically two subunits already know in S. cerevisiae, Med9 and Med11, but still not identified in the S. pombe Mediator. Genetic analysis has shown that med9......In the past several years great attention has been dedicated to the characterization of the Mediator complex in a different range of model organisms. Mediator is a conserved co-activator complex involved in transcriptional regulation and it conveys signals from regulatory transcription factors...... to the basal transcription machinery. Mediator was initially isolated from Saccharomyces cerevisiae based on its ability to render a RNA polymerase II in vitro transcription system responsive to activators. Additionally, structural studies have revealed striking structural similarities between S. cerevisiae...

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

    Science.gov (United States)

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

    2018-01-03

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-01-15

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

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

    Science.gov (United States)

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

    2017-05-01

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

  3. Discrimination, acculturation, acculturative stress, and Latino psychological distress: a moderated mediational model.

    Science.gov (United States)

    Torres, Lucas; Driscoll, Mark W; Voell, Maria

    2012-01-01

    Prior research has found that perceived discrimination is associated with adverse mental health outcomes among Latinos. However, the process by which this relationship occurs remains an understudied area. The present study investigated the role of acculturative stress in underlying the relationship between perceived discrimination and Latino psychological distress. Also examined was the ability of acculturation to serve as a moderator between perceived discrimination and acculturative stress. Among a sample of Latino adults (N = 669), moderated mediational analyses revealed that acculturative stress mediated the perceived discrimination-psychological distress relationship, and that the link between perceived discrimination and acculturative stress was moderated by Anglo behavioral orientation but not Latino behavioral orientation. The findings are discussed within a stress and coping perspective that identifies the psychological consequences associated with perceived discrimination and acculturative stress.

  4. Potential microRNA-mediated oncogenic intercellular communication revealed by pan-cancer analysis

    Science.gov (United States)

    Li, Yue; Zhang, Zhaolei

    2014-11-01

    Carcinogenesis consists of oncogenesis and metastasis, and intriguingly microRNAs (miRNAs) are involved in both processes. Although aberrant miRNA activities are prevalent in diverse tumor types, the exact mechanisms for how they regulate cancerous processes are not always clear. To this end, we performed a large-scale pan-cancer analysis via a novel probabilistic approach to infer recurrent miRNA-target interactions implicated in 12 cancer types using data from The Cancer Genome Atlas. We discovered ~20,000 recurrent miRNA regulations, which are enriched for cancer-related miRNAs/genes. Notably, miRNA 200 family (miR-200/141/429) is among the most prominent miRNA regulators, which is known to be involved in metastasis. Importantly, the recurrent miRNA regulatory network is not only enriched for cancer pathways but also for extracellular matrix (ECM) organization and ECM-receptor interactions. The results suggest an intriguing cancer mechanism involving miRNA-mediated cell-to-cell communication, which possibly involves delivery of tumorigenic miRNA messengers to adjacent cells via exosomes. Finally, survival analysis revealed 414 recurrent-prognostic associations, where both gene and miRNA involved in each interaction conferred significant prognostic power in one or more cancer types. Together, our comprehensive pan-cancer analysis provided not only biological insights into metastasis but also brought to bear the clinical relevance of the proposed recurrent miRNA-gene associations.

  5. Personality and leader effectiveness: a moderated mediation model of leadership self-efficacy, job demands, and job autonomy.

    Science.gov (United States)

    Ng, Kok-Yee; Ang, Soon; Chan, Kim-Yin

    2008-07-01

    The trait theory of leadership is advanced by a joint investigation of the mediating role of (a) leadership self-efficacy (LSE = leader's perceived capabilities to perform leader roles) in linking neuroticism, extraversion, and conscientiousness with leader effectiveness and (b) the moderating role of job demands and job autonomy in influencing the mediation. Using K. J. Preacher, D. D. Rucker, and A. F. Hayes' (2007) moderated mediation framework, the authors tested the model (over a 2-year period) with matched data from 394 military leaders and their supervisors. Results showed that LSE mediated the relationships for neuroticism, extraversion, and conscientiousness with leader effectiveness. Moderated mediation analyses further revealed that LSE mediated the relationships for (a) all 3 personality variables for only those leaders with low job demands; (b) neuroticism and conscientiousness for only those leaders with high job autonomy; and (c) extraversion, regardless of a leader's level of job autonomy. Results underscore the importance of accounting for leaders' situational contexts when examining the relationships between personality, LSE, and effectiveness.

  6. Role of very late antigen-1 in T-cell-mediated immunity to systemic viral infection

    DEFF Research Database (Denmark)

    Ørding Kauffmann, Susanne; Thomsen, Allan Randrup; Christensen, Jan Pravsgaard

    2006-01-01

    or their distribution between lymphoid and nonlymphoid organs. Regarding a functional role of VLA-1, we found that intracerebral infection of both VLA-1(-/-) and wild-type (wt) mice resulted in lethal T-cell-mediated meningitis, and quantitative and qualitative analyses of the cellular exudate did not reveal any...... significant differences between the two strains. Expression of VLA-1 was also found to be redundant regarding the ability of effector T cells to eliminate virus from internal organs of i.v. infected mice. Using delayed-type hypersensitivity (DTH) assays to evaluate subdermal CD8(+) T......, the current findings indicate that the expression of VLA-1 is not pivotal for T-cell-mediated antiviral immunity to a systemic infection....

  7. Histone modifications influence mediator interactions with chromatin

    Science.gov (United States)

    Zhu, Xuefeng; Zhang, Yongqiang; Bjornsdottir, Gudrun; Liu, Zhongle; Quan, Amy; Costanzo, Michael; Dávila López, Marcela; Westholm, Jakub Orzechowski; Ronne, Hans; Boone, Charles; Gustafsson, Claes M.; Myers, Lawrence C.

    2011-01-01

    The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. Genome wide localization studies have demonstrated that Mediator occupancy not only correlates with high levels of transcription, but that the complex also is present at transcriptionally silenced locations. We provide evidence that Mediator localization is guided by an interaction with histone tails, and that this interaction is regulated by their post-translational modifications. A quantitative, high-density genetic interaction map revealed links between Mediator components and factors affecting chromatin structure, especially histone deacetylases. Peptide binding assays demonstrated that pure wild-type Mediator forms stable complexes with the tails of Histone H3 and H4. These binding assays also showed Mediator—histone H4 peptide interactions are specifically inhibited by acetylation of the histone H4 lysine 16, a residue critical in transcriptional silencing. Finally, these findings were validated by tiling array analysis that revealed a broad correlation between Mediator and nucleosome occupancy in vivo, but a negative correlation between Mediator and nucleosomes acetylated at histone H4 lysine 16. Our studies show that chromatin structure and the acetylation state of histones are intimately connected to Mediator localization. PMID:21742760

  8. Mediation of the bidirectional relations between obesity and depression among women.

    Science.gov (United States)

    Vittengl, Jeffrey R

    2018-06-01

    Past research established that obesity increases risk for development of depression, and depression increases risk for development of obesity. The current study tested physical impairment (difficulty with instrumental activities of daily living), social dysfunction (low social support and high social strain), and emotional eating (using food to cope with stress) as mediators of the bidirectional, longitudinal relations between depression and obesity. A national sample of mid-life adults in the United States (N = 7108) was assessed at three time points over 18 years. Depression predicted increases in obesity, and obesity predicted increases in depression, for women but not for men. Among women, path analyses revealed that physical impairment, social dysfunction, and emotional eating mediated development of obesity from depression, and that physical impairment and emotional eating mediated development of depression from obesity. These results suggest that prevention or treatment of obesity-linked depression and depression-linked obesity in women may need to address multiple connections between these disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Identifying cis-mediators for trans-eQTLs across many human tissues using genomic mediation analysis.

    Science.gov (United States)

    Yang, Fan; Wang, Jiebiao; Pierce, Brandon L; Chen, Lin S

    2017-11-01

    The impact of inherited genetic variation on gene expression in humans is well-established. The majority of known expression quantitative trait loci (eQTLs) impact expression of local genes ( cis -eQTLs). More research is needed to identify effects of genetic variation on distant genes ( trans -eQTLs) and understand their biological mechanisms. One common trans -eQTLs mechanism is "mediation" by a local ( cis ) transcript. Thus, mediation analysis can be applied to genome-wide SNP and expression data in order to identify transcripts that are " cis -mediators" of trans -eQTLs, including those " cis -hubs" involved in regulation of many trans -genes. Identifying such mediators helps us understand regulatory networks and suggests biological mechanisms underlying trans -eQTLs, both of which are relevant for understanding susceptibility to complex diseases. The multitissue expression data from the Genotype-Tissue Expression (GTEx) program provides a unique opportunity to study cis -mediation across human tissue types. However, the presence of complex hidden confounding effects in biological systems can make mediation analyses challenging and prone to confounding bias, particularly when conducted among diverse samples. To address this problem, we propose a new method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC). It enables the search of a very large pool of variables, and adaptively selects potential confounding variables for each mediation test. Analyses of simulated data and GTEx data demonstrate that the adaptive selection of confounders by GMAC improves the power and precision of mediation analysis. Application of GMAC to GTEx data provides new insights into the observed patterns of cis -hubs and trans -eQTL regulation across tissue types. © 2017 Yang et al.; Published by Cold Spring Harbor Laboratory Press.

  10. Understanding and Using Mediators and Moderators

    Science.gov (United States)

    Wu, Amery D.; Zumbo, Bruno D.

    2008-01-01

    Mediation and moderation are two theories for refining and understanding a causal relationship. Empirical investigation of mediators and moderators requires an integrated research design rather than the data analyses driven approach often seen in the literature. This paper described the conceptual foundation, research design, data analysis, as…

  11. Comparative analyses reveal different consequences of two oxidative stress inducers, gamma irradiation and potassium tellurite, in the extremophile Deinococcus radiodurans

    International Nuclear Information System (INIS)

    Narasimha, Anaganti; Basu, Bhakti; Apte, Shree Kumar

    2014-01-01

    Proteomic and mass spectrometric analyses revealed differential responses of D. radiodurans to two oxidative stressors. While both elicited oxidative stress alleviation response, major divergence was observed at the level of DNA repair, metabolic pathways and protein homeostasis. Response to gamma irradiation was focused on DNA repair and ROS scavenging but supported metabolism as well as protein homeostasis. Tellurite, induced oxidative stress alleviation but decreased reducing affected and adversely affected metabolism and protein homeostasis

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

    Science.gov (United States)

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

    2018-01-01

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

  13. Keep Up the Good Work! Age-Moderated Mediation Model on Intention to Retire

    Directory of Open Access Journals (Sweden)

    Paola Dordoni

    2017-10-01

    Full Text Available In European nations, the aging of the workforce is a major issue which is increasingly addressed both in national and organizational policies in order to sustain older workers' employability and to encourage longer working lives. Particularly older workers' employability can be viewed an important issue as this has the potential to motivate them for their work and change their intention to retire. Based on lifespan development theories and Van der Heijden's ‘employability enhancement model’, this paper develops and tests an age-moderated mediation model (which refers to the processes that we want to test in this model, linking older workers' (55 years old and over perceptions of job support for learning (job-related factor and perceptions of negative age stereotypes on productivity (organizational factor, on the one hand, and their intention to retire, on the other hand, via their participation in employability enhancing activities, being the mediator in our model. A total of 2,082 workers aged 55 years and above were included in the analyses. Results revealed that the two proposed relationships between the predictors and intention to retire were mediated by participation in employability enhancing activities, reflecting two mechanisms through which work context affects intention to retire (namely ‘a gain spiral and a loss spiral’. Multi-Group SEM analyses, distinguishing between two age groups (55–60 and 61–65 years old, revealed different paths for the two distinguished groups of older workers. Employability mediated the relationship between perceptions of job support for learning and intention to retire in both age groups, whereas it only mediated the relationship between perceptions of negative age stereotypes and intention to retire in the 55–60 group. From our empirical study, we may conclude that employability is an important factor in the light of older workers' intention to retire. In order to motivate this category of

  14. Relationship between Individual and Organizational Learning: Mediating Role of Team Learning

    Directory of Open Access Journals (Sweden)

    Monika Stelmaszczyk

    2016-12-01

    Full Text Available The aim of this paper is to recognize the relationships between individual and organizational learning while considering team learning as a mediator of these relationships. The research object is a large Polish enterprise specializing in the production of cast-iron items. In order to test assumed research hypotheses, statistical analyses were conducted using the IBM SPSS Statistics Suite, version 20. The suite helped conduct correlation analyses concatenation, line regression analyses and mediation analyses using the PROCESS macro by Hayes and Preacher. The research results show a statistically significant relationship between individual learning and each of the five dimensions of organizational learning [clarity of purpose and mission; leadership commitment and empowerment; knowledge transfer; experimentation and rewards; and teamwork and group problem solving]. What is more, they prove that team learning is a mediator of a relationship between individual and organizational learning. Interestingly, only one full mediation has been observed while researching the mediative effect of team learning in relation to each out of the five dimensions of organizational learning. It occurred in relation to experimentation and rewards. In the remaining cases these were partial mediations.

  15. Expectancies Mediate the Relations Among Pain Catastrophizing, Fear of Movement, and Return to Work Outcomes After Whiplash Injury.

    Science.gov (United States)

    Carriere, Junie S; Thibault, Pascal; Milioto, Maria; Sullivan, Michael J L

    2015-12-01

    Pain catastrophizing and fear of movement have been identified as key predictors of prolonged work disability after whiplash injury. However, little is known about the processes by which pain catastrophizing and fear of movement affect return to work. This study investigated the mediating role of expectancies on the relations between pain catastrophizing and return to work, and between fear of movement and return to work after whiplash injury. The study sample consisted of 154 individuals with whiplash injury who were enrolled in a multidisciplinary pain rehabilitation program. Participants completed measures of pain catastrophizing, fear of movement, and return-to-work expectancies after admission to a rehabilitation program. A follow-up telephone interview was used to assess work status 1 year after discharge. Consistent with previous research, analyses revealed that expectancies, pain catastrophizing, and fear of movement were significant predictors of return to work at 1-year follow-up. Regression analyses (bootstrapping) revealed that expectancies partially mediated the relation between catastrophizing and return to work. Expectancies completely mediated the relation between fear of movement and return to work. The significant predictive and mediating role of expectancies on return to work argues for the inclusion of expectancies as a specific target of intervention for individuals with whiplash injury. The findings suggest that expectancies might be part of the pathways by which pain catastrophizing and fear of movement affect return-to-work outcomes after whiplash injury. The findings argue for greater attention to return-to-work expectancies as a risk factor for problematic recovery outcomes as well as a target of intervention. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  16. Multi-omics analysis identifies genes mediating the extension of cell walls in the Arabidopsis thaliana root elongation zone

    DEFF Research Database (Denmark)

    Wilson, Michael H; Holman, Tara J; Sørensen, Iben

    2015-01-01

    Plant cell wall composition is important for regulating growth rates, especially in roots. However, neither analyses of cell wall composition nor transcriptomes on their own can comprehensively reveal which genes and processes are mediating growth and cell elongation rates. This study reveals...... the benefits of carrying out multiple analyses in combination. Sections of roots from five anatomically and functionally defined zones in Arabidopsis thaliana were prepared and divided into three biological replicates. We used glycan microarrays and antibodies to identify the major classes of glycans......)cellular localization of many epitopes. Extensins were localized in epidermal and cortex cell walls, while AGP glycans were specific to different tissues from root-hair cells to the stele. The transcriptome analysis found several gene families peaking in the REZ. These included a large family of peroxidases (which...

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

    Science.gov (United States)

    Steeger, Christine M; Gondoli, Dawn M

    2013-04-01

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

  18. Global terrestrial water storage connectivity revealed using complex climate network analyses

    Science.gov (United States)

    Sun, A. Y.; Chen, J.; Donges, J.

    2015-07-01

    Terrestrial water storage (TWS) exerts a key control in global water, energy, and biogeochemical cycles. Although certain causal relationship exists between precipitation and TWS, the latter quantity also reflects impacts of anthropogenic activities. Thus, quantification of the spatial patterns of TWS will not only help to understand feedbacks between climate dynamics and the hydrologic cycle, but also provide new insights and model calibration constraints for improving the current land surface models. This work is the first attempt to quantify the spatial connectivity of TWS using the complex network theory, which has received broad attention in the climate modeling community in recent years. Complex networks of TWS anomalies are built using two global TWS data sets, a remote sensing product that is obtained from the Gravity Recovery and Climate Experiment (GRACE) satellite mission, and a model-generated data set from the global land data assimilation system's NOAH model (GLDAS-NOAH). Both data sets have 1° × 1° grid resolutions and cover most global land areas except for permafrost regions. TWS networks are built by first quantifying pairwise correlation among all valid TWS anomaly time series, and then applying a cutoff threshold derived from the edge-density function to retain only the most important features in the network. Basinwise network connectivity maps are used to illuminate connectivity of individual river basins with other regions. The constructed network degree centrality maps show the TWS anomaly hotspots around the globe and the patterns are consistent with recent GRACE studies. Parallel analyses of networks constructed using the two data sets reveal that the GLDAS-NOAH model captures many of the spatial patterns shown by GRACE, although significant discrepancies exist in some regions. Thus, our results provide further measures for constraining the current land surface models, especially in data sparse regions.

  19. Smokers' increased risk for disability pension: social confounding or health-mediated effects? Gender-specific analyses of the Hordaland Health Study cohort.

    Science.gov (United States)

    Haukenes, Inger; Riise, Trond; Haug, Kjell; Farbu, Erlend; Maeland, John Gunnar

    2013-09-01

    Studies indicate that cigarette smokers have an increased risk for disability pension, presumably mediated by adverse health effects. However, smoking is also related to socioeconomic status. The current study examined the association between smoking and subsequent disability pension, and whether the association is explained by social confounding and/or health-related mediation. A subsample of 7934 men and 8488 women, aged 40-46, from the Hordaland Health Study, Norway (1997-1999), provided baseline information on smoking status, self-reported health measures and socioeconomic status. Outcome was register-based disability pension from 12 months after baseline to end of 2004. Gender stratified Cox regression analyses were used adjusted for socioeconomic status, physical activity, self-reported health and musculoskeletal pain sites. A total of 155 (2%) men and 333 (3.9%) women were granted disability pension during follow-up. The unadjusted disability risk associated with heavy smoking versus non-smoking was 1.88 (95% CI 1.23 to 2.89) among men and 3.06 (95% CI 2.23 to 4.20) among women. In multivariate analyses, adjusting for socioeconomic status, HRs were 1.33 (95% CI 0.84 to 2.11) among men and 2.22 (95% CI 1.58 to 3.13) among women. Final adjustment for physical activity, self-reported health and musculoskeletal pain further reduced the effect of heavy smoking in women (HR=1.53, 95% CI 1.09 to 2.16). Socioeconomic status confounded the smoking-related risk for disability pension; for female heavy smokers, however, a significant increased risk persisted after adjustment. Women may be particularly vulnerable to heavy smoking and to its sociomedical consequences, such as disability pension.

  20. Human iPSC-Derived Neuronal Model of Tau-A152T Frontotemporal Dementia Reveals Tau-Mediated Mechanisms of Neuronal Vulnerability

    Directory of Open Access Journals (Sweden)

    M. Catarina Silva

    2016-09-01

    Full Text Available Frontotemporal dementia (FTD and other tauopathies characterized by focal brain neurodegeneration and pathological accumulation of proteins are commonly associated with tau mutations. However, the mechanism of neuronal loss is not fully understood. To identify molecular events associated with tauopathy, we studied induced pluripotent stem cell (iPSC-derived neurons from individuals carrying the tau-A152T variant. We highlight the potential of in-depth phenotyping of human neuronal cell models for pre-clinical studies and identification of modulators of endogenous tau toxicity. Through a panel of biochemical and cellular assays, A152T neurons showed accumulation, redistribution, and decreased solubility of tau. Upregulation of tau was coupled to enhanced stress-inducible markers and cell vulnerability to proteotoxic, excitotoxic, and mitochondrial stressors, which was rescued upon CRISPR/Cas9-mediated targeting of tau or by pharmacological activation of autophagy. Our findings unmask tau-mediated perturbations of specific pathways associated with neuronal vulnerability, revealing potential early disease biomarkers and therapeutic targets for FTD and other tauopathies.

  1. Mediators of Effects of a Selective Family-Focused Violence Prevention Approach for Middle School Students

    Science.gov (United States)

    2013-01-01

    This study examined how parenting and family characteristics targeted in a selective prevention program mediated effects on key youth proximal outcomes related to violence perpetration. The selective intervention was evaluated within the context of a multi-site trial involving random assignment of 37 schools to four conditions: a universal intervention composed of a student social-cognitive curriculum and teacher training, a selective family-focused intervention with a subset of high-risk students, a condition combining these two interventions, and a no-intervention control condition. Two cohorts of sixth-grade students (total N=1,062) exhibiting high levels of aggression and social influence were the sample for this study. Analyses of pre-post change compared to controls using intent-to-treat analyses found no significant effects. However, estimates incorporating participation of those assigned to the intervention and predicted participation among those not assigned revealed significant positive effects on student aggression, use of aggressive strategies for conflict management, and parental estimation of student’s valuing of achievement. Findings also indicated intervention effects on two targeted family processes: discipline practices and family cohesion. Mediation analyses found evidence that change in these processes mediated effects on some outcomes, notably aggressive behavior and valuing of school achievement. Results support the notion that changing parenting practices and the quality of family relationships can prevent the escalation in aggression and maintain positive school engagement for high-risk youth. PMID:21932067

  2. Genomic and transcriptomic comparison of allergen and silver nanoparticle-induced mast cell degranulation reveals novel non-immunoglobulin E mediated mechanisms.

    Science.gov (United States)

    Johnson, Monica; Alsaleh, Nasser; Mendoza, Ryan P; Persaud, Indushekhar; Bauer, Alison K; Saba, Laura; Brown, Jared M

    2018-01-01

    Mast cells represent a crucial cell type in host defense; however, maladaptive responses are contributing factors in the pathogenesis of allergic diseases. Previous work in our laboratory has shown that exposure to silver nanoparticles (AgNPs) results in mast cell degranulation via a non-immunoglobulin E (IgE) mechanism. In this study, we utilized a systems biology approach to identify novel genetic factors playing a role in AgNP-induced mast cell degranulation compared to the classical activation by antigen-mediated FcεRI crosslinking. Mast cell degranulation was assessed in bone marrow-derived mast cells isolated from 23 strains of mice following exposure to AgNPs or FcεRI crosslinking with dinitrophenyl (DNP). Utilizing strain-dependent mast cell degranulation, an association mapping study identified 3 chromosomal regions that were significantly associated with mast cell degranulation by AgNP and one non-overlapping region associated with DNP-mediated degranulation. Two of the AgNP-associated regions correspond to genes previously reported to be associated with allergic disorders (Trac2 on chromosome 1 and Traf6 on chromosome 2) and an uncharacterized gene identified on chromosome 1 (Fam126b). In conjunction, RNA-sequencing performed on mast cells from the high and low responder strains revealed 3754 and 34 differentially expressed genes that were unique to DNP and AgNP exposures, respectively. Select candidate genes include Ptger4, a gene encoding a G-protein coupled receptor in addition to a multifunctional adaptor protein, Txnip, that may be driving mast cell degranulation by AgNP. Taken together, we identified novel genes that have not been previously shown to play a role in nanoparticle-mediated mast cell activation. With further functional evaluation in the future, these genes may be potential therapeutic targets in the treatment of non-IgE mediated mast cell-linked disorders.

  3. Practical Guidance for Conducting Mediation Analysis With Multiple Mediators Using Inverse Odds Ratio Weighting

    OpenAIRE

    Nguyen, Quynh C.; Osypuk, Theresa L.; Schmidt, Nicole M.; Glymour, M. Maria; Tchetgen Tchetgen, Eric J.

    2015-01-01

    Despite the recent flourishing of mediation analysis techniques, many modern approaches are difficult to implement or applicable to only a restricted range of regression models. This report provides practical guidance for implementing a new technique utilizing inverse odds ratio weighting (IORW) to estimate natural direct and indirect effects for mediation analyses. IORW takes advantage of the odds ratio's invariance property and condenses information on the odds ratio for the relationship be...

  4. Caenorhabditis elegans reveals a FxNPxY-independent low-density lipoprotein receptor internalization mechanism mediated by epsin1

    Science.gov (United States)

    Kang, Yuan-Lin; Yochem, John; Bell, Leslie; Sorensen, Erika B.; Chen, Lihsia; Conner, Sean D.

    2013-01-01

    Low-density lipoprotein receptor (LDLR) internalization clears cholesterol-laden LDL particles from circulation in humans. Defects in clathrin-dependent LDLR endocytosis promote elevated serum cholesterol levels and can lead to atherosclerosis. However, our understanding of the mechanisms that control LDLR uptake remains incomplete. To identify factors critical to LDLR uptake, we pursued a genome-wide RNA interference screen using Caenorhabditis elegans LRP-1/megalin as a model for LDLR transport. In doing so, we discovered an unanticipated requirement for the clathrin-binding endocytic adaptor epsin1 in LDLR endocytosis. Epsin1 depletion reduced LDLR internalization rates in mammalian cells, similar to the reduction observed following clathrin depletion. Genetic and biochemical analyses of epsin in C. elegans and mammalian cells uncovered a requirement for the ubiquitin-interaction motif (UIM) as critical for receptor transport. As the epsin UIM promotes the internalization of some ubiquitinated receptors, we predicted LDLR ubiquitination as necessary for endocytosis. However, engineered ubiquitination-impaired LDLR mutants showed modest internalization defects that were further enhanced with epsin1 depletion, demonstrating epsin1-mediated LDLR endocytosis is independent of receptor ubiquitination. Finally, we provide evidence that epsin1-mediated LDLR uptake occurs independently of either of the two documented internalization motifs (FxNPxY or HIC) encoded within the LDLR cytoplasmic tail, indicating an additional internalization mechanism for LDLR. PMID:23242996

  5. Peer relationship and adolescent smartphone addiction: The mediating role of self-esteem and the moderating role of the need to belong.

    Science.gov (United States)

    Wang, Pengcheng; Zhao, Meng; Wang, Xingchao; Xie, Xiaochun; Wang, Yuhui; Lei, Li

    2017-12-01

    Background and aims Adolescent smartphone addiction has received increased attention in recent years, and peer relationship has been found to be a protective factor in adolescent smartphone. However, little is known about the mediating and moderating mechanisms underlying this relation. The aim of this study was to investigate (a) the mediating role of self-esteem in the association between student-student relationship and smartphone addiction, and (b) the moderating role of the need to belong in the indirect relationship between student-student relationship and adolescent smartphone addiction. Methods This model was examined with 768 Chinese adolescents (mean age = 16.81 years, SD = 0.73); the participants completed measurements regarding student-student relationship, self-esteem, the need to belong, and smartphone addiction. Results The correlation analyses indicated that student-student relationship was significantly negatively associated with adolescent smartphone addiction, and the need to belong was significantly positively associated with adolescent smartphone addiction. Mediation analyses revealed that self-esteem partially mediated the link between student-student relationship and adolescent smartphone addiction. Moderated mediation further indicated that the mediated path was weaker for adolescents with lower levels of the need to belong. Discussion and conclusion High self-esteem could be a protective factor against smartphone addiction for adolescents with a strong need to belong as these students appeared to be at elevated risk of developing smartphone addiction.

  6. The Pleasure Evoked by Sad Music Is Mediated by Feelings of Being Moved.

    Science.gov (United States)

    Vuoskoski, Jonna K; Eerola, Tuomas

    2017-01-01

    Why do we enjoy listening to music that makes us sad? This question has puzzled music psychologists for decades, but the paradox of "pleasurable sadness" remains to be solved. Recent findings from a study investigating the enjoyment of sad films suggest that the positive relationship between felt sadness and enjoyment might be explained by feelings of being moved (Hanich et al., 2014). The aim of the present study was to investigate whether feelings of being moved also mediated the enjoyment of sad music. In Experiment 1, 308 participants listened to five sad music excerpts and rated their liking and felt emotions. A multilevel mediation analysis revealed that the initial positive relationship between liking and felt sadness ( r = 0.22) was fully mediated by feelings of being moved. Experiment 2 explored the interconnections of perceived sadness, beauty, and movingness in 27 short music excerpts that represented independently varying levels of sadness and beauty. Two multilevel mediation analyses were carried out to test competing hypotheses: (A) that movingness mediates the effect of perceived sadness on liking, or (B) that perceived beauty mediates the effect of sadness on liking. Stronger support was obtained for Hypothesis A. Our findings suggest that - similarly to the enjoyment of sad films - the aesthetic appreciation of sad music is mediated by being moved. We argue that felt sadness may contribute to the enjoyment of sad music by intensifying feelings of being moved.

  7. The Pleasure Evoked by Sad Music Is Mediated by Feelings of Being Moved

    Science.gov (United States)

    Vuoskoski, Jonna K.; Eerola, Tuomas

    2017-01-01

    Why do we enjoy listening to music that makes us sad? This question has puzzled music psychologists for decades, but the paradox of “pleasurable sadness” remains to be solved. Recent findings from a study investigating the enjoyment of sad films suggest that the positive relationship between felt sadness and enjoyment might be explained by feelings of being moved (Hanich et al., 2014). The aim of the present study was to investigate whether feelings of being moved also mediated the enjoyment of sad music. In Experiment 1, 308 participants listened to five sad music excerpts and rated their liking and felt emotions. A multilevel mediation analysis revealed that the initial positive relationship between liking and felt sadness (r = 0.22) was fully mediated by feelings of being moved. Experiment 2 explored the interconnections of perceived sadness, beauty, and movingness in 27 short music excerpts that represented independently varying levels of sadness and beauty. Two multilevel mediation analyses were carried out to test competing hypotheses: (A) that movingness mediates the effect of perceived sadness on liking, or (B) that perceived beauty mediates the effect of sadness on liking. Stronger support was obtained for Hypothesis A. Our findings suggest that – similarly to the enjoyment of sad films – the aesthetic appreciation of sad music is mediated by being moved. We argue that felt sadness may contribute to the enjoyment of sad music by intensifying feelings of being moved. PMID:28377740

  8. Mediation Analysis: A Practitioner's Guide.

    Science.gov (United States)

    VanderWeele, Tyler J

    2016-01-01

    This article provides an overview of recent developments in mediation analysis, that is, analyses used to assess the relative magnitude of different pathways and mechanisms by which an exposure may affect an outcome. Traditional approaches to mediation in the biomedical and social sciences are described. Attention is given to the confounding assumptions required for a causal interpretation of direct and indirect effect estimates. Methods from the causal inference literature to conduct mediation in the presence of exposure-mediator interactions, binary outcomes, binary mediators, and case-control study designs are presented. Sensitivity analysis techniques for unmeasured confounding and measurement error are introduced. Discussion is given to extensions to time-to-event outcomes and multiple mediators. Further flexible modeling strategies arising from the precise counterfactual definitions of direct and indirect effects are also described. The focus throughout is on methodology that is easily implementable in practice across a broad range of potential applications.

  9. Real-time single-molecule tethered particle motion experiments reveal the kinetics and mechanisms of Cre-mediated site-specific recombination

    Science.gov (United States)

    Fan, Hsiu-Fang

    2012-01-01

    Tyrosine family recombinases (YRs) are widely utilized in genome engineering systems because they can easily direct DNA rearrangement. Cre recombinases, one of the most commonly used types of YRs, catalyze site-specific recombination between two loxP sites without the need for high-energy cofactors, other accessory proteins or a specific DNA target sequence between the loxP sites. Previous structural, analytical ultracentrifuge and electrophoretic analyses have provided details of the reaction kinetics and mechanisms of Cre recombinase activity; whether there are reaction intermediates or side pathways involved has been left unaddressed. Using tethered particle motion (TPM), the Cre-mediated site-specific recombination process has been delineated, from beginning to end, at the single-molecule level, including the formation of abortive complexes and wayward complexes blocking inactive nucleoprotein complexes from entering the recombination process. Reversibility in the strand-cleavage/-ligation process and the formation of a thermally stable Holliday junction intermediate were observed within the Cre-mediated site-specific recombination process. Rate constants for each elementary step, which explain the overall reaction outcomes under various conditions, were determined. Taking the findings of this study together, they demonstrate the potential of single-molecule methodology as an alternative approach for exploring reaction mechanisms in detail. PMID:22467208

  10. Statistical modeling implicates neuroanatomical circuit mediating stress relief by 'comfort' food.

    Science.gov (United States)

    Ulrich-Lai, Yvonne M; Christiansen, Anne M; Wang, Xia; Song, Seongho; Herman, James P

    2016-07-01

    A history of eating highly palatable foods reduces physiological and emotional responses to stress. For instance, we have previously shown that limited sucrose intake (4 ml of 30 % sucrose twice daily for 14 days) reduces hypothalamic-pituitary-adrenocortical (HPA) axis responses to stress. However, the neural mechanisms underlying stress relief by such 'comfort' foods are unclear, and could reveal an endogenous brain pathway for stress mitigation. As such, the present work assessed the expression of several proteins related to neuronal activation and/or plasticity in multiple stress- and reward-regulatory brain regions of rats after limited sucrose (vs. water control) intake. These data were then subjected to a series of statistical analyses, including Bayesian modeling, to identify the most likely neurocircuit mediating stress relief by sucrose. The analyses suggest that sucrose reduces HPA activation by dampening an excitatory basolateral amygdala-medial amygdala circuit, while also potentiating an inhibitory bed nucleus of the stria terminalis principle subdivision-mediated circuit, resulting in reduced HPA activation after stress. Collectively, the results support the hypothesis that sucrose limits stress responses via plastic changes to the structure and function of stress-regulatory neural circuits. The work also illustrates that advanced statistical methods are useful approaches to identify potentially novel and important underlying relationships in biological datasets.

  11. Mediating effects of self-stigma on the relationship between perceived stigma and psychosocial outcomes among psychiatric outpatients: findings from a cross-sectional survey in Singapore

    Science.gov (United States)

    Picco, Louisa; Lau, Ying Wen; Pang, Shirlene; Abdin, Edimansyah; Vaingankar, Janhavi Ajit; Chong, Siow Ann; Subramaniam, Mythily

    2017-01-01

    Objectives To examine whether self-stigma mediates the relationship between perceived stigma and quality of life, self-esteem and general functioning among outpatients with depression, schizophrenia, anxiety and obsessive-compulsive disorder (OCD). Design Cross-sectional survey. Setting Outpatient clinics at a tertiary psychiatric hospital in Singapore. Participants 280 outpatients with a primary clinical diagnosis of either schizophrenia, depression, anxiety or OCD. Methods Data were collected in relation to self-stigma, perceived stigma, self-esteem, functioning and quality of life. In order to examine the mediating role of self-stigma on the relationship between perceived stigma and psychosocial outcomes, bootstrapping mediation analyses were used. Results Mediation analyses revealed that the relationship between perceived stigma and psychosocial outcomes was subject to the effects of self-stigma among the overall sample. Separate mediation analyses were conducted by diagnoses and showed differences in the mediating effects of self-stigma. Among the whole sample and the subsample with OCD, self-stigma mediated the relationship between perceived stigma and all psychosocial outcomes. For those with anxiety, depression and schizophrenia, the mediating effects of self-stigma were present in all relationships except (1) perceived stigma with physical health in the anxiety sample, (2) perceived stigma with social relationships in the depression sample and (3) perceived stigma with physical health in the schizophrenia sample. Conclusions The mediating effects of self-stigma on the relationship between perceived stigma and various psychosocial outcomes are evident and differ across diagnoses. Interventions to address and reduce the effects of self-stigma along with targeted treatments and psychoeducation to assist people with mental illness overcome or better manage self-stigma while providing them the skills to counteract public stigma are needed. PMID:28851803

  12. Mitochondrial dysfunction, oxidative stress and apoptosis revealed by proteomic and transcriptomic analyses of the striata in two mouse models of Parkinson’s disease

    Energy Technology Data Exchange (ETDEWEB)

    Chin, Mark H.; Qian, Weijun; Wang, Haixing; Petyuk, Vladislav A.; Bloom, Joshua S.; Sforza, Daniel M.; Lacan, Goran; Liu, Dahai; Khan, Arshad H.; Cantor, Rita M.; Bigelow, Diana J.; Melega, William P.; Camp, David G.; Smith, Richard D.; Smith, Desmond J.

    2008-02-10

    The molecular mechanisms underlying the changes in the nigrostriatal pathway in Parkinson disease (PD) are not completely understood. Here we use mass spectrometry and microarrays to study the proteomic and transcriptomic changes in the striatum of two mouse models of PD, induced by the distinct neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Proteomic analyses resulted in the identification and relative quantification of 912 proteins with two or more unique peptides and 85 proteins with significant abundance changes following neurotoxin treatment. Similarly, microarray analyses revealed 181 genes with significant changes in mRNA following neurotoxin treatment. The combined protein and gene list provides a clearer picture of the potential mechanisms underlying neurodegeneration observed in PD. Functional analysis of this combined list revealed a number of significant categories, including mitochondrial dysfunction, oxidative stress response and apoptosis. Additionally, codon usage and miRNAs may play an important role in translational control in the striatum. These results constitute one of the largest datasets integrating protein and transcript changes for these neurotoxin models with many similar endpoint phenotypes but distinct mechanisms.

  13. Negative symptoms mediate the relationship between neurocognition and function in individuals at ultrahigh risk for psychosis

    DEFF Research Database (Denmark)

    Glenthøj, L B; Jepsen, Jens Richardt Møllegaard; Hjorthøj, Carsten

    2017-01-01

    -Risk Social Challenge task and the Scale for the Assessment of Negative Symptoms respectively. Four instruments were used to assess overall functioning, and one instrument assessed quality of life encompassing social functioning. RESULTS: The cross-sectional analyses revealed that neurocognition was related......OBJECTIVE: Neurocognition is known to impact functioning in individuals at ultrahigh risk (UHR) for psychosis, but studies investigating potential mediators of this relationship are scarce. Building on evidence from schizophrenia spectrum disorders, the study tested whether negative symptoms...... and social skills act as mediators between neurocognition and functional outcome in UHR individuals. METHODS: Ultrahigh risk participants (N = 84) underwent neurocognitive testing using the Brief Assessment of Cognition in Schizophrenia. Social skills and negative symptoms were assessed using the High...

  14. Reconstitution of DNA strand exchange mediated by Rhp51 recombinase and two mediators.

    Directory of Open Access Journals (Sweden)

    Yumiko Kurokawa

    2008-04-01

    Full Text Available In the fission yeast Schizosaccharomyces pombe, genetic evidence suggests that two mediators, Rad22 (the S. pombe Rad52 homolog and the Swi5-Sfr1 complex, participate in a common pathway of Rhp51 (the S. pombe Rad51 homolog-mediated homologous recombination (HR and HR repair. Here, we have demonstrated an in vitro reconstitution of the central step of DNA strand exchange during HR. Our system consists entirely of homogeneously purified proteins, including Rhp51, the two mediators, and replication protein A (RPA, which reflects genetic requirements in vivo. Using this system, we present the first robust biochemical evidence that concerted action of the two mediators directs the loading of Rhp51 onto single-stranded DNA (ssDNA precoated with RPA. Dissection of the reaction reveals that Rad22 overcomes the inhibitory effect of RPA on Rhp51-Swi5-Sfr1-mediated strand exchange. In addition, Rad22 negates the requirement for a strict order of protein addition to the in vitro system. However, despite the presence of Rad22, Swi5-Sfr1 is still essential for strand exchange. Importantly, Rhp51, but neither Rad22 nor the Swi5-Sfr1 mediator, is the factor that displaces RPA from ssDNA. Swi5-Sfr1 stabilizes Rhp51-ssDNA filaments in an ATP-dependent manner, and this stabilization is correlated with activation of Rhp51 for the strand exchange reaction. Rad22 alone cannot activate the Rhp51 presynaptic filament. AMP-PNP, a nonhydrolyzable ATP analog, induces a similar stabilization of Rhp51, but this stabilization is independent of Swi5-Sfr1. However, hydrolysis of ATP is required for processive strand transfer, which results in the formation of a long heteroduplex. Our in vitro reconstitution system has revealed that the two mediators have indispensable, but distinct, roles for mediating Rhp51 loading onto RPA-precoated ssDNA.

  15. The mediating role of disgust sensitivity and thought-action fusion between religiosity and obsessive compulsive symptoms.

    Science.gov (United States)

    Inozu, Mujgan; Ulukut, Fulya Ozcanli; Ergun, Gokce; Alcolado, Gillian M

    2014-10-01

    Psychological theories of obsessions and compulsions have long recognised that strict religious codes and moral standards might promote thought-action fusion (TAF) appraisals. These appraisals have been implicated in the transformation of normally occurring intrusions into clinically distressing obsessions. Furthermore, increased disgust sensitivity has also been reported to be associated with obsessive compulsive (OC) symptoms. No research, however, has investigated the mediating roles of TAF and disgust sensitivity between religiosity and OC symptoms. This study was composed of 244 undergraduate students who completed measures of OC symptoms, TAF, disgust sensitivity, religiosity and negative effect. Analyses revealed that the relationship between religiosity and OC symptoms was mediated by TAF and disgust sensitivity. More importantly, the mediating role of TAF was not different across OC symptom subtypes, whereas the mediating role of disgust sensitivity showed different patterns across OC symptom subtypes. These findings indicate that the tendency for highly religious Muslims to experience greater OC symptoms is related to their heightened beliefs about disgust sensitivity and the importance of thoughts. © 2014 International Union of Psychological Science.

  16. Mediator MED23 Links Pigmentation and DNA Repair through the Transcription Factor MITF.

    Science.gov (United States)

    Xia, Min; Chen, Kun; Yao, Xiao; Xu, Yichi; Yao, Jiaying; Yan, Jun; Shao, Zhen; Wang, Gang

    2017-08-22

    DNA repair is related to many physiological and pathological processes, including pigmentation. Little is known about the role of the transcriptional cofactor Mediator complex in DNA repair and pigmentation. Here, we demonstrate that Mediator MED23 plays an important role in coupling UV-induced DNA repair to pigmentation. The loss of Med23 specifically impairs the pigmentation process in melanocyte-lineage cells and in zebrafish. Med23 deficiency leads to enhanced nucleotide excision repair (NER) and less DNA damage following UV radiation because of the enhanced expression and recruitment of NER factors to chromatin for genomic stability. Integrative analyses of melanoma cells reveal that MED23 controls the expression of a melanocyte master regulator, Mitf, by modulating its distal enhancer activity, leading to opposing effects on pigmentation and DNA repair. Collectively, the Mediator MED23/MITF axis connects DNA repair to pigmentation, thus providing molecular insights into the DNA damage response and skin-related diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. Association between Perceived Discrimination in Healthcare Settings and HIV Medication Adherence: Mediating Psychosocial Mechanisms.

    Science.gov (United States)

    Turan, Bulent; Rogers, Anna Joy; Rice, Whitney S; Atkins, Ghislaine C; Cohen, Mardge H; Wilson, Tracey E; Adimora, Adaora A; Merenstein, Daniel; Adedimeji, Adebola; Wentz, Eryka L; Ofotokun, Igho; Metsch, Lisa; Tien, Phyllis C; Johnson, Mallory O; Turan, Janet M; Weiser, Sheri D

    2017-12-01

    There is insufficient research on the impact of perceived discrimination in healthcare settings on adherence to antiretroviral therapy (ART), particularly among women living with HIV, and even less is known about psychosocial mechanisms that may mediate this association. Cross-sectional analyses were conducted in a sample of 1356 diverse women living with HIV enrolled in the Women's Interagency HIV Study (WIHS), a multi-center cohort study. Indirect effects analysis with bootstrapping was used to examine the potential mediating roles of internalized stigma and depressive symptoms in the association between perceived discrimination in healthcare settings and ART adherence. Perceived discrimination in healthcare settings was negatively associated with optimal (95% or better) ART adherence (adjusted odds ratio (AOR) = 0.81, p = 0.02, 95% confidence interval (CI) [0.68, 0.97]). Furthermore, internalization of stigma and depressive symptoms mediated the perceived discrimination-adherence association: Serial mediation analyses revealed a significant indirect effect of perceived discrimination in healthcare settings on ART adherence, first through internalized HIV stigma, and then through depressive symptoms (B = - 0.08, SE = 0.02, 95% CI [- 0.12, - 0.04]). Perceiving discrimination in healthcare settings may contribute to internalization of HIV-related stigma, which in turn may lead to depressive symptoms, with downstream adverse effects on ART adherence among women. These findings can guide the design of interventions to reduce discrimination in healthcare settings, as well as interventions targeting psychosocial mechanisms that may impact the ability of women living with HIV to adhere to ART regimens.

  18. Prayer and pain: the mediating role of positive re-appraisal.

    Science.gov (United States)

    Dezutter, Jessie; Wachholtz, Amy; Corveleyn, Jozef

    2011-12-01

    The present study explored in a sample of Flemish pain patients the role of prayer as a possible individual factor in pain management. The focus on prayer as a personal religious factor fits with the current religious landscape in Western-Europe where personal religious factors are more important than organizational dimensions of religion. Our study is framed in the transactional theory of stress and coping by testing first, whether prayer was related with pain severity and pain tolerance and second, whether cognitive positive re-appraisal was a mediating mechanism in the association between prayer and pain. We expected that prayer would be related to pain tolerance in reducing the impact of the pain on patient's daily life, but not necessarily to pain severity. A cross-sectional questionnaire design was adopted in order to measure demographics, prayer, pain outcomes (i.e., pain severity and pain tolerance), and cognitive positive re-appraisal. Two hundred and two chronic pain (CP) patients, all members of a Flemish national patients association, completed the questionnaires. Correlational analyses showed that prayer was significantly related with pain tolerance, but not with pain severity. However, ancillary analyses revealed a moderational effect of religious affiliation in the relationship between prayer and pain severity as well as pain tolerance. Furthermore, mediation analysis revealed that cognitive positive re-appraisal was indeed an underlying mechanism in the relationship between prayer and pain tolerance. This study affirms the importance to distinguish between pain severity and pain tolerance, and indicates that prayer can play a role in pain management, especially for religious pain patients. Further, the findings can be framed within the transactional theory of stress and coping as the results indicate that positive re-appraisal might be an important underlying mechanism in the association between prayer and pain.

  19. [The mediating role of the interpersonal schemas between parenting styles and psychological symptoms: a schema focused view].

    Science.gov (United States)

    Soygüt, Gonca; Cakir, Zehra

    2009-01-01

    The first aim of this study was to examine the relationships between perceived parenting styles and interpersonal schemas. The second purpose was to investigate the mediator role of interpersonal schemas between perceived parenting styles and psychological symptoms. University students (N=94), ages ranging between 17-26, attending to different faculty and classes, have completed Interpersonal Schema Questionnaire, Young Parenting Inventory and Symptom Check List-90. A series of regression analyses revealed that perceived parenting styles have predictive power on a number of interpersonal schemas. Further analyses pointed out that the mediator role of Hostility situation of interpersonal schemas between psychological symptoms and normative, belittling/criticizing, pessimistic/worried parenting styles on the mother forms (Sobel z= 1.94-2.08, p parenting styles (Sobel z= 2.20-2.86, p parenting styles on interpersonal schemas. Moreover, the mediator role of interpersonal schemas between perceived parenting styles and psychological symptoms was also observed. Excluding pessimistic/anxious parenting styles, perceived parenting styles of mothers and fathers differed in their relation to psychological symptoms. In overall evaluation, we believe that, although schemas and parental styles have some universalities in relation to their impacts on psychological health, further research is necessary to address their implications and possible paternal differences in our collectivistic cultural context.

  20. Structural analyses of Legionella LepB reveal a new GAP fold that catalytically mimics eukaryotic RasGAP.

    Science.gov (United States)

    Yu, Qin; Hu, Liyan; Yao, Qing; Zhu, Yongqun; Dong, Na; Wang, Da-Cheng; Shao, Feng

    2013-06-01

    Rab GTPases are emerging targets of diverse bacterial pathogens. Here, we perform biochemical and structural analyses of LepB, a Rab GTPase-activating protein (GAP) effector from Legionella pneumophila. We map LepB GAP domain to residues 313-618 and show that the GAP domain is Rab1 specific with a catalytic activity higher than the canonical eukaryotic TBC GAP and the newly identified VirA/EspG family of bacterial RabGAP effectors. Exhaustive mutation analyses identify Arg444 as the arginine finger, but no catalytically essential glutamine residues. Crystal structures of LepB313-618 alone and the GAP domain of Legionella drancourtii LepB in complex with Rab1-GDP-AlF3 support the catalytic role of Arg444, and also further reveal a 3D architecture and a GTPase-binding mode distinct from all known GAPs. Glu449, structurally equivalent to TBC RabGAP glutamine finger in apo-LepB, undergoes a drastic movement upon Rab1 binding, which induces Rab1 Gln70 side-chain flipping towards GDP-AlF3 through a strong ionic interaction. This conformationally rearranged Gln70 acts as the catalytic cis-glutamine, therefore uncovering an unexpected RasGAP-like catalytic mechanism for LepB. Our studies highlight an extraordinary structural and catalytic diversity of RabGAPs, particularly those from bacterial pathogens.

  1. Statistical modeling implicates neuroanatomical circuit mediating stress relief by ‘comfort’ food

    Science.gov (United States)

    Ulrich-Lai, Yvonne M.; Christiansen, Anne M.; Wang, Xia; Song, Seongho; Herman, James P.

    2015-01-01

    A history of eating highly-palatable foods reduces physiological and emotional responses to stress. For instance, we have previously shown that limited sucrose intake (4 ml of 30% sucrose twice daily for 14 days) reduces hypothalamic-pituitary-adrenocortical (HPA) axis responses to stress. However, the neural mechanisms underlying stress relief by such ‘comfort’ foods are unclear, and could reveal an endogenous brain pathway for stress mitigation. As such, the present work assessed the expression of several proteins related to neuronal activation and/or plasticity in multiple stress- and reward-regulatory brain regions of rats after limited sucrose (vs. water control) intake. These data were then subjected to a series of statistical analyses, including Bayesian modeling, to identify the most likely neurocircuit mediating stress relief by sucrose. The analyses suggest that sucrose reduces HPA activation by dampening an excitatory basolateral amygdala - medial amygdala circuit, while also potentiating an inhibitory bed nucleus of the stria terminalis principle subdivision-mediated circuit, resulting in reduced HPA activation after stress. Collectively, the results support the hypothesis that sucrose limits stress responses via plastic changes to the structure and function of stress-regulatory neural circuits. The work also illustrates that advanced statistical methods are useful approaches to identify potentially novel and important underlying relationships in biological data sets. PMID:26246177

  2. Jasmonic acid-mediated defense suppresses brassinosteroid-mediated susceptibility to Rice black streaked dwarf virus infection in rice.

    Science.gov (United States)

    He, Yuqing; Zhang, Hehong; Sun, Zongtao; Li, Junmin; Hong, Gaojie; Zhu, Qisong; Zhou, Xuebiao; MacFarlane, Stuart; Yan, Fei; Chen, Jianping

    2017-04-01

    Plant hormones play a vital role in plant immune responses. However, in contrast to the relative wealth of information on hormone-mediated immunity in dicot plants, little information is available on monocot-virus defense systems. We used a high-throughput-sequencing approach to compare the global gene expression of Rice black-streaked dwarf virus (RBSDV)-infected rice plants with that of healthy plants. Exogenous hormone applications and transgenic rice were used to test RBSDV infectivity and pathogenicity. Our results revealed that the jasmonic acid (JA) pathway was induced while the brassinosteroid (BR) pathway was suppressed in infected plants. Foliar application of methyl jasmonate (MeJA) or brassinazole (BRZ) resulted in a significant reduction in RBSDV incidence, while epibrassinolide (BL) treatment increased RBSDV infection. Infection studies using coi1-13 and Go mutants demonstrated JA-mediated resistance and BR-mediated susceptibility to RBSDV infection. A mixture of MeJA and BL treatment resulted in a significant reduction in RBSDV infection compared with a single BL treatment. MeJA application efficiently suppressed the expression of BR pathway genes, and this inhibition depended on the JA coreceptor OsCOI1. Collectively, our results reveal that JA-mediated defense can suppress the BR-mediated susceptibility to RBSDV infection. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  3. The effects of anxiety and depression on stress-related growth among Chinese army recruits: Resilience and coping as mediators.

    Science.gov (United States)

    Yu, Yongju; Peng, Li; Liu, Botao; Liu, Yunbo; Li, Min; Chen, Long; Xie, Junrun; Li, Jing; Li, Jiawen

    2016-09-01

    Stress-related growth can occur after various traumas or stressful events. In order to investigate how anxiety and depression relate to stress-related growth, this study was conducted with 443 Chinese army recruits who had just finished a 3-month recruit training program. Path analyses revealed that resilience and positive/negative coping partially mediated the effect of anxiety on perceived stress-related growth, while negative coping fully mediated the relationship between depression and perceived stress-related growth. Moreover, positive coping partially carried the influence of resilience on perceived stress-related growth. Anxiety and depression may be potential targets for intervention to enhance the development of stress-related growth among Chinese army recruits. © The Author(s) 2015.

  4. Multiple spectroscopic analyses reveal the fate and metabolism of sulfamide herbicide triafamone in agricultural environments

    International Nuclear Information System (INIS)

    Wang, Mengcen; Qian, Yuan; Liu, Xiaoyu; Wei, Peng; Deng, Man; Wang, Lei; Wu, Huiming; Zhu, Guonian

    2017-01-01

    Triafamone, a sulfamide herbicide, has been extensively utilized for weed control in rice paddies in Asia. However, its fate and transformation in the environment have not been established. Through a rice paddy microcosm-based simulation trial combined with multiple spectroscopic analyses, we isolated and identified three novel metabolites of triafamone, including hydroxyl triafamone (HTA), hydroxyl triafamone glycoside (HTAG), and oxazolidinedione triafamone (OTA). When triafamone was applied to rice paddies at a concentration of 34.2 g active ingredient/ha, this was predominantly distributed in the paddy soil and water, and then rapidly dissipated in accordance with the first-order rate model, with half-lives of 4.3–11.0 days. As the main transformation pathway, triafamone was assimilated by the rice plants and was detoxified into HTAG, whereas the rest was reduced into HTA with subsequent formation of OTA. At the senescence stage, brown rice had incurred triafamone at a concentration of 0.0016 mg/kg, but the hazard quotient was <1, suggesting that long-term consumption of the triafamone-containing brown rice is relatively safe. The findings of the present study indicate that triafamone is actively metabolized in the agricultural environment, and elucidation of the link between environmental exposure to these triazine or oxazolidinedione moieties that contain metabolites and their potential impacts is warranted. - Highlights: • Multiple spectroscopic analyses were applied to investigate agrochemicals transformation in environment. • Three novel compounds were isolated and identified as triafamone metabolites. • The fate and transformation pathway of triafamone in rice paddy were revealed. • Long-term consumption of the triafamone-containing brown rice is relatively safe. • Elucidation of environmental impacts by exposure to these triazine or oxazolidinedione metabolites is warranted. - Triafamone rapidly dissipates in agricultural environments

  5. Sequence and expression analyses of porcine ISG15 and ISG43 genes.

    Science.gov (United States)

    Huang, Jiangnan; Zhao, Shuhong; Zhu, Mengjin; Wu, Zhenfang; Yu, Mei

    2009-08-01

    The coding sequences of porcine interferon-stimulated gene 15 (ISG15) and the interferon-stimulated gene (ISG43) were cloned from swine spleen mRNA. The amino acid sequences deduced from porcine ISG15 and ISG43 genes coding sequence shared 24-75% and 29-83% similarity with ISG15s and ISG43s from other vertebrates, respectively. Structural analyses revealed that porcine ISG15 comprises two ubiquitin homologues motifs (UBQ) domain and a conserved C-terminal LRLRGG conjugating motif. Porcine ISG43 contains an ubiquitin-processing proteases-like domain. Phylogenetic analyses showed that porcine ISG15 and ISG43 were mostly related to rat ISG15 and cattle ISG43, respectively. Using quantitative real-time PCR assay, significant increased expression levels of porcine ISG15 and ISG43 genes were detected in porcine kidney endothelial cells (PK15) cells treated with poly I:C. We also observed the enhanced mRNA expression of three members of dsRNA pattern-recognition receptors (PRR), TLR3, DDX58 and IFIH1, which have been reported to act as critical receptors in inducing the mRNA expression of ISG15 and ISG43 genes. However, we did not detect any induced mRNA expression of IFNalpha and IFNbeta, suggesting that transcriptional activations of ISG15 and ISG43 were mediated through IFN-independent signaling pathway in the poly I:C treated PK15 cells. Association analyses in a Landrace pig population revealed that ISG15 c.347T>C (BstUI) polymorphism and the ISG43 c.953T>G (BccI) polymorphism were significantly associated with hematological parameters and immune-related traits.

  6. Social Adversity and Antisocial Behavior: Mediating Effects of Autonomic Nervous System Activity.

    Science.gov (United States)

    Fagan, Shawn E; Zhang, Wei; Gao, Yu

    2017-11-01

    The display of antisocial behaviors in children and adolescents has been of interest to criminologists and developmental psychologists for years. Exposure to social adversity is a well-documented predictor of antisocial behavior. Additionally, measures of autonomic nervous system (ANS) activity, including heart rate variability (HRV), pre-ejection period (PEP), and heart rate, have been associated with antisocial behaviors including rule-breaking and aggression. Social neuroscience research has begun to investigate how neurobiological underpinnings affect the relationship between social adversity and antisocial/psychopathic behavior in children and adolescents. This study investigated the potential mediating effects of ANS activity on the relationship between social adversity and antisocial behavior in a group of 7- to 10-year-old children from the community (N = 339; 48.2% male). Moderated multiple mediation analyses revealed that low resting heart rate, but not PEP or HRV, mediated the relationship between social adversity and antisocial behavior in males only. Social adversity but not ANS measures were associated with antisocial behavior in females. Findings have implications for understanding the neural influences that underlie antisocial behavior, illustrate the importance of the social environment regarding the expression of these behaviors, and highlight essential gender differences.

  7. Crystal structure of the UBR-box from UBR6/FBXO11 reveals domain swapping mediated by zinc binding.

    Science.gov (United States)

    Muñoz-Escobar, Juliana; Kozlov, Guennadi; Gehring, Kalle

    2017-10-01

    The UBR-box is a 70-residue zinc finger domain present in the UBR family of E3 ubiquitin ligases that directly binds N-terminal degradation signals in substrate proteins. UBR6, also called FBXO11, is an UBR-box containing E3 ubiquitin ligase that does not bind N-terminal signals. Here, we present the crystal structure of the UBR-box domain from human UBR6. The dimeric crystal structure reveals a unique form of domain swapping mediated by zinc coordination, where three independent protein chains come together to regenerate the topology of the monomeric UBR-box fold. Analysis of the structure suggests that the absence of N-terminal residue binding arises from the lack of an amino acid binding pocket. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

  8. Mediation designs for tobacco prevention research

    Science.gov (United States)

    MacKinnon, David P.; Taborga, Marcia P.; Morgan-Lopez, Antonio A.

    2010-01-01

    This paper describes research designs and statistical analyses to investigate how tobacco prevention programs achieve their effects on tobacco use. A theoretical approach to program development and evaluation useful for any prevention program guides the analysis. The theoretical approach focuses on action theory for how the program affects mediating variables and on conceptual theory for how mediating variables are related to tobacco use. Information on the mediating mechanisms by which tobacco prevention programs achieve effects is useful for the development of efficient programs and provides a test of the theoretical basis of prevention efforts. Examples of these potential mediating mechanisms are described including mediated effects through attitudes, social norms, beliefs about positive consequences, and accessibility to tobacco. Prior research provides evidence that changes in social norms are a critical mediating mechanism for successful tobacco prevention. Analysis of mediating variables in single group designs with multiple mediators are described as well as multiple group randomized designs which are the most likely to accurately uncover important mediating mechanisms. More complicated dismantling and constructive designs are described and illustrated based on current findings from tobacco research. Mediation analysis for categorical outcomes and more complicated statistical methods are outlined. PMID:12324176

  9. Revealing the cerebral regions and networks mediating vulnerability to depression: oxidative metabolism mapping of rat brain.

    Science.gov (United States)

    Harro, Jaanus; Kanarik, Margus; Kaart, Tanel; Matrov, Denis; Kõiv, Kadri; Mällo, Tanel; Del Río, Joaquin; Tordera, Rosa M; Ramirez, Maria J

    2014-07-01

    The large variety of available animal models has revealed much on the neurobiology of depression, but each model appears as specific to a significant extent, and distinction between stress response, pathogenesis of depression and underlying vulnerability is difficult to make. Evidence from epidemiological studies suggests that depression occurs in biologically predisposed subjects under impact of adverse life events. We applied the diathesis-stress concept to reveal brain regions and functional networks that mediate vulnerability to depression and response to chronic stress by collapsing data on cerebral long term neuronal activity as measured by cytochrome c oxidase histochemistry in distinct animal models. Rats were rendered vulnerable to depression either by partial serotonergic lesion or by maternal deprivation, or selected for a vulnerable phenotype (low positive affect, low novelty-related activity or high hedonic response). Environmental adversity was brought about by applying chronic variable stress or chronic social defeat. Several brain regions, most significantly median raphe, habenula, retrosplenial cortex and reticular thalamus, were universally implicated in long-term metabolic stress response, vulnerability to depression, or both. Vulnerability was associated with higher oxidative metabolism levels as compared to resilience to chronic stress. Chronic stress, in contrast, had three distinct patterns of effect on oxidative metabolism in vulnerable vs. resilient animals. In general, associations between regional activities in several brain circuits were strongest in vulnerable animals, and chronic stress disrupted this interrelatedness. These findings highlight networks that underlie resilience to stress, and the distinct response to stress that occurs in vulnerable subjects. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Autonomous and controlled motivational regulations for multiple health-related behaviors: between- and within-participants analyses

    Science.gov (United States)

    Hagger, M.S.; Hardcastle, S.J.; Chater, A.; Mallett, C.; Pal, S.; Chatzisarantis, N.L.D.

    2014-01-01

    Self-determination theory has been applied to the prediction of a number of health-related behaviors with self-determined or autonomous forms of motivation generally more effective in predicting health behavior than non-self-determined or controlled forms. Research has been confined to examining the motivational predictors in single health behaviors rather than comparing effects across multiple behaviors. The present study addressed this gap in the literature by testing the relative contribution of autonomous and controlling motivation to the prediction of a large number of health-related behaviors, and examining individual differences in self-determined motivation as a moderator of the effects of autonomous and controlling motivation on health behavior. Participants were undergraduate students (N = 140) who completed measures of autonomous and controlled motivational regulations and behavioral intention for 20 health-related behaviors at an initial occasion with follow-up behavioral measures taken four weeks later. Path analysis was used to test a process model for each behavior in which motivational regulations predicted behavior mediated by intentions. Some minor idiosyncratic findings aside, between-participants analyses revealed significant effects for autonomous motivational regulations on intentions and behavior across the 20 behaviors. Effects for controlled motivation on intentions and behavior were relatively modest by comparison. Intentions mediated the effect of autonomous motivation on behavior. Within-participants analyses were used to segregate the sample into individuals who based their intentions on autonomous motivation (autonomy-oriented) and controlled motivation (control-oriented). Replicating the between-participants path analyses for the process model in the autonomy- and control-oriented samples did not alter the relative effects of the motivational orientations on intention and behavior. Results provide evidence for consistent effects

  11. Mediated Instruction and Redundancy Remediation in Sciences in ...

    African Journals Online (AJOL)

    The data were analyzed using t-test statistics. Data analysis revealed that use of mediated instruction significantly removed redundancy for science students also the use of mediated instruction influenced academic achievement of science students in secondary schools. Some of the recommendations include that science ...

  12. Best (but oft-forgotten) practices: mediation analysis.

    Science.gov (United States)

    Fairchild, Amanda J; McDaniel, Heather L

    2017-06-01

    This contribution in the "Best (but Oft-Forgotten) Practices" series considers mediation analysis. A mediator (sometimes referred to as an intermediate variable, surrogate endpoint, or intermediate endpoint) is a third variable that explains how or why ≥2 other variables relate in a putative causal pathway. The current article discusses mediation analysis with the ultimate intention of helping nutrition researchers to clarify the rationale for examining mediation, avoid common pitfalls when using the model, and conduct well-informed analyses that can contribute to improving causal inference in evaluations of underlying mechanisms of effects on nutrition-related behavioral and health outcomes. We give specific attention to underevaluated limitations inherent in common approaches to mediation. In addition, we discuss how to conduct a power analysis for mediation models and offer an applied example to demonstrate mediation analysis. Finally, we provide an example write-up of mediation analysis results as a model for applied researchers. © 2017 American Society for Nutrition.

  13. Energy National Mediator activity report 2009

    International Nuclear Information System (INIS)

    2009-01-01

    After some data illustrating the activity of the Energy National Mediator in 2009, and an interview of a representative of this institution who comments its practice, this report proposes the opinions of the different involved actors (communities, consumer associations, providers, and so on) about the mediator. It puts the adopted strategy in perspective from the past year to the coming one. It describes the missions: information, advice, protection. It reports actions, recommendations and facts for 2009 in terms of consumer information, group mediation, poverty management, samples of analysed disputes. It presents the social organisation and gives a financial assessment of the institution

  14. BDNF mediates improvements in executive function following a 1-year exercise intervention

    Directory of Open Access Journals (Sweden)

    Regina Lynn Leckie

    2014-12-01

    Full Text Available Executive function declines with age, but engaging in aerobic exercise may attenuate decline. One mechanism by which aerobic exercise may preserve executive function is through the up-regulation of brain-derived neurotropic factor (BDNF, which also declines with age. The present study examined BDNF as a mediator of the effects of a 1-year walking intervention on executive function in 90 older adults (mean age = 66.82. Participants were randomized to a stretching and toning control group or a moderate intensity walking intervention group. BDNF serum levels and performance on a task-switching paradigm were collected at baseline and follow-up. We found that age moderated the effect of intervention group on changes in BDNF levels, with those in the highest age quartile showing the greatest increase in BDNF after 1-year of moderate intensity walking exercise (p = .036. The mediation analyses revealed that BDNF mediated the effect of the intervention on task-switch accuracy, but did so as a function of age, such that exercise-induced changes in BDNF mediated the effect of exercise on task-switch performance only for individuals over the age of 71. These results demonstrate that both age and BDNF serum levels are important factors to consider when investigating the mechanisms by which exercise interventions influence cognitive outcomes, particularly in elderly populations.

  15. Genome-wide occupancy profile of mediator and the Srb8-11 module reveals interactions with coding regions

    DEFF Research Database (Denmark)

    Zhu, Xuefeng; Wirén, Marianna; Sinha, Indranil

    2006-01-01

    Mediator exists in a free form containing the Med12, Med13, CDK8, and CycC subunits (the Srb8-11 module) and a smaller form, which lacks these four subunits and associates with RNA polymerase II (Pol II), forming a holoenzyme. We use chromatin immunoprecipitation (ChIP) and DNA microarrays...... to investigate genome-wide localization of Mediator and the Srb8-11 module in fission yeast. Mediator and the Srb8-11 module display similar binding patterns, and interactions with promoters and upstream activating sequences correlate with increased transcription activity. Unexpectedly, Mediator also interacts...... with the downstream coding region of many genes. These interactions display a negative bias for positions closer to the 5' ends of open reading frames (ORFs) and appear functionally important, because downregulation of transcription in a temperature-sensitive med17 mutant strain correlates with increased Mediator...

  16. Genomic analysis reveals a potential role for cell cycle perturbation in HCV-mediated apoptosis of cultured hepatocytes.

    Directory of Open Access Journals (Sweden)

    Kathie-Anne Walters

    2009-01-01

    Full Text Available The mechanisms of liver injury associated with chronic HCV infection, as well as the individual roles of both viral and host factors, are not clearly defined. However, it is becoming increasingly clear that direct cytopathic effects, in addition to immune-mediated processes, play an important role in liver injury. Gene expression profiling during multiple time-points of acute HCV infection of cultured Huh-7.5 cells was performed to gain insight into the cellular mechanism of HCV-associated cytopathic effect. Maximal induction of cell-death-related genes and appearance of activated caspase-3 in HCV-infected cells coincided with peak viral replication, suggesting a link between viral load and apoptosis. Gene ontology analysis revealed that many of the cell-death genes function to induce apoptosis in response to cell cycle arrest. Labeling of dividing cells in culture followed by flow cytometry also demonstrated the presence of significantly fewer cells in S-phase in HCV-infected relative to mock cultures, suggesting HCV infection is associated with delayed cell cycle progression. Regulation of numerous genes involved in anti-oxidative stress response and TGF-beta1 signaling suggest these as possible causes of delayed cell cycle progression. Significantly, a subset of cell-death genes regulated during in vitro HCV infection was similarly regulated specifically in liver tissue from a cohort of HCV-infected liver transplant patients with rapidly progressive fibrosis. Collectively, these data suggest that HCV mediates direct cytopathic effects through deregulation of the cell cycle and that this process may contribute to liver disease progression. This in vitro system could be utilized to further define the cellular mechanism of this perturbation.

  17. Proteomic analysis of HIV-1 Nef cellular binding partners reveals a role for exocyst complex proteins in mediating enhancement of intercellular nanotube formation

    Directory of Open Access Journals (Sweden)

    Mukerji Joya

    2012-06-01

    Full Text Available Abstract Background HIV-1 Nef protein contributes to pathogenesis via multiple functions that include enhancement of viral replication and infectivity, alteration of intracellular trafficking, and modulation of cellular signaling pathways. Nef stimulates formation of tunneling nanotubes and virological synapses, and is transferred to bystander cells via these intercellular contacts and secreted microvesicles. Nef associates with and activates Pak2, a kinase that regulates T-cell signaling and actin cytoskeleton dynamics, but how Nef promotes nanotube formation is unknown. Results To identify Nef binding partners involved in Pak2-association dependent Nef functions, we employed tandem mass spectrometry analysis of Nef immunocomplexes from Jurkat cells expressing wild-type Nef or Nef mutants defective for the ability to associate with Pak2 (F85L, F89H, H191F and A72P, A75P in NL4-3. We report that wild-type, but not mutant Nef, was associated with 5 components of the exocyst complex (EXOC1, EXOC2, EXOC3, EXOC4, and EXOC6, an octameric complex that tethers vesicles at the plasma membrane, regulates polarized exocytosis, and recruits membranes and proteins required for nanotube formation. Additionally, Pak2 kinase was associated exclusively with wild-type Nef. Association of EXOC1, EXOC2, EXOC3, and EXOC4 with wild-type, but not mutant Nef, was verified by co-immunoprecipitation assays in Jurkat cells. Furthermore, shRNA-mediated depletion of EXOC2 in Jurkat cells abrogated Nef-mediated enhancement of nanotube formation. Using bioinformatic tools, we visualized protein interaction networks that reveal functional linkages between Nef, the exocyst complex, and the cellular endocytic and exocytic trafficking machinery. Conclusions Exocyst complex proteins are likely a key effector of Nef-mediated enhancement of nanotube formation, and possibly microvesicle secretion. Linkages revealed between Nef and the exocyst complex suggest a new paradigm of

  18. The effect of sleep quality on academic performance is mediated by Internet use time: DADOS study.

    Science.gov (United States)

    Adelantado-Renau, Mireia; Diez-Fernandez, Ana; Beltran-Valls, Maria Reyes; Soriano-Maldonado, Alberto; Moliner-Urdiales, Diego

    2018-05-19

    The aims of the present study were to analyze the association of sleep patterns with academic and cognitive performance in adolescents, and to test the potential mediating effect of different activities of screen media usage on this association. A sample of 269 adolescents (140 boys) aged 14 years from the baseline data of the Deporte, ADOlescencia y Salud study completed questionnaires about sleep quality, cognitive performance, and leisure-time sedentary behaviors. Sleep duration was objectively computed using a wrist-worn GENEActiv accelerometer and academic performance was analyzed through school records. Sleep quality (but not sleep duration) was associated with all the academic performance indicators (all p<0.05). Analysis of covariance revealed higher grades among adolescents with better sleep quality (PSQI≤5; all p<0.05). These analyses showed no differences regarding cognitive performance. Internet use time was revealed as a mediator of the association between sleep quality and academic performance, being significant for all academic performance indicators (P M ranging from 15.5% to 16.0%). The association between sleep quality and academic performance in adolescents is mediated by time of Internet use. Overall, reducing Internet use in adolescents could be an achievable intervention for improving sleep quality, with potentially positive effects on academic performance. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  19. Influence of Leaders' Psychological Capital on Their Followers: Multilevel Mediation Effect of Organizational Identification

    Science.gov (United States)

    Chen, Qishan; Wen, Zhonglin; Kong, Yurou; Niu, Jun; Hau, Kit-Tai

    2017-01-01

    We investigated the relationships between leaders' and their followers' psychological capital and organizational identification in a Chinese community. Participants included 423 followers on 34 work teams, each with its respective team leader. Hierarchical linear models (HLM) were used in the analyses to delineate the relationships among participants' demographic background (gender, age, marital status, and educational level), human capital, and tenure. The results revealed that leaders' psychological capital positively influenced their followers' psychological capital through the mediation effect of enhancing followers' organizational identification. The implications of these findings, the study's limitations, and directions for future research are discussed. PMID:29075218

  20. Friends' cultural orientation as a mediator between familial ethnic socialization and ethnic identity among Mexican-origin adolescent girls.

    Science.gov (United States)

    Kim, Peter Seung Yoo; Bámaca-Colbert, Mayra Y; Jian, Ni; Gonzales-Backen, Melinda A

    2017-04-01

    Research has indicated that ethnic identity protects ethnic minority youth on various indicators of adjustment, but there is a dearth of research pertaining to contextual influences on ethnic identity. Our study investigated how familial ethnic socialization and best friend's orientation toward Mexican culture influenced ethnic identity among Mexican-origin girls. Using a 3-wave longitudinal sample of 175 Mexican-origin adolescent girls (Mage = 13.75), the current study examined best friend's Mexican cultural orientation as a mediator between familial ethnic socialization and ethnic identity with structural equation modeling. Multigroup analyses were conducted to examine potential age and generational status differences within the model. Analyses revealed that familial ethnic socialization promoted ethnic identity exploration and resolution 3.5 years later and that this effect was mediated by best friend's Mexican cultural orientation. No significant differences were found across age or generational status groups. Our study highlights the contribution of peer context to ethnic identity and its role in the process by which familial ethnic socialization influences ethnic identity during adolescence. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  1. Coherent enhancement of resonance-mediated multiphoton absorption

    International Nuclear Information System (INIS)

    Zhang, Shian; Zhang, Hui; Jia, Tianqing; Wang, Zugeng; Sun, Zhenrong

    2010-01-01

    In this paper, we theoretically investigate the coherent enhancement of resonance-mediated (2+2) four-photon absorption. It is found that by shaping the spectral phase with a π phase step, the resonance-mediated (2+2) four-photon transition probability can be enhanced. Furthermore, the coherent enhancement dependences on the detuning between the two two-photon absorptions, laser spectral bandwidth and laser centre frequency are explicitly discussed and analysed. We believe these theoretical results may play an important role in enhancing more complex resonance-mediated multiphoton absorption processes.

  2. Practical guidance for conducting mediation analysis with multiple mediators using inverse odds ratio weighting.

    Science.gov (United States)

    Nguyen, Quynh C; Osypuk, Theresa L; Schmidt, Nicole M; Glymour, M Maria; Tchetgen Tchetgen, Eric J

    2015-03-01

    Despite the recent flourishing of mediation analysis techniques, many modern approaches are difficult to implement or applicable to only a restricted range of regression models. This report provides practical guidance for implementing a new technique utilizing inverse odds ratio weighting (IORW) to estimate natural direct and indirect effects for mediation analyses. IORW takes advantage of the odds ratio's invariance property and condenses information on the odds ratio for the relationship between the exposure (treatment) and multiple mediators, conditional on covariates, by regressing exposure on mediators and covariates. The inverse of the covariate-adjusted exposure-mediator odds ratio association is used to weight the primary analytical regression of the outcome on treatment. The treatment coefficient in such a weighted regression estimates the natural direct effect of treatment on the outcome, and indirect effects are identified by subtracting direct effects from total effects. Weighting renders treatment and mediators independent, thereby deactivating indirect pathways of the mediators. This new mediation technique accommodates multiple discrete or continuous mediators. IORW is easily implemented and is appropriate for any standard regression model, including quantile regression and survival analysis. An empirical example is given using data from the Moving to Opportunity (1994-2002) experiment, testing whether neighborhood context mediated the effects of a housing voucher program on obesity. Relevant Stata code (StataCorp LP, College Station, Texas) is provided. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Small interference RNA profiling reveals the essential role of human membrane trafficking genes in mediating the infectious entry of dengue virus

    Directory of Open Access Journals (Sweden)

    Chu Justin

    2010-02-01

    Full Text Available Abstract Background Dengue virus (DENV is the causative agent of Dengue fever and the life-threatening Dengue Haemorrhagic fever or Dengue shock syndrome. In the absence of anti-viral agents or vaccine, there is an urgent need to develop an effective anti-viral strategy against this medically important viral pathogen. The initial interplay between DENV and the host cells may represent one of the potential anti-viral targeting sites. Currently the involvements of human membrane trafficking host genes or factors that mediate the infectious cellular entry of dengue virus are not well defined. Results In this study, we have used a targeted small interfering RNA (siRNA library to identify and profile key cellular genes involved in processes of endocytosis, cytoskeletal dynamics and endosome trafficking that are important and essential for DENV infection. The infectious entry of DENV into Huh7 cells was shown to be potently inhibited by siRNAs targeting genes associated with clathrin-mediated endocytosis. The important role of clathrin-mediated endocytosis was confirmed by the expression of well-characterized dominant-negative mutants of genes in this pathway and by using the clathrin endocytosis inhibitor chlorpromazine. Furthermore, DENV infection was shown to be sensitive to the disruption of human genes in regulating the early to late endosomal trafficking as well as the endosomal acidic pH. The importance and involvement of both actin and microtubule dynamics in mediating the infectious entry of DENV was also revealed in this study. Conclusions Together, the findings from this study have provided a detail profiling of the human membrane trafficking cellular genes and the mechanistic insight into the interplay of these host genes with DENV to initiate an infection, hence broadening our understanding on the entry pathway of this medically important viral pathogen. These data may also provide a new potential avenue for development of anti

  4. Patterns and processes of Mycobacterium bovis evolution revealed by phylogenomic analyses

    Science.gov (United States)

    Mycobacterium bovis is an important animal pathogen worldwide that parasitizes wild and domesticated vertebrate livestock as well as humans. A comparison of the five M. bovis complete genomes from UK, South Korea, Brazil and USA revealed four novel large-scale structural variations of at least 2,000...

  5. High-Throughput microRNA and mRNA Sequencing Reveals that microRNAs May Be Involved in Melatonin-Mediated Cold Tolerance in Citrullus Lanatus L.

    Directory of Open Access Journals (Sweden)

    Hao Li

    2016-08-01

    Full Text Available Transcriptional regulation of cold-responsive genes is crucial for exogenous melatonin-mediated cold tolerance in plants. Nonetheless, how melatonin regulates cold-responsive genes is largely unknown. In this study, we found that exogenous melatonin improved cold tolerance in watermelon by regulating expression of microRNAs (miRNAs. We identified a set of miRNAs that were regulated by melatonin under unstressed or cold conditions. Importantly, mRNA-seq analysis revealed that melatonin-induced downregulation of some miRNAs, such as miR159-5p, miR858, miR8029-3p, and novel-m0048-3p correlated with the upregulation of target genes involved in signal transduction (CDPK, BHLH, WRKY, MYB, and DREB and protection/detoxification (LEA and MDAR under cold stress. These results suggest that miRNAs may be involved in melatonin-mediated cold tolerance in watermelon by negatively regulating the expression of target mRNAs.

  6. High-Throughput MicroRNA and mRNA Sequencing Reveals That MicroRNAs May Be Involved in Melatonin-Mediated Cold Tolerance in Citrullus lanatus L.

    Science.gov (United States)

    Li, Hao; Dong, Yuchuan; Chang, Jingjing; He, Jie; Chen, Hejie; Liu, Qiyan; Wei, Chunhua; Ma, Jianxiang; Zhang, Yong; Yang, Jianqiang; Zhang, Xian

    2016-01-01

    Transcriptional regulation of cold-responsive genes is crucial for exogenous melatonin-mediated cold tolerance in plants. Nonetheless, how melatonin regulates cold-responsive genes is largely unknown. In this study, we found that exogenous melatonin improved cold tolerance in watermelon by regulating expression of microRNAs (miRNAs). We identified a set of miRNAs that were regulated by melatonin under unstressed or cold conditions. Importantly, mRNA-seq analysis revealed that melatonin-induced downregulation of some miRNAs, such as miR159-5p, miR858, miR8029-3p, and novel-m0048-3p correlated with the upregulation of target genes involved in signal transduction (CDPK, BHLH, WRKY, MYB, and DREB) and protection/detoxification (LEA and MDAR) under cold stress. These results suggest that miRNAs may be involved in melatonin-mediated cold tolerance in watermelon by negatively regulating the expression of target mRNAs. PMID:27574526

  7. Mediation analysis in nursing research: a methodological review.

    Science.gov (United States)

    Liu, Jianghong; Ulrich, Connie

    2016-12-01

    Mediation statistical models help clarify the relationship between independent predictor variables and dependent outcomes of interest by assessing the impact of third variables. This type of statistical analysis is applicable for many clinical nursing research questions, yet its use within nursing remains low. Indeed, mediational analyses may help nurse researchers develop more effective and accurate prevention and treatment programs as well as help bridge the gap between scientific knowledge and clinical practice. In addition, this statistical approach allows nurse researchers to ask - and answer - more meaningful and nuanced questions that extend beyond merely determining whether an outcome occurs. Therefore, the goal of this paper is to provide a brief tutorial on the use of mediational analyses in clinical nursing research by briefly introducing the technique and, through selected empirical examples from the nursing literature, demonstrating its applicability in advancing nursing science.

  8. Integrated in silico Analyses of Regulatory and Metabolic Networks of Synechococcus sp. PCC 7002 Reveal Relationships between Gene Centrality and Essentiality

    Directory of Open Access Journals (Sweden)

    Hyun-Seob Song

    2015-03-01

    Full Text Available Cyanobacteria dynamically relay environmental inputs to intracellular adaptations through a coordinated adjustment of photosynthetic efficiency and carbon processing rates. The output of such adaptations is reflected through changes in transcriptional patterns and metabolic flux distributions that ultimately define growth strategy. To address interrelationships between metabolism and regulation, we performed integrative analyses of metabolic and gene co-expression networks in a model cyanobacterium, Synechococcus sp. PCC 7002. Centrality analyses using the gene co-expression network identified a set of key genes, which were defined here as “topologically important.” Parallel in silico gene knock-out simulations, using the genome-scale metabolic network, classified what we termed as “functionally important” genes, deletion of which affected growth or metabolism. A strong positive correlation was observed between topologically and functionally important genes. Functionally important genes exhibited variable levels of topological centrality; however, the majority of topologically central genes were found to be functionally essential for growth. Subsequent functional enrichment analysis revealed that both functionally and topologically important genes in Synechococcus sp. PCC 7002 are predominantly associated with translation and energy metabolism, two cellular processes critical for growth. This research demonstrates how synergistic network-level analyses can be used for reconciliation of metabolic and gene expression data to uncover fundamental biological principles.

  9. Planning Abilities in Bilingual and Monolingual Children: Role of Verbal Mediation

    Science.gov (United States)

    Gangopadhyay, Ishanti; McDonald, Margarethe; Ellis Weismer, Susan; Kaushanskaya, Margarita

    2018-01-01

    We examined the role of verbal mediation in planning performance of English–Spanish-speaking bilingual children and monolingual English-speaking children, between the ages of 9 and 12 years. To measure planning, children were administered the Tower of London (ToL) task. In a dual-task paradigm, children completed ToL problems under three conditions: with no secondary task (baseline), with articulatory suppression, and with non-verbal motor suppression. Analyses revealed generally shorter planning times for bilinguals than monolinguals but both groups performed similarly on number of moves and execution times. Additionally, bilingual children were more efficient at planning throughout the duration of the task while monolingual children showed significant gains with more practice. Children’s planning times under articulatory suppression were significantly shorter than under motor suppression as well as the baseline condition, and there was no difference in planning times between monolingual and bilingual children during articulatory suppression. These results demonstrate that bilingualism influences performance on a complex EF measure like planning, and that these effects are not related to verbal mediation. PMID:29593620

  10. Planning Abilities in Bilingual and Monolingual Children: Role of Verbal Mediation.

    Science.gov (United States)

    Gangopadhyay, Ishanti; McDonald, Margarethe; Ellis Weismer, Susan; Kaushanskaya, Margarita

    2018-01-01

    We examined the role of verbal mediation in planning performance of English-Spanish-speaking bilingual children and monolingual English-speaking children, between the ages of 9 and 12 years. To measure planning, children were administered the Tower of London (ToL) task. In a dual-task paradigm, children completed ToL problems under three conditions: with no secondary task (baseline), with articulatory suppression, and with non-verbal motor suppression. Analyses revealed generally shorter planning times for bilinguals than monolinguals but both groups performed similarly on number of moves and execution times. Additionally, bilingual children were more efficient at planning throughout the duration of the task while monolingual children showed significant gains with more practice. Children's planning times under articulatory suppression were significantly shorter than under motor suppression as well as the baseline condition, and there was no difference in planning times between monolingual and bilingual children during articulatory suppression. These results demonstrate that bilingualism influences performance on a complex EF measure like planning, and that these effects are not related to verbal mediation.

  11. Function and regulation of the Mediator complex.

    Science.gov (United States)

    Conaway, Ronald C; Conaway, Joan Weliky

    2011-04-01

    Over the past few years, advances in biochemical and genetic studies of the structure and function of the Mediator complex have shed new light on its subunit architecture and its mechanism of action in transcription by RNA polymerase II (pol II). The development of improved methods for reconstitution of recombinant Mediator subassemblies is enabling more in-depth analyses of basic features of the mechanisms by which Mediator interacts with and controls the activity of pol II and the general initiation factors. The discovery and characterization of multiple, functionally distinct forms of Mediator characterized by the presence or absence of the Cdk8 kinase module have led to new insights into how Mediator functions in both Pol II transcription activation and repression. Finally, progress in studies of the mechanisms by which the transcriptional activation domains (ADs) of DNA binding transcription factors target Mediator have brought to light unexpected complexities in the way Mediator participates in signal transduction. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Childhood abuse and depression in adulthood: The mediating role of allostatic load.

    Science.gov (United States)

    Scheuer, Sandra; Wiggert, Nicole; Brückl, Tanja Maria; Awaloff, Yvonne; Uhr, Manfred; Lucae, Susanne; Kloiber, Stefan; Holsboer, Florian; Ising, Marcus; Wilhelm, Frank H

    2018-04-22

    Traumatic experiences during childhood are considered a major risk factor for depression in adulthood. Childhood trauma may induce physiological dysregulation with long-term effects of increased allostatic load until adulthood, which may lead to depression. Thus, our aim was to investigate whether allostatic load - which represents a multi-system measure of physiological dysregulation - mediates the association between childhood trauma and adult depression. The study sample consisted of 324 depressed inpatients participating in the Munich Antidepressant Response Signature (MARS) project and 261 mentally healthy control participants. The mediation analysis using a case-control approach included childhood trauma, i.e., physical and sexual abuse, as predictor variables and an allostatic load index comprised of 12 stress-related biomarkers as mediator. Age and sex were included as covariates. Mediation analyses revealed that the influence of physical abuse, but not sexual abuse, during childhood on depression in adulthood was mediated by allostatic load. This effect was moderated by age: particularly young (18-42 years) and middle-aged (43-54 years) adults with a history of physical abuse during childhood exhibited high allostatic load, which in turn was associated with increased rates of depression, but this was not the case for older participants (55-81 years). Results support the theoretical assumption of allostatic load mediating the effect of physical abuse during childhood on depression in adulthood. This predominantly holds for younger participants, while depression in older participants was independent of physical abuse and allostatic load. The effect of sexual abuse on depression, however, was not mediated by allostatic load. Identifying allostatic load biomarkers prospectively in the developmental course of depression is an important target for future research. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Integrating mediation and moderation to advance theory development and testing.

    Science.gov (United States)

    Karazsia, Bryan T; Berlin, Kristoffer S; Armstrong, Bridget; Janicke, David M; Darling, Katherine E

    2014-03-01

    The concepts and associated analyses of mediation and moderation are important to the field of psychology. Although pediatric psychologists frequently incorporate mediation and moderation in their theories and empirical research, on few occasions have we integrated mediation and moderation. In this article, conceptual reasons for integrating mediation and moderation are offered. We illustrate a model that integrates mediation and moderation. In our illustration, the strength of an indirect or a mediating effect varied as a function of a moderating variable. Clinical implications of the integration of mediation and moderation are discussed, as is the potential of integrated models to advance research programs in pediatric psychology.

  14. AGROBEST: an efficient Agrobacterium-mediated transient expression method for versatile gene function analyses in Arabidopsis seedlings

    Science.gov (United States)

    2014-01-01

    Background Transient gene expression via Agrobacterium-mediated DNA transfer offers a simple and fast method to analyze transgene functions. Although Arabidopsis is the most-studied model plant with powerful genetic and genomic resources, achieving highly efficient and consistent transient expression for gene function analysis in Arabidopsis remains challenging. Results We developed a highly efficient and robust Agrobacterium-mediated transient expression system, named AGROBEST (Agrobacterium-mediated enhanced seedling transformation), which achieves versatile analysis of diverse gene functions in intact Arabidopsis seedlings. Using β-glucuronidase (GUS) as a reporter for Agrobacterium-mediated transformation assay, we show that the use of a specific disarmed Agrobacterium strain with vir gene pre-induction resulted in homogenous GUS staining in cotyledons of young Arabidopsis seedlings. Optimization with AB salts in plant culture medium buffered with acidic pH 5.5 during Agrobacterium infection greatly enhanced the transient expression levels, which were significantly higher than with two existing methods. Importantly, the optimized method conferred 100% infected seedlings with highly increased transient expression in shoots and also transformation events in roots of ~70% infected seedlings in both the immune receptor mutant efr-1 and wild-type Col-0 seedlings. Finally, we demonstrated the versatile applicability of the method for examining transcription factor action and circadian reporter-gene regulation as well as protein subcellular localization and protein–protein interactions in physiological contexts. Conclusions AGROBEST is a simple, fast, reliable, and robust transient expression system enabling high transient expression and transformation efficiency in Arabidopsis seedlings. Demonstration of the proof-of-concept experiments elevates the transient expression technology to the level of functional studies in Arabidopsis seedlings in addition to previous

  15. Youth internalizing symptoms, sleep-related problems, and disordered eating attitudes and behaviors: A moderated mediation analysis.

    Science.gov (United States)

    Chardon, Marie L; Janicke, David M; Carmody, Julia K; Dumont-Driscoll, Marilyn C

    2016-04-01

    Internalizing symptoms increase the risk for disordered eating; however, the mechanism through which this relationship occurs remains unclear. Sleep-related problems may be a potential link as they are associated with both emotional functioning and disordered eating. The present study aims to evaluate the mediating roles of two sleep-related problems (sleep disturbance and daytime sleepiness) in the relationship between youth internalizing symptoms and disordered eating, and to explore if age moderates these relations. Participants were 225 youth (8-17years) attending a primary care appointment. Youth and legal guardians completed questionnaires about youth disordered eating attitudes and behaviors, internalizing symptoms, sleep disturbance, and daytime sleepiness. Mediation and moderated mediation analyses were utilized. The mediation model revealed both youth sleep disturbance and daytime sleepiness independently mediated the association between internalizing symptoms and disordered eating attitudes and behaviors, and explained 18% of the variance in disordered eating. The moderated mediation model including youth age accounted for 21% of the variance in disordered eating; youth age significantly interacted with sleep disturbance, but not with daytime sleepiness, to predict disordered eating. Sleep disturbance only mediated the relationship between internalizing symptoms and disordered eating in youth 12years old and younger, while daytime sleepiness was a significant mediator regardless of age. As sleep-related problems are frequently improved with the adoption of health behaviors conducive to good sleep, these results may suggest a relatively modifiable and cost-effective target to reduce youth risk for disordered eating. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. A national cohort study of parental socioeconomic status and non-fatal suicidal behaviour-the mediating role of school performance

    Directory of Open Access Journals (Sweden)

    Jablonska Beata

    2012-01-01

    Full Text Available Abstract Background A link between low parental socioeconomic status and mental health problems in offspring is well established in previous research. The mechanisms that explain this link are largely unknown. The present study investigated whether school performance was a mediating and/or moderating factor in the path between parental socioeconomic status and the risk of hospital admission for non-fatal suicidal behaviour. Methods A national cohort of 447 929 children born during 1973-1977 was followed prospectively in the National Patient Discharge Register from the end of their ninth and final year of compulsory school until 2001. Multivariate Cox proportional hazards and linear regression analyses were performed to test whether the association between parental socioeconomic status and non-fatal suicidal behaviour was mediated or moderated by school performance. Results The results of a series of multiple regression analyses, adjusted for demographic variables, revealed that school performance was as an important mediator in the relationship between parental socioeconomic status and risk of non-fatal suicidal behaviour, accounting for 60% of the variance. The hypothesized moderation of parental socioeconomic status-non-fatal suicidal behaviour relationship by school performance was not supported. Conclusions School performance is an important mediator through which parental socioeconomic status translates into a risk for non-fatal suicidal behaviour. Prevention efforts aimed to reduce socioeconomic inequalities in non-fatal suicidal behaviour among young people will need to consider socioeconomic inequalities in school performance.

  17. The mediating role of social capital in the association between neighbourhood income inequality and body mass index.

    Science.gov (United States)

    Mackenbach, Joreintje D; Lakerveld, Jeroen; van Oostveen, Yavanna; Compernolle, Sofie; De Bourdeaudhuij, Ilse; Bárdos, Helga; Rutter, Harry; Glonti, Ketevan; Oppert, Jean-Michel; Charreire, Helene; Brug, Johannes; Nijpels, Giel

    2017-04-01

    Neighbourhood income inequality may contribute to differences in body weight. We explored whether neighbourhood social capital mediated the association of neighbourhood income inequality with individual body mass index (BMI). A total of 4126 adult participants from 48 neighbourhoods in France, Hungary, the Netherlands and the UK provided information on their levels of income, perceptions of neighbourhood social capital and BMI. Factor analysis of the 13-item social capital scale revealed two social capital constructs: social networks and social cohesion. Neighbourhood income inequality was defined as the ratio of the amount of income earned by the top 20% and the bottom 20% in a given neighbourhood. Two single mediation analyses-using multilevel linear regression analyses-with neighbourhood social networks and neighbourhood social cohesion as possible mediators-were conducted using MacKinnon's product-of-coefficients method, adjusted for age, gender, education and absolute household income. Higher neighbourhood income inequality was associated with elevated levels of BMI and lower levels of neighbourhood social networks and neighbourhood social cohesion. High levels of neighbourhood social networks were associated with lower BMI. Results stratified by country demonstrate that social networks fully explained the association between income inequality and BMI in France and the Netherlands. Social cohesion was only a significant mediating variable for Dutch participants. The results suggest that in some European urban regions, neighbourhood social capital plays a large role in the association between neighbourhood income inequality and individual BMI. © The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

  18. 'Not good enough:' Exploring self-criticism's role as a mediator between childhood emotional abuse & adult binge eating.

    Science.gov (United States)

    Feinson, Marjorie C; Hornik-Lurie, Tzipi

    2016-12-01

    Empirical studies have identified emotional abuse in childhood (CEA) as a risk factor with long-term implications for psychological problems. Indeed, recent studies indicate it is more prevalent than behavioral forms of abuse, (i.e. childhood sexual and physical abuse) and the childhood trauma most clearly associated with subsequent eating pathology in adulthood. However, relatively little is understood about the mechanisms linking these distal experiences. This study explores three psychological mechanisms - self-criticism (SC), depression and anxiety symptoms - as plausible mediators that may account for the relationship between CEA and binge eating (BE) among adult women. Detailed telephone interviews conducted with a community-based sample of 498 adult women (mean age 44) assess BE, CEA and SC along with the most frequently researched psychological variables, anxiety and depression. Regression analyses reveal that BE is partially explained by CEA along with the three mediators. Bootstrapping analysis, which compares multiple mediators within a single model using thousands of repeated random sampling observations from the data set, reveals a striking finding: SC is the only psychological variable that makes a significant contribution to explaining BE severity. The unique role of punitive self-evaluations vis-à-vis binge eating warrants additional research and, in the interim, that clinicians consider broadening treatment interventions accordingly. Copyright © 2016. Published by Elsevier Ltd.

  19. Revealing climate modes in steric sea levels: lessons learned from satellite geodesy, objective analyses and ocean reanalyses

    Science.gov (United States)

    Pfeffer, J.; Tregoning, P.; Purcell, A. P.

    2017-12-01

    Due to increased greenhouse gases emissions, the oceans are accumulating heat. In response to the ocean circulation and atmospheric forcing, the heat is irregularly redistributed within the oceans, causing sea level to rise at variable rates in space and time. These rates of steric expansion are extremely difficult to assess because of the sparsity of in-situ hydrographic observations available within the course of the 20th century. We compare here three methods to reconstruct the steric sea levels over the past 13, 25 and 58 years based on satellite geodesy, objective analyses and ocean reanalyses. The interannual to decadal variability of each dataset is explored with a model merging six climate indices representative of the natural variability of the ocean and climate system. Consistent regional patterns are identified for the Pacific Decadal Oscillation (PDO) and El Niño Southern Oscillation (ENSO) in all datasets at all timescales. Despite the short time coverage (13 years), the combination of satellite geodetic data (altimetry and GRACE) also reveals significant steric responses to the North Pacific Gyre Oscillation (NPGO), Indian Dipole (IOD) and Indian ocean basinwide (IOBM) mode. The richer information content in the ocean reanalyses allows us to recover the regional fingerprints of the PDO, ENSO, NPGO, IOD and IOBM, but also of the Atlantic Multidecadal Oscillation (AMO) acting over longer time scales (40 to 60 years). Therefore, ocean reanalyses, coupled with climate mode analyses, constitute innovative and promising tools to investigate the mechanisms triggering the variability of sea level rise over the past decades.

  20. Beliefs about unmet interpersonal needs mediate the relation between conflictual family relations and borderline personality features in young adult females.

    Science.gov (United States)

    Kalpakci, Allison; Venta, Amanda; Sharp, Carla

    2014-01-01

    Central to most theories of borderline personality disorder (BPD) is the notion that the family environment interacts with genetically-based vulnerabilities to influence the development of BPD, with particular attention given to risk conferred by conflictual familial relations. However, the extent to which family conflict may relate to the development of BPD via related interpersonal beliefs is currently unknown. This study sought to test the hypothesis that the concurrent relation between conflictual family relations and borderline features in female college students is explained by beliefs associated with real or perceived unmet interpersonal needs (captured by Joiner's [2005] Interpersonal Psychological Theory, specifically thwarted belongingness and perceived burdensomeness). The sample included 267 female undergraduates ages 18-25 years (M = 20.86; SD = 1.80). Level of borderline personality features, unmet interpersonal needs, and family conflict were assessed. Bivariate analyses revealed significant relations between both thwarted belongingness and perceived burdensomeness, conflictual family relations, and borderline features. Multivariate analyses revealed that thwarted belongingness and perceived burdensomeness both mediated the relation between family conflict and borderline personality features, thus supporting a multiple mediation model. This cross-sectional study is a preliminary step towards confirming the broad theoretical hypothesis that conflictual family relations relate to beliefs about thwarted belongingness and perceived burdensomeness, which, in turn, relate to borderline personality pathology. Limitations and areas of future research are discussed.

  1. Cutaneous nociceptors lack sensitisation, but reveal μ-opioid receptor-mediated reduction in excitability to mechanical stimulation in neuropathy

    Directory of Open Access Journals (Sweden)

    Schmidt Yvonne

    2012-11-01

    Full Text Available Abstract Background Peripheral nerve injuries often trigger a hypersensitivity to tactile stimulation. Behavioural studies demonstrated efficient and side effect-free analgesia mediated by opioid receptors on peripheral sensory neurons. However, mechanistic approaches addressing such opioid properties in painful neuropathies are lacking. Here we investigated whether opioids can directly inhibit primary afferent neuron transmission of mechanical stimuli in neuropathy. We analysed the mechanical thresholds, the firing rates and response latencies of sensory fibres to mechanical stimulation of their cutaneous receptive fields. Results Two weeks following a chronic constriction injury of the saphenous nerve, mice developed a profound mechanical hypersensitivity in the paw innervated by the damaged nerve. Using an in vitro skin-nerve preparation we found no changes in the mechanical thresholds and latencies of sensory fibres from injured nerves. The firing rates to mechanical stimulation were unchanged or reduced following injury. Importantly, μ-opioid receptor agonist [D-Ala2,N-Me-Phe4,Gly5]-ol-enkephalin (DAMGO significantly elevated the mechanical thresholds of nociceptive Aδ and C fibres. Furthermore, DAMGO substantially diminished the mechanically evoked discharges of C nociceptors in injured nerves. These effects were blocked by DAMGO washout and pre-treatment with the selective μ-opioid receptor antagonist Cys2-Tyr3-Orn5-Pen7-amide. DAMGO did not alter the responses of sensory fibres in uninjured nerves. Conclusions Our findings suggest that behaviourally manifested neuropathy-induced mechanosensitivity does not require a sensitised state of cutaneous nociceptors in damaged nerves. Yet, nerve injury renders nociceptors sensitive to opioids. Prevention of action potential generation or propagation in nociceptors might represent a cellular mechanism underlying peripheral opioid-mediated alleviation of mechanical hypersensitivity in neuropathy.

  2. Genome-wide Comparative Analyses Reveal the Dynamic Evolution of Nucleotide-Binding Leucine-Rich Repeat Gene Family among Solanaceae Plants

    Directory of Open Access Journals (Sweden)

    Eunyoung Seo

    2016-08-01

    Full Text Available Plants have evolved an elaborate innate immune system against invading pathogens. Within this system, intracellular nucleotide-binding leucine-rich repeat (NLR immune receptors are known play critical roles in effector-triggered immunity (ETI plant defense. We performed genome-wide identification and classification of NLR-coding sequences from the genomes of pepper, tomato, and potato using fixed criteria. We then compared genomic duplication and evolution features. We identified intact 267, 443, and 755 NLR-encoding genes in tomato, potato, and pepper genomes, respectively. Phylogenetic analyses and classification of Solanaceae NLRs revealed that the majority of NLR super family members fell into 14 subgroups, including a TIR-NLR (TNL subgroup and 13 non-TNL subgroups. Specific subgroups have expanded in each genome, with the expansion in pepper showing subgroup-specific physical clusters. Comparative analysis of duplications showed distinct duplication patterns within pepper and among Solanaceae plants suggesting subgroup- or species-specific gene duplication events after speciation, resulting in divergent evolution. Taken together, genome-wide analyses of NLR family members provide insights into their evolutionary history in Solanaceae. These findings also provide important foundational knowledge for understanding NLR evolution and will empower broader characterization of disease resistance genes to be used for crop breeding.

  3. Secondary mediation and regression analyses of the PTClinResNet database: determining causal relationships among the International Classification of Functioning, Disability and Health levels for four physical therapy intervention trials.

    Science.gov (United States)

    Mulroy, Sara J; Winstein, Carolee J; Kulig, Kornelia; Beneck, George J; Fowler, Eileen G; DeMuth, Sharon K; Sullivan, Katherine J; Brown, David A; Lane, Christianne J

    2011-12-01

    Each of the 4 randomized clinical trials (RCTs) hosted by the Physical Therapy Clinical Research Network (PTClinResNet) targeted a different disability group (low back disorder in the Muscle-Specific Strength Training Effectiveness After Lumbar Microdiskectomy [MUSSEL] trial, chronic spinal cord injury in the Strengthening and Optimal Movements for Painful Shoulders in Chronic Spinal Cord Injury [STOMPS] trial, adult stroke in the Strength Training Effectiveness Post-Stroke [STEPS] trial, and pediatric cerebral palsy in the Pediatric Endurance and Limb Strengthening [PEDALS] trial for children with spastic diplegic cerebral palsy) and tested the effectiveness of a muscle-specific or functional activity-based intervention on primary outcomes that captured pain (STOMPS, MUSSEL) or locomotor function (STEPS, PEDALS). The focus of these secondary analyses was to determine causal relationships among outcomes across levels of the International Classification of Functioning, Disability and Health (ICF) framework for the 4 RCTs. With the database from PTClinResNet, we used 2 separate secondary statistical approaches-mediation analysis for the MUSSEL and STOMPS trials and regression analysis for the STEPS and PEDALS trials-to test relationships among muscle performance, primary outcomes (pain related and locomotor related), activity and participation measures, and overall quality of life. Predictive models were stronger for the 2 studies with pain-related primary outcomes. Change in muscle performance mediated or predicted reductions in pain for the MUSSEL and STOMPS trials and, to some extent, walking speed for the STEPS trial. Changes in primary outcome variables were significantly related to changes in activity and participation variables for all 4 trials. Improvement in activity and participation outcomes mediated or predicted increases in overall quality of life for the 3 trials with adult populations. Variables included in the statistical models were limited to those

  4. Characterization of Eosinophil Adhesion to TNF-a-Activated Endothelium Under Flow Conditions: a4 Integrins Mediate Initial Attachment, and E-Selectin Mediates Rolling

    NARCIS (Netherlands)

    Ulfman, L.H.; Kuijper, P.H.M.; Linden, J.A.M. van der; Lammers, J.W.J.; Zwaginga, Jaap Jan; Koenderman, L.

    1999-01-01

    The multistep model of leukocyte adhesion reveals that selectins mediate rolling interactions and that integrins mediate firm adhesion processes. In this study, the interaction between eosinophils and TNF-a-activated HUVEC (second or third passage) was studied under flow conditions (0.8 and 3.2

  5. Bibliometric Analyses Reveal Patterns of Collaboration between ASMS Members

    Science.gov (United States)

    Palmblad, Magnus; van Eck, Nees Jan

    2018-03-01

    We have explored the collaborative network of the current American Society for Mass Spectrometry (ASMS) membership using bibliometric methods. The analysis shows that 4249 members are connected in a single, large, co-authorship graph, including the majority of the most published authors in the field of mass spectrometry. The map reveals topographical differences between university groups and national laboratories, and that the co-authors with the strongest links have long worked together at the same location. We have collected and summarized information on the geographical distribution of members, showing a high coverage of active researchers in North America and Western Europe. Looking at research fields, we could also identify a number of new or `hot' topics among ASMS members. Interactive versions of the maps are available on-line at https://goo.gl/UBNFMQ (collaborative network) and https://goo.gl/WV25vm (research topics). [Figure not available: see fulltext.

  6. Mediation Analysis with Survival Outcomes: Accelerated Failure Time vs. Proportional Hazards Models.

    Science.gov (United States)

    Gelfand, Lois A; MacKinnon, David P; DeRubeis, Robert J; Baraldi, Amanda N

    2016-01-01

    Survival time is an important type of outcome variable in treatment research. Currently, limited guidance is available regarding performing mediation analyses with survival outcomes, which generally do not have normally distributed errors, and contain unobserved (censored) events. We present considerations for choosing an approach, using a comparison of semi-parametric proportional hazards (PH) and fully parametric accelerated failure time (AFT) approaches for illustration. We compare PH and AFT models and procedures in their integration into mediation models and review their ability to produce coefficients that estimate causal effects. Using simulation studies modeling Weibull-distributed survival times, we compare statistical properties of mediation analyses incorporating PH and AFT approaches (employing SAS procedures PHREG and LIFEREG, respectively) under varied data conditions, some including censoring. A simulated data set illustrates the findings. AFT models integrate more easily than PH models into mediation models. Furthermore, mediation analyses incorporating LIFEREG produce coefficients that can estimate causal effects, and demonstrate superior statistical properties. Censoring introduces bias in the coefficient estimate representing the treatment effect on outcome-underestimation in LIFEREG, and overestimation in PHREG. With LIFEREG, this bias can be addressed using an alternative estimate obtained from combining other coefficients, whereas this is not possible with PHREG. When Weibull assumptions are not violated, there are compelling advantages to using LIFEREG over PHREG for mediation analyses involving survival-time outcomes. Irrespective of the procedures used, the interpretation of coefficients, effects of censoring on coefficient estimates, and statistical properties should be taken into account when reporting results.

  7. Mediation Analysis with Survival Outcomes: Accelerated Failure Time vs. Proportional Hazards Models

    Science.gov (United States)

    Gelfand, Lois A.; MacKinnon, David P.; DeRubeis, Robert J.; Baraldi, Amanda N.

    2016-01-01

    Objective: Survival time is an important type of outcome variable in treatment research. Currently, limited guidance is available regarding performing mediation analyses with survival outcomes, which generally do not have normally distributed errors, and contain unobserved (censored) events. We present considerations for choosing an approach, using a comparison of semi-parametric proportional hazards (PH) and fully parametric accelerated failure time (AFT) approaches for illustration. Method: We compare PH and AFT models and procedures in their integration into mediation models and review their ability to produce coefficients that estimate causal effects. Using simulation studies modeling Weibull-distributed survival times, we compare statistical properties of mediation analyses incorporating PH and AFT approaches (employing SAS procedures PHREG and LIFEREG, respectively) under varied data conditions, some including censoring. A simulated data set illustrates the findings. Results: AFT models integrate more easily than PH models into mediation models. Furthermore, mediation analyses incorporating LIFEREG produce coefficients that can estimate causal effects, and demonstrate superior statistical properties. Censoring introduces bias in the coefficient estimate representing the treatment effect on outcome—underestimation in LIFEREG, and overestimation in PHREG. With LIFEREG, this bias can be addressed using an alternative estimate obtained from combining other coefficients, whereas this is not possible with PHREG. Conclusions: When Weibull assumptions are not violated, there are compelling advantages to using LIFEREG over PHREG for mediation analyses involving survival-time outcomes. Irrespective of the procedures used, the interpretation of coefficients, effects of censoring on coefficient estimates, and statistical properties should be taken into account when reporting results. PMID:27065906

  8. Mediation Analysis with Survival Outcomes: Accelerated Failure Time Versus Proportional Hazards Models

    Directory of Open Access Journals (Sweden)

    Lois A Gelfand

    2016-03-01

    Full Text Available Objective: Survival time is an important type of outcome variable in treatment research. Currently, limited guidance is available regarding performing mediation analyses with survival outcomes, which generally do not have normally distributed errors, and contain unobserved (censored events. We present considerations for choosing an approach, using a comparison of semi-parametric proportional hazards (PH and fully parametric accelerated failure time (AFT approaches for illustration.Method: We compare PH and AFT models and procedures in their integration into mediation models and review their ability to produce coefficients that estimate causal effects. Using simulation studies modeling Weibull-distributed survival times, we compare statistical properties of mediation analyses incorporating PH and AFT approaches (employing SAS procedures PHREG and LIFEREG, respectively under varied data conditions, some including censoring. A simulated data set illustrates the findings.Results: AFT models integrate more easily than PH models into mediation models. Furthermore, mediation analyses incorporating LIFEREG produce coefficients that can estimate causal effects, and demonstrate superior statistical properties. Censoring introduces bias in the coefficient estimate representing the treatment effect on outcome – underestimation in LIFEREG, and overestimation in PHREG. With LIFEREG, this bias can be addressed using an alternative estimate obtained from combining other coefficients, whereas this is not possible with PHREG.Conclusions: When Weibull assumptions are not violated, there are compelling advantages to using LIFEREG over PHREG for mediation analyses involving survival-time outcomes. Irrespective of the procedures used, the interpretation of coefficients, effects of censoring on coefficient estimates, and statistical properties should be taken into account when reporting results.

  9. Best (but oft-forgotten) practices: mediation analysis12

    Science.gov (United States)

    McDaniel, Heather L

    2017-01-01

    This contribution in the “Best (but Oft-Forgotten) Practices” series considers mediation analysis. A mediator (sometimes referred to as an intermediate variable, surrogate endpoint, or intermediate endpoint) is a third variable that explains how or why ≥2 other variables relate in a putative causal pathway. The current article discusses mediation analysis with the ultimate intention of helping nutrition researchers to clarify the rationale for examining mediation, avoid common pitfalls when using the model, and conduct well-informed analyses that can contribute to improving causal inference in evaluations of underlying mechanisms of effects on nutrition-related behavioral and health outcomes. We give specific attention to underevaluated limitations inherent in common approaches to mediation. In addition, we discuss how to conduct a power analysis for mediation models and offer an applied example to demonstrate mediation analysis. Finally, we provide an example write-up of mediation analysis results as a model for applied researchers. PMID:28446497

  10. Iron homeostasis in Arabidopsis thaliana: transcriptomic analyses reveal novel FIT-regulated genes, iron deficiency marker genes and functional gene networks.

    Science.gov (United States)

    Mai, Hans-Jörg; Pateyron, Stéphanie; Bauer, Petra

    2016-10-03

    FIT (FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) is the central regulator of iron uptake in Arabidopsis thaliana roots. We performed transcriptome analyses of six day-old seedlings and roots of six week-old plants using wild type, a fit knock-out mutant and a FIT over-expression line grown under iron-sufficient or iron-deficient conditions. We compared genes regulated in a FIT-dependent manner depending on the developmental stage of the plants. We assembled a high likelihood dataset which we used to perform co-expression and functional analysis of the most stably iron deficiency-induced genes. 448 genes were found FIT-regulated. Out of these, 34 genes were robustly FIT-regulated in root and seedling samples and included 13 novel FIT-dependent genes. Three hundred thirty-one genes showed differential regulation in response to the presence and absence of FIT only in the root samples, while this was the case for 83 genes in the seedling samples. We assembled a virtual dataset of iron-regulated genes based on a total of 14 transcriptomic analyses of iron-deficient and iron-sufficient wild-type plants to pinpoint the best marker genes for iron deficiency and analyzed this dataset in depth. Co-expression analysis of this dataset revealed 13 distinct regulons part of which predominantly contained functionally related genes. We could enlarge the list of FIT-dependent genes and discriminate between genes that are robustly FIT-regulated in roots and seedlings or only in one of those. FIT-regulated genes were mostly induced, few of them were repressed by FIT. With the analysis of a virtual dataset we could filter out and pinpoint new candidates among the most reliable marker genes for iron deficiency. Moreover, co-expression and functional analysis of this virtual dataset revealed iron deficiency-induced and functionally distinct regulons.

  11. Commentary: Mediation Analysis, Causal Process, and Cross-Sectional Data

    Science.gov (United States)

    Shrout, Patrick E.

    2011-01-01

    Maxwell, Cole, and Mitchell (2011) extended the work of Maxwell and Cole (2007), which raised important questions about whether mediation analyses based on cross-sectional data can shed light on longitudinal mediation process. The latest article considers longitudinal processes that can only be partially explained by an intervening variable, and…

  12. Detoxifying symbiosis: microbe-mediated detoxification of phytotoxins and pesticides in insects.

    Science.gov (United States)

    Itoh, Hideomi; Tago, Kanako; Hayatsu, Masahito; Kikuchi, Yoshitomo

    2018-04-12

    Covering: up to 2018Insects live in a world full of toxic compounds such as plant toxins and manmade pesticides. To overcome the effects of these toxins, herbivorous insects have evolved diverse, elaborate mechanisms of resistance, such as toxin avoidance, target-site alteration, and detoxification. These resistance mechanisms are thought to be encoded by the insects' own genomes, and in many cases, this holds true. However, recent omics analyses, in conjunction with classic culture-dependent analyses, have revealed that a number of insects possess specific gut microorganisms, some of which significantly contribute to resistance against phytotoxins and pesticides by degrading such chemical compounds. Here, we review recent advances in our understanding on the symbiont-mediated degradation of natural and artificial toxins, with a special emphasis on their underlying genetic basis, focus on the importance of environmental microbiota as a resource of toxin-degrading microorganisms, and discuss the ecological and evolutionary significance of these symbiotic associations.

  13. Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells

    Science.gov (United States)

    Kraehling, Jan R.; Chidlow, John H.; Rajagopal, Chitra; Sugiyama, Michael G.; Fowler, Joseph W.; Lee, Monica Y.; Zhang, Xinbo; Ramírez, Cristina M.; Park, Eon Joo; Tao, Bo; Chen, Keyang; Kuruvilla, Leena; Larriveé, Bruno; Folta-Stogniew, Ewa; Ola, Roxana; Rotllan, Noemi; Zhou, Wenping; Nagle, Michael W.; Herz, Joachim; Williams, Kevin Jon; Eichmann, Anne; Lee, Warren L.; Fernández-Hernando, Carlos; Sessa, William C.

    2016-01-01

    In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma still readily traverses the endothelium. To identify the pathways of LDL uptake, a genome-wide RNAi screen was performed in endothelial cells and cross-referenced with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake of LDL into endothelial cells via an unusual endocytic pathway that diverts the ligand from lysosomal degradation and promotes LDL transcytosis. The endothelium-specific genetic ablation of Alk1 in Ldlr-KO animals leads to less LDL uptake into the aortic endothelium, showing its physiological role in endothelial lipoprotein metabolism. In summary, identification of pathways mediating LDLR-independent uptake of LDL may provide unique opportunities to block the initiation of LDL accumulation in the vessel wall or augment hepatic LDLR-dependent clearance of LDL. PMID:27869117

  14. Proliferative, necrotizing and crescentic immune complex-mediated glomerulonephritis in a cat

    Directory of Open Access Journals (Sweden)

    Carolyn Gross

    2015-09-01

    Full Text Available Case Summary A 5-year-old cat was examined for vomiting and anorexia of 2 days’ duration. Azotemia, hyperphosphatemia and hypoalbuminemia were the main biochemical findings. Serial analyses of the urine revealed isosthenuria, proteinuria and eventual glucosuria. Hyperechoic perirenal fat was detected surrounding the right kidney by ultrasonography. Histopathologic evaluation of ante-mortem ultrasound-guided needle biopsies of the right kidney was consistent with proliferative, necrotizing and crescentic glomerulonephritis with fibrin thrombi, proteinaceous and red blood cell casts, and moderate multifocal chronic-active interstitial nephritis. Owing to a lack of clinical improvement, the cat was eventually euthanized. Post-mortem renal biopsies were processed for light microscopy, transmission electron microscopy and immunofluorescence. This revealed severe focal proliferative and necrotizing glomerulonephritis with cellular crescent formation, podocyte injury and secondary segmental sclerosis. Ultrastructural analysis revealed scattered electron-dense deposits in the mesangium, and immunofluorescence demonstrated positive granular staining for λ light chains, consistent with immune complex-mediated glomerulonephritis. Severe diffuse acute tubular epithelial injury and numerous red blood cell casts were also seen. Relevance and novel information To our knowledge, this is the first report of naturally occurring proliferative, necrotizing and crescentic immune complex glomerulonephritis in a cat.

  15. Excessive Time on Social Networking Sites and Disordered Eating Behaviors Among Undergraduate Students: Appearance and Weight Esteem as Mediating Pathways.

    Science.gov (United States)

    Murray, Marisa; Maras, Danijela; Goldfield, Gary S

    2016-12-01

    Social networking sites (SNS) are a popular form of communication among undergraduate students. Body image concerns and disordered eating behaviors are also quite prevalent among this population. Maladaptive use of SNS has been associated with disordered eating behaviors; however, the mechanisms remain unclear. The present study examined if body image concerns (e.g., appearance and weight esteem) mediate the relationship between excessive time spent on SNS and disordered eating behaviors (restrained and emotional eating). The sample included 383 (70.2 percent female) undergraduate students (mean age = 23.08 years, standard deviation = 3.09) who completed self-report questionnaires related to SNS engagement, body image, disordered eating behaviors, and demographics. Parallel multiple mediation and moderated mediation analyses revealed that lower weight and appearance esteem mediated the relationship between excessive time on SNS and restrained eating for males and females, whereas appearance esteem mediated the relationship between excessive time on SNS and emotional eating for females only. The study adds to the literature by highlighting mediational pathways and gender differences. Intervention research is needed to determine if teaching undergraduate students more adaptive ways of using SNS or reducing exposure to SNS reduces body dissatisfaction and disordered eating in this high-risk population.

  16. Multiple mediation analysis of the relationship between rapid naming and reading

    DEFF Research Database (Denmark)

    Poulsen, Mads; Juul, Holger; Elbro, Carsten

    2015-01-01

    It is well established that rapid automatised naming (RAN) correlates with reading ability. Despite several attempts, no single component process (mediator) has been identified that fully accounts for the correlation. The present paper estimated the explanatory value of several mediators....... The influence of the mediators on the RAN-reading correlation was estimated as indirect effects in mediation analyses. Phonological awareness and letter knowledge significantly mediated the RAN-reading relationship, each accounted for a moderate part of the correlation between RAN and reading fluency. Thus...

  17. Mediator structure and rearrangements required for holoenzyme formation.

    Science.gov (United States)

    Tsai, Kuang-Lei; Yu, Xiaodi; Gopalan, Sneha; Chao, Ti-Chun; Zhang, Ying; Florens, Laurence; Washburn, Michael P; Murakami, Kenji; Conaway, Ronald C; Conaway, Joan W; Asturias, Francisco J

    2017-04-13

    The conserved Mediator co-activator complex has an essential role in the regulation of RNA polymerase II transcription in all eukaryotes. Understanding the structure and interactions of Mediator is crucial for determining how the complex influences transcription initiation and conveys regulatory information to the basal transcription machinery. Here we present a 4.4 Å resolution cryo-electron microscopy map of Schizosaccharomyces pombe Mediator in which conserved Mediator subunits are individually resolved. The essential Med14 subunit works as a central backbone that connects the Mediator head, middle and tail modules. Comparison with a 7.8 Å resolution cryo-electron microscopy map of a Mediator-RNA polymerase II holoenzyme reveals that changes in the structure of Med14 facilitate a large-scale Mediator rearrangement that is essential for holoenzyme formation. Our study suggests that access to different conformations and crosstalk between structural elements are essential for the Mediator regulation mechanism, and could explain the capacity of the complex to integrate multiple regulatory signals.

  18. Testing Cross-Sectional and Prospective Mediators of Internalized Heterosexism on Heavy Drinking, Alcohol Problems, and Psychological Distress Among Heavy Drinking Men Who Have Sex With Men.

    Science.gov (United States)

    Kuerbis, Alexis; Mereish, Ethan H; Hayes, Marie; Davis, Christine M; Shao, Sijing; Morgenstern, Jon

    2017-01-01

    Minority stress theory is one of the primary theories used to understand substance use among lesbian, gay, and bisexual populations. This study tested whether drinking to cope with stress (DTC), loneliness, and gay community participation (GCP) mediated the relationship between one type of minority stress (i.e., internalized heterosexism) and behavioral health outcomes. Using secondary data analysis and the PROCESS procedure, relationships between internalized heterosexism, the mediators (DTC, loneliness, and GCP), and outcomes (heavy drinking, alcohol problems, and psychological distress) were explored, both cross-sectionally and in a lagged manner, among both treatment-seeking and non-treatment-seeking problem drinking men who have sex with men. Problem drinkers (N = 187) were assessed, provided brief normative feedback about their drinking, given the choice to receive brief alcohol use disorder treatment or change on their own, and then followed for 9 months. Cross-sectional findings revealed that internalized heterosexism was significantly associated with heavy drinking, alcohol problems, and psychological distress. DTC emerged as a significant mediator of internalized heterosexism for all the health outcomes. Loneliness and GCP were significant mediators of internalized heterosexism for alcohol problems and psychological distress. Multiple mediation models reveal that all three mediators significantly contribute to internalized heterosexism's effect on health outcomes. Lagged analyses did not yield any significant indirect effects. DTC, loneliness, and GCP all play an integral, mediational role in the relationship between internalized heterosexism and alcohol problems and psychological distress. Findings underscore the necessity of addressing internalized heterosexism in psychosocial interventions along with coping skills training, emphasizing culturally relevant social support and loneliness.

  19. From Animal House to Old School: a multiple mediation analysis of the association between college drinking movie exposure and freshman drinking and its consequences.

    Science.gov (United States)

    Osberg, Timothy M; Billingsley, Katherine; Eggert, Meredith; Insana, Maribeth

    2012-08-01

    Does exposure to college drinking movies impact upon subsequent college student drinking? If so, what mechanisms mediate such an effect? In the first study to address these questions, we assessed college drinking movie exposure in a sample of 479 college freshmen early in their first semester and examined its relation to subsequent drinking and drinking consequences one month later. Hypothesized mediators of this effect included college alcohol beliefs (beliefs that drinking is central to college life), positive and negative alcohol expectancies, and descriptive and injunctive norms. Using bootstrapping procedures, results indicated that movie exposure exerted direct effects on both drinking and drinking consequences. Movie exposure also had significant indirect effects on drinking through all of the hypothesized mediators, with the exception of negative alcohol expectancies. All mediated movie exposure's effects on drinking consequences, with the exception of injunctive norms. Contrast analyses revealed that college alcohol beliefs had the strongest mediational effects in the relationship between movie exposure and both drinking and consequences. The implications of these findings for precollege alcohol education programs are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Exposure to peer delinquency as a mediator between self-report pubertal timing and delinquency: A longitudinal study of mediation

    Science.gov (United States)

    Negriff, Sonya; Ji, Juye; Trickett, Penelope K.

    2013-01-01

    This study examined exposure to peer delinquency as a mediator between pubertal timing and self-reported delinquency longitudinally and whether this mediational model was moderated by either gender or maltreatment experience. Data were obtained from Time 1, 2, and 3 of a longitudinal study of maltreatment and development. At Time 1 the sample comprised 454 children aged 9–13 years. Analyses via structural equation modeling supported full mediation. Gender did not moderate this mediational relationship, but maltreatment experience did. The results show that early maturing males and females are both at risk for being exposed to peers that may draw them into delinquent behavior. Additionally, the mechanism linking early pubertal timing to delinquency differs depending on maltreatment experience. PMID:21262055

  1. The Mediator Complex and Lipid Metabolism.

    Science.gov (United States)

    Zhang, Yi; Xiaoli; Zhao, Xiaoping; Yang, Fajun

    2013-03-01

    The precise control of gene expression is essential for all biological processes. In addition to DNA-binding transcription factors, numerous transcription cofactors contribute another layer of regulation of gene transcription in eukaryotic cells. One of such transcription cofactors is the highly conserved Mediator complex, which has multiple subunits and is involved in various biological processes through directly interacting with relevant transcription factors. Although the current understanding on the biological functions of Mediator remains incomplete, research in the past decade has revealed an important role of Mediator in regulating lipid metabolism. Such function of Mediator is dependent on specific transcription factors, including peroxisome proliferator-activated receptor-gamma (PPARγ) and sterol regulatory element-binding proteins (SREBPs), which represent the master regulators of lipid metabolism. The medical significance of these findings is apparent, as aberrant lipid metabolism is intimately linked to major human diseases, such as type 2 diabetes and cardiovascular disease. Here, we briefly review the functions and molecular mechanisms of Mediator in regulation of lipid metabolism.

  2. Interspecies introgressive hybridization in spiny frogs Quasipaa (Family Dicroglossidae) revealed by analyses on multiple mitochondrial and nuclear genes.

    Science.gov (United States)

    Zhang, Qi-Peng; Hu, Wen-Fang; Zhou, Ting-Ting; Kong, Shen-Shen; Liu, Zhi-Fang; Zheng, Rong-Quan

    2018-01-01

    Introgression may lead to discordant patterns of variation among loci and traits. For example, previous phylogeographic studies on the genus Quasipaa detected signs of genetic introgression from genetically and morphologically divergent Quasipaa shini or Quasipaa spinosa . In this study, we used mitochondrial and nuclear DNA sequence data to verify the widespread introgressive hybridization in the closely related species of the genus Quasipaa , evaluate the level of genetic diversity, and reveal the formation mechanism of introgressive hybridization. In Longsheng, Guangxi Province, signs of asymmetrical nuclear introgression were detected between Quasipaa boulengeri and Q. shini . Unidirectional mitochondrial introgression was revealed from Q. spinosa to Q. shini . By contrast, bidirectional mitochondrial gene introgression was detected between Q. spinosa and Q. shini in Lushan, Jiangxi Province. Our study also detected ancient hybridizations between a female Q. spinosa and a male Q. jiulongensis in Zhejiang Province. Analyses on mitochondrial and nuclear genes verified three candidate cryptic species in Q. spinosa , and a cryptic species may also exist in Q. boulengeri . However, no evidence of introgressive hybridization was found between Q. spinosa and Q. boulengeri . Quasipaa exilispinosa from all the sampling localities appeared to be deeply divergent from other communities. Our results suggest widespread introgressive hybridization in closely related species of Quasipaa and provide a fundamental basis for illumination of the forming mechanism of introgressive hybridization, classification of species, and biodiversity assessment in Quasipaa .

  3. Structural basis for alpha fetoprotein-mediated inhibition of caspase-3 activity in hepatocellular carcinoma cells.

    Science.gov (United States)

    Lin, Bo; Zhu, Mingyue; Wang, Wenting; Li, Wei; Dong, Xu; Chen, Yi; Lu, Yan; Guo, Junli; Li, Mengsen

    2017-10-01

    Alpha-fetoprotein (AFP) is an early serum growth factor in the foetal liver development and hepatic carcinogenesis; However, the precise biological role of cytoplasmic AFP remains elusive. Although we recently demonstrated that cytoplasmic AFP might interact with caspase-3 and inhibit the signal transduction of apoptosis in human hepatocellular carcinoma (HCC) cells, the details of this interaction are not clear. To reveal the molecular relationship between AFP and caspase-3, we performed molecular docking, co-immunoprecipitation (Co-IP), laser confocal microscopy, site-directed mutagenesis and functional experiments to analyse the key amino acid residues in the binding site of caspase-3. The results of Co-IP, laser confocal microscopy and functional analyses were consistent with the computational model. We also used the model to explain why AFP cannot bind to caspase-8. These results provide the molecular basis for the AFP-mediated inhibition of caspase-3 activity in HCC cells. Altogether, we found that AFP interacts with caspase-3 through precise amino acids, namely loop-4 residues Glu-248, Asp-253 and His-257. The results further demonstrated that AFP plays a critical role in the inhibition of the apoptotic signal transduction that mediated by caspase-3. Thus, AFP might represent a novel biotarget for the therapy of HCC patients. © 2017 UICC.

  4. When ab ≠ c - c': published errors in the reports of single-mediator models.

    Science.gov (United States)

    Petrocelli, John V; Clarkson, Joshua J; Whitmire, Melanie B; Moon, Paul E

    2013-06-01

    Accurate reports of mediation analyses are critical to the assessment of inferences related to causality, since these inferences are consequential for both the evaluation of previous research (e.g., meta-analyses) and the progression of future research. However, upon reexamination, approximately 15% of published articles in psychology contain at least one incorrect statistical conclusion (Bakker & Wicherts, Behavior research methods, 43, 666-678 2011), disparities that beget the question of inaccuracy in mediation reports. To quantify this question of inaccuracy, articles reporting standard use of single-mediator models in three high-impact journals in personality and social psychology during 2011 were examined. More than 24% of the 156 models coded failed an equivalence test (i.e., ab = c - c'), suggesting that one or more regression coefficients in mediation analyses are frequently misreported. The authors cite common sources of errors, provide recommendations for enhanced accuracy in reports of single-mediator models, and discuss implications for alternative methods.

  5. Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma

    International Nuclear Information System (INIS)

    Rumbajan, Janette Mareska; Aoki, Shigehisa; Kohashi, Kenichi; Oda, Yoshinao; Hata, Kenichiro; Saji, Tsutomu; Taguchi, Tomoaki; Tajiri, Tatsuro; Soejima, Hidenobu; Joh, Keiichiro; Maeda, Toshiyuki; Souzaki, Ryota; Mitsui, Kazumasa; Higashimoto, Ken; Nakabayashi, Kazuhiko; Yatsuki, Hitomi; Nishioka, Kenichi; Harada, Ryoko

    2013-01-01

    Aberrant methylation at imprinted differentially methylated regions (DMRs) in human 11p15.5 has been reported in many tumors including hepatoblastoma. However, the methylation status of imprinted DMRs in imprinted loci scattered through the human genome has not been analyzed yet in any tumors. The methylation statuses of 33 imprinted DMRs were analyzed in 12 hepatoblastomas and adjacent normal liver tissue by MALDI-TOF MS and pyrosequencing. Uniparental disomy (UPD) and copy number abnormalities were investigated with DNA polymorphisms. Among 33 DMRs analyzed, 18 showed aberrant methylation in at least 1 tumor. There was large deviation in the incidence of aberrant methylation among the DMRs. KvDMR1 and IGF2-DMR0 were the most frequently hypomethylated DMRs. INPP5Fv2-DMR and RB1-DMR were hypermethylated with high frequencies. Hypomethylation was observed at certain DMRs not only in tumors but also in a small number of adjacent histologically normal liver tissue, whereas hypermethylation was observed only in tumor samples. The methylation levels of long interspersed nuclear element-1 (LINE-1) did not show large differences between tumor tissue and normal liver controls. Chromosomal abnormalities were also found in some tumors. 11p15.5 and 20q13.3 loci showed the frequent occurrence of both genetic and epigenetic alterations. Our analyses revealed tumor-specific aberrant hypermethylation at some imprinted DMRs in 12 hepatoblastomas with additional suggestion for the possibility of hypomethylation prior to tumor development. Some loci showed both genetic and epigenetic alterations with high frequencies. These findings will aid in understanding the development of hepatoblastoma

  6. Perceived organizational support and intention to remain: The mediating roles of career success and self-esteem.

    Science.gov (United States)

    Liu, Jingying; Liu, Yan-Hui

    2016-04-01

    The aim of this study was to explore the relationships among perceived organizational support, career success, self-esteem and intention to remain. A cross-sectional study was designed, and subjects were recruited from six nonprofit organizations in China in spring 2015. A convenience sample of 610 nurses answered a survey with questions related to their ideas about their work. Structural equation modelling analyses were conducted. The results revealed that perceived organizational support was positively associated with intention to remain and career success, which, in turn, mediated the relationship between perceived organizational support and intention to remain. We also found that self-esteem mediated the relationships between perceived organizational support and career success and between career success and intention to remain. Higher perceived organizational support, career success and self-esteem can increase intention to remain in Chinese nurses. © 2015 John Wiley & Sons Australia, Ltd.

  7. The crystal structure of the AhRR-ARNT heterodimer reveals the structural basis of the repression of AhR-mediated transcription.

    Science.gov (United States)

    Sakurai, Shunya; Shimizu, Toshiyuki; Ohto, Umeharu

    2017-10-27

    2,3,7,8-Tetrachlorodibenzo- p -dioxin and related compounds are extraordinarily potent environmental toxic pollutants. Most of the 2,3,7,8-tetrachlorodibenzo- p -dioxin toxicities are mediated by aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor belonging to the basic helix-loop-helix (bHLH) Per-ARNT-Sim (PAS) family. Upon ligand binding, AhR forms a heterodimer with AhR nuclear translocator (ARNT) and induces the expression of genes involved in various biological responses. One of the genes induced by AhR encodes AhR repressor (AhRR), which also forms a heterodimer with ARNT and represses the activation of AhR-dependent transcription. The control of AhR activation is critical for managing AhR-mediated diseases, but the mechanisms by which AhRR represses AhR activation remain poorly understood, because of the lack of structural information. Here, we determined the structure of the AhRR-ARNT heterodimer by X-ray crystallography, which revealed an asymmetric intertwined domain organization presenting structural features that are both conserved and distinct among bHLH-PAS family members. The structures of AhRR-ARNT and AhR-ARNT were similar in the bHLH-PAS-A region, whereas the PAS-B of ARNT in the AhRR-ARNT complex exhibited a different domain arrangement in this family reported so far. The structure clearly disclosed that AhRR competitively represses AhR binding to ARNT and target DNA and further suggested the existence of an AhRR-ARNT-specific repression mechanism. This study provides a structural basis for understanding the mechanism by which AhRR represses AhR-mediated gene transcription. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Three genetic stocks of frigate tuna Auxis thazard thazard (Lacepede, 1800) along the Indian coast revealed from sequence analyses of mitochondrial DNA D-loop region

    Digital Repository Service at National Institute of Oceanography (India)

    GirishKumar; Kunal, S.P.; Menezes, M.R.; Meena, R.M.

    revealed from sequence analyses of mitochondrial DNA D-loop region Name of authors: 1. Girish Kumar* Biological Oceanography Division (BOD) National Institute of Oceanography (NIO) Dona Paula, Goa 403004, India. Email: girishkumar....nio@gmail.com Tel: +919766548060 2. Swaraj Priyaranjan Kunal Biological Oceanography Division (BOD) National Institute of Oceanography (NIO) Dona Paula, Goa 403004, India. Email: swar.mbt@gmail.com 3. Maria Rosalia Menezes Biological Oceanography...

  9. Intragenomic matching reveals a huge potential for miRNA-mediated regulation in plants

    DEFF Research Database (Denmark)

    Lindow, Morten; Jacobsen, Anders; Nygaard, Sanne

    2007-01-01

    indicates that only a few of the candidates are conserved between the species. We conclude that there is a large potential for miRNA-mediated regulatory interactions encoded in the genomes of the investigated plants. We hypothesize that some of these interactions may be realized under special environmental...

  10. A critical role of platelet TGF-β release in podoplanin-mediated tumour invasion and metastasis.

    Science.gov (United States)

    Takemoto, Ai; Okitaka, Mina; Takagi, Satoshi; Takami, Miho; Sato, Shigeo; Nishio, Makoto; Okumura, Sakae; Fujita, Naoya

    2017-02-08

    The tumour microenvironment is critical for various characteristics of tumour malignancies. Platelets, as part of the tumour microenvironment, are associated with metastasis formation via increasing the rate of tumour embolus formation in microvasculature. However, the mechanisms underlying the ability of tumour cells to acquire invasiveness and extravasate into target organs at the site of embolization remain unclear. In this study, we reported that platelet aggregation-inducing factor podoplanin expressed on tumour cell surfaces were found to not only promote the formation of tumour-platelet aggregates via interaction with platelets, but also induced the epithelial-mesenchymal transition (EMT) of tumour cells by enhancing transforming growth factor-β (TGF-β) release from platelets. In vitro and in vivo analyses revealed that podoplanin-mediated EMT resulted in increased invasiveness and extravasation of tumour cells. Treatment of mice with a TGF-β-neutralizing antibody statistically suppressed podoplanin-mediated distant metastasis in vivo, suggesting that podoplanin promoted haematogenous metastasis in part by releasing TGF-β from platelets that was essential for EMT of tumour cells. Therefore, our findings suggested that blocking the TGF-β signalling pathway might be a promising strategy for suppressing podoplanin-mediated haematogenous metastasis in vivo.

  11. The Relationship Between Perceived Parental Bonding and Bullying: The Mediating Role of Empathy

    Directory of Open Access Journals (Sweden)

    Effrosyni Mitsopoulou

    2013-03-01

    Full Text Available Despite the importance of parenting in the development of empathy in children as well as their involvement in bullying behaviours, no study has ever examined the mediating role of empathy in the relationship between parental bonding and bullying and victimization. The present study aims in examining these relationships. Participants included 504 children (255 boys, 246 girls from different primary schools of Crete. The standard version of the Peer Experiences Questionnaire was used to assess experiences in bullying behaviours, the Parental Bonding Instrument was used to assess self-reported sense of care and overprotection from the mother and father separately, whereas empathy was assessed using the Greek version of Bryant’s Empathy Index. A series of multiple regression analyses were conducted. Results showed that boys scored significantly higher on average with respect to Victimisation of Others, and girls scored higher to specific sub-factors of empathy. It was also found that in the case of Care Mother, Sadness and Understanding of Feelings were significant mediators of Victimization of Others. Further, in the subsample of boys it was revealed that Sadness and Understanding of Feelings were significant mediators of the relationship between Care Mother and Victimization of Others. Implications for counselling interventions are also discussed.

  12. Learning climate and feedback as predictors of dental students' self-determined motivation: The mediating role of basic psychological needs satisfaction.

    Science.gov (United States)

    Orsini, C; Binnie, V; Wilson, S; Villegas, M J

    2018-05-01

    The aim of this study was to test the mediating role of the satisfaction of dental students' basic psychological needs of autonomy, competence and relatedness on the association between learning climate, feedback and student motivation. The latter was based on the self-determination theory's concepts of differentiation of autonomous motivation, controlled motivation and amotivation. A cross-sectional correlational study was conducted where 924 students completed self-reported questionnaires measuring motivation, perception of the learning climate, feedback and basic psychological needs satisfaction. Descriptive statistics, Cronbach's alpha scores and bivariate correlations were computed. Mediation of basic needs on each predictor-outcome association was tested based on a series of regression analyses. Finally, all variables were integrated into one structural equation model, controlling for the effects of age, gender and year of study. Cronbach's alpha scores were acceptable (.655 to .905). Correlation analyses showed positive and significant associations between both an autonomy-supportive learning climate and the quantity and quality of feedback received, and students' autonomous motivation, which decreased and became negative when correlated with controlled motivation and amotivation, respectively. Regression analyses revealed that these associations were indirect and mediated by how these predictors satisfied students' basic psychological needs. These results were corroborated by the structural equation analysis, in which data fit the model well and regression paths were in the expected direction. An autonomy-supportive learning climate and the quantity and quality of feedback were positive predictors of students' autonomous motivation and negative predictors of amotivation. However, this was an indirect association mediated by the satisfaction of students' basic psychological needs. Consequently, supporting students' needs of autonomy, competence and

  13. Emotion Dysregulation Mediates the Relation between Mindfulness and Rejection Sensitivity.

    Science.gov (United States)

    Velotti, Patrizia; Garofalo, Carlo; Bizzi, Fabiola

    2015-09-01

    The role of rejection sensitivity (RS; the tendency to anxiously expect, readily perceive, and overreact to implied or overt interpersonal rejection) in psychopathology has mainly been studied with regard to borderline personality disorder (BPD). In the present study, we first sought to extend previous evidence of heightened RS in a clinical group with psychiatric disorders other than BPD, when compared with a community sample. Then, we tested whether emotion dysregulation and mindfulness were associated with RS in both sample, further hypothesizing that emotion dysregulation would mediate the relation between mindfulness deficits and RS. We adopted a cross-sectional design involving 191 psychiatric patients and 277 community participants (total N=468). All participants completed the Rejection Sensitivity Questionnaire, the Five Facet Mindfulness Questionnaire, and the Difficulties in Emotion Regulation Scale. Our hypotheses were supported, with psychiatric patients reporting greater levels of rejection sensitivity and emotion dysregulation, and lower level of mindfulness. Mindfulness deficits and emotion dysregulation explained a significant amount of variance in RS, in both samples. Finally, bootstrap analyses revealed that mindfulness deficits played an indirect effect on RS through the mediating role of emotion dysregulation. In particular, two different patterns emerged. Among psychiatric patients, an impairment in the ability to assume a non-judgmental stance towards own thoughts and feelings was related to RS through the mediation of limited access to emotion regulation strategies. Conversely, in the community sample, overall emotion dysregulation mediated the effect of lack of attention and awareness for present activities and experience on RS. Longitudinal studies could help in delineating etiological models of RS, and the joint role of deficits in mindfulness and emotion regulation should inform treatment programs.

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

    Science.gov (United States)

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

    2016-08-01

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

  15. Mediatized Extreme Right Activism and Discourse

    DEFF Research Database (Denmark)

    Peters, Rikke Alberg

    2015-01-01

    This paper presents a case study of the German neo-fascist network The Immortals (Die Unsterblichen) who in 2011 performed a flash-mob disseminated on YouTube for the so- called ‘Become Immortal’ campaign. The street protest was designed for and adapted to the specific characteristics of online...... activism. It is a good example of how new contentious action repertoires in which online and street activism intertwine have also spread to extreme right groups. Despite its neo-fascist and extreme right content the ‘Become Immortal’ campaign serves as an illustrative case for the study of mediated...... and mediatized activism. In order to analyse of the protest form, the visual aesthetics and the discourse of ‘The Immortals’, the paper mobilises two concepts from media and communication studies: mediation and mediatization. It will be argued that that the current transformation of the extreme right: that is...

  16. "You've got a friend in me": can social networks mediate the relationship between mood and MCI?

    Science.gov (United States)

    Yates, Jennifer A; Clare, Linda; Woods, Robert T

    2017-07-13

    Social networks can change with age, for reasons that are adaptive or unwanted. Social engagement is beneficial to both mental health and cognition, and represents a potentially modifiable factor. Consequently this study explored this association and assessed whether the relationship between mild cognitive impairment (MCI) and mood problems was mediated by social networks. This study includes an analysis of data from the Cognitive Function and Ageing Study Wales (CFAS Wales). CFAS Wales Phase 1 data were collected from 2010 to 2013 by conducting structured interviews with older people aged over 65 years of age living in urban and rural areas of Wales, and included questions that assessed cognitive functioning, mood, and social networks. Regression analyses were used to investigate the associations between individual variables and the mediating role of social networks. Having richer social networks was beneficial to both mood and cognition. Participants in the MCI category had weaker social networks than participants without cognitive impairment, whereas stronger social networks were associated with a decrease in the odds of experiencing mood problems, suggesting that they may offer a protective effect against anxiety and depression. Regression analyses revealed that social networks are a significant mediator of the relationship between MCI and mood problems. These findings are important, as mood problems are a risk factor for progression from MCI to dementia, so interventions that increase and strengthen social networks may have beneficial effects on slowing the progression of cognitive decline.

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

    Science.gov (United States)

    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.

  18. Mediator: A key regulator of plant development.

    Science.gov (United States)

    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.

  19. Isolation of Chromatin from Dysfunctional Telomeres Reveals an Important Role for Ring1b in NHEJ-Mediated Chromosome Fusions

    Directory of Open Access Journals (Sweden)

    Cristina Bartocci

    2014-05-01

    Full Text Available When telomeres become critically short, DNA damage response factors are recruited at chromosome ends, initiating a cellular response to DNA damage. We performed proteomic isolation of chromatin fragments (PICh in order to define changes in chromatin composition that occur upon onset of acute telomere dysfunction triggered by depletion of the telomere-associated factor TRF2. This unbiased purification of telomere-associated proteins in functional or dysfunctional conditions revealed the dynamic changes in chromatin composition that take place at telomeres upon DNA damage induction. On the basis of our results, we describe a critical role for the polycomb group protein Ring1b in nonhomologous end-joining (NHEJ-mediated end-to-end chromosome fusions. We show that cells with reduced levels of Ring1b have a reduced ability to repair uncapped telomeric chromatin. Our data represent an unbiased isolation of chromatin undergoing DNA damage and are a valuable resource to map the changes in chromatin composition in response to DNA damage activation.

  20. The mediator complex in genomic and non-genomic signaling in cancer.

    Science.gov (United States)

    Weber, Hannah; Garabedian, Michael J

    2018-05-01

    Mediator is a conserved, multi-subunit macromolecular machine divided structurally into head, middle, and tail modules, along with a transiently associating kinase module. Mediator functions as an integrator of transcriptional regulatory activity by interacting with DNA-bound transcription factors and with RNA polymerase II (Pol II) to both activate and repress gene expression. Mediator has been shown to affect multiple steps in transcription, including chromatin looping between enhancers and promoters, pre-initiation complex formation, transcriptional elongation, and mRNA splicing. Individual Mediator subunits participate in regulation of gene expression by the estrogen and androgen receptors and are altered in a number of endocrine cancers, including breast and prostate cancer. In addition to its role in genomic signaling, MED12 has been implicated in non-genomic signaling by interacting with and activating TGF-beta receptor 2 in the cytoplasm. Recent structural studies have revealed extensive inter-domain interactions and complex architecture of the Mediator-Pol II complex, suggesting that Mediator is capable of reorganizing its conformation and composition to fit cellular needs. We propose that alterations in Mediator subunit expression that occur in various cancers could impact the organization and function of Mediator, resulting in changes in gene expression that promote malignancy. A better understanding of the role of Mediator in cancer could reveal new approaches to the diagnosis and treatment of Mediator-dependent endocrine cancers, especially in settings of therapy resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Endocannabinoids mediate neuron-astrocyte communication.

    Science.gov (United States)

    Navarrete, Marta; Araque, Alfonso

    2008-03-27

    Cannabinoid receptors play key roles in brain function, and cannabinoid effects in brain physiology and drug-related behavior are thought to be mediated by receptors present in neurons. Neuron-astrocyte communication relies on the expression by astrocytes of neurotransmitter receptors. Yet, the expression of cannabinoid receptors by astrocytes in situ and their involvement in the neuron-astrocyte communication remain largely unknown. We show that hippocampal astrocytes express CB1 receptors that upon activation lead to phospholipase C-dependent Ca2+ mobilization from internal stores. These receptors are activated by endocannabinoids released by neurons, increasing astrocyte Ca2+ levels, which stimulate glutamate release that activates NMDA receptors in pyramidal neurons. These results demonstrate the existence of endocannabinoid-mediated neuron-astrocyte communication, revealing that astrocytes are targets of cannabinoids and might therefore participate in the physiology of cannabinoid-related addiction. They also reveal the existence of an endocannabinoid-glutamate signaling pathway where astrocytes serve as a bridge for nonsynaptic interneuronal communication.

  2. Genome and metagenome enabled analyses reveal new insight into the global biogeography and potential urea utilization in marine Thaumarchaeota.

    Science.gov (United States)

    Ahlgren, N.; Parada, A. E.; Fuhrman, J. A.

    2016-02-01

    Marine Thaumarchaea are an abundant, important group of marine microbial communities as they fix carbon, oxidize ammonium, and thus contribute to key N and C cycles in the oceans. From an enrichment culture, we have sequenced the complete genome of a new Thaumarchaeota strain, SPOT01. Analysis of this genome and other Thaumarchaeal genomes contributes new insight into its role in N cycling and clarifies the broader biogeography of marine Thaumarchaeal genera. Phylogenomics of Thaumarchaeota genomes reveal coherent separation into clusters roughly equivalent to the genus level, and SPOT01 represents a new genus of marine Thaumarchaea. Competitive fragment recruitment of globally distributed metagenomes from TARA, Ocean Sampling Day, and those generated from a station off California shows that the SPOT01 genus is often the most abundant genus, especially where total Thaumarchaea are most abundant in the overall community. The SPOT01 genome contains urease genes allowing it to use an alternative form of N. Genomic and metagenomic analysis also reveal that among planktonic genomes and populations, the urease genes in general are more frequently found in members of the SPOT01 genus and another genus dominant in deep waters, thus we predict these two genera contribute most significantly to urea utilization among marine Thaumarchaea. Recruitment also revealed broader biogeographic and ecological patterns of the putative genera. The SPOT01 genus was most abundant at colder temperatures (45 degrees). The genus containing Nitrosopumilus maritimus had the highest temperature range, and the genus containing Candidatus Nitrosopelagicus brevis was typically most abundant at intermediate temperatures and intermediate latitudes ( 35-45 degrees). Together these genome and metagenome enabled analyses provide significant new insight into the ecology and biogeochemical contributions of marine archaea.

  3. Employees’ Perceptions of Corporate Social Responsibility and Job Performance: A Sequential Mediation Model

    Directory of Open Access Journals (Sweden)

    Inyong Shin

    2016-05-01

    Full Text Available In spite of the increasing importance of corporate social responsibility (CSR and employee job performance, little is still known about the links between the socially responsible actions of organizations and the job performance of their members. In order to explain how employees’ perceptions of CSR influence their job performance, this study first examines the relationships between perceived CSR, organizational identification, job satisfaction, and job performance, and then develops a sequential mediation model by fully integrating these links. The results of structural equation modeling analyses conducted for 250 employees at hotels in South Korea offered strong support for the proposed model. We found that perceived CSR was indirectly and positively associated with job performance sequentially mediated first through organizational identification and then job satisfaction. This study theoretically contributes to the CSR literature by revealing the sequential mechanism through which employees’ perceptions of CSR affect their job performance, and offers practical implications by stressing the importance of employees’ perceptions of CSR. Limitations of this study and future research directions are discussed.

  4. Anxiety, affect, self-esteem, and stress: mediation and moderation effects on depression.

    Science.gov (United States)

    Nima, Ali Al; Rosenberg, Patricia; Archer, Trevor; Garcia, Danilo

    2013-01-01

    Mediation analysis investigates whether a variable (i.e., mediator) changes in regard to an independent variable, in turn, affecting a dependent variable. Moderation analysis, on the other hand, investigates whether the statistical interaction between independent variables predict a dependent variable. Although this difference between these two types of analysis is explicit in current literature, there is still confusion with regard to the mediating and moderating effects of different variables on depression. The purpose of this study was to assess the mediating and moderating effects of anxiety, stress, positive affect, and negative affect on depression. Two hundred and two university students (males  = 93, females  = 113) completed questionnaires assessing anxiety, stress, self-esteem, positive and negative affect, and depression. Mediation and moderation analyses were conducted using techniques based on standard multiple regression and hierarchical regression analyses. The results indicated that (i) anxiety partially mediated the effects of both stress and self-esteem upon depression, (ii) that stress partially mediated the effects of anxiety and positive affect upon depression, (iii) that stress completely mediated the effects of self-esteem on depression, and (iv) that there was a significant interaction between stress and negative affect, and between positive affect and negative affect upon depression. The study highlights different research questions that can be investigated depending on whether researchers decide to use the same variables as mediators and/or moderators.

  5. The relationship between low levels of mindfulness skills and pathological worry: the mediating role of psychological inflexibility

    Directory of Open Access Journals (Sweden)

    Francisco J. Ruiz

    2014-10-01

    Full Text Available Mindfulness-based interventions have recently been proposed for the treatment of generalized anxiety disorder (GAD. However, the specific nature of the relationship between mindfulness skills and pathological worry is still not very well known. This study analyzes the mediating role of psychological inflexibility-a central construct in the acceptance and commitment therapy (ACT model of psychopathology-in the effect of mindfulness skills on pathological worry. A total of 132 nonclinical participants completed questionnaires assessing the constructs of interest: the Penn State Worry Questionnaire (PSWQ, the Acceptance and Action Questionnaire - II (AAQ-II, and the Kentucky Inventory of Mindfulness Skills (KIMS. Because the Spanish translation of the KIMS used lacked of a formal validation, its psychometric properties and factor structure were previously evaluated. This process led to a reduced version of the KIMS that showed good internal consistency and factor structure. Mediation analyses revealed that psychological inflexibility fully mediated the effects of mindfulness skills as a set on pathological worry. Regarding specific mindfulness skills, psychological inflexibility was shown to be a mediator and suppressor, respectively, of the relationship between acceptance without judgment and act with awareness on worry. Results are discussed emphasizing the need of using mindfulness exercises to promote psychological flexibility.

  6. Mediator Variables in Headache Research: Methodological Critique and Exemplar Using Self-Efficacy as a Mediator of the Relationship Between Headache Severity and Disability.

    Science.gov (United States)

    Peck, Kelly R; Smitherman, Todd A

    2015-09-01

    Despite advances in headache medicine, there remains little research on process-related variables that mediate relations between headache and outcomes, as well as limited dissemination of optimal statistical methodology for conducting mediation analyses. The present paper thus aims to promote and demonstrate a contemporary approach to mediation analysis as applied to headache. An overview of a contemporary path-analytic approach to mediation analysis is presented, with an empirical exemplar for illustrative purposes. In the exemplar, headache management self-efficacy (HMSE) was proposed as a mediator between headache severity and disability. The sample included 907 young adults (M age = 19.03 [SD = 2.26]; 70.8% female) with primary headache. Direct and indirect effects of headache severity on headache disability through HMSE were assessed using the espoused methods. Pain severity was positively associated with headache disability (β = 2.91, 95% confidence interval [CI; 2.62, 3.19]) and negatively associated with HMSE (β = -3.50, 95% CI [-4.24, -2.76]); HMSE was negatively associated with headache disability (β = 0.07, 95% CI [-0.09, -0.04]). A positive indirect effect of pain severity on disability through HMSE was identified (point estimate = 0.24, 95% CI [0.14, 0.34]); thus, self-efficacy mediated the association between pain severity and disability. The proposed mediation model accounted for 38% of total variance in disability (P headache literature. In one exemplar application, self-efficacy partially accounted for the disability resulting from headache. We advocate for increased attention to intervening variables in headache via dissemination of contemporary mediation analyses. © 2015 American Headache Society.

  7. A default Bayesian hypothesis test for mediation.

    Science.gov (United States)

    Nuijten, Michèle B; Wetzels, Ruud; Matzke, Dora; Dolan, Conor V; Wagenmakers, Eric-Jan

    2015-03-01

    In order to quantify the relationship between multiple variables, researchers often carry out a mediation analysis. In such an analysis, a mediator (e.g., knowledge of a healthy diet) transmits the effect from an independent variable (e.g., classroom instruction on a healthy diet) to a dependent variable (e.g., consumption of fruits and vegetables). Almost all mediation analyses in psychology use frequentist estimation and hypothesis-testing techniques. A recent exception is Yuan and MacKinnon (Psychological Methods, 14, 301-322, 2009), who outlined a Bayesian parameter estimation procedure for mediation analysis. Here we complete the Bayesian alternative to frequentist mediation analysis by specifying a default Bayesian hypothesis test based on the Jeffreys-Zellner-Siow approach. We further extend this default Bayesian test by allowing a comparison to directional or one-sided alternatives, using Markov chain Monte Carlo techniques implemented in JAGS. All Bayesian tests are implemented in the R package BayesMed (Nuijten, Wetzels, Matzke, Dolan, & Wagenmakers, 2014).

  8. Biofilm growth program and architecture revealed by single-cell live imaging

    Science.gov (United States)

    Yan, Jing; Sabass, Benedikt; Stone, Howard; Wingreen, Ned; Bassler, Bonnie

    Biofilms are surface-associated bacterial communities. Little is known about biofilm structure at the level of individual cells. We image living, growing Vibrio cholerae biofilms from founder cells to ten thousand cells at single-cell resolution, and discover the forces underpinning the architectural evolution of the biofilm. Mutagenesis, matrix labeling, and simulations demonstrate that surface-adhesion-mediated compression causes V. cholerae biofilms to transition from a two-dimensional branched morphology to a dense, ordered three-dimensional cluster. We discover that directional proliferation of rod-shaped bacteria plays a dominant role in shaping the biofilm architecture, and this growth pattern is controlled by a single gene. Competition analyses reveal the advantages of the dense growth mode in providing the biofilm with superior mechanical properties. We will further present continuum theory to model the three-dimensional growth of biofilms at the solid-liquid interface as well as solid-air interface.

  9. Power Analysis for Complex Mediational Designs Using Monte Carlo Methods

    Science.gov (United States)

    Thoemmes, Felix; MacKinnon, David P.; Reiser, Mark R.

    2010-01-01

    Applied researchers often include mediation effects in applications of advanced methods such as latent variable models and linear growth curve models. Guidance on how to estimate statistical power to detect mediation for these models has not yet been addressed in the literature. We describe a general framework for power analyses for complex…

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

    Science.gov (United States)

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

    2017-03-01

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

  11. POWER ANALYSIS FOR COMPLEX MEDIATIONAL DESIGNS USING MONTE CARLO METHODS

    OpenAIRE

    Thoemmes, Felix; MacKinnon, David P.; Reiser, Mark R.

    2010-01-01

    Applied researchers often include mediation effects in applications of advanced methods such as latent variable models and linear growth curve models. Guidance on how to estimate statistical power to detect mediation for these models has not yet been addressed in the literature. We describe a general framework for power analyses for complex mediational models. The approach is based on the well known technique of generating a large number of samples in a Monte Carlo study, and estimating power...

  12. Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase.

    Science.gov (United States)

    Nishikawa, Hiroyuki; Ooka, Seido; Sato, Ko; Arima, Kei; Okamoto, Joji; Klevit, Rachel E; Fukuda, Mamoru; Ohta, Tomohiko

    2004-02-06

    The breast and ovarian cancer suppressor BRCA1 acquires significant ubiquitin ligase activity when bound to BARD1 as a RING heterodimer. Although the activity may well be important for the role of BRCA1 as a tumor suppressor, the biochemical consequence of the activity is not yet known. Here we report that BRCA1-BARD1 catalyzes Lys-6-linked polyubiquitin chain formation. K6R mutation of ubiquitin dramatically reduces the polyubiquitin products mediated by BRCA1-BARD1 in vitro. BRCA1-BARD1 preferentially utilizes ubiquitin with a single Lys residue at Lys-6 or Lys-29 to mediate autoubiquitination of BRCA1 in vivo. Furthermore, mass spectrometry analysis identified the Lys-6-linked branched ubiquitin fragment from the polyubiquitin chain produced by BRCA1-BARD1 using wild type ubiquitin. The BRCA1-BARD1-mediated Lys-6-linked polyubiquitin chains are deubiquitinated by 26 S proteasome in vitro, whereas autoubiquitinated CUL1 through Lys-48-linked polyubiquitin chains is degraded. Proteasome inhibitors do not alter the steady state level of the autoubiquitinated BRCA1 in vivo. Hence, the results indicate that BRCA1-BARD1 mediates novel polyubiquitin chains that may be distinctly edited by 26 S proteasome from conventional Lys-48-linked polyubiquitin chains.

  13. Demonstration and Dialogue: Mediation in Swedish Nuclear Waste Management

    International Nuclear Information System (INIS)

    Elam, Mark; Lidberg, Maria; Soneryd, Linda; Sundqvist, Goeran

    2009-01-01

    This report analyses mediation and mediators in Swedish nuclear waste management. Mediation is about establishing agreement and building common knowledge. It is argued that demonstrations and dialogue are the two prominent approaches to mediation in Swedish nuclear waste management. Mediation through demonstration is about showing, displaying, and pointing out a path to safe disposal for inspection. It implies a strict division between demonstrator and audience. Mediation through dialogue on the other hand, is about collective acknowledgements of uncertainty and suspensions of judgement creating room for broader discussion. In Sweden, it is the Swedish Nuclear Fuel and Waste Management Co. (SKB) that is tasked with finding a method and a site for the final disposal of the nation's nuclear waste. Two different legislative frameworks cover this process. In accordance with the Act on Nuclear Activities, SKB is required to demonstrate the safety of its planned nuclear waste management system to the government, while in respect of the Swedish Environmental Code, they are obliged to organize consultations with the public. How SKB combines these requirements is the main question under investigation in this report in relation to materials deriving from three empirical settings: 1) SKB's safety analyses, 2) SKB's public consultation activities and 3) the 'dialogue projects', initiated by other actors than SKB broadening the public arena for discussion. In conclusion, an attempt is made to characterise the long- term interplay of demonstration and dialogue in Swedish nuclear waste management

  14. Calpain-Mediated Degradation of Drebrin by Excitotoxicity In vitro and In vivo.

    Directory of Open Access Journals (Sweden)

    Takahiko Chimura

    Full Text Available The level of drebrin, an evolutionarily conserved f-actin-binding protein that regulates synaptic structure and function, is reduced in the brains of patients with chronic neurodegenerative diseases such as Alzheimer's disease (AD and Down's syndrome (DS. It was suggested that excitotoxic neuronal death caused by overactivation of NMDA-type glutamate receptors (NMDARs occurs in AD and DS; however, the relationship between excitotoxicity and drebrin loss is unknown. Here, we show that drebrin is a novel target of calpain-mediated proteolysis under excitotoxic conditions induced by the overactivation of NMDARs. In cultured rodent neurons, degradation of drebrin was confirmed by the detection of proteolytic fragments, as well as a reduction in the amount of full-length drebrin. Notably, the NMDA-induced degradation of drebrin in mature neurons occurred concomitantly with a loss of f-actin. Furthermore, pharmacological inhibition of f-actin loss facilitated the drebrin degradation, suggesting a functional linkage between f-actin and drebrin degradation. Biochemical analyses using purified drebrin and calpain revealed that calpain degraded drebrin directly in vitro. Furthermore, cerebral ischemia also induced the degradation of drebrin in vivo. These findings suggest that calpain-mediated degradation of drebrin is a fundamental pathology of neurodegenerative diseases mediated by excitotoxicity, regardless of whether they are acute or chronic. Drebrin regulates the synaptic clustering of NMDARs; therefore, degradation of drebrin under excitotoxic conditions may modulate NMDAR-mediated signal transductions, including pro-survival signaling. Overall, the results presented here provide novel insights into the molecular basis of cellular responses to excitotoxicity in vitro and in vivo.

  15. When mothers have serious mental health problems: parenting as a proximal mediator.

    Science.gov (United States)

    Oyserman, Daphna; Bybee, Deborah; Mowbray, Carol; Hart-Johnson, Tamera

    2005-08-01

    Maternal mental health (MMH) problems are associated with lack of confidence in one's parenting, overly lax or too harsh discipline, and child academic underperformance. We asked if parenting mediates the effect of MMH problems on academic outcomes even among mothers with serious mental illness (n=164). Structural equation analyses show a significant association between MMH problems and permissive (lack of parenting confidence, lack of follow through) parenting and verbal hostility as well as worse academic outcomes (school recorded grades, teacher reported behaviour). Permissive parenting completely mediated the direct effect of MMH on academic outcomes. Further analyses showed that the mediation effect was attributed to a single component of permissive parenting-lack of parenting confidence.

  16. Comprehensive transcriptome analyses correlated with untargeted metabolome reveal differentially expressed pathways in response to cell wall alterations.

    Science.gov (United States)

    Reem, Nathan T; Chen, Han-Yi; Hur, Manhoi; Zhao, Xuefeng; Wurtele, Eve Syrkin; Li, Xu; Li, Ling; Zabotina, Olga

    2018-03-01

    This research provides new insights into plant response to cell wall perturbations through correlation of transcriptome and metabolome datasets obtained from transgenic plants expressing cell wall-modifying enzymes. Plants respond to changes in their cell walls in order to protect themselves from pathogens and other stresses. Cell wall modifications in Arabidopsis thaliana have profound effects on gene expression and defense response, but the cell signaling mechanisms underlying these responses are not well understood. Three transgenic Arabidopsis lines, two with reduced cell wall acetylation (AnAXE and AnRAE) and one with reduced feruloylation (AnFAE), were used in this study to investigate the plant responses to cell wall modifications. RNA-Seq in combination with untargeted metabolome was employed to assess differential gene expression and metabolite abundance. RNA-Seq results were correlated with metabolite abundances to determine the pathways involved in response to cell wall modifications introduced in each line. The resulting pathway enrichments revealed the deacetylation events in AnAXE and AnRAE plants induced similar responses, notably, upregulation of aromatic amino acid biosynthesis and changes in regulation of primary metabolic pathways that supply substrates to specialized metabolism, particularly those related to defense responses. In contrast, genes and metabolites of lipid biosynthetic pathways and peroxidases involved in lignin polymerization were downregulated in AnFAE plants. These results elucidate how primary metabolism responds to extracellular stimuli. Combining the transcriptomics and metabolomics datasets increased the power of pathway prediction, and demonstrated the complexity of pathways involved in cell wall-mediated signaling.

  17. Visual attention and emotional memory: recall of aversive pictures is partially mediated by concurrent task performance.

    Science.gov (United States)

    Pottage, Claire L; Schaefer, Alexandre

    2012-02-01

    The emotional enhancement of memory is often thought to be determined by attention. However, recent evidence using divided attention paradigms suggests that attention does not play a significant role in the formation of memories for aversive pictures. We report a study that investigated this question using a paradigm in which participants had to encode lists of randomly intermixed negative and neutral pictures under conditions of full attention and divided attention followed by a free recall test. Attention was divided by a highly demanding concurrent task tapping visual processing resources. Results showed that the advantage in recall for aversive pictures was still present in the DA condition. However, mediation analyses also revealed that concurrent task performance significantly mediated the emotional enhancement of memory under divided attention. This finding suggests that visual attentional processes play a significant role in the formation of emotional memories. PsycINFO Database Record (c) 2012 APA, all rights reserved

  18. Dislocation Interactions in Olivine Revealed by HR-EBSD

    Science.gov (United States)

    Wallis, David; Hansen, Lars N.; Britton, T. Ben; Wilkinson, Angus J.

    2017-10-01

    Interactions between dislocations potentially provide a control on strain rates produced by dislocation motion during creep of rocks at high temperatures. However, it has been difficult to establish the dominant types of interactions and their influence on the rheological properties of creeping rocks due to a lack of suitable observational techniques. We apply high-angular resolution electron backscatter diffraction to map geometrically necessary dislocation (GND) density, elastic strain, and residual stress in experimentally deformed single crystals of olivine. Short-range interactions are revealed by cross correlation of GND density maps. Spatial correlations between dislocation types indicate that noncollinear interactions may impede motion of proximal dislocations at temperatures of 1000°C and 1200°C. Long-range interactions are revealed by autocorrelation of GND density maps. These analyses reveal periodic variations in GND density and sign, with characteristic length scales on the order of 1-10 μm. These structures are spatially associated with variations in elastic strain and residual stress on the order of 10-3 and 100 MPa, respectively. Therefore, short-range interactions generate local accumulations of dislocations, leading to heterogeneous internal stress fields that influence dislocation motion over longer length scales. The impacts of these short- and/or long-range interactions on dislocation velocities may therefore influence the strain rate of the bulk material and are an important consideration for future models of dislocation-mediated deformation mechanisms in olivine. Establishing the types and impacts of dislocation interactions that occur across a range of laboratory and natural deformation conditions will help to establish the reliability of extrapolating laboratory-derived flow laws to real Earth conditions.

  19. Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    VanderWeele, T J; Vansteelandt, S

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

  20. Comparative Analyses of Nonpathogenic, Opportunistic, and Totally Pathogenic Mycobacteria Reveal Genomic and Biochemical Variabilities and Highlight the Survival Attributes of Mycobacterium tuberculosis

    Science.gov (United States)

    Singh, Yadvir; Kohli, Sakshi; Ahmad, Javeed; Ehtesham, Nasreen Z.; Tyagi, Anil K.

    2014-01-01

    ABSTRACT Mycobacterial evolution involves various processes, such as genome reduction, gene cooption, and critical gene acquisition. Our comparative genome size analysis of 44 mycobacterial genomes revealed that the nonpathogenic (NP) genomes were bigger than those of opportunistic (OP) or totally pathogenic (TP) mycobacteria, with the TP genomes being smaller yet variable in size—their genomic plasticity reflected their ability to evolve and survive under various environmental conditions. From the 44 mycobacterial species, 13 species, representing TP, OP, and NP, were selected for genomic-relatedness analyses. Analysis of homologous protein-coding genes shared between Mycobacterium indicus pranii (NP), Mycobacterium intracellulare ATCC 13950 (OP), and Mycobacterium tuberculosis H37Rv (TP) revealed that 4,995 (i.e., ~95%) M. indicaus pranii proteins have homology with M. intracellulare, whereas the homologies among M. indicus pranii, M. intracellulare ATCC 13950, and M. tuberculosis H37Rv were significantly lower. A total of 4,153 (~79%) M. indicus pranii proteins and 4,093 (~79%) M. intracellulare ATCC 13950 proteins exhibited homology with the M. tuberculosis H37Rv proteome, while 3,301 (~82%) and 3,295 (~82%) M. tuberculosis H37Rv proteins showed homology with M. indicus pranii and M. intracellulare ATCC 13950 proteomes, respectively. Comparative metabolic pathway analyses of TP/OP/NP mycobacteria showed enzymatic plasticity between M. indicus pranii (NP) and M. intracellulare ATCC 13950 (OP), Mycobacterium avium 104 (OP), and M. tuberculosis H37Rv (TP). Mycobacterium tuberculosis seems to have acquired novel alternate pathways with possible roles in metabolism, host-pathogen interactions, virulence, and intracellular survival, and by implication some of these could be potential drug targets. PMID:25370496

  1. A longitudinal investigation of the mediating role of self-esteem and body importance in the relationship between stress and body dissatisfaction in adolescent females and males.

    Science.gov (United States)

    Murray, Kristen; Rieger, Elizabeth; Byrne, Don

    2013-09-01

    Body dissatisfaction is particularly prevalent during adolescence and has recently been linked to stress in females and males. However, prospective studies are needed to better understand the relationship between stress and body dissatisfaction. The present study investigates the direction of this association and the mediating role of self-esteem and body image importance. A sample of 298 adolescent females and males in Grades 7 to 10 (ages 12 to 17 years) were surveyed at two time points over a one-year period. Hierarchical regression analyses revealed that stress significantly predicted body dissatisfaction one year later. Furthermore, a multiple mediation analysis controlling for gender revealed a significant indirect effect in both cross-sectional and longitudinal models, indicating that stress predicts reductions in self-esteem and increases in body importance, which in turn predict body dissatisfaction. These findings suggest that stress, self-esteem, and body importance should be included in programmes aimed at improving body dissatisfaction. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Computational modeling reveals dendritic origins of GABA(A-mediated excitation in CA1 pyramidal neurons.

    Directory of Open Access Journals (Sweden)

    Naomi Lewin

    Full Text Available GABA is the key inhibitory neurotransmitter in the adult central nervous system, but in some circumstances can lead to a paradoxical excitation that has been causally implicated in diverse pathologies from endocrine stress responses to diseases of excitability including neuropathic pain and temporal lobe epilepsy. We undertook a computational modeling approach to determine plausible ionic mechanisms of GABA(A-dependent excitation in isolated post-synaptic CA1 hippocampal neurons because it may constitute a trigger for pathological synchronous epileptiform discharge. In particular, the interplay intracellular chloride accumulation via the GABA(A receptor and extracellular potassium accumulation via the K/Cl co-transporter KCC2 in promoting GABA(A-mediated excitation is complex. Experimentally it is difficult to determine the ionic mechanisms of depolarizing current since potassium transients are challenging to isolate pharmacologically and much GABA signaling occurs in small, difficult to measure, dendritic compartments. To address this problem and determine plausible ionic mechanisms of GABA(A-mediated excitation, we built a detailed biophysically realistic model of the CA1 pyramidal neuron that includes processes critical for ion homeostasis. Our results suggest that in dendritic compartments, but not in the somatic compartments, chloride buildup is sufficient to cause dramatic depolarization of the GABA(A reversal potential and dominating bicarbonate currents that provide a substantial current source to drive whole-cell depolarization. The model simulations predict that extracellular K(+ transients can augment GABA(A-mediated excitation, but not cause it. Our model also suggests the potential for GABA(A-mediated excitation to promote network synchrony depending on interneuron synapse location - excitatory positive-feedback can occur when interneurons synapse onto distal dendritic compartments, while interneurons projecting to the perisomatic

  3. Bliss and Loewe interaction analyses of clinically relevant drug combinations in human colon cancer cell lines reveal complex patterns of synergy and antagonism.

    Science.gov (United States)

    Kashif, Muhammad; Andersson, Claes; Mansoori, Sharmineh; Larsson, Rolf; Nygren, Peter; Gustafsson, Mats G

    2017-11-28

    We analyzed survival effects for 15 different pairs of clinically relevant anti-cancer drugs in three iso-genic pairs of human colorectal cancer carcinoma cell lines, by applying for the first time our novel software (R package) called COMBIA. In our experiments iso-genic pairs of cell lines were used, differing only with respect to a single clinically important KRAS or BRAF mutation. Frequently, concentration dependent but mutation independent joint Bliss and Loewe synergy/antagonism was found statistically significant. Four combinations were found synergistic/antagonistic specifically to the parental (harboring KRAS or BRAF mutation) cell line of the corresponding iso-genic cell lines pair. COMBIA offers considerable improvements over established software for synergy analysis such as MacSynergy™ II as it includes both Bliss (independence) and Loewe (additivity) analyses, together with a tailored non-parametric statistical analysis employing heteroscedasticity, controlled resampling, and global (omnibus) testing. In many cases Loewe analyses found significant synergistic as well as antagonistic effects in a cell line at different concentrations of a tested drug combination. By contrast, Bliss analysis found only one type of significant effect per cell line. In conclusion, the integrated Bliss and Loewe interaction analysis based on non-parametric statistics may provide more robust interaction analyses and reveal complex patterns of synergy and antagonism.

  4. Psychological distress as a mediator in the relationships between biopsychosocial factors and disordered eating among Malaysian university students.

    Science.gov (United States)

    Gan, Wan Ying; Mohd Nasir, Mohd Taib; Zalilah, Mohd Shariff; Hazizi, Abu Saad

    2012-12-01

    The mechanism linking biopsychosocial factors to disordered eating among university students is not well understood especially among Malaysians. This study aimed to examine the mediating role of psychological distress in the relationships between biopsychosocial factors and disordered eating among Malaysian university students. A self-administered questionnaire measured self-esteem, body image, social pressures to be thin, weight-related teasing, psychological distress, and disordered eating in 584 university students (59.4% females and 40.6% males). Body weight and height were measured. Structural equation modeling analysis revealed that the partial mediation model provided good fit to the data. Specifically, the relationships between self-esteem and weight-related teasing with disordered eating were mediated by psychological distress. In contrast, only direct relationships between body weight status, body image, and social pressures to be thin with disordered eating were found and were not mediated by psychological distress. Furthermore, multigroup analyses indicated that the model was equivalent for both genders but not for ethnic groups. There was a negative relationship between body weight status and psychological distress for Chinese students, whereas this was not the case among Malay students. Intervention and prevention programs on psychological distress may be beneficial in reducing disordered eating among Malaysian university students. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Influence of Goal Contents on Exercise Addiction: Analysing the Mediating Effect of Passion for Exercise.

    Science.gov (United States)

    Sicilia, Álvaro; Alcaraz-Ibáñez, Manuel; Lirola, María-Jesús; Burgueño, Rafael

    2017-10-01

    Based on the self-determination theory (Deci and Ryan, 1985, 2000), the purpose of this study was to examine the effects of exercise goal contents on exercise addiction, taking into account the mediating effects of passion for exercise. A total of 384 university students (284 men and 100 women; M age = 20.31, SD = 3.10) completed a questionnaire that measured exercise frequency and intensity, exercise goal contents (e.g. intrinsic: social affiliation, health management, skill development; extrinsic: image and social recognition), passion for exercise (e.g. harmonious and obsessive), and exercise addiction. After controlling the exercise frequency and intensity effects, results showed that goal contents did not directly predict exercise addiction. However, mediation analysis showed that goal contents predicted addiction through passion for exercise. These results support a motivational sequence in which extrinsic versus intrinsic goals influence exercise addiction because such goals are positively associated with obsessive passion for exercise and negatively associated with harmonious passion.

  6. Influence of Goal Contents on Exercise Addiction: Analysing the Mediating Effect of Passion for Exercise

    Directory of Open Access Journals (Sweden)

    Sicilia Álvaro

    2017-10-01

    Full Text Available Based on the self-determination theory (Deci and Ryan, 1985, 2000, the purpose of this study was to examine the effects of exercise goal contents on exercise addiction, taking into account the mediating effects of passion for exercise. A total of 384 university students (284 men and 100 women; Mage = 20.31, SD = 3.10 completed a questionnaire that measured exercise frequency and intensity, exercise goal contents (e.g. intrinsic: social affiliation, health management, skill development; extrinsic: image and social recognition, passion for exercise (e.g. harmonious and obsessive, and exercise addiction. After controlling the exercise frequency and intensity effects, results showed that goal contents did not directly predict exercise addiction. However, mediation analysis showed that goal contents predicted addiction through passion for exercise. These results support a motivational sequence in which extrinsic versus intrinsic goals influence exercise addiction because such goals are positively associated with obsessive passion for exercise and negatively associated with harmonious passion.

  7. Anxiety, affect, self-esteem, and stress: mediation and moderation effects on depression.

    Directory of Open Access Journals (Sweden)

    Ali Al Nima

    Full Text Available Mediation analysis investigates whether a variable (i.e., mediator changes in regard to an independent variable, in turn, affecting a dependent variable. Moderation analysis, on the other hand, investigates whether the statistical interaction between independent variables predict a dependent variable. Although this difference between these two types of analysis is explicit in current literature, there is still confusion with regard to the mediating and moderating effects of different variables on depression. The purpose of this study was to assess the mediating and moderating effects of anxiety, stress, positive affect, and negative affect on depression.Two hundred and two university students (males  = 93, females  = 113 completed questionnaires assessing anxiety, stress, self-esteem, positive and negative affect, and depression. Mediation and moderation analyses were conducted using techniques based on standard multiple regression and hierarchical regression analyses.The results indicated that (i anxiety partially mediated the effects of both stress and self-esteem upon depression, (ii that stress partially mediated the effects of anxiety and positive affect upon depression, (iii that stress completely mediated the effects of self-esteem on depression, and (iv that there was a significant interaction between stress and negative affect, and between positive affect and negative affect upon depression.The study highlights different research questions that can be investigated depending on whether researchers decide to use the same variables as mediators and/or moderators.

  8. Anxiety, Affect, Self-Esteem, and Stress: Mediation and Moderation Effects on Depression

    Science.gov (United States)

    Nima, Ali Al; Rosenberg, Patricia; Archer, Trevor; Garcia, Danilo

    2013-01-01

    Background Mediation analysis investigates whether a variable (i.e., mediator) changes in regard to an independent variable, in turn, affecting a dependent variable. Moderation analysis, on the other hand, investigates whether the statistical interaction between independent variables predict a dependent variable. Although this difference between these two types of analysis is explicit in current literature, there is still confusion with regard to the mediating and moderating effects of different variables on depression. The purpose of this study was to assess the mediating and moderating effects of anxiety, stress, positive affect, and negative affect on depression. Methods Two hundred and two university students (males  = 93, females  = 113) completed questionnaires assessing anxiety, stress, self-esteem, positive and negative affect, and depression. Mediation and moderation analyses were conducted using techniques based on standard multiple regression and hierarchical regression analyses. Main Findings The results indicated that (i) anxiety partially mediated the effects of both stress and self-esteem upon depression, (ii) that stress partially mediated the effects of anxiety and positive affect upon depression, (iii) that stress completely mediated the effects of self-esteem on depression, and (iv) that there was a significant interaction between stress and negative affect, and between positive affect and negative affect upon depression. Conclusion The study highlights different research questions that can be investigated depending on whether researchers decide to use the same variables as mediators and/or moderators. PMID:24039896

  9. ATHENA/INTRA analyses for ITER, NSSR-2

    International Nuclear Information System (INIS)

    Shen, Kecheng; Eriksson, John; Sjoeberg, A.

    1999-02-01

    The present report is a summary report including thermal-hydraulic analyses made at Studsvik Eco and Safety AB for the ITER NSSR-2 safety documentation. The objective of the analyses was to reveal the safety characteristics of various heat transfer systems at specified operating conditions and to indicate the conditions for which there were obvious risks of jeopardising the structural integrity of the coolant systems. In the latter case also some analyses were made to indicate conceivable mitigating measures for maintaining the integrity.The analyses were primarily concerned with the First Wall and Divertor heat transfer systems. Several enveloping transients were analysed with associated specific flow and heat load boundary conditions. The analyses were performed with the ATHENA and INTRA codes

  10. ATHENA/INTRA analyses for ITER, NSSR-2

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Kecheng; Eriksson, John; Sjoeberg, A

    1999-02-01

    The present report is a summary report including thermal-hydraulic analyses made at Studsvik Eco and Safety AB for the ITER NSSR-2 safety documentation. The objective of the analyses was to reveal the safety characteristics of various heat transfer systems at specified operating conditions and to indicate the conditions for which there were obvious risks of jeopardising the structural integrity of the coolant systems. In the latter case also some analyses were made to indicate conceivable mitigating measures for maintaining the integrity.The analyses were primarily concerned with the First Wall and Divertor heat transfer systems. Several enveloping transients were analysed with associated specific flow and heat load boundary conditions. The analyses were performed with the ATHENA and INTRA codes 8 refs, 14 figs, 15 tabs

  11. Underestimation of species richness in neotropical frogs revealed by mtDNA analyses.

    Directory of Open Access Journals (Sweden)

    Antoine Fouquet

    2007-10-01

    Full Text Available Amphibians are rapidly vanishing. At the same time, it is most likely that the number of amphibian species is highly underestimated. Recent DNA barcoding work has attempted to define a threshold between intra- and inter-specific genetic distances to help identify candidate species. In groups with high extinction rates and poorly known species boundaries, like amphibians, such tools may provide a way to rapidly evaluate species richness.Here we analyse published and new 16S rDNA sequences from 60 frog species of Amazonia-Guianas to obtain a minimum estimate of the number of undescribed species in this region. We combined isolation by distance, phylogenetic analyses, and comparison of molecular distances to evaluate threshold values for the identification of candidate species among these frogs.In most cases, geographically distant populations belong to genetically highly distinct lineages that could be considered as candidate new species. This was not universal among the taxa studied and thus widespread species of Neotropical frogs really do exist, contrary to previous assumptions. Moreover, the many instances of paraphyly and the wide overlap between distributions of inter- and intra-specific distances reinforce the hypothesis that many cryptic species remain to be described. In our data set, pairwise genetic distances below 0.02 are strongly correlated with geographical distances. This correlation remains statistically significant until genetic distance is 0.05, with no such relation thereafter. This suggests that for higher distances allopatric and sympatric cryptic species prevail. Based on our analyses, we propose a more inclusive pairwise genetic distance of 0.03 between taxa to target lineages that could correspond to candidate species.Using this approach, we identify 129 candidate species, two-fold greater than the 60 species included in the current study. This leads to estimates of around 170 to 460 frog taxa unrecognized in Amazonia

  12. Quantitative proteomics reveals new insights into calcium-mediated resistance mechanisms in Aspergillus flavus against the antifungal protein PgAFP in cheese.

    Science.gov (United States)

    Delgado, Josué; Owens, Rebecca A; Doyle, Sean; Núñez, Félix; Asensio, Miguel A

    2017-09-01

    The ability of Aspergillus flavus to produce aflatoxins in dairy products presents a potential hazard. The antifungal protein PgAFP from Penicillium chrysogenum inhibits various foodborne toxigenic fungi, including Aspergillus flavus. However, PgAFP did not inhibit A. flavus growth in cheese, which was related to the associated cation content. CaCl 2 increased A. flavus permeability and prevented PgAFP-mediated inhibition in potato dextrose broth (PDB). PgAFP did not elicit any additional increase in permeability of CaCl 2 -incubated A. flavus. Furthermore, PgAFP did not alter metabolic capability, chitin deposition, or hyphal viability of A. flavus grown with CaCl 2 . Comparative proteomic analysis after PgAFP treatment of A. flavus in calcium-enriched PDB revealed increased abundance of 125 proteins, including oxidative stress-related proteins, as determined by label-free mass spectrometry (MS)-based proteomics. Seventy proteins were found at lower abundance, with most involved in metabolic pathways and biosynthesis of secondary metabolites. These changes do not support the blockage of potential PgAFP receptors in A. flavus by calcium as the main cause of the protective role. A. flavus resistance appears to be mediated by calcineurin, G-protein, and γ-glutamyltranspeptidase that combat oxidative stress and impede apoptosis. These findings could serve to design strategies to improve PgAFP activity against aflatoxigenic moulds in dairy products. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Specificity in mediated pathways by anxiety symptoms linking adolescent stress profiles to depressive symptoms: Results of a moderated mediation approach.

    Science.gov (United States)

    Anyan, Frederick; Bizumic, Boris; Hjemdal, Odin

    2018-03-01

    We investigated the specificity in mediated pathways that separately link specific stress dimensions through anxiety to depressive symptoms and the protective utility of resilience. Thus, this study goes beyond lumping together potential mediating and moderating processes that can explain the relations between stress and (symptoms of) psychopathology and the buffering effect of resilience. Ghanaian adolescents between 13 and 17 years (female = 285; male = 244) completed the Adolescent Stress Questionnaire (ASQ), Spielberger State Anxiety Inventory (STAI), Short Mood Feeling Questionnaire (SMFQ) and the Resilience Scale for Adolescents (READ). Independent samples t-test, multivariate analysis of covariance with follow-up tests and moderated mediation analyses were performed. Evidences were found for specificity in the associations between dimensions of adolescent stressors and depressive symptoms independent of transient anxiety. Transient anxiety partly accounted for the indirect effects of eight stress dimensions on depressive symptoms. Except stress of school attendance and school/leisure conflict, resilience moderated the indirect effects of specific stress dimensions on depressive symptoms. Results suggested differences in how Ghanaian adolescents view the various stress dimensions, and mediated pathways associated with anxiety and depressive symptoms. Use of cross-sectional data does not show causal process and temporal changes over time. Findings support and clarify the specificity in the interrelations and mediated pathways among dimensions of adolescent stress, transient anxiety, and depressive symptoms. Conditional process analyses shows that resilience does not only buffer direct, but also indirect psychological adversities. Interventions for good mental health may focus on low resilience subgroups in specific stress dimensions while minimizing transient anxiety. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. The mediating role of nurses' professional commitment in the relationship between core self-evaluation and job satisfaction.

    Science.gov (United States)

    Barać, Ivana; Prlić, Nada; Plužarić, Jadranka; Farčić, Nikolina; Kovačević, Suzana

    2018-05-11

    The aim of this study was to examine the degree to which it is possible to predict job satisfaction in hospital nurses based on core self-evaluation and the nurses' professional commitment. Psychological constructs of nurses' professional commitment could predict a level of job satisfaction. A cross-sectional design was applied. Data were collected between April 2016 and November 2016 from 584 nurses of the University Hospital Osijek. Core Self-Evaluation Scale (CSES), Job Satisfaction Survey (JSS) and Nurses' professional commitment scale (NPCS) were administrated to the study participants. Confirmatory factor analyses were conducted to test the validity of each questionnaire. Structural equation modeling was used to test the prediction of nurses' professional commitment and core self-evaluation on job satisfaction. Nurses' professional commitment is variable, which functions as a mediator between predictor (CSE) and criterion variable (JS). As a mediator, it explains what the effect is, provided that correlations between all variables are significant. The correlation analyses reveal significant positive correlations between job satisfaction and core self evaluation (r = 0.441, p > 0.001) and also between job satisfaction and nurses' professional commitment (r = 0.464, p > 0.001). Furthermore, core self evaluation significantly and positively correlates with nurses' professional commitment (r = 0.402, p > 0.001). The results showed that nurses' professional commitment mediates the relationship between core self evaluation and job satisfaction. Bootstrap analysis showed that core self evaluation partially mediated the relationship between nurses' professional commitment and job satisfaction ( β = 0.78, p core self evaluation on job satisfaction through nurses' professional commitment was also significant (β = 0.17, p < 0.001**). Nurses who are more committed to their work, regardless of the structure of personality, have greater satisfaction in their work. This

  15. Metabarcoding and metabolome analyses of copepod grazing reveal feeding preference and linkage to metabolite classes in dynamic microbial plankton communities.

    Science.gov (United States)

    Ray, Jessica L; Althammer, Julia; Skaar, Katrine S; Simonelli, Paolo; Larsen, Aud; Stoecker, Diane; Sazhin, Andrey; Ijaz, Umer Z; Quince, Christopher; Nejstgaard, Jens C; Frischer, Marc; Pohnert, Georg; Troedsson, Christofer

    2016-11-01

    In order to characterize copepod feeding in relation to microbial plankton community dynamics, we combined metabarcoding and metabolome analyses during a 22-day seawater mesocosm experiment. Nutrient amendment of mesocosms promoted the development of haptophyte (Phaeocystis pouchetii)- and diatom (Skeletonema marinoi)-dominated plankton communities in mesocosms, in which Calanus sp. copepods were incubated for 24 h in flow-through chambers to allow access to prey particles (<500 μm). Copepods and mesocosm water sampled six times spanning the experiment were analysed using metabarcoding, while intracellular metabolite profiles of mesocosm plankton communities were generated for all experimental days. Taxon-specific metabarcoding ratios (ratio of consumed prey to available prey in the surrounding seawater) revealed diverse and dynamic copepod feeding selection, with positive selection on large diatoms, heterotrophic nanoflagellates and fungi, while smaller phytoplankton, including P. pouchetii, were passively consumed or even negatively selected according to our indicator. Our analysis of the relationship between Calanus grazing ratios and intracellular metabolite profiles indicates the importance of carbohydrates and lipids in plankton succession and copepod-prey interactions. This molecular characterization of Calanus sp. grazing therefore provides new evidence for selective feeding in mixed plankton assemblages and corroborates previous findings that copepod grazing may be coupled to the developmental and metabolic stage of the entire prey community rather than to individual prey abundances. © 2016 John Wiley & Sons Ltd.

  16. Tear Mediators in Corneal Ectatic Disorders.

    Directory of Open Access Journals (Sweden)

    Dorottya Pásztor

    Full Text Available To compare the concentrations of 11 tear mediators in order to reveal the biochemical difference between pellucid marginal degeneration (PMD and keratoconus (KC.We have designed a cross-sectional study in which patients with corneal ectasia based on slit-lamp biomicroscopy and Pentacam HR (keratometry values (K1, K2, Kmax, astigmatism, minimal radius of curvature (Rmin, corneal thickness (Apex and Min, indices (surface variation, vertical asymmetry, keratoconus, central keratoconus, height asymmetry and decentration were enrolled. Eyes of keratoconic patients were similar to the PMD patients in age and severity (K2, Kmax and Rmin. Non-stimulated tear samples were collected from nine eyes of seven PMD patients, 55 eyes of 55 KC patients and 24 eyes of 24 healthy controls. The mediators' (interleukin -6, -10, chemokine ligand 5, -8, -10, matrix metalloproteinase (MMP -9, -13, tissue inhibitor of metalloproteinases (TIMP-1, tissue plasminogen activator, plasminogen activator inhibitor, nerve growth factor concentrations were measured using Cytometric Bead Array.MMP-9 was the only mediator which presented relevant variances between the two patient groups (p = 0.005. The ratios of MMP-9 and TIMP-1 were 2.45, 0.40 and 0.23 in PMD, KC and the controls, respectively.As far as we are aware, this is the first study that aims to reveal the biochemical differences between PMD and KC. Further studies of biomarkers to investigate the precise role of these mediators need to be defined, and it is important to confirm the observed changes in a larger study to gain further insights into the molecular alterations in PMD.

  17. The Mediatization of Politics in Contemporary Scandinavian Film and Television

    DEFF Research Database (Denmark)

    Bondebjerg, Ib

    2015-01-01

    the relation between media, public figures and the citizen. In this article, I will discuss main positions in theories on the mediatization of politics. I will also discuss and analyse three types of film and television genres that reflect this mediatization of politics in Scandinavian film and television...... culture: the political documentary, the political drama and the “nordic noir” crime genre....

  18. FRET biosensors reveal AKAP-mediated shaping of subcellular PKA activity and a novel mode of Ca(2+)/PKA crosstalk.

    Science.gov (United States)

    Schott, Micah B; Gonowolo, Faith; Maliske, Benjamin; Grove, Bryon

    2016-04-01

    Scaffold proteins play a critical role in cellular homeostasis by anchoring signaling enzymes in close proximity to downstream effectors. In addition to anchoring static enzyme complexes, some scaffold proteins also form dynamic signalosomes that can traffic to different subcellular compartments upon stimulation. Gravin (AKAP12), a multivalent scaffold, anchors PKA and other enzymes to the plasma membrane under basal conditions, but upon [Ca(2+)]i elevation, is rapidly redistributed to the cytosol. Because gravin redistribution also impacts PKA localization, we postulate that gravin acts as a calcium "switch" that modulates PKA-substrate interactions at the plasma membrane, thus facilitating a novel crosstalk mechanism between Ca(2+) and PKA-dependent pathways. To assess this, we measured the impact of gravin-V5/His expression on compartmentalized PKA activity using the FRET biosensor AKAR3 in cultured cells. Upon treatment with forskolin or isoproterenol, cells expressing gravin-V5/His showed elevated levels of plasma membrane PKA activity, but cytosolic PKA activity levels were reduced compared with control cells lacking gravin. This effect required both gravin interaction with PKA and localization at the plasma membrane. Pretreatment with calcium-elevating agents thapsigargin or ATP caused gravin redistribution away from the plasma membrane and prevented gravin from elevating PKA activity levels at the membrane. Importantly, this mode of Ca(2+)/PKA crosstalk was not observed in cells expressing a gravin mutant that resisted calcium-mediated redistribution from the cell periphery. These results reveal that gravin impacts subcellular PKA activity levels through the spatial targeting of PKA, and that calcium elevation modulates downstream β-adrenergic/PKA signaling through gravin redistribution, thus supporting the hypothesis that gravin mediates crosstalk between Ca(2+) and PKA-dependent signaling pathways. Based on these results, AKAP localization dynamics may

  19. FRET biosensors reveal AKAP-mediated shaping of subcellular PKA activity and a novel mode of Ca2+/PKA crosstalk

    Science.gov (United States)

    Schott, Micah; Gonowolo, Faith; Maliske, Ben; Grove, Bryon

    2016-01-01

    Scaffold proteins play a critical role in cellular homeostasis by anchoring signaling enzymes in close proximity to downstream effectors. In addition to anchoring static enzyme complexes, some scaffold proteins also form dynamic signalosomes that can traffic to different subcellular compartments upon stimulation. Gravin (AKAP12), a multivalent scaffold, anchors PKA and other enzymes to the plasma membrane under basal conditions, but upon [Ca2+]i elevation, is rapidly redistributed to the cytosol. Because gravin redistribution also impacts PKA localization, we postulate that gravin acts as a calcium “switch” that modulates PKA-substrate interactions at the plasma membrane, thus facilitating a novel crosstalk mechanism between Ca2+ and PKA-dependent pathways. To assess this, we measured the impact of gravin-V5/His expression on compartmentalized PKA activity using the FRET biosensor AKAR3 in cultured cells. Upon treatment with forskolin or isoproterenol, cells expressing gravin-V5/His showed elevated levels of plasma membrane PKA activity, but cytosolic PKA activity levels were reduced compared with control cells lacking gravin. This effect required both gravin interaction with PKA and localization at the plasma membrane. Pretreatment with calcium-elevating agents thapsigargin or ATP caused gravin redistribution away from the plasma membrane and prevented gravin from elevating PKA activity levels at the membrane. Importantly, this mode of Ca2+/PKA crosstalk was not observed in cells expressing a gravin mutant that resists calcium-mediated redistribution from the cell periphery. These results reveal that gravin impacts subcellular PKA activity levels through the spatial targeting of PKA, and that calcium elevation modulates downstream β-adrenergic/PKA signaling through gravin redistribution, thus supporting the hypothesis that gravin mediates crosstalk between Ca2+ and PKA-dependent signaling pathways. Based on these results, AKAP localization dynamics may

  20. Histo-chemical and biochemical analysis reveals association of er1 mediated powdery mildew resistance and redox balance in pea.

    Science.gov (United States)

    Mohapatra, Chinmayee; Chand, Ramesh; Navathe, Sudhir; Sharma, Sandeep

    2016-09-01

    Powdery mildew caused by Erysiphe pisi is one of the important diseases responsible for heavy yield losses in pea crop worldwide. The most effective method of controlling the disease is the use of resistant varieties. The resistance to powdery mildew in pea is recessive and governed by a single gene er1. The objective of present study is to investigate if er1 mediated powdery mildew resistance is associated with changes in the redox status of the pea plant. 16 pea genotypes were screened for powdery mildew resistance in field condition for two years and, also, analyzed for the presence/absence of er1 gene. Histochemical analysis with DAB and NBT staining indicates accumulation of reactive oxygen species (ROS) in surrounding area of powdery mildew infection which was higher in susceptible genotypes as compared to resistant genotypes. A biochemical study revealed that the activity of superoxide dismutase (SOD) and catalase, enzymes involved in scavenging ROS, was increased in, both, resistant and susceptible genotypes after powdery mildew infection. However, both enzymes level was always higher in resistant than susceptible genotypes throughout time course of infection. Moreover, irrespective of any treatment, the total phenol (TP) and malondialdehyde (MDA) content was significantly high and low in resistant genotypes, respectively. The powdery mildew infection elevated the MDA content but decreased the total phenol in pea genotypes. Statistical analysis showed a strong positive correlation between AUDPC and MDA; however, a negative correlation was observed between AUDPC and SOD, CAT and TP. Heritability of antioxidant was also high. The study identified few novel genotypes resistant to powdery mildew infection that carried the er1 gene and provided further clue that er1 mediated defense response utilizes antioxidant machinery to confer powdery mildew resistance in pea. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Liang He

    2016-10-01

    Full Text Available Age-related diseases may result from shared biological mechanisms in intrinsic processes of aging. Genetic effects on age-related diseases are often modulated by environmental factors due to their little contribution to fitness or are mediated through certain endophenotypes. Identification of genetic variants with pleiotropic effects on both common complex diseases and endophenotypes may reveal potential conflicting evolutionary pressures and deliver new insights into shared genetic contribution to healthspan and lifespan. Here, we performed pleiotropic meta-analyses of genetic variants using five NIH-funded datasets by integrating univariate summary statistics for age-related diseases and endophenotypes. We investigated three groups of traits: (1 endophenotypes such as blood glucose, blood pressure, lipids, hematocrit, and body mass index, (2 time-to-event outcomes such as the age-at-onset of diabetes mellitus (DM, cancer, cardiovascular diseases (CVDs and neurodegenerative diseases (NDs, and (3 both combined. In addition to replicating previous findings, we identify seven novel genome-wide significant loci (< 5e-08, out of which five are low-frequency variants. Specifically, from Group 2, we find rs7632505 on 3q21.1 in SEMA5B, rs460976 on 21q22.3 (1 kb from TMPRSS2 and rs12420422 on 11q24.1 predominantly associated with a variety of CVDs, rs4905014 in ITPK1 associated with stroke and heart failure, rs7081476 on 10p12.1 in ANKRD26 associated with multiple diseases including DM, CVDs, and NDs. From Group 3, we find rs8082812 on 18p11.22 and rs1869717 on 4q31.3 associated with both endophenotypes and CVDs. Our follow-up analyses show that rs7632505, rs4905014, and rs8082812 have age-dependent effects on coronary heart disease or stroke. Functional annotation suggests that most of these SNPs are within regulatory regions or DNase clusters and in linkage disequilibrium with expression quantitative trait loci, implying their potential regulatory

  2. Mediation, identification, and plausibility: an illustration using children's mental health services.

    Science.gov (United States)

    Foster, E Michael

    2014-10-01

    Analyses of mediation are important for understanding the effects of mental health services and treatments. The most common approach is to add potential mediators as regressors and to estimate the direct and indirect effects of the treatment of interest. This practice makes the strong assumption that the mediator itself does not suffer from unobserved confounding--that it is as if randomly assigned. In many instances, this assumption seems rather implausible. The objective of this article is to describe the identification problem that represents the fundamental challenge of causal inference. It outlines how mediation complicates identification and considers several identification strategies. The goal of this article is not to propose a new method for handling mediation or to identify a best method for doing so. The latter, in fact, is impossible. The contribution of the article is to illustrate how one can think about possible approaches to mediation in the context of a specific empirical study. Using data from a large evaluation of a demonstration project in children's mental health services (n = 763), the article illustrates identification strategies. That demonstration improved service delivery in several ways but primarily by offering services "intermediate" between inpatient and outpatient. These analyses focus on the impact of these intermediate services on 6-month improvement in a behavior checklist commonly used to measure psychopathology and competence among children and youths. The results highlight how different identification strategies produce different answers to key questions. These alternative findings have to be assessed in light of substantive knowledge of the program involved. The analyses generally support the notion that children and youths treated at the demonstration site who received intermediate services benefited from them. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  3. Interpreting instructional cues in task switching procedures: the role of mediator retrieval.

    Science.gov (United States)

    Logan, Gordon D; Schneider, Darryl W

    2006-03-01

    In 3 experiments the role of mediators in task switching with transparent and nontransparent cues was examined. Subjects switched between magnitude (greater or less than 5) and parity (odd or even) judgments of single digits. A cue-target congruency effect indicated mediator use: subjects responded faster to congruent cue-target combinations (e.g., ODD-3) than to incongruent cue-target combinations (e.g., ODD-4). Experiment 1 revealed significant congruency effects with transparent word cues (ODD, EVEN, HIGH, and LOW) and with relatively transparent letter cues (O, E, H, and L) but not with nontransparent letter cues (D, V, G, and W). Experiment 2 revealed significant congruency effects after subjects who were trained with nontransparent letter cues were informed of the relations between cues and word mediators halfway through the experiment. Experiment 3 showed that congruency effects with relatively transparent letter cues diminished over 10 sessions of practice, suggesting that subjects used mediators less as practice progressed. The results are discussed in terms of the role of mediators in interpreting instructional cues.

  4. Subunit architecture and functional modular rearrangements of the transcriptional mediator complex.

    Science.gov (United States)

    Tsai, Kuang-Lei; Tomomori-Sato, Chieri; Sato, Shigeo; Conaway, Ronald C; Conaway, Joan W; Asturias, Francisco J

    2014-06-05

    The multisubunit Mediator, comprising ∼30 distinct proteins, plays an essential role in gene expression regulation by acting as a bridge between DNA-binding transcription factors and the RNA polymerase II (RNAPII) transcription machinery. Efforts to uncover the Mediator mechanism have been hindered by a poor understanding of its structure, subunit organization, and conformational rearrangements. By overcoming biochemical and image analysis hurdles, we obtained accurate EM structures of yeast and human Mediators. Subunit localization experiments, docking of partial X-ray structures, and biochemical analyses resulted in comprehensive mapping of yeast Mediator subunits and a complete reinterpretation of our previous Mediator organization model. Large-scale Mediator rearrangements depend on changes at the interfaces between previously described Mediator modules, which appear to be facilitated by factors conducive to transcription initiation. Conservation across eukaryotes of Mediator structure, subunit organization, and RNA polymerase II interaction suggest conservation of fundamental aspects of the Mediator mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Honeybee glucose oxidase—its expression in honeybee workers and comparative analyses of its content and H2O2-mediated antibacterial activity in natural honeys

    Science.gov (United States)

    Bucekova, Marcela; Valachova, Ivana; Kohutova, Lenka; Prochazka, Emanuel; Klaudiny, Jaroslav; Majtan, Juraj

    2014-08-01

    Antibacterial properties of honey largely depend on the accumulation of hydrogen peroxide (H2O2), which is generated by glucose oxidase (GOX)-mediated conversion of glucose in diluted honey. However, honeys exhibit considerable variation in their antibacterial activity. Therefore, the aim of the study was to identify the mechanism behind the variation in this activity and in the H2O2 content in honeys associated with the role of GOX in this process. Immunoblots and in situ hybridization analyses demonstrated that gox is solely expressed in the hypopharyngeal glands of worker bees performing various tasks and not in other glands or tissues. Real-time PCR with reference genes selected for worker heads shows that the gox expression progressively increases with ageing of the youngest bees and nurses and reached the highest values in processor bees. Immunoblot analysis of honey samples revealed that GOX is a regular honey component but its content significantly varied among honeys. Neither botanical source nor geographical origin of honeys affected the level of GOX suggesting that some other factors such as honeybee nutrition and/or genetic/epigenetic factors may take part in the observed variation. A strong correlation was found between the content of GOX and the level of generated H2O2 in honeys except honeydew honeys. Total antibacterial activity of most honey samples against Pseudomonas aeruginosa isolate significantly correlated with the H2O2 content. These results demonstrate that the level of GOX can significantly affect the total antibacterial activity of honey. They also support an idea that breeding of novel honeybee lines expressing higher amounts of GOX could help to increase the antibacterial efficacy of the hypopharyngeal gland secretion that could have positive influence on a resistance of colonies against bacterial pathogens.

  6. Cocaine induces astrocytosis through ER stress-mediated activation of autophagy

    Science.gov (United States)

    Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

    2016-01-01

    ABSTRACT Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation. PMID:27337297

  7. Recent breakthroughs in metabolomics promise to reveal the cryptic chemical traits that mediate plant community composition, character evolution and lineage diversification.

    Science.gov (United States)

    Sedio, Brian E

    2017-05-01

    Contents 952 I. 952 II. 953 III. 955 IV. 956 V. 957 957 References 957 SUMMARY: Much of our understanding of the mechanisms by which biotic interactions shape plant communities has been constrained by the methods available to study the diverse secondary chemistry that defines plant relationships with other organisms. Recent innovations in analytical chemistry and bioinformatics promise to reveal the cryptic chemical traits that mediate plant ecology and evolution by facilitating simultaneous structural comparisons of hundreds of unknown molecules to each other and to libraries of known compounds. Here, I explore the potential for mass spectrometry and nuclear magnetic resonance metabolomics to enable unprecedented tests of seminal, but largely untested hypotheses that propose a fundamental role for plant chemical defenses against herbivores and pathogens in the evolutionary origins and ecological coexistence of plant species diversity. © 2017 The Author. New Phytologist © 2017 New Phytologist Trust.

  8. Mediator phosphorylation prevents stress response transcription during non-stress conditions.

    Science.gov (United States)

    Miller, Christian; Matic, Ivan; Maier, Kerstin C; Schwalb, Björn; Roether, Susanne; Strässer, Katja; Tresch, Achim; Mann, Matthias; Cramer, Patrick

    2012-12-28

    The multiprotein complex Mediator is a coactivator of RNA polymerase (Pol) II transcription that is required for the regulated expression of protein-coding genes. Mediator serves as an end point of signaling pathways and regulates Pol II transcription, but the mechanisms it uses are not well understood. Here, we used mass spectrometry and dynamic transcriptome analysis to investigate a functional role of Mediator phosphorylation in gene expression. Affinity purification and mass spectrometry revealed that Mediator from the yeast Saccharomyces cerevisiae is phosphorylated at multiple sites of 17 of its 25 subunits. Mediator phosphorylation levels change upon an external stimulus set by exposure of cells to high salt concentrations. Phosphorylated sites in the Mediator tail subunit Med15 are required for suppression of stress-induced changes in gene expression under non-stress conditions. Thus dynamic and differential Mediator phosphorylation contributes to gene regulation in eukaryotic cells.

  9. Thought-action fusion as a mediator of religiosity and obsessive-compulsive symptoms.

    Science.gov (United States)

    Williams, Alishia D; Lau, Gloria; Grisham, Jessica R

    2013-06-01

    Thought-action fusion (TAF), or maladaptive cognitions regarding the relationship between mental events and behaviours, has been implicated in the development and maintenance of obsessive-compulsive disorder (OCD). As some religions promote TAF-like appraisals, it has been proposed that religiosity may play a role in the transformation of normally occurring intrusive thoughts into clinically distressing obsessions. No research, however, has experimentally investigated the mediating role of TAF on the relationship between religiosity and OC symptoms. 85 Christian, Jewish, and Atheist/Agnostic participants were exposed to an experimental thought-induction protocol and reported on their associated levels of distress, guilt, feelings of responsibility, and urge to suppress target intrusions experienced during a 5-min monitoring period. Participants also completed measures of obsessive-compulsive symptomatology, TAF beliefs, and general psychopathology. Using PROCESS and bootstrapping analyses, a test of the conditional indirect effects of religiosity on obsessive-compulsive symptoms revealed that Christianity moderated the effects of religiosity on moral TAF beliefs, which in turn mediated the relationship between religiosity and obsessive-compulsive symptoms. Furthermore, in the Christian group, moral TAF beliefs mediated the relationship between religiosity and ratings of guilt and responsibility following the experimental protocol. The use of university students with moderate levels of religiosity. Collectively the results suggest that obsessional thinking is not attributable to religion per se, but that teachings underlying certain religious doctrines may fuel TAF beliefs that are implicated in the maintenance of OCD. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. The neural mechanisms of affect infusion in social economic decision-making: a mediating role of the anterior insula.

    Science.gov (United States)

    Harlé, Katia M; Chang, Luke J; van 't Wout, Mascha; Sanfey, Alan G

    2012-05-15

    Though emotions have been shown to have sometimes dramatic effects on decision-making, the neural mechanisms mediating these biases are relatively unexplored. Here, we investigated how incidental affect (i.e. emotional states unrelated to the decision at hand) may influence decisions, and how these biases are implemented in the brain. Nineteen adult participants made decisions which involved accepting or rejecting monetary offers from others in an Ultimatum Game while undergoing functional magnetic resonance imaging (fMRI). Prior to each set of decisions, participants watched a short video clip aimed at inducing either a sad or neutral emotional state. Results demonstrated that, as expected, sad participants rejected more unfair offers than those in the neutral condition. Neuroimaging analyses revealed that receiving unfair offers while in a sad mood elicited activity in brain areas related to aversive emotional states and somatosensory integration (anterior insula) and to cognitive conflict (anterior cingulate cortex). Sad participants also showed a diminished sensitivity in neural regions associated with reward processing (ventral striatum). Importantly, insular activation uniquely mediated the relationship between sadness and decision bias. This study is the first to reveal how subtle mood states can be integrated at the neural level to influence decision-making. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Genetic and biochemical evidences reveal novel insights into the ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 41; Issue 4. Genetic and biochemical evidences reveal novel insights into the mechanism underlying Saccharomyces cerevisiae Sae2-mediated abrogation of DNA replication stress. INDRAJEET GHODKE K MUNIYAPPA. ARTICLE Volume 41 Issue 4 December 2016 pp ...

  12. Direct and Mediated Effects of a Social-Emotional and Character Development Program on Adolescent Substance Use

    Directory of Open Access Journals (Sweden)

    Kendra M. Lewis

    2012-04-01

    Full Text Available Mitigating and preventing substance use among adolescents requires approaches that address the multitude of factors that influence this behavior. Such approaches must be tested, not only for evidence of empirical effectiveness, but also to determine the mechanisms by which they are successful. The aims of the present study were twofold: 1 To determine the effectiveness of a school-based social-emotional and character development (SECD program, Positive Action (PA, in reducing substance use (SU among a sample of U.S. youth living in a low-income, urban environment, and 2 to test one mechanism by which the program achieves its success. We used longitudinal mediation analysis to test the hypotheses that: 1 students attending PA intervention schools engage in significantly less SU than students attending control schools, 2 students attending PA intervention schools show significantly better change in SECD than students attending control schools, and 3 the effect of the PA intervention on SU is mediated by the change in SECD. Analyses revealed program effects on both SECD and SU, a relationship between SECD and SU, and the effects of PA on SU were completely mediated by changes in SECD. Future research directions and implications for school-based social-emotional and character development efforts and substance use prevention are addressed.

  13. Mitochondrial DNA analyses revealed low genetic diversity in the endangered Indian wild ass Equus hemionus khur.

    Science.gov (United States)

    Khaire, Devendra; Atkulwar, Ashwin; Farah, Sameera; Baig, Mumtaz

    2017-09-01

    The Indian wild ass Equus hemionus khur, belonging to ass-like equid branch, inhabits the dry and arid desert of the Little Rann of Kutch, Gujarat. The E. h. khur is the sole survivor of Asiatic wild ass species/subspecies in South Asia. To provide first ever insights into the genetic diversity, phylogeny, and demography of the endangered Indian wild ass, we sampled 52 free-ranging individuals from the Little Rann of Kutch by using a non-invasive methodology. The sequencing of 230 bp in cytochrome b (Cyt b) and displacement loop (D-loop) region revealed that current ∼4000 extant population of Indian wild ass harbours low genetic diversity. Phylogenetic analyses confirmed that E. h. khur, E. h. onager, and E. h. kulan belong to a single strict monophyletic clade. Therefore, we suggest the delimitation of the five E. hemionus subspecies in vogue to a single species E. hemionus. The application of molecular clock confirmed that the Asiatic wild ass had undergone diversification 0.65 Million years ago. Demographic measurements assessed using a Bayesian skyline plot demonstrated decline in the maternal effective population size of the Indian wild ass during different periods; these periods coincided with the origin and rise of the Indus civilization in the northwest of the Indian subcontinent during the Neolithic. In conclusion, maintaining high genetic diversity in the existing isolated population of 4000 Indian wild asses inhabiting the wild ass sanctuary is important compared with subspecies preservation alone.

  14. Regulatory complexity revealed by integrated cytological and RNA-seq analyses of meiotic substages in mouse spermatocytes.

    Science.gov (United States)

    Ball, Robyn L; Fujiwara, Yasuhiro; Sun, Fengyun; Hu, Jianjun; Hibbs, Matthew A; Handel, Mary Ann; Carter, Gregory W

    2016-08-12

    The continuous and non-synchronous nature of postnatal male germ-cell development has impeded stage-specific resolution of molecular events of mammalian meiotic prophase in the testis. Here the juvenile onset of spermatogenesis in mice is analyzed by combining cytological and transcriptomic data in a novel computational analysis that allows decomposition of the transcriptional programs of spermatogonia and meiotic prophase substages. Germ cells from testes of individual mice were obtained at two-day intervals from 8 to 18 days post-partum (dpp), prepared as surface-spread chromatin and immunolabeled for meiotic stage-specific protein markers (STRA8, SYCP3, phosphorylated H2AFX, and HISTH1T). Eight stages were discriminated cytologically by combinatorial antibody labeling, and RNA-seq was performed on the same samples. Independent principal component analyses of cytological and transcriptomic data yielded similar patterns for both data types, providing strong evidence for substage-specific gene expression signatures. A novel permutation-based maximum covariance analysis (PMCA) was developed to map co-expressed transcripts to one or more of the eight meiotic prophase substages, thereby linking distinct molecular programs to cytologically defined cell states. Expression of meiosis-specific genes is not substage-limited, suggesting regulation of substage transitions at other levels. This integrated analysis provides a general method for resolving complex cell populations. Here it revealed not only features of meiotic substage-specific gene expression, but also a network of substage-specific transcription factors and relationships to potential target genes.

  15. The function of the Mediator complex in plant immunity.

    Science.gov (United States)

    An, Chuanfu; Mou, Zhonglin

    2013-03-01

    Upon pathogen infection, plants undergo dramatic transcriptome reprogramming to shift from normal growth and development to immune response. During this rapid process, the multiprotein Mediator complex has been recognized as an important player to fine-tune gene-specific and pathway-specific transcriptional reprogramming by acting as an adaptor/coregulator between sequence-specific transcription factor and RNA polymerase II (RNAPII). Here, we review current understanding of the role of five functionally characterized Mediator subunits (MED8, MED15, MED16, MED21 and MED25) in plant immunity. All these Mediator subunits positively regulate resistance against leaf-infecting biotrophic bacteria or necrotrophic fungi. While MED21 appears to regulate defense against fungal pathogens via relaying signals from upstream regulators and chromatin modification to RNAPII, the other four Mediator subunits locate at different positions of the defense network to convey phytohormone signal(s). Fully understanding the role of Mediator in plant immunity needs to characterize more Mediator subunits in both Arabidopsis and other plant species. Identification of interacting proteins of Mediator subunits will further help to reveal their specific regulatory mechanisms in plant immunity.

  16. Functional characterisation of an intron retaining K+ transporter of barley reveals intron-mediated alternate splicing

    KAUST Repository

    Shahzad, K.; Rauf, M.; Ahmed, M.; Malik, Z. A.; Habib, I.; Ahmed, Z.; Mahmood, K.; Ali, R.; Masmoudi, K.; Lemtiri-Chlieh, Fouad; Gehring, Christoph A; Berkowitz, G. A.; Saeed, N. A.

    2015-01-01

    Intron retention in transcripts and the presence of 5 and 3 splice sites within these introns mediate alternate splicing, which is widely observed in animals and plants. Here, functional characterisation of the K+ transporter, HvHKT2;1, with stably

  17. Redefining the modular organization of the core Mediator complex.

    Science.gov (United States)

    Wang, Xuejuan; Sun, Qianqian; Ding, Zhenrui; Ji, Jinhua; Wang, Jianye; Kong, Xiao; Yang, Jianghong; Cai, Gang

    2014-07-01

    The Mediator complex plays an essential role in the regulation of eukaryotic transcription. The Saccharomyces cerevisiae core Mediator comprises 21 subunits, which are organized into Head, Middle and Tail modules. Previously, the Head module was assigned to a distinct dense domain at the base, and the Middle and Tail modules were identified to form a tight structure above the Head module, which apparently contradicted findings from many biochemical and functional studies. Here, we compared the structures of the core Mediator and its subcomplexes, especially the first 3D structure of the Head + Middle modules, which permitted an unambiguous assignment of the three modules. Furthermore, nanogold labeling pinpointing four Mediator subunits from different modules conclusively validated the modular assignment, in which the Head and Middle modules fold back on one another and form the upper portion of the core Mediator, while the Tail module forms a distinct dense domain at the base. The new modular model of the core Mediator has reconciled the previous inconsistencies between the structurally and functionally defined Mediator modules. Collectively, these analyses completely redefine the modular organization of the core Mediator, which allow us to integrate the structural and functional information into a coherent mechanism for the Mediator's modularity and regulation in transcription initiation.

  18. Organophotocatalysis: Insights into the Mechanistic Aspects of Thiourea-Mediated Intermolecular [2+2] Photocycloadditions.

    Science.gov (United States)

    Vallavoju, Nandini; Selvakumar, Sermadurai; Pemberton, Barry C; Jockusch, Steffen; Sibi, Mukund P; Sivaguru, Jayaraman

    2016-04-25

    Mechanistic investigations of the intermolecular [2+2] photocycloaddition of coumarin with tetramethylethylene mediated by thiourea catalysts reveal that the reaction is enabled by a combination of minimized aggregation, enhanced intersystem crossing, and altered excited-state lifetime(s). These results clarify how the excited-state reactivity can be manipulated through catalyst-substrate interactions and reveal a third mechanistic pathway for thiourea-mediated organo-photocatalysis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Synthesis and Characterization of Optically Active Fractal Seed Mediated Silver Nickel Bimetallic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Joseph Adeyemi Adekoya

    2014-01-01

    Full Text Available The synthesis of new seed mediated AgNi allied bimetallic nanocomposites was successfully carried out by the successive reduction of the metal ions in diethylene glycol, ethylene glycol, glycerol, and pentaerythritol solutions, with concomitant precipitation of Ag/Ni bimetal sols. The optical measurement revealed the existence of distinct band edge with surface plasmon resonance (SPR in the region of 400–425 nm and excitonic emission with maximum peak at 382 nm which were reminiscent of cluster-in-cluster surface enriched bimetallic silver-nickel sols. The morphological characterization by transmission electron microscopy, high resolution transmission electron microscopy, and X-ray diffraction analyses complimented by surface scan using X-ray photoelectron spectroscopy strongly supported the formation of intimately alloyed face-centered silver/nickel nanoclusters.

  20. Phenotype specific analyses reveal distinct regulatory mechanism for chronically activated p53.

    Directory of Open Access Journals (Sweden)

    Kristina Kirschner

    2015-03-01

    Full Text Available The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context, and persistent p53 activation has recently been implicated in tumor suppression and senescence. However, genome-wide information about p53-target gene regulation has been derived mostly from acute genotoxic conditions. Using ChIP-seq and expression data, we have found distinct p53 binding profiles between acutely activated (through DNA damage and chronically activated (in senescent or pro-apoptotic conditions p53. Compared to the classical 'acute' p53 binding profile, 'chronic' p53 peaks were closely associated with CpG-islands. Furthermore, the chronic CpG-island binding of p53 conferred distinct expression patterns between senescent and pro-apoptotic conditions. Using the p53 targets seen in the chronic conditions together with external high-throughput datasets, we have built p53 networks that revealed extensive self-regulatory 'p53 hubs' where p53 and many p53 targets can physically interact with each other. Integrating these results with public clinical datasets identified the cancer-associated lipogenic enzyme, SCD, which we found to be directly repressed by p53 through the CpG-island promoter, providing a mechanistic link between p53 and the 'lipogenic phenotype', a hallmark of cancer. Our data reveal distinct phenotype associations of chronic p53 targets that underlie specific gene regulatory mechanisms.

  1. The core regulatory network of the abscisic acid pathway in banana: genome-wide identification and expression analyses during development, ripening, and abiotic stress.

    Science.gov (United States)

    Hu, Wei; Yan, Yan; Shi, Haitao; Liu, Juhua; Miao, Hongxia; Tie, Weiwei; Ding, Zehong; Ding, XuPo; Wu, Chunlai; Liu, Yang; Wang, Jiashui; Xu, Biyu; Jin, Zhiqiang

    2017-08-29

    Abscisic acid (ABA) signaling plays a crucial role in developmental and environmental adaptation processes of plants. However, the PYL-PP2C-SnRK2 families that function as the core components of ABA signaling are not well understood in banana. In the present study, 24 PYL, 87 PP2C, and 11 SnRK2 genes were identified from banana, which was further supported by evolutionary relationships, conserved motif and gene structure analyses. The comprehensive transcriptomic analyses showed that banana PYL-PP2C-SnRK2 genes are involved in tissue development, fruit development and ripening, and response to abiotic stress in two cultivated varieties. Moreover, comparative expression analyses of PYL-PP2C-SnRK2 genes between BaXi Jiao (BX) and Fen Jiao (FJ) revealed that PYL-PP2C-SnRK2-mediated ABA signaling might positively regulate banana fruit ripening and tolerance to cold, salt, and osmotic stresses. Finally, interaction networks and co-expression assays demonstrated that the core components of ABA signaling were more active in FJ than in BX in response to abiotic stress, further supporting the crucial role of the genes in tolerance to abiotic stress in banana. This study provides new insights into the complicated transcriptional control of PYL-PP2C-SnRK2 genes, improves the understanding of PYL-PP2C-SnRK2-mediated ABA signaling in the regulation of fruit development, ripening, and response to abiotic stress, and identifies some candidate genes for genetic improvement of banana.

  2. Do attentional capacities and processing speed mediate the effect of age on executive functioning?

    Science.gov (United States)

    Gilsoul, Jessica; Simon, Jessica; Hogge, Michaël; Collette, Fabienne

    2018-02-06

    The executive processes are well known to decline with age, and similar data also exists for attentional capacities and processing speed. Therefore, we investigated whether these two last nonexecutive variables would mediate the effect of age on executive functions (inhibition, shifting, updating, and dual-task coordination). We administered a large battery of executive, attentional and processing speed tasks to 104 young and 71 older people, and we performed mediation analyses with variables showing a significant age effect. All executive and processing speed measures showed age-related effects while only the visual scanning task performance (selective attention) was explained by age when controlled for gender and educational level. Regarding mediation analyses, visual scanning partially mediated the age effect on updating while processing speed partially mediated the age effect on shifting, updating and dual-task coordination. In a more exploratory way, inhibition was also found to partially mediate the effect of age on the three other executive functions. Attention did not greatly influence executive functioning in aging while, in agreement with the literature, processing speed seems to be a major mediator of the age effect on these processes. Interestingly, the global pattern of results seems also to indicate an influence of inhibition but further studies are needed to confirm the role of that variable as a mediator and its relative importance by comparison with processing speed.

  3. Big data analyses reveal patterns and drivers of the movements of southern elephant seals

    KAUST Repository

    Rodrí guez, J. P.; Ferná ndez-Gracia, Juan; Thums, Michele; Hindell, Mark A.; Sequeira, Ana M. M.; Meekan, Mark G.; Costa, Daniel P.; Guinet, Christophe; Harcourt, R.; McMahon, Clive R.; Muelbert, Monica; Duarte, Carlos M.; Eguí luz, V. M.

    2017-01-01

    The growing number of large databases of animal tracking provides an opportunity for analyses of movement patterns at the scales of populations and even species. We used analytical approaches, developed to cope with

  4. Big data analyses reveal patterns and drivers of the movements of southern elephant seals

    KAUST Repository

    Rodríguez, Jorge P.

    2017-03-02

    The growing number of large databases of animal tracking provides an opportunity for analyses of movement patterns at the scales of populations and even species. We used analytical approaches, developed to cope with

  5. [(35)S]-GTPgammaS autoradiography reveals alpha(2) adrenoceptor-mediated G-protein activation in amygdala and lateral septum.

    Science.gov (United States)

    Newman-Tancredi, A; Chaput, C; Touzard, M; Millan, M J

    2000-04-03

    alpha(2)-adrenoceptor-mediated G-protein activation was examined by [(35)S]-GTPgammaS autoradiography. In alpha(2)-adrenoceptor-rich regions (amygdala, lateral septum), noradrenaline stimulated [(35)S]-GTPgammaS binding. These actions were abolished by the selective alpha(2) antagonist, atipamezole. Conversely, in caudate nucleus, which expresses few alpha(2) receptors, noradrenaline-induced stimulation was not inhibited by atipamezole, suggesting that it is not mediated by alpha(2)-adrenoceptors.

  6. Metabonomics reveals drastic changes in anti-inflammatory/pro-resolving polyunsaturated fatty acids-derived lipid mediators in leprosy disease.

    Directory of Open Access Journals (Sweden)

    Julio J Amaral

    Full Text Available Despite considerable efforts over the last decades, our understanding of leprosy pathogenesis remains limited. The complex interplay between pathogens and hosts has profound effects on host metabolism. To explore the metabolic perturbations associated with leprosy, we analyzed the serum metabolome of leprosy patients. Samples collected from lepromatous and tuberculoid patients before and immediately after the conclusion of multidrug therapy (MDT were subjected to high-throughput metabolic profiling. Our results show marked metabolic alterations during leprosy that subside at the conclusion of MDT. Pathways showing the highest modulation were related to polyunsaturated fatty acid (PUFA metabolism, with emphasis on anti-inflammatory, pro-resolving omega-3 fatty acids. These results were confirmed by eicosanoid measurements through enzyme-linked immunoassays. Corroborating the repertoire of metabolites altered in sera, metabonomic analysis of skin specimens revealed alterations in the levels of lipids derived from lipase activity, including PUFAs, suggesting a high lipid turnover in highly-infected lesions. Our data suggest that omega-6 and omega-3, PUFA-derived, pro-resolving lipid mediators contribute to reduced tissue damage irrespectively of pathogen burden during leprosy disease. Our results demonstrate the utility of a comprehensive metabonomic approach for identifying potential contributors to disease pathology that may facilitate the development of more targeted treatments for leprosy and other inflammatory diseases.

  7. Does Parental Mediation of Media Influence Child Outcomes? A Meta-Analysis on Media Time, Aggression, Substance Use, and Sexual Behavior

    Science.gov (United States)

    Collier, Kevin M.; Coyne, Sarah M.; Rasmussen, Eric E.; Hawkins, Alan J.; Padilla-Walker, Laura M.; Erickson, Sage E.; Memmott-Elison, Madison K.

    2016-01-01

    The current study examined how parental mediation of media (restrictive mediation, active mediation, and coviewing) influenced child outcomes. Three meta-analyses, 1 for each type of mediation, were conducted on a total of 57 studies. Each analysis assessed the effectiveness of parental mediation on 4 pertinent child outcomes: media use,…

  8. Comparative physiological, metabolomic, and transcriptomic analyses reveal mechanisms of improved abiotic stress resistance in bermudagrass [Cynodon dactylon (L). Pers.] by exogenous melatonin

    Science.gov (United States)

    Shi, Haitao; Jiang, Chuan; Ye, Tiantian; Tan, Dun-xian; Reiter, Russel J.; Zhang, Heng; Liu, Renyi; Chan, Zhulong

    2015-01-01

    Melatonin (N-acetyl-5-methoxytryptamine), a well-known animal hormone, is also involved in plant development and abiotic stress responses. In this study, it is shown that exogenous application of melatonin conferred improved salt, drought, and cold stress resistances in bermudagrass. Moreover, exogenous melatonin treatment alleviated reactive oxygen species (ROS) burst and cell damage induced by abiotic stress; this involved activation of several antioxidants. Additionally, melatonin-pre-treated plants exhibited higher concentrations of 54 metabolites, including amino acids, organic acids, sugars, and sugar alcohols, than non-treated plants under abiotic stress conditions. Genome-wide transcriptomic profiling identified 3933 transcripts (2361 up-regulated and 1572 down-regulated) that were differentially expressed in melatonin-treated plants versus controls. Pathway and gene ontology (GO) term enrichment analyses revealed that genes involved in nitrogen metabolism, major carbohydrate metabolism, tricarboxylic acid (TCA)/org transformation, transport, hormone metabolism, metal handling, redox, and secondary metabolism were over-represented after melatonin pre-treatment. Taken together, this study provides the first evidence of the protective roles of exogenous melatonin in the bermudagrass response to abiotic stresses, partially via activation of antioxidants and modulation of metabolic homeostasis. Notably, metabolic and transcriptomic analyses showed that the underlying mechanisms of melatonin could involve major reorientation of photorespiratory and carbohydrate and nitrogen metabolism. PMID:25225478

  9. Integrative functional analyses using rainbow trout selected for tolerance to plant diets reveal nutrigenomic signatures for soy utilization without the concurrence of enteritis.

    Directory of Open Access Journals (Sweden)

    Jason Abernathy

    Full Text Available Finding suitable alternative protein sources for diets of carnivorous fish species remains a major concern for sustainable aquaculture. Through genetic selection, we created a strain of rainbow trout that outperforms parental lines in utilizing an all-plant protein diet and does not develop enteritis in the distal intestine, as is typical with salmonids on long-term plant protein-based feeds. By incorporating this strain into functional analyses, we set out to determine which genes are critical to plant protein utilization in the absence of gut inflammation. After a 12-week feeding trial with our selected strain and a control trout strain fed either a fishmeal-based diet or an all-plant protein diet, high-throughput RNA sequencing was completed on both liver and muscle tissues. Differential gene expression analyses, weighted correlation network analyses and further functional characterization were performed. A strain-by-diet design revealed differential expression ranging from a few dozen to over one thousand genes among the various comparisons and tissues. Major gene ontology groups identified between comparisons included those encompassing central, intermediary and foreign molecule metabolism, associated biosynthetic pathways as well as immunity. A systems approach indicated that genes involved in purine metabolism were highly perturbed. Systems analysis among the tissues tested further suggests the interplay between selection for growth, dietary utilization and protein tolerance may also have implications for nonspecific immunity. By combining data from differential gene expression and co-expression networks using selected trout, along with ontology and pathway analyses, a set of 63 candidate genes for plant diet tolerance was found. Risk loci in human inflammatory bowel diseases were also found in our datasets, indicating rainbow trout selected for plant-diet tolerance may have added utility as a potential biomedical model.

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

    Science.gov (United States)

    Laurin, Raphael

    2013-01-01

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

  11. RNA-seq analyses reveal insights into the function of respiratory nitrate reductase of the diazotroph Herbaspirillum seropedicae.

    Science.gov (United States)

    Bonato, Paloma; Batista, Marcelo B; Camilios-Neto, Doumit; Pankievicz, Vânia C S; Tadra-Sfeir, Michelle Z; Monteiro, Rose Adele; Pedrosa, Fabio O; Souza, Emanuel M; Chubatsu, Leda S; Wassem, Roseli; Rigo, Liu Un

    2016-09-01

    Herbaspirillum seropedicae is a nitrogen-fixing β-proteobacterium that associates with roots of gramineous plants. In silico analyses revealed that H. seropedicae genome has genes encoding a putative respiratory (NAR) and an assimilatory nitrate reductase (NAS). To date, little is known about nitrate metabolism in H. seropedicae, and, as this bacterium cannot respire nitrate, the function of NAR remains unknown. This study aimed to investigate the function of NAR in H. seropedicae and how it metabolizes nitrate in a low aerated-condition. RNA-seq transcriptional profiling in the presence of nitrate allowed us to pinpoint genes important for nitrate metabolism in H. seropedicae, including nitrate transporters and regulatory proteins. Additionally, both RNA-seq data and physiological characterization of a mutant in the catalytic subunit of NAR (narG mutant) showed that NAR is not required for nitrate assimilation but is required for: (i) production of high levels of nitrite, (ii) production of NO and (iii) dissipation of redox power, which in turn lead to an increase in carbon consumption. In addition, wheat plants showed an increase in shoot dry weight only when inoculated with H. seropedicae wild type, but not with the narG mutant, suggesting that NAR is important to H. seropedicae-wheat interaction. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  12. Prefrontal mediation of emotion regulation in social anxiety disorder during laughter perception.

    Science.gov (United States)

    Kreifelts, Benjamin; Brück, Carolin; Ethofer, Thomas; Ritter, Jan; Weigel, Lena; Erb, Michael; Wildgruber, Dirk

    2017-02-01

    Social anxiety disorder (SAD) is characterized by negatively biased perception of social cues and deficits in emotion regulation. While negatively biased perception is thought to maintain social anxiety, emotion regulation represents an ability necessary to overcome both biased perception and social anxiety. Here, we used laughter as a social threat in a functional magnetic resonance imaging (fMRI) study to identify cerebral mediators linking SAD with attention and interpretation biases and their modification through cognitive emotion regulation in the form of reappraisal. We found that reappraisal abolished the negative laughter interpretation bias in SAD and that this process was directly mediated through activation patterns of the left dorsolateral prefrontal cortex (DLPFC) serving as a cerebral pivot between biased social perception and its normalization through reappraisal. Connectivity analyses revealed reduced prefrontal control over threat-processing sensory cortices (here: the temporal voice area) during cognitive emotion regulation in SAD. Our results indicate a central role for the left DLPFC in SAD which might represent a valuable target for future research on interventions either aiming to directly modulate cognitive emotion regulation in SAD or to evaluate its potential as physiological marker for psychotherapeutic interventions relying on emotion regulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Association between social support and health-related quality of life among Chinese rural elders in nursing homes: the mediating role of resilience.

    Science.gov (United States)

    Wu, Menglian; Yang, Yang; Zhang, Dan; Zhao, Xia; Sun, Yaoyao; Xie, Hui; Jia, Jihui; Su, Yonggang; Li, Yuqin

    2018-03-01

    This study aims to confirm the relationship between social support and health-related quality of life (HRQOL) among rural Chinese elders in nursing homes, and to examine the mediating role of resilience in the impact of social support on HRQOL. A cross-sectional survey of 205 elders aged 60 and above was conducted in five rural public nursing homes. Sociodemographic characteristics, the SF-36 questionnaire, and information about social support and resilience were collected. The researchers administered the questionnaires to the participants in a face-to-face setting. Descriptive analysis and a correlation matrix were used to indicate characteristics of the participants and bivariate correlations, respectively. The mediation analyses, composed of regression analysis and PROCESS analysis, were preformed to test both direct and indirect effects of social support on HRQOL, namely the mediating role of resilience. Social support was positively related to HRQOL (β = 0.303, p social support and HRQOL was confirmed (a*b bootstrapped 95% confidence interval = [0.098, 0.257]), which revealed that social support had an indirect effect on HRQOL through resilience. Resilience partially mediates the relationship between social support and HRQOL. The mediation model provides a better understanding of how social support and resilience work together to affect HRQOL, and it could guide the interventions in health care for promoting HRQOL among Chinese rural elders in nursing homes.

  14. Inflammatory Mediators Associated With Pressure Ulcer Development in Individuals With Pneumonia After Traumatic Spinal Cord Injury: A Pilot Study.

    Science.gov (United States)

    Krishnan, Shilpa; Vodovotz, Yoram; Karg, Patricia E; Constantine, Gregory; Sowa, Gwendolyn A; Constantine, Florica J; Brienza, David M

    2017-09-01

    To identify the inflammatory mediators around the time of pneumonia onset associated with concurrent or later onset of pressure ulcers (PUs). Retrospective. Acute hospitalization and inpatient rehabilitation unit of a university medical center. Individuals (N=86) with traumatic spinal cord injury (SCI) were included in the initial analyses. Fifteen of the 86 developed pneumonia and had inflammatory mediator data available. Of these 15, 7 developed PUs and 8 did not. Not applicable. Twenty-three inflammatory mediators in plasma and urine were assayed. The differences in concentrations of plasma and urine inflammatory mediators between the closest time point before and after the diagnosis of pneumonia were calculated. Initial chi-square analysis revealed a significant (P=.02) association between pneumonia and PUs. Individuals with SCI and diagnosed pneumonia had nearly double the risk for developing PUs compared with those with no pneumonia. In individuals with pneumonia, Mann-Whitney U exact tests suggested an association (Ppneumonia. These findings suggest that a relatively small increase in plasma TNF-α, and decreases in urine TNF-α, GM-CSF, and IL-15 from just before to just after the diagnosis of pneumonia could be markers for an increased risk of PUs in individuals with pneumonia after traumatic SCI. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  15. Mediation analysis of alcohol consumption, DNA methylation, and epithelial ovarian cancer.

    Science.gov (United States)

    Wu, Dongyan; Yang, Haitao; Winham, Stacey J; Natanzon, Yanina; Koestler, Devin C; Luo, Tiane; Fridley, Brooke L; Goode, Ellen L; Zhang, Yanbo; Cui, Yuehua

    2018-03-01

    Epigenetic factors and consumption of alcohol, which suppresses DNA methylation, may influence the development and progression of epithelial ovarian cancer (EOC). However, there is a lack of understanding whether these factors interact to affect the EOC risk. In this study, we aimed to gain insight into this relationship by identifying leukocyte-derived DNA methylation markers acting as potential mediators of alcohol-associated EOC. We implemented a causal inference test (CIT) and the VanderWeele and Vansteelandt multiple mediator model to examine CpG sites that mediate the association between alcohol consumption and EOC risk. We modified one step of the CIT by adopting a high-dimensional inference procedure. The data were based on 196 cases and 202 age-matched controls from the Mayo Clinic Ovarian Cancer Case-Control Study. Implementation of the CIT test revealed two CpG sites (cg09358725, cg11016563), which represent potential mediators of the relationship between alcohol consumption and EOC case-control status. Implementation of the VanderWeele and Vansteelandt multiple mediator model further revealed that these two CpGs were the key mediators. Decreased methylation at both CpGs was more common in cases who drank alcohol at the time of enrollment vs. those who did not. cg11016563 resides in TRPC6 which has been previously shown to be overexpressed in EOC. These findings suggest two CpGs may serve as novel biomarkers for EOC susceptibility.

  16. Review: Oliver Märker & Matthias Trénel (Eds.) (2003). Online-Mediation. Neue Medien in der Konfliktvermittlung – mit Beispielen aus Politik und Wirtschaft [Online-Mediation. New Media in Conflict Resolution—with Examples from Politics and Industry

    OpenAIRE

    Nicola Döring

    2004-01-01

    Online-Mediation deals with conflict resolution methods that are carried out partially or completely online. The book analyses online mediation as a socio-technical system through the means of the computer-based technological platform deeply interwoven with conflict-related social communication. The first part of the book discusses the multiple options and restrictions of online communication in moderation and mediation processes. For example, one advantage of online mediation is that geograp...

  17. Do sedentary behaviors mediate associations between socio-demographic characteristics and BMI in women living in socio-economically disadvantaged neighborhoods?

    Science.gov (United States)

    Compernolle, Sofie; De Cocker, Katrien; Abbott, Gavin; Verloigne, Maïté; Cardon, Greet; De Bourdeaudhuij, Ilse; Ball, Kylie

    2015-04-09

    Women living in deprived neighborhoods are a risk group for overweight and obesity, particularly during the childbearing years. Several socio-demographic characteristics may compound this risk, but little is known about why this might be the case. Sedentary behaviors are emerging as a socio-demographically patterned risk factor for obesity. The purpose of the present study was to assess socio-demographic differences in sedentary behaviors, and to examine whether these behaviors could explain the relation between socio-demographic variables and BMI (BMI) in this risk group. Women aged 18-46 years were recruited from 40 urban and 40 rural deprived neighborhoods in Victoria, Australia. In total, 3879 women reported socio-demographic variables (age, educational level, employment status, marital status, number of children, residential location and country of birth), sedentary behaviors (television time, computer time, total screen time and total sedentary time), physical activity, and height and weight, which were used to calculate BMI. For each socio-demographic variable, four single mediation models were conducted using two-level mixed-models regression analyses. Mediating effects were examined using the MacKinnon product-of-coefficients procedure and the Sobel test. All socio-demographic variables were significantly associated with sedentary behaviors. Single mediation analyses revealed that television time (αβ = 0.017, 95% CI = 0.000, 0.030) and total screen time (αβ = 0.006, 95% CI = 0.000, 0.012) mediated 14.1% and 4.9% of the relationship between educational level and BMI, respectively. Total screen time mediated 45.1% of the relationship between employment status and BMI (αβ = -0.020, 95% CI = -0.033, -0.006), and television time mediated 8.2% of the relationship between country of birth and BMI (αβ = -0.008, 95% CI = -0.016, -0.001). Sedentary behaviors differed depending on socio-demographic characteristics, and partly

  18. Relationship between Individual and Organizational Learning: Mediating Role of Team Learning

    OpenAIRE

    Monika Stelmaszczyk

    2016-01-01

    The aim of this paper is to recognize the relationships between individual and organizational learning while considering team learning as a mediator of these relationships. The research object is a large Polish enterprise specializing in the production of cast-iron items. In order to test assumed research hypotheses, statistical analyses were conducted using the IBM SPSS Statistics Suite, version 20. The suite helped conduct correlation analyses concatenation, line regression analyses and med...

  19. Structural and biochemical analyses of a Clostridium perfringens sortase D transpeptidase

    Energy Technology Data Exchange (ETDEWEB)

    Suryadinata, Randy, E-mail: randy.suryadinata@csiro.au; Seabrook, Shane A.; Adams, Timothy E.; Nuttall, Stewart D.; Peat, Thomas S., E-mail: randy.suryadinata@csiro.au [Commonwealth Scientific and Industrial Research Organisation, 343 Royal Parade, Parkville, Victoria 3052 (Australia)

    2015-06-30

    The structure of C. perfringens sortase D was determined at 1.99 Å resolution. Comparative biochemical and structural analyses revealed that this transpeptidase may represent a new subclass of the sortase D family. The assembly and anchorage of various pathogenic proteins on the surface of Gram-positive bacteria is mediated by the sortase family of enzymes. These cysteine transpeptidases catalyze a unique sorting signal motif located at the C-terminus of their target substrate and promote the covalent attachment of these proteins onto an amino nucleophile located on another protein or on the bacterial cell wall. Each of the six distinct classes of sortases displays a unique biological role, with sequential activation of multiple sortases often observed in many Gram-positive bacteria to decorate their peptidoglycans. Less is known about the members of the class D family of sortases (SrtD), but they have a suggested role in spore formation in an oxygen-limiting environment. Here, the crystal structure of the SrtD enzyme from Clostridium perfringens was determined at 1.99 Å resolution. Comparative analysis of the C. perfringens SrtD structure reveals the typical eight-stranded β-barrel fold observed in all other known sortases, along with the conserved catalytic triad consisting of cysteine, histidine and arginine residues. Biochemical approaches further reveal the specifics of the SrtD catalytic activity in vitro, with a significant preference for the LPQTGS sorting motif. Additionally, the catalytic activity of SrtD is most efficient at 316 K and can be further improved in the presence of magnesium cations. Since C. perfringens spores are heat-resistant and lead to foodborne illnesses, characterization of the spore-promoting sortase SrtD may lead to the development of new antimicrobial agents.

  20. The 'revealed preferences' theory: Assumptions and conjectures

    International Nuclear Information System (INIS)

    Green, C.H.

    1983-01-01

    Being kind of intuitive psychology the 'Revealed-Preferences'- theory based approaches towards determining the acceptable risks are a useful method for the generation of hypotheses. In view of the fact that reliability engineering develops faster than methods for the determination of reliability aims the Revealed-Preferences approach is a necessary preliminary help. Some of the assumptions on which the 'Revealed-Preferences' theory is based will be identified and analysed and afterwards compared with experimentally obtained results. (orig./DG) [de

  1. Mediating the relation between workplace stressors and distress in ID support staff: comparison between the roles of psychological inflexibility and coping styles.

    Science.gov (United States)

    Kurz, A Solomon; Bethay, J Scott; Ladner-Graham, Jennifer M

    2014-10-01

    The present study examined how different patterns of coping influence psychological distress for staff members in programs serving individuals with intellectual disabilities. With a series of path models, we examined the relative usefulness of constructs (i.e., wishful thinking and psychological inflexibility) from two distinct models of coping (i.e., the transactional model and the psychological flexibility models, respectively) as mediators to explain how workplace stressors lead to psychological distress in staff serving individuals with intellectual disabilities. Analyses involved self-report questionnaires from 128 staff members (84% female; 71% African American) from a large, state-funded residential program for individuals with intellectual and physical disabilities in the southern United States of America. Cross-sectional path models using bootstrapped standard errors and confidence intervals revealed both wishful thinking and psychological inflexibility mediated the relation between workplace stressors and psychological distress when they were included in separate models. However, when both variables were included in a multiple mediator model, only psychological inflexibility remained a significant mediator. The results suggest psychological inflexibility and the psychological flexibility model may be particularly useful for further investigation on the causes and amelioration of workplace-related stress in ID settings. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Direct and indirect associations between social anxiety and nicotine dependence and cessation problems: multiple mediator analyses.

    Science.gov (United States)

    Buckner, Julia D; Farris, Samantha G; Schmidt, Norman B; Zvolensky, Michael J

    2014-06-01

    Little empirical work has evaluated why socially anxious smokers are especially vulnerable to more severe nicotine dependence and cessation failure. Presumably, these smokers rely on cigarettes to help them manage their chronically elevated negative affect elicited by a wide array of social contexts. The current study examined the direct and indirect effects of social anxiety cross-sectionally in regard to a range of smoking processes among 466 treatment-seeking smokers. Negative affect and negative affect reduction motives were examined as mediators of the relations of social anxiety with nicotine dependence and cessation problems. Social anxiety was directly and robustly associated with perceived barriers to smoking cessation and problems experienced during past quit attempts. Social anxiety was also associated with greater nicotine dependence and smoking inflexibility indirectly through negative affect and negative affect smoking motives. Negative affect and smoking to reduce negative affect mediated these relations. These findings document the important role of negative affect and negative affect reduction motives in the relationships of social anxiety with nicotine dependence and cessation problems.

  3. Ten ways to improve the use of statistical mediation analysis in the practice of child and adolescent treatment research

    NARCIS (Netherlands)

    Maric, M.; Wiers, R.W.; Prins, P.J.M.

    2012-01-01

    Despite guidelines and repeated calls from the literature, statistical mediation analysis in youth treatment outcome research is rare. Even more concerning is that many studies that have reported mediation analyses do not fulfill basic requirements for mediation analysis, providing inconclusive data

  4. Molecular simulations of lipid-mediated protein-protein interactions

    NARCIS (Netherlands)

    de Meyer, F.J.M.; Venturoli, M.; Smit, B.

    2008-01-01

    Recent experimental results revealed that lipid-mediated interactions due to hydrophobic forces may be important in determining the protein topology after insertion in the membrane, in regulating the protein activity, in protein aggregation and in signal transduction. To gain insight into the

  5. Importance of Mediator complex in the regulation and integration of diverse signaling pathways in plants.

    Science.gov (United States)

    Samanta, Subhasis; Thakur, Jitendra K

    2015-01-01

    Basic transcriptional machinery in eukaryotes is assisted by a number of cofactors, which either increase or decrease the rate of transcription. Mediator complex is one such cofactor, and recently has drawn a lot of interest because of its integrative power to converge different signaling pathways before channeling the transcription instructions to the RNA polymerase II machinery. Like yeast and metazoans, plants do possess the Mediator complex across the kingdom, and its isolation and subunit analyses have been reported from the model plant, Arabidopsis. Genetic, and molecular analyses have unraveled important regulatory roles of Mediator subunits at every stage of plant life cycle starting from flowering to embryo and organ development, to even size determination. It also contributes immensely to the survival of plants against different environmental vagaries by the timely activation of its resistance mechanisms. Here, we have provided an overview of plant Mediator complex starting from its discovery to regulation of stoichiometry of its subunits. We have also reviewed involvement of different Mediator subunits in different processes and pathways including defense response pathways evoked by diverse biotic cues. Wherever possible, attempts have been made to provide mechanistic insight of Mediator's involvement in these processes.

  6. Crystal structure of the Alcanivorax borkumensis YdaH transporter reveals an unusual topology

    Science.gov (United States)

    Bolla, Jani Reddy; Su, Chih-Chia; Delmar, Jared A.; Radhakrishnan, Abhijith; Kumar, Nitin; Chou, Tsung-Han; Long, Feng; Rajashankar, Kanagalaghatta R.; Yu, Edward W.

    2015-04-01

    The potential of the folic acid biosynthesis pathway as a target for the development of antibiotics has been clinically validated. However, many pathogens have developed resistance to these antibiotics, prompting a re-evaluation of potential drug targets within the pathway. The ydaH gene of Alcanivorax borkumensis encodes an integral membrane protein of the AbgT family of transporters for which no structural information was available. Here we report the crystal structure of A. borkumensis YdaH, revealing a dimeric molecule with an architecture distinct from other families of transporters. YdaH is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins that suggest a plausible pathway for substrate transport. Further analyses also suggest that YdaH could act as an antibiotic efflux pump and mediate bacterial resistance to sulfonamide antimetabolite drugs.

  7. Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency

    Science.gov (United States)

    Cacchiarelli, Davide; Trapnell, Cole; Ziller, Michael J.; Soumillon, Magali; Cesana, Marcella; Karnik, Rahul; Donaghey, Julie; Smith, Zachary D.; Ratanasirintrawoot, Sutheera; Zhang, Xiaolan; Ho Sui, Shannan J.; Wu, Zhaoting; Akopian, Veronika; Gifford, Casey A.; Doench, John; Rinn, John L.; Daley, George Q.; Meissner, Alexander; Lander, Eric S.; Mikkelsen, Tarjei S.

    2015-01-01

    Summary Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered reactivation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies. PMID:26186193

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

    African Journals Online (AJOL)

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

  9. Demonstration and Dialogue: Mediation in Swedish Nuclear Waste Management. Deliverable D10

    International Nuclear Information System (INIS)

    Elam, Mark; Sundqvist, Goeran; Lidberg, Maria; Soneryd, Linda

    2008-10-01

    This report analyses mediation and mediators in Swedish nuclear waste management. Mediation is about establishing agreement and building common knowledge. It is argued that demonstrations and dialogue are the two prominent approaches to mediation in Swedish nuclear waste management. Mediation through demonstration is about showing, displaying, and pointing out a path to safe disposal for inspection. It implies a strict division between demonstrator and audience. Mediation through dialogue on the other hand, is about collective acknowledgements of uncertainty and suspensions of judgement creating room for broader discussion. In Sweden, it is the Swedish Nuclear Fuel and Waste Management Co. (SKB) that is tasked with finding a method and a site for the final disposal of the nation's nuclear waste. Two different legislative frameworks cover this process. In accordance with the Act on Nuclear Activities, SKB is required to demonstrate the safety of its planned nuclear waste management system to the government, while in respect of the Swedish Environmental Code, they are obliged to organize consultations with the public. How SKB combines these requirements is the main question under investigation in this report in relation to materials deriving from three empirical settings: 1) SKB's safety analyses, 2) SKB's public consultation activities and 3) the 'dialogue projects', initiated by other actors than SKB broadening the public arena for discussion. In conclusion, an attempt is made to characterise the long-term interplay of demonstration and dialogue in Swedish nuclear waste management

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

    Science.gov (United States)

    Vuorre, Matti; Bolger, Niall

    2017-12-15

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

  11. Confounding in statistical mediation analysis: What it is and how to address it.

    Science.gov (United States)

    Valente, Matthew J; Pelham, William E; Smyth, Heather; MacKinnon, David P

    2017-11-01

    Psychology researchers are often interested in mechanisms underlying how randomized interventions affect outcomes such as substance use and mental health. Mediation analysis is a common statistical method for investigating psychological mechanisms that has benefited from exciting new methodological improvements over the last 2 decades. One of the most important new developments is methodology for estimating causal mediated effects using the potential outcomes framework for causal inference. Potential outcomes-based methods developed in epidemiology and statistics have important implications for understanding psychological mechanisms. We aim to provide a concise introduction to and illustration of these new methods and emphasize the importance of confounder adjustment. First, we review the traditional regression approach for estimating mediated effects. Second, we describe the potential outcomes framework. Third, we define what a confounder is and how the presence of a confounder can provide misleading evidence regarding mechanisms of interventions. Fourth, we describe experimental designs that can help rule out confounder bias. Fifth, we describe new statistical approaches to adjust for measured confounders of the mediator-outcome relation and sensitivity analyses to probe effects of unmeasured confounders on the mediated effect. All approaches are illustrated with application to a real counseling intervention dataset. Counseling psychologists interested in understanding the causal mechanisms of their interventions can benefit from incorporating the most up-to-date techniques into their mediation analyses. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  12. Psychosocial Predictors of Relationship Conflict Styles as Mediated by Emotional Intelligence

    Directory of Open Access Journals (Sweden)

    Nicole M. Monteiro

    2015-05-01

    Full Text Available This study investigated the influence of age, gender, and emotional intelligence (EI on conflict management styles among dating age adults in Botswana. A mixed survey and quasi-experimental design was used to assess the relationship between age and gender and the mediating influence of EI on participants’ preferred conflict management strategies (avoidance, competition, compromise, accommodation, and collaboration in response to violent and nonviolent relationship conflict. One hundred fifty-two participants were surveyed before (with the Wong and Law Emotional Intelligence Scale and after (with the Conflict Style Questionnaire watching video clips of nonviolent and violent relationship conflict. Correlations, t tests, and regression analyses were conducted. Findings revealed that women were more likely than men to report use of collaboration conflict strategies in response to the nonviolent video, and men were more likely than women to report accommodation strategies in response to the violent video. In the regression analysis, gender was a significant predictor of accommodation conflict style in response to the violent video, and EI had a significant independent and partial mediating relationship with compromise in response to the violent situation and collaboration in response to both violent and nonviolent conflict situations. Findings highlight the important role of EI in the use of higher-level relationship conflict strategies. Implications in the way of communication and conflict management for dating age adults and couples are discussed.

  13. Mediation Analysis with Multiple Mediators

    OpenAIRE

    VanderWeele, T.J.; Vansteelandt, S.

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects throu...

  14. Mediating the Maltreatment-Delinquency Relationship: The Role of Triad Gang Membership.

    Science.gov (United States)

    Chui, Wing Hong; Khiatani, Paul Vinod

    2018-02-01

    The primary aim of this article is to examine the role of triad affiliation in mediating the relationship between child maltreatment (neglect, punishment, emotional abuse, and sexual abuse) and delinquency among active young gang members in Hong Kong. A sample of 177 gang members aged 12 to 24 was recruited to complete a questionnaire with the assistance of a youth outreach social work team. Neglect was identified as the most common form of maltreatment, followed by emotional abuse, punishment, and sexual abuse. Mediation analyses confirmed that triad affiliation acts as a mediating variable in the child maltreatment-delinquency relationship, except in cases of sexual abuse. Only the relationship between punishment and delinquency was found to be fully mediated by triad affiliation; partial mediation effects were found for neglect and emotional abuse. Recommendations for child protection and youth workers are provided.

  15. [The Relationship Between Marital Adjustment and Psychological Symptoms in Women: The Mediator Roles of Coping Strategies and Gender Role Attitudes].

    Science.gov (United States)

    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, prole 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.

  16. DE71 suppresses thyroid hormone-mediated dendritogenesis and ...

    African Journals Online (AJOL)

    olayemitoyin

    Summary: Polybrominated diphenylethers (PBDEs) are synthesized ... Taken together, our study clearly reveals that DE71 can impair TH-mediated .... calbindin-28 K antibody and fluorescein ... spectral type inverted microscope IX81, ..... Steppan, L., Kerkvliet, N.I. (1994). ... Toxicology 86: 49-61. ... Ph.D. Dissertation.

  17. Is Customer Orientation of Employees Sustainable? A Moderated Mediation Analysis

    Directory of Open Access Journals (Sweden)

    Junya Cai

    2017-07-01

    Full Text Available While existing literature has addressed the benefits of customer orientation, less is known about its negative outcomes. This study investigates the mediating effect of emotional dissonance on the relationship between customer orientation and unethical decision-making, and whether this mediating effect is moderated by occupation. A sample of 727 doctors and nurses from three Chinese hospitals completed anonymous questionnaires regarding customer orientation, emotional dissonance, and unethical decision-making. Our findings reveal that the positive relationship between customer orientation and unethical decision-making is fully mediated by emotional dissonance. Furthermore, the mediating effect of emotional dissonance is moderated by occupation, which suggests that the mediating effect of emotional dissonance is stronger for doctors. This study contributes to our understanding of how and for whom customer orientation results in unethical decision-making, and suggests the need to take occupation into account in preventing the negative outcomes of customer orientation.

  18. Combined metabonomic and quantitative real-time PCR analyses reveal systems metabolic changes in Jurkat T-cells treated with HIV-1 Tat protein.

    Science.gov (United States)

    Liao, Wenting; Tan, Guangguo; Zhu, Zhenyu; Chen, Qiuli; Lou, Ziyang; Dong, Xin; Zhang, Wei; Pan, Wei; Chai, Yifeng

    2012-11-02

    HIV-1 Tat protein is released by infected cells and can affect bystander uninfected T cells and induce numerous biological responses which contribute to its pathogenesis. To elucidate the complex pathogenic mechanism, we conducted a comprehensive investigation on Tat protein-related extracellular and intracellular metabolic changes in Jurkat T-cells using combined gas chromatography-mass spectrometry (GC-MS), reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) and a hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS)-based metabonomics approach. Quantitative real-time PCR (qRT-PCR) analyses were further employed to measure expressions of several relevant enzymes together with perturbed metabolic pathways. Combined metabonomic and qRT-PCR analyses revealed that HIV-1 Tat caused significant and comprehensive metabolic changes, as represented by significant changes of 37 metabolites and 10 relevant enzymes in HIV-1 Tat-treated cells. Using MetaboAnalyst 2.0, it was found that 11 pathways (Impact-value >0.10) among the regulated pathways were acutely perturbed, including sphingolipid metabolism, glycine, serine and threonine metabolism, pyruvate metabolism, inositol phosphate metabolism, arginine and proline metabolism, citrate cycle, phenylalanine metabolism, tryptophan metabolism, pentose phosphate pathway, glycerophospholipid metabolism, glycolysis or gluconeogenesis. These results provide metabolic evidence of the complex pathogenic mechanism of HIV-1 Tat protein as a "viral toxin", and would help obligate Tat protein as "an important target" for therapeutic intervention and vaccine development.

  19. Comparative physiological, metabolomic, and transcriptomic analyses reveal mechanisms of improved abiotic stress resistance in bermudagrass [Cynodon dactylon (L). Pers.] by exogenous melatonin.

    Science.gov (United States)

    Shi, Haitao; Jiang, Chuan; Ye, Tiantian; Tan, Dun-Xian; Reiter, Russel J; Zhang, Heng; Liu, Renyi; Chan, Zhulong

    2015-02-01

    Melatonin (N-acetyl-5-methoxytryptamine), a well-known animal hormone, is also involved in plant development and abiotic stress responses. In this study, it is shown that exogenous application of melatonin conferred improved salt, drought, and cold stress resistances in bermudagrass. Moreover, exogenous melatonin treatment alleviated reactive oxygen species (ROS) burst and cell damage induced by abiotic stress; this involved activation of several antioxidants. Additionally, melatonin-pre-treated plants exhibited higher concentrations of 54 metabolites, including amino acids, organic acids, sugars, and sugar alcohols, than non-treated plants under abiotic stress conditions. Genome-wide transcriptomic profiling identified 3933 transcripts (2361 up-regulated and 1572 down-regulated) that were differentially expressed in melatonin-treated plants versus controls. Pathway and gene ontology (GO) term enrichment analyses revealed that genes involved in nitrogen metabolism, major carbohydrate metabolism, tricarboxylic acid (TCA)/org transformation, transport, hormone metabolism, metal handling, redox, and secondary metabolism were over-represented after melatonin pre-treatment. Taken together, this study provides the first evidence of the protective roles of exogenous melatonin in the bermudagrass response to abiotic stresses, partially via activation of antioxidants and modulation of metabolic homeostasis. Notably, metabolic and transcriptomic analyses showed that the underlying mechanisms of melatonin could involve major reorientation of photorespiratory and carbohydrate and nitrogen metabolism. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  20. Platyhelminth Venom Allergen-Like (VAL) proteins: revealing structural diversity, class-specific features and biological associations across the phylum

    Science.gov (United States)

    CHALMERS, IAIN W.; HOFFMANN, KARL F.

    2012-01-01

    SUMMARY During platyhelminth infection, a cocktail of proteins is released by the parasite to aid invasion, initiate feeding, facilitate adaptation and mediate modulation of the host immune response. Included amongst these proteins is the Venom Allergen-Like (VAL) family, part of the larger sperm coating protein/Tpx-1/Ag5/PR-1/Sc7 (SCP/TAPS) superfamily. To explore the significance of this protein family during Platyhelminthes development and host interactions, we systematically summarize all published proteomic, genomic and immunological investigations of the VAL protein family to date. By conducting new genomic and transcriptomic interrogations to identify over 200 VAL proteins (228) from species in all 4 traditional taxonomic classes (Trematoda, Cestoda, Monogenea and Turbellaria), we further expand our knowledge related to platyhelminth VAL diversity across the phylum. Subsequent phylogenetic and tertiary structural analyses reveal several class-specific VAL features, which likely indicate a range of roles mediated by this protein family. Our comprehensive analysis of platyhelminth VALs represents a unifying synopsis for understanding diversity within this protein family and a firm context in which to initiate future functional characterization of these enigmatic members. PMID:22717097

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

    OpenAIRE

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

    2012-01-01

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

  2. Comparative analyses of population-scale phenomic data in electronic medical records reveal race-specific disease networks

    Science.gov (United States)

    Glicksberg, Benjamin S.; Li, Li; Badgeley, Marcus A.; Shameer, Khader; Kosoy, Roman; Beckmann, Noam D.; Pho, Nam; Hakenberg, Jörg; Ma, Meng; Ayers, Kristin L.; Hoffman, Gabriel E.; Dan Li, Shuyu; Schadt, Eric E.; Patel, Chirag J.; Chen, Rong; Dudley, Joel T.

    2016-01-01

    Motivation: Underrepresentation of racial groups represents an important challenge and major gap in phenomics research. Most of the current human phenomics research is based primarily on European populations; hence it is an important challenge to expand it to consider other population groups. One approach is to utilize data from EMR databases that contain patient data from diverse demographics and ancestries. The implications of this racial underrepresentation of data can be profound regarding effects on the healthcare delivery and actionability. To the best of our knowledge, our work is the first attempt to perform comparative, population-scale analyses of disease networks across three different populations, namely Caucasian (EA), African American (AA) and Hispanic/Latino (HL). Results: We compared susceptibility profiles and temporal connectivity patterns for 1988 diseases and 37 282 disease pairs represented in a clinical population of 1 025 573 patients. Accordingly, we revealed appreciable differences in disease susceptibility, temporal patterns, network structure and underlying disease connections between EA, AA and HL populations. We found 2158 significantly comorbid diseases for the EA cohort, 3265 for AA and 672 for HL. We further outlined key disease pair associations unique to each population as well as categorical enrichments of these pairs. Finally, we identified 51 key ‘hub’ diseases that are the focal points in the race-centric networks and of particular clinical importance. Incorporating race-specific disease comorbidity patterns will produce a more accurate and complete picture of the disease landscape overall and could support more precise understanding of disease relationships and patient management towards improved clinical outcomes. Contacts: rong.chen@mssm.edu or joel.dudley@mssm.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27307606

  3. THE EFFECTS OF EMOTIONAL LABOR ON JOB ATTITUDES OF HOTEL EMPLOYEES: MEDIATING AND MODERATING ROLES OF SOCIAL SUPPORT AND JOB AUTONOMY

    Directory of Open Access Journals (Sweden)

    Fatma Nur IPLIK

    2014-07-01

    Full Text Available With increasing competition among hotels, managing employees seems to be important issue in delivering services to customers effectively. This issue also affects the firms’ outcomes and incomes. Thus, hotels as service providing firms must be able to manage the emotions of employees in order to increase the quality of services and to create value for customers. Controlling emotions of employees also contribute to gain competitive advantage across rivals. The objective of this paper is to reveal the effects of emotional labor on job attitudes of hotel employees by considering the mediating and moderating roles of social support and job autonomy. To this end, a questionnaire was employed to employees of hotels operating in Antalya Province. Results of the analyses support that emotional labor has a negative effect on emotional exhaustion. Emotional labor also has a positive effect on job satisfaction. In addition mediating and moderating roles of job autonomy and social support between emotional exhaustion and emotional labor, and emotional labor and job satisfaction.

  4. Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain.

    Directory of Open Access Journals (Sweden)

    Jacqueline C Lieblein-Boff

    Full Text Available Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510 were excluded. In addition, moderate correlations with xenobiotic relationships (2 or those driven by single outliers (3 were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region-specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development.

  5. Patient-provider relationship as mediator between adult attachment and self-management in primary care patients with multiple chronic conditions.

    Science.gov (United States)

    Brenk-Franz, Katja; Strauß, Bernhard; Tiesler, Fabian; Fleischhauer, Christian; Schneider, Nico; Gensichen, Jochen

    2017-06-01

    The conceptual model of attachment theory has been applied to understand the predispositions of patients in medical care and the patient-provider relationship. In patients with chronic conditions insecure attachment was connected to poorer self-management. The patient-provider relationship is associated with a range of health related outcomes and self-management skills. We determined whether the quality of the patient-provider relationship mediates the link between adult attachment and self-management among primary care patients with multiple chronic diseases. 209 patients with a minimum of three chronic diseases (including type II diabetes, hypertension and at least one other chronic condition) between the ages of 50 and 85 from eight general practices were included in the APRICARE cohort study. Adult attachment was measured via self-report (ECR-RD), self-management skills by the FERUS and the patient-provider relationship by the PRA-D. The health status and chronicity were assessed by the GP. Multiple mediation analyses were used to examine whether aspects of the patient-provider relationship (communication, information, affectivity) are a mediators of associations between adult attachment and self-management. The analysis revealed that the quality of the patient-provider relationship mediated the effect of attachment on self-management in patients with multiple chronic conditions. Particularly the quality of communication and information over the course of treatment has a significant mediating influence. A personalized, attachment-related approach that promotes active patient-provider communication and gives information about the treatment to the patient may improve self-management skills in patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Comparative Genome Analyses of Serratia marcescens FS14 Reveals Its High Antagonistic Potential

    Science.gov (United States)

    Li, Pengpeng; Kwok, Amy H. Y.; Jiang, Jingwei; Ran, Tingting; Xu, Dongqing; Wang, Weiwu; Leung, Frederick C.

    2015-01-01

    S. marcescens FS14 was isolated from an Atractylodes macrocephala Koidz plant that was infected by Fusarium oxysporum and showed symptoms of root rot. With the completion of the genome sequence of FS14, the first comprehensive comparative-genomic analysis of the Serratia genus was performed. Pan-genome and COG analyses showed that the majority of the conserved core genes are involved in basic cellular functions, while genomic factors such as prophages contribute considerably to genome diversity. Additionally, a Type I restriction-modification system, a Type III secretion system and tellurium resistance genes are found in only some Serratia species. Comparative analysis further identified that S. marcescens FS14 possesses multiple mechanisms for antagonism against other microorganisms, including the production of prodigiosin, bacteriocins, and multi-antibiotic resistant determinants as well as chitinases. The presence of two evolutionarily distinct Type VI secretion systems (T6SSs) in FS14 may provide further competitive advantages for FS14 against other microbes. To our knowledge, this is the first report of comparative analysis on T6SSs in the genus, which identifies four types of T6SSs in Serratia spp.. Competition bioassays of FS14 against the vital plant pathogenic bacterium Ralstonia solanacearum and fungi Fusarium oxysporum and Sclerotinia sclerotiorum were performed to support our genomic analyses, in which FS14 demonstrated high antagonistic activities against both bacterial and fungal phytopathogens. PMID:25856195

  7. Comparative genome analyses of Serratia marcescens FS14 reveals its high antagonistic potential.

    Science.gov (United States)

    Li, Pengpeng; Kwok, Amy H Y; Jiang, Jingwei; Ran, Tingting; Xu, Dongqing; Wang, Weiwu; Leung, Frederick C

    2015-01-01

    S. marcescens FS14 was isolated from an Atractylodes macrocephala Koidz plant that was infected by Fusarium oxysporum and showed symptoms of root rot. With the completion of the genome sequence of FS14, the first comprehensive comparative-genomic analysis of the Serratia genus was performed. Pan-genome and COG analyses showed that the majority of the conserved core genes are involved in basic cellular functions, while genomic factors such as prophages contribute considerably to genome diversity. Additionally, a Type I restriction-modification system, a Type III secretion system and tellurium resistance genes are found in only some Serratia species. Comparative analysis further identified that S. marcescens FS14 possesses multiple mechanisms for antagonism against other microorganisms, including the production of prodigiosin, bacteriocins, and multi-antibiotic resistant determinants as well as chitinases. The presence of two evolutionarily distinct Type VI secretion systems (T6SSs) in FS14 may provide further competitive advantages for FS14 against other microbes. To our knowledge, this is the first report of comparative analysis on T6SSs in the genus, which identifies four types of T6SSs in Serratia spp.. Competition bioassays of FS14 against the vital plant pathogenic bacterium Ralstonia solanacearum and fungi Fusarium oxysporum and Sclerotinia sclerotiorum were performed to support our genomic analyses, in which FS14 demonstrated high antagonistic activities against both bacterial and fungal phytopathogens.

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

    Science.gov (United States)

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

    2016-01-01

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

  9. Does the parasite-mediated selection drive the MHC class IIB diversity in wild populations of European chub (Squalius cephalus)?

    Science.gov (United States)

    Seifertová, Mária; Jarkovský, Jiří; Šimková, Andrea

    2016-04-01

    The genes of major histocompatibility complex (MHC) provide an excellent opportunity to study host-parasite relationships because they are expected to evolve in response to parasites and variation in parasite communities. In this study, we investigated the potential role of parasite-mediated selection acting on MHC class IIB (DAB) genes in European chub (Squalius cephalus) natural populations. We found significant differences between populations in metazoan parasites, neutral and adaptive genetic diversities. The analyses based on pairwise data revealed that populations with dissimilar MHC allelic profiles were geographically distant populations with significantly different diversity in microsatellites and a dissimilar composition of parasite communities. The results from the generalized estimating equations method (GEE) on the level of individuals revealed that metazoan parasite load in European chub was influenced by the diversity of DAB alleles as well as by the diversity of neutral genetic markers and host traits reflecting condition and immunocompetence. The multivariate co-inertia analysis showed specific associations between DAB alleles and parasite species. DAB1-like alleles were more involved in associations with ectoparasites, while DAB3-like alleles were positively associated with endoparasites which could suggest potential differences between DAB genes caused by different selection pressure. Our study revealed that parasite-mediated selection is not the only variable affecting MHC diversity in European chub; however, we strongly support the role of neutral processes as the main driver of DAB diversity across populations. In addition, our study contributes to the understanding of the evolution of MHC genes in wild living fish.

  10. Bidirectional relationship between sleep and optimism with depressive mood as a mediator: A longitudinal study of Chinese working adults.

    Science.gov (United States)

    Lau, Esther Yuet Ying; Harry Hui, C; Cheung, Shu-Fai; Lam, Jasmine

    2015-11-01

    Sleep and optimism are important psycho-biological and personality constructs, respectively. However, very little work has examined the causal relationship between them, and none has examined the potential mechanisms operating in the relationship. This study aimed to understand whether sleep quality was a cause or an effect of optimism, and whether depressive mood could explain the relationship. Internet survey data were collected from 987 Chinese working adults (63.4% female, 92.4% full-time workers, 27.0% married, 90.2% Hong Kong residents, mean age=32.59 at three time-points, spanning about 19 months). Measures included a Chinese attributional style questionnaire, the Pittsburgh Sleep Quality Index, and the Depression Anxiety Stress Scale. Cross-sectional analyses revealed moderate correlations among sleep quality, depressive mood, and optimism. Cross-lagged analyses showed a bidirectional causality between optimism and sleep. Path analysis demonstrated that depressive mood fully mediated the influence of optimism on sleep quality, and it partially mediated the influence of sleep quality on optimism. Optimism improves sleep. Poor sleep makes a pessimist. The effects of sleep quality on optimism could not be fully explained by depressive mood, highlighting the unique role of sleep on optimism. Understanding the mechanisms of the feedback loop of sleep quality, mood, and optimism may provide insights for clinical interventions for individuals presented with mood-related problems. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Do smoking and fruit and vegetable intake mediate the association between socio-economic status and plasma carotenoids?

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    Kvaavik, Elisabeth; Totland, Torunn H; Bastani, Nasser; Kjøllesdal, Marte K; Tell, Grethe S; Andersen, Lene F

    2014-08-01

    The aim was to study whether the association between educational attainment and antioxidant status is mediated by smoking and fruit and vegetable intake. Cross-sectional analyses of the Oslo Youth Study 2006 wave were carried out. Information about education, smoking habits and diet was collected by questionnaire for 261 subjects (142 women and 119 men aged 38-42 years). Blood samples, height and weight measurements were taken by the participants' General Practitioner. Blood were analysed for plasma carotenoids. Linear regression analyses were used to examine whether smoking and fruit and vegetable intake mediate the association between education and plasma carotenoids. Educational level was positively associated with β-cryptoxanthin, α-carotene and lutein/zeaxanthin, but not with total carotenoids, β-carotene or lycopene. Education was negatively associated with smoking and positively associated with fruit and vegetable intake. Smoking was negatively associated with β-cryptoxanthin, and fruit and vegetable intake was positively associated with β-cryptoxanthin (adjusted for educational level). Moreover, cigarette consumption mediated the association between education and β-cryptoxanthin by 37%, while fruit and vegetable intake mediated this association by 18%. The total mediation effect was 55%. Smoking seemed to be more important as a mediator between education and plasma levels of β-cryptoxanthin than the intake of fruit and vegetables, but more studies are needed to establish the relative importance of smoking and diet as mediators of the association between education and antioxidant status. © The Author 2013. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

  12. Light-Mediated Kinetic Control Reveals the Temporal Effect of the Raf/MEK/ERK Pathway in PC12 Cell Neurite Outgrowth

    Science.gov (United States)

    Zhang, Kai; Duan, Liting; Ong, Qunxiang; Lin, Ziliang; Varman, Pooja Mahendra; Sung, Kijung; Cui, Bianxiao

    2014-01-01

    It has been proposed that differential activation kinetics allows cells to use a common set of signaling pathways to specify distinct cellular outcomes. For example, nerve growth factor (NGF) and epidermal growth factor (EGF) induce different activation kinetics of the Raf/MEK/ERK signaling pathway and result in differentiation and proliferation, respectively. However, a direct and quantitative linkage between the temporal profile of Raf/MEK/ERK activation and the cellular outputs has not been established due to a lack of means to precisely perturb its signaling kinetics. Here, we construct a light-gated protein-protein interaction system to regulate the activation pattern of the Raf/MEK/ERK signaling pathway. Light-induced activation of the Raf/MEK/ERK cascade leads to significant neurite outgrowth in rat PC12 pheochromocytoma cell lines in the absence of growth factors. Compared with NGF stimulation, light stimulation induces longer but fewer neurites. Intermittent on/off illumination reveals that cells achieve maximum neurite outgrowth if the off-time duration per cycle is shorter than 45 min. Overall, light-mediated kinetic control enables precise dissection of the temporal dimension within the intracellular signal transduction network. PMID:24667437

  13. Trends in Mediation Analysis in Nursing Research: Improving Current Practice.

    Science.gov (United States)

    Hertzog, Melody

    2018-06-01

    The purpose of this study was to describe common approaches used by nursing researchers to test mediation models and evaluate them within the context of current methodological advances. MEDLINE was used to locate studies testing a mediation model and published from 2004 to 2015 in nursing journals. Design (experimental/correlation, cross-sectional/longitudinal, model complexity) and analysis (method, inclusion of test of mediated effect, violations/discussion of assumptions, sample size/power) characteristics were coded for 456 studies. General trends were identified using descriptive statistics. Consistent with findings of reviews in other disciplines, evidence was found that nursing researchers may not be aware of the strong assumptions and serious limitations of their analyses. Suggestions for strengthening the rigor of such studies and an overview of current methods for testing more complex models, including longitudinal mediation processes, are presented.

  14. Spatial genetic analyses reveal cryptic population structure and migration patterns in a continuously harvested grey wolf (Canis lupus population in north-eastern Europe.

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    Maris Hindrikson

    Full Text Available Spatial genetics is a relatively new field in wildlife and conservation biology that is becoming an essential tool for unravelling the complexities of animal population processes, and for designing effective strategies for conservation and management. Conceptual and methodological developments in this field are therefore critical. Here we present two novel methodological approaches that further the analytical possibilities of STRUCTURE and DResD. Using these approaches we analyse structure and migrations in a grey wolf (Canislupus population in north-eastern Europe. We genotyped 16 microsatellite loci in 166 individuals sampled from the wolf population in Estonia and Latvia that has been under strong and continuous hunting pressure for decades. Our analysis demonstrated that this relatively small wolf population is represented by four genetic groups. We also used a novel methodological approach that uses linear interpolation to statistically test the spatial separation of genetic groups. The new method, which is capable of using program STRUCTURE output, can be applied widely in population genetics to reveal both core areas and areas of low significance for genetic groups. We also used a recently developed spatially explicit individual-based method DResD, and applied it for the first time to microsatellite data, revealing a migration corridor and barriers, and several contact zones.

  15. Linking and Psychological Functioning in a Chinese Sample: The Multiple Mediation of Response to Positive Affect

    Science.gov (United States)

    Yang, Hongfei; Li, Juan

    2016-01-01

    The present study examined the associations between linking, response to positive affect, and psychological functioning in Chinese college students. The results of conducting multiple mediation analyses indicated that emotion- and self-focused positive rumination mediated the relationship between linking and psychological functioning, whereas…

  16. Abundant genetic overlap between blood lipids and immune-mediated diseases indicates shared molecular genetic mechanisms.

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    Ole A Andreassen

    Full Text Available Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS to investigate shared single nucleotide polymorphisms (SNPs between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals, applying new False Discovery Rate (FDR methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG, low density lipoproteins (LDL, high density lipoproteins (HDL] and a selection of archetypal immune-mediated diseases (Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis. We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88, LDL (n = 87 and HDL (n = 52. Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2 and intestinal host-microbe interactions (e.g. ATG16L1. We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents.

  17. Ultraviolet Radiation and the Slug Transcription Factor Induce Proinflammatory and Immunomodulatory Mediator Expression in Melanocytes

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    Stephanie H. Shirley

    2012-01-01

    Full Text Available Despite extensive investigation, the precise contribution of the ultraviolet radiation (UVR component of sunlight to melanoma etiology remains unclear. UVR induces keratinocytes to secrete proinflammatory and immunomodulatory mediators that promote inflammation and skin tumor development; expression of the slug transcription factor in keratinocytes is required for maximal production of these mediators. In the present studies we examined the possibility that UVR-exposed melanocytes also produce proinflammatory mediators and that Slug is important in this process. Microarray studies revealed that both UVR exposure and Slug overexpression altered transcription of a variety of proinflammatory mediators by normal human melanocytes; some of these mediators are also known to stimulate melanocyte growth and migration. There was little overlap in the spectra of cytokines produced by the two stimuli. However IL-20 was similarly induced by both stimuli and the NFκB pathway appeared to be important in both circumstances. Further exploration of UVR-induced and Slug-dependent pathways of cytokine induction in melanocytes may reveal novel targets for melanoma therapy.

  18. Immediate Supervisors’ Leadership Behaviour and Employees’ Organizational Commitment: Do Pay and Promotion Mediate the Nexus?

    Directory of Open Access Journals (Sweden)

    Emmanuel Yaw Ampofo

    2016-09-01

    Full Text Available This study examines the mediating effect of motivational factors of pay and promotion on transformational leadership and organizational commitment relationship in Unilever Ghana using a quantitative, non-experimental, cross-sectional and analytical survey design study. The results of the study revealed significant positive relationship between transformational leadership style and affective commitment, continuance commitment, and normative commitment. However, the results of the study revealed no significant mediation of pay in the relationship between transformational leadership style and affective commitment, continuance commitment, and normative commitment. Additionally, no significant mediation of promotion was found in the relationship between transformational leadership and affective commitment, transformational leadership and continuance commitment, and transformational leadership and normative commitment. Managers’ adoption of transformational leadership behavior as a key strategy to get employees committed to the organizations will be of great significance because motivational factors such as pay and promotion do not mediate the transformational leadership and organizational commitment relationship. This is a maiden empirical research in Ghana where motivational factors are used as mediators in transformational leadership and organizational commitment relationship.

  19. Post-genomic analyses of fungal lignocellulosic biomass degradation reveal the unexpected potential of the plant pathogen Ustilago maydis

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    Couturier Marie

    2012-02-01

    Full Text Available Abstract Background Filamentous fungi are potent biomass degraders due to their ability to thrive in ligno(hemicellulose-rich environments. During the last decade, fungal genome sequencing initiatives have yielded abundant information on the genes that are putatively involved in lignocellulose degradation. At present, additional experimental studies are essential to provide insights into the fungal secreted enzymatic pools involved in lignocellulose degradation. Results In this study, we performed a wide analysis of 20 filamentous fungi for which genomic data are available to investigate their biomass-hydrolysis potential. A comparison of fungal genomes and secretomes using enzyme activity profiling revealed discrepancies in carbohydrate active enzymes (CAZymes sets dedicated to plant cell wall. Investigation of the contribution made by each secretome to the saccharification of wheat straw demonstrated that most of them individually supplemented the industrial Trichoderma reesei CL847 enzymatic cocktail. Unexpectedly, the most striking effect was obtained with the phytopathogen Ustilago maydis that improved the release of total sugars by 57% and of glucose by 22%. Proteomic analyses of the best-performing secretomes indicated a specific enzymatic mechanism of U. maydis that is likely to involve oxido-reductases and hemicellulases. Conclusion This study provides insight into the lignocellulose-degradation mechanisms by filamentous fungi and allows for the identification of a number of enzymes that are potentially useful to further improve the industrial lignocellulose bioconversion process.

  20. Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes.

    Science.gov (United States)

    Paatero, Ilkka; Casals, Eudald; Niemi, Rasmus; Özliseli, Ezgi; Rosenholm, Jessica M; Sahlgren, Cecilia

    2017-08-21

    Mesoporous silica nanoparticles (MSNs) are extensively explored as drug delivery systems, but in depth understanding of design-toxicity relationships is still scarce. We used zebrafish (Danio rerio) embryos to study toxicity profiles of differently surface functionalized MSNs. Embryos with the chorion membrane intact, or dechoroniated embryos, were incubated or microinjected with amino (NH 2 -MSNs), polyethyleneimine (PEI-MSNs), succinic acid (SUCC-MSNs) or polyethyleneglycol (PEG-MSNs) functionalized MSNs. Toxicity was assessed by viability and cardiovascular function. NH 2 -MSNs, SUCC-MSNs and PEG-MSNs were well tolerated, 50 µg/ml PEI-MSNs induced 100% lethality 48 hours post fertilization (hpf). Dechoroniated embryos were more sensitive and 10 µg/ml PEI-MSNs reduced viability to 5% at 96hpf. Sensitivity to PEG- and SUCC-, but not NH 2 -MSNs, was also enhanced. Typically cardiovascular toxicity was evident prior to lethality. Confocal microscopy revealed that PEI-MSNs penetrated into the embryos whereas PEG-, NH2- and SUCC-MSNs remained aggregated on the skin surface. Direct exposure of inner organs by microinjecting NH 2 -MSNs and PEI-MSNs demonstrated that the particles displayed similar toxicity indicating that functionalization affects the toxicity profile by influencing penetrance through biological barriers. The data emphasize the need for careful analyses of toxicity mechanisms in relevant models and constitute an important knowledge step towards the development of safer and sustainable nanotherapies.

  1. Mediation analysis with time varying exposures and mediators.

    Science.gov (United States)

    VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J

    2017-06-01

    In this paper we consider causal mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are time-varying confounders affected by prior exposure and mediator, natural direct and indirect effects are not identified. However, we define a randomized interventional analogue of natural direct and indirect effects that are identified in this setting. The formula that identifies these effects we refer to as the "mediational g-formula." When there is no mediation, the mediational g-formula reduces to Robins' regular g-formula for longitudinal data. When there are no time-varying confounders affected by prior exposure and mediator values, then the mediational g-formula reduces to a longitudinal version of Pearl's mediation formula. However, the mediational g-formula itself can accommodate both mediation and time-varying confounders and constitutes a general approach to mediation analysis with time-varying exposures and mediators.

  2. Transcriptomic analyses reveal novel genes with sexually dimorphic expression in the zebrafish gonad and brain.

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    Rajini Sreenivasan

    Full Text Available BACKGROUND: Our knowledge on zebrafish reproduction is very limited. We generated a gonad-derived cDNA microarray from zebrafish and used it to analyze large-scale gene expression profiles in adult gonads and other organs. METHODOLOGY/PRINCIPAL FINDINGS: We have identified 116638 gonad-derived zebrafish expressed sequence tags (ESTs, 21% of which were isolated in our lab. Following in silico normalization, we constructed a gonad-derived microarray comprising 6370 unique, full-length cDNAs from differentiating and adult gonads. Labeled targets from adult gonad, brain, kidney and 'rest-of-body' from both sexes were hybridized onto the microarray. Our analyses revealed 1366, 881 and 656 differentially expressed transcripts (34.7% novel that showed highest expression in ovary, testis and both gonads respectively. Hierarchical clustering showed correlation of the two gonadal transcriptomes and their similarities to those of the brains. In addition, we have identified 276 genes showing sexually dimorphic expression both between the brains and between the gonads. By in situ hybridization, we showed that the gonadal transcripts with the strongest array signal intensities were germline-expressed. We found that five members of the GTP-binding septin gene family, from which only one member (septin 4 has previously been implicated in reproduction in mice, were all strongly expressed in the gonads. CONCLUSIONS/SIGNIFICANCE: We have generated a gonad-derived zebrafish cDNA microarray and demonstrated its usefulness in identifying genes with sexually dimorphic co-expression in both the gonads and the brains. We have also provided the first evidence of large-scale differential gene expression between female and male brains of a teleost. Our microarray would be useful for studying gonad development, differentiation and function not only in zebrafish but also in related teleosts via cross-species hybridizations. Since several genes have been shown to play similar

  3. Ten Ways to Improve the Use of Statistical Mediation Analysis in the Practice of Child and Adolescent Treatment Research

    Science.gov (United States)

    Maric, Marija; Wiers, Reinout W.; Prins, Pier J. M.

    2012-01-01

    Despite guidelines and repeated calls from the literature, statistical mediation analysis in youth treatment outcome research is rare. Even more concerning is that many studies that "have" reported mediation analyses do not fulfill basic requirements for mediation analysis, providing inconclusive data and clinical implications. As a result, after…

  4. Ethnic discrimination and Latino depression: The mediating role of traumatic stress symptoms and alcohol use.

    Science.gov (United States)

    Torres, Lucas; Vallejo, Leticia G

    2015-10-01

    Previous research has established a link between ethnic discrimination and poor mental health, yet the process by which this relationship occurs remains unclear. It has been hypothesized that the potential mechanisms accounting for the negative consequences of ethnic discrimination may be through stress responses and health behaviors (Pascoe & Smart Richman, 2009). The present study sought to examine the role of traumatic stress symptoms and alcohol use in mediating the relationship between ethnic discrimination and depressive symptoms. Two aspects of ethnic discrimination were assessed, namely source of discrimination and reaction to discrimination. The sample for the current study included 244 adult Latinos averaging approximately 40 years of age (SD = 15.29; range 18-85). Participants, which were comprised of mainly women (66%, n = 156), completed a series of paper-and-pencil questionnaires. Multiple mediator analyses revealed that, among U.S.-born but not foreign-born Latinos, both source of discrimination and reaction to discrimination were related to increased traumatic stress symptoms, which, in turn, was associated with depressive symptomatology. The traumatic stress symptoms pathway showed a robust indirect effect while alcohol use was not a statistically significant mediator. These major findings suggest that, while ethnic discrimination has a direct effect on depression, increased traumatic stress can account for this relationship particularly for U.S.-born Latinos. The findings are discussed within a stress and coping framework. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  5. Child/Adolescent's ADHD and Parenting Stress: The Mediating Role of Family Impact and Conduct Problems.

    Science.gov (United States)

    Muñoz-Silva, Alicia; Lago-Urbano, Rocio; Sanchez-Garcia, Manuel; Carmona-Márquez, José

    2017-01-01

    Objective: The demands of parenting are usually associated with some stress, and elevated levels of stress may affect the parent-child relationships and parenting practices. This is especially the case of families where children have special needs conditions or disorders, like Attention Deficit Hyperactivity Disorder (ADHD). Method: This study examined parenting stress among mothers of children and adolescents with ADHD. The sample comprised 126 mothers of girls (36; 29%) and boys (90; 71%) aged 6-17 years old. Results: Mothers reported their own stress levels as well as the children and adolescents' variables (severity of their ADHD symptoms, conduct, and emotional problems) and family-contextual variables (negative impact on family's social life, impact on couple relationship, and perceived social support). Hierarchical multiple regression showed that (a) negative impact on social life and conduct problems were the strongest predictors of mother's stress. Bootstrap mediation analyses revealed that (b) the association between child and adolescent's ADHD and parenting stress was mediated by children's conduct problems and by negative impact on family's social life, and not by children's emotional problems nor by mother's perceived social support. The mediation analysis also suggested (c) a pathway from child/adolescent's ADHD through children's conduct problems and then through their negative impact on family's social life to mother's parenting stress. Conclusion: These results suggest that both child/adolescent's and family factors should be considered in the designing of interventions for reducing parenting stress in families of children and adolescents with ADHD.

  6. Comparative genome analyses of Serratia marcescens FS14 reveals its high antagonistic potential.

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    Pengpeng Li

    Full Text Available S. marcescens FS14 was isolated from an Atractylodes macrocephala Koidz plant that was infected by Fusarium oxysporum and showed symptoms of root rot. With the completion of the genome sequence of FS14, the first comprehensive comparative-genomic analysis of the Serratia genus was performed. Pan-genome and COG analyses showed that the majority of the conserved core genes are involved in basic cellular functions, while genomic factors such as prophages contribute considerably to genome diversity. Additionally, a Type I restriction-modification system, a Type III secretion system and tellurium resistance genes are found in only some Serratia species. Comparative analysis further identified that S. marcescens FS14 possesses multiple mechanisms for antagonism against other microorganisms, including the production of prodigiosin, bacteriocins, and multi-antibiotic resistant determinants as well as chitinases. The presence of two evolutionarily distinct Type VI secretion systems (T6SSs in FS14 may provide further competitive advantages for FS14 against other microbes. To our knowledge, this is the first report of comparative analysis on T6SSs in the genus, which identifies four types of T6SSs in Serratia spp.. Competition bioassays of FS14 against the vital plant pathogenic bacterium Ralstonia solanacearum and fungi Fusarium oxysporum and Sclerotinia sclerotiorum were performed to support our genomic analyses, in which FS14 demonstrated high antagonistic activities against both bacterial and fungal phytopathogens.

  7. Concurrent growth rate and transcript analyses reveal essential gene stringency in Escherichia coli.

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    Shan Goh

    Full Text Available BACKGROUND: Genes essential for bacterial growth are of particular scientific interest. Many putative essential genes have been identified or predicted in several species, however, little is known about gene expression requirement stringency, which may be an important aspect of bacterial physiology and likely a determining factor in drug target development. METHODOLOGY/PRINCIPAL FINDINGS: Working from the premise that essential genes differ in absolute requirement for growth, we describe silencing of putative essential genes in E. coli to obtain a titration of declining growth rates and transcript levels by using antisense peptide nucleic acids (PNA and expressed antisense RNA. The relationship between mRNA decline and growth rate decline reflects the degree of essentiality, or stringency, of an essential gene, which is here defined by the minimum transcript level for a 50% reduction in growth rate (MTL(50. When applied to four growth essential genes, both RNA silencing methods resulted in MTL(50 values that reveal acpP as the most stringently required of the four genes examined, with ftsZ the next most stringently required. The established antibacterial targets murA and fabI were less stringently required. CONCLUSIONS: RNA silencing can reveal stringent requirements for gene expression with respect to growth. This method may be used to validate existing essential genes and to quantify drug target requirement.

  8. Explaining the effects of a 1-year intervention promoting a low fat diet in adolescent girls: a mediation analysis

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    Maes Lea

    2007-11-01

    Full Text Available Abstract Background Although it is important to investigate how interventions work, no formal mediation analyses have been conducted to explain behavioral outcomes in school-based fat intake interventions in adolescents. The aim of the present study was to examine mediation effects of changes in psychosocial determinants of dietary fat intake (attitude, social support, self-efficacy, perceived benefits and barriers on changes in fat intake in adolescent girls. Methods Data from a 1-year prospective intervention study were used. A random sample of 804 adolescent girls was included in the study. Girls in the intervention group (n = 415 were exposed to a multi-component school-based intervention program, combining environmental changes with a computer tailored fat intake intervention and parental support. Fat intake and psychosocial determinants of fat intake were measured with validated self-administered questionnaires. To assess mediating effects, a product-of-coefficient test, appropriate for cluster randomized controlled trials, was used. Results None of the examined psychosocial factors showed a reliable mediating effect on changes in fat intake. The single-mediator model revealed a statistically significant suppression effect of perceived barriers on changes in fat intake (p = 0.011. In the multiple-mediator model, this effect was no longer significant, which was most likely due to changes in perceived barriers being moderately related to changes in self-efficacy (-0.30 and attitude (-0.25. The overall mediated-suppressed effect of the examined psychosocial factors was virtually zero (total mediated effect = 0.001; SE = 7.22; p = 0.992. Conclusion Given the lack of intervention effects on attitudes, social support, self-efficacy and perceived benefits and barriers, it is suggested that future interventions should focus on the identification of effective strategies for changing these theoretical mediators in the desired direction

  9. Comparative genomics reveals diversity among xanthomonads infecting tomato and pepper

    LENUS (Irish Health Repository)

    Potnis, Neha

    2011-03-11

    Abstract Background Bacterial spot of tomato and pepper is caused by four Xanthomonas species and is a major plant disease in warm humid climates. The four species are distinct from each other based on physiological and molecular characteristics. The genome sequence of strain 85-10, a member of one of the species, Xanthomonas euvesicatoria (Xcv) has been previously reported. To determine the relationship of the four species at the genome level and to investigate the molecular basis of their virulence and differing host ranges, draft genomic sequences of members of the other three species were determined and compared to strain 85-10. Results We sequenced the genomes of X. vesicatoria (Xv) strain 1111 (ATCC 35937), X. perforans (Xp) strain 91-118 and X. gardneri (Xg) strain 101 (ATCC 19865). The genomes were compared with each other and with the previously sequenced Xcv strain 85-10. In addition, the molecular features were predicted that may be required for pathogenicity including the type III secretion apparatus, type III effectors, other secretion systems, quorum sensing systems, adhesins, extracellular polysaccharide, and lipopolysaccharide determinants. Several novel type III effectors from Xg strain 101 and Xv strain 1111 genomes were computationally identified and their translocation was validated using a reporter gene assay. A homolog to Ax21, the elicitor of XA21-mediated resistance in rice, and a functional Ax21 sulfation system were identified in Xcv. Genes encoding proteins with functions mediated by type II and type IV secretion systems have also been compared, including enzymes involved in cell wall deconstruction, as contributors to pathogenicity. Conclusions Comparative genomic analyses revealed considerable diversity among bacterial spot pathogens, providing new insights into differences and similarities that may explain the diverse nature of these strains. Genes specific to pepper pathogens, such as the O-antigen of the lipopolysaccharide cluster

  10. Workplace ostracism And workplace behaviors: A moderated mediation model of perceived stress and psychological empowerment.

    Science.gov (United States)

    Chung, Yang Woon

    2018-05-01

    Workplace ostracism research has examined numerous underlying mechanisms to understand the link between workplace ostracism and behavioral outcomes. Ostracism has been suggested to be an interpersonal stressor; however, research has not investigated workplace ostracism from a stress perspective. Therefore, the study investigated the mediating effect of perceived stress for the relationships between workplace ostracism and helping behavior, voicing behavior, and task performance. The study also investigated the moderating effect of psychological empowerment for the relationships between perceived stress and behavioral outcomes. The study design was a three-wave self-reported questionnaire. The study sampled 225 full-time employees in South Korea and regression analyses with bootstrapping were conducted to test the moderated mediation models. The bootstrapped 95% CI around the indirect effects did not contain zero; therefore, perceived stress mediated the relationship between workplace ostracism and helping behavior (-.06), voicing behavior (-.07), and task performance (-.07). Further, the moderated mediation analyses found perceived stress mediated the relationships between workplace ostracism and behavioral outcomes only when individuals perceived low levels of psychological empowerment. The findings suggest that workplace ostracism is a stressor and psychological empowerment can mitigate the negative effects of ostracism on behavioral outcomes.

  11. Importance of Mediator complex in the regulation and integration of diverse signaling pathways in plants

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    Subhasis eSamanta

    2015-09-01

    Full Text Available Basic transcriptional machinery in eukaryotes is assisted by a number of cofactors, which either increase or decrease the rate of transcription. Mediator complex is one such cofactor, and recently has drawn a lot of interest because of its integrative power to converge different signaling pathways before channelling the transcription instructions to the RNA polymerase II machinery. Like yeast and metazoans, plants do possess the Mediator complex across the kingdom, and its isolation and subunit analyses have been reported from the model plant, Arabidopsis. Genetic and molecular analyses have unravelled important regulatory roles of Mediator subunits at every stage of plant life cycle starting from flowering to embryo and organ development, to even size determination. It also contributes immensely to the survival of plants against different environmental vagaries by the timely activation of its resistance mechanisms. Here, we have provided an overview of plant Mediator complex starting from its discovery to regulation of stoichiometry of its subunits. We have also reviewed involvement of different Mediator subunits in different processes and pathways including defense response pathways evoked by diverse biotic cues. Wherever possible, attempts have been made to provide mechanistic insight of Mediator’s involvement in these processes.

  12. Is the Relationship Between Marital Adjustment and Parenting Stress Mediated or Moderated by Parenting Alliance?

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    Elena Camisasca

    2014-05-01

    Full Text Available The purpose of this study was to explore the mediating and moderating effects of parenting alliance on the relationship between marital adjustment, as represented by the dimensions dyadic consensus, dyadic satisfaction, dyadic cohesion, and affectional expression, and maternal and paternal stress. Self-report data were gathered from 236 Italian families (236 mothers: M = 40.9; SD = 4.4 and 236 fathers: M = 42.9; SD = 4.8 of children aged 6–11 years (M = 8.6; SD = 1.7. A set of regression analyses were conducted to examine whether parenting alliance mediates or moderates the relationship between marital adjustment and parenting stress. Regression analyses were consistent with a model of coparenting as a mediator but not as a moderator of the relationship between marital adjustment and parenting stress. In the case of mothers, parenting alliance mediates the relationships between two dimensions of marital adjustment (dyadic consensus and dyadic cohesion on parenting stress; in the case of fathers, parenting alliance serves as a mediator of the relationship between the marital adjustment (in terms of dyadic satisfaction and parenting stress. Implications for future research and interventions are discussed.

  13. Comparative analyses of population-scale phenomic data in electronic medical records reveal race-specific disease networks.

    Science.gov (United States)

    Glicksberg, Benjamin S; Li, Li; Badgeley, Marcus A; Shameer, Khader; Kosoy, Roman; Beckmann, Noam D; Pho, Nam; Hakenberg, Jörg; Ma, Meng; Ayers, Kristin L; Hoffman, Gabriel E; Dan Li, Shuyu; Schadt, Eric E; Patel, Chirag J; Chen, Rong; Dudley, Joel T

    2016-06-15

    Underrepresentation of racial groups represents an important challenge and major gap in phenomics research. Most of the current human phenomics research is based primarily on European populations; hence it is an important challenge to expand it to consider other population groups. One approach is to utilize data from EMR databases that contain patient data from diverse demographics and ancestries. The implications of this racial underrepresentation of data can be profound regarding effects on the healthcare delivery and actionability. To the best of our knowledge, our work is the first attempt to perform comparative, population-scale analyses of disease networks across three different populations, namely Caucasian (EA), African American (AA) and Hispanic/Latino (HL). We compared susceptibility profiles and temporal connectivity patterns for 1988 diseases and 37 282 disease pairs represented in a clinical population of 1 025 573 patients. Accordingly, we revealed appreciable differences in disease susceptibility, temporal patterns, network structure and underlying disease connections between EA, AA and HL populations. We found 2158 significantly comorbid diseases for the EA cohort, 3265 for AA and 672 for HL. We further outlined key disease pair associations unique to each population as well as categorical enrichments of these pairs. Finally, we identified 51 key 'hub' diseases that are the focal points in the race-centric networks and of particular clinical importance. Incorporating race-specific disease comorbidity patterns will produce a more accurate and complete picture of the disease landscape overall and could support more precise understanding of disease relationships and patient management towards improved clinical outcomes. rong.chen@mssm.edu or joel.dudley@mssm.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

  14. Genome-wide scans between two honeybee populations reveal putative signatures of human-mediated selection.

    Science.gov (United States)

    Parejo, M; Wragg, D; Henriques, D; Vignal, A; Neuditschko, M

    2017-12-01

    Human-mediated selection has left signatures in the genomes of many domesticated animals, including the European dark honeybee, Apis mellifera mellifera, which has been selected by apiculturists for centuries. Using whole-genome sequence information, we investigated selection signatures in spatially separated honeybee subpopulations (Switzerland, n = 39 and France, n = 17). Three different test statistics were calculated in windows of 2 kb (fixation index, cross-population extended haplotype homozygosity and cross-population composite likelihood ratio) and combined into a recently developed composite selection score. Applying a stringent false discovery rate of 0.01, we identified six significant selective sweeps distributed across five chromosomes covering eight genes. These genes are associated with multiple molecular and biological functions, including regulation of transcription, receptor binding and signal transduction. Of particular interest is a selection signature on chromosome 1, which corresponds to the WNT4 gene, the family of which is conserved across the animal kingdom with a variety of functions. In Drosophila melanogaster, WNT4 alleles have been associated with differential wing, cross vein and abdominal phenotypes. Defining phenotypic characteristics of different Apis mellifera ssp., which are typically used as selection criteria, include colour and wing venation pattern. This signal is therefore likely to be a good candidate for human mediated-selection arising from different applied breeding practices in the two managed populations. © 2017 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.

  15. Mediator kinase module and human tumorigenesis.

    Science.gov (United States)

    Clark, Alison D; Oldenbroek, Marieke; Boyer, Thomas G

    2015-01-01

    Mediator is a conserved multi-subunit signal processor through which regulatory informatiosn conveyed by gene-specific transcription factors is transduced to RNA Polymerase II (Pol II). In humans, MED13, MED12, CDK8 and Cyclin C (CycC) comprise a four-subunit "kinase" module that exists in variable association with a 26-subunit Mediator core. Genetic and biochemical studies have established the Mediator kinase module as a major ingress of developmental and oncogenic signaling through Mediator, and much of its function in signal-dependent gene regulation derives from its resident CDK8 kinase activity. For example, CDK8-targeted substrate phosphorylation impacts transcription factor half-life, Pol II activity and chromatin chemistry and functional status. Recent structural and biochemical studies have revealed a precise network of physical and functional subunit interactions required for proper kinase module activity. Accordingly, pathologic change in this activity through altered expression or mutation of constituent kinase module subunits can have profound consequences for altered signaling and tumor formation. Herein, we review the structural organization, biological function and oncogenic potential of the Mediator kinase module. We focus principally on tumor-associated alterations in kinase module subunits for which mechanistic relationships as opposed to strictly correlative associations are established. These considerations point to an emerging picture of the Mediator kinase module as an oncogenic unit, one in which pathogenic activation/deactivation through component change drives tumor formation through perturbation of signal-dependent gene regulation. It follows that therapeutic strategies to combat CDK8-driven tumors will involve targeted modulation of CDK8 activity or pharmacologic manipulation of dysregulated CDK8-dependent signaling pathways.

  16. Deficits in recognizing disgust facial expressions and Internet addiction: Perceived stress as a mediator.

    Science.gov (United States)

    Chen, Zhongting; Poon, Kai-Tak; Cheng, Cecilia

    2017-08-01

    Studies have examined social maladjustment among individuals with Internet addiction, but little is known about their deficits in specific social skills and the underlying psychological mechanisms. The present study filled these gaps by (a) establishing a relationship between deficits in facial expression recognition and Internet addiction, and (b) examining the mediating role of perceived stress that explains this hypothesized relationship. Ninety-seven participants completed validated questionnaires that assessed their levels of Internet addiction and perceived stress, and performed a computer-based task that measured their facial expression recognition. The results revealed a positive relationship between deficits in recognizing disgust facial expression and Internet addiction, and this relationship was mediated by perceived stress. However, the same findings did not apply to other facial expressions. Ad hoc analyses showed that recognizing disgust was more difficult than recognizing other facial expressions, reflecting that the former task assesses a social skill that requires cognitive astuteness. The present findings contribute to the literature by identifying a specific social skill deficit related to Internet addiction and by unveiling a psychological mechanism that explains this relationship, thus providing more concrete guidelines for practitioners to strengthen specific social skills that mitigate both perceived stress and Internet addiction. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  17. Tobacco withdrawal symptoms mediate motivation to reinstate smoking during abstinence.

    Science.gov (United States)

    Aguirre, Claudia G; Madrid, Jillian; Leventhal, Adam M

    2015-08-01

    Withdrawal-based theories of addiction hypothesize that motivation to reinstate drug use following acute abstinence is mediated by withdrawal symptoms. Experimental tests of this hypothesis in the tobacco literature are scant and may be subject to methodological limitations. This study utilized a robust within-subject laboratory experimental design to investigate the extent to which composite tobacco withdrawal symptomatology level and 3 unique withdrawal components (i.e., low positive affect, negative affect, and urge to smoke) mediated the effect of smoking abstinence on motivation to reinstate smoking. Smokers (≥10 cigarettes per day; N = 286) attended 2 counterbalanced sessions at which abstinence duration was differentially manipulated (1 hr vs. 17 hr). At both sessions, participants reported current withdrawal symptoms and subsequently completed a task in which they were monetarily rewarded proportional to the length of time they delayed initiating smoking, with shorter latency reflecting stronger motivation to reinstate smoking. Abstinence reduced latency to smoking initiation and positive affect and increased composite withdrawal symptom level, urge, and negative affect. Abstinence-induced reductions in latency to initiating smoking were mediated by each withdrawal component, with stronger effects operating through urge. Combined analyses suggested that urge, negative affect, and low positive affect operate through empirically unique mediational pathways. Secondary analyses suggested similar effects on smoking quantity, few differences among specific urge and affect subtypes, and that dependence amplifies some abstinence effects. This study provides the first experimental evidence that within-person variation in abstinence impacts motivation to reinstate drug use through withdrawal. Urge, negative affect, and low positive affect may reflect unique withdrawal-mediated mechanisms underlying tobacco addiction. (c) 2015 APA, all rights reserved).

  18. The role of life skills promotion in substance abuse prevention: a mediation analysis.

    Science.gov (United States)

    Bühler, Anneke; Schröder, Elke; Silbereisen, Rainer K

    2008-08-01

    Research has shown that life skills programs are the most effective single activity in school-based substance abuse prevention. However, little is known about the processes through which they are effective. This study examines whether an evidence-based prevention program targeting general competence is effective through the promotion of knowledge about life skills and enhanced related behaviors. Based on a sample of 442 fifth graders participating in a quasi-experimental prevention study, as expected, mediation analyses revealed that increased knowledge about life skills paralleled an increase in students' distant attitudes toward alcohol and nicotine use. Unexpectedly, behaviors manifesting enhanced life skills were found not only among program participants who remained experimental/non-smokers or stopped smoking but also among smokers. In general, findings suggest that favorable prevention outcomes may be influenced through building knowledge about general life skills. The notion of uniform mechanisms of effectiveness in prevention programs is discussed.

  19. RNA-Seq analysis reveals insight into enhanced rice Xa7-mediated bacterial blight resistance at high temperature.

    Directory of Open Access Journals (Sweden)

    Stephen P Cohen

    Full Text Available Plant disease is a major challenge to agriculture worldwide, and it is exacerbated by abiotic environmental factors. During some plant-pathogen interactions, heat stress allows pathogens to overcome host resistance, a phenomenon which could severely impact crop productivity considering the global warming trends associated with climate change. Despite the importance of this phenomenon, little is known about the underlying molecular mechanisms. To better understand host plant responses during simultaneous heat and pathogen stress, we conducted a transcriptomics experiment for rice plants (cultivar IRBB61 containing Xa7, a bacterial blight disease resistance (R gene, that were infected with Xanthomonas oryzae, the bacterial blight pathogen of rice, during high temperature stress. Xa7-mediated resistance is unusual relative to resistance mediated by other R genes in that it functions better at high temperatures. Using RNA-Seq technology, we identified 8,499 differentially expressed genes as temperature responsive in rice cultivar IRBB61 experiencing susceptible and resistant interactions across three time points. Notably, genes in the plant hormone abscisic acid biosynthesis and response pathways were up-regulated by high temperature in both mock-treated plants and plants experiencing a susceptible interaction and were suppressed by high temperature in plants exhibiting Xa7-mediated resistance. Genes responsive to salicylic acid, an important plant hormone for disease resistance, were down-regulated by high temperature during both the susceptible and resistant interactions, suggesting that enhanced Xa7-mediated resistance at high temperature is not dependent on salicylic acid signaling. A DNA sequence motif similar to known abscisic acid-responsive cis-regulatory elements was identified in the promoter region upstream of genes up-regulated in susceptible but down-regulated in resistant interactions. The results of our study suggest that the plant

  20. SOCIAL COMPETENCE AND PSYCHOLOGICAL VULNERABILITY: THE MEDIATING ROLE OF FLOURISHING.

    Science.gov (United States)

    Uysal, Recep

    2015-10-01

    This study examined whether flourishing mediated the social competence and psychological vulnerability. Participants were 259 university students (147 women, 112 men; M age = 21.3 yr., SD = 1.7) who completed the Turkish versions of the Perceived Social Competence Scale, the Flourishing Scale, and the Psychological Vulnerability Scale. Mediation models were tested using the bootstrapping method to examine indirect effects. Consistent with the hypotheses, the results indicated a positive relationship between social competence and flourishing, and a negative relationship between social competence and psychological vulnerability. Results of the bootstrapping method revealed that flourishing significantly mediated the relationship between social competence and psychological vulnerability. The significance and limitations of the results were discussed.

  1. SPSS and SAS programming for the testing of mediation models.

    Science.gov (United States)

    Dudley, William N; Benuzillo, Jose G; Carrico, Mineh S

    2004-01-01

    Mediation modeling can explain the nature of the relation among three or more variables. In addition, it can be used to show how a variable mediates the relation between levels of intervention and outcome. The Sobel test, developed in 1990, provides a statistical method for determining the influence of a mediator on an intervention or outcome. Although interactive Web-based and stand-alone methods exist for computing the Sobel test, SPSS and SAS programs that automatically run the required regression analyses and computations increase the accessibility of mediation modeling to nursing researchers. To illustrate the utility of the Sobel test and to make this programming available to the Nursing Research audience in both SAS and SPSS. The history, logic, and technical aspects of mediation testing are introduced. The syntax files sobel.sps and sobel.sas, created to automate the computation of the regression analysis and test statistic, are available from the corresponding author. The reported programming allows the user to complete mediation testing with the user's own data in a single-step fashion. A technical manual included with the programming provides instruction on program use and interpretation of the output. Mediation modeling is a useful tool for describing the relation between three or more variables. Programming and manuals for using this model are made available.

  2. Theoretical and experimental insights into the ·OH-mediated mineralization mechanism of flutriafol

    International Nuclear Information System (INIS)

    Liu, Siqi; Zhou, Xiezhen; Han, Weiqing; Li, Jiansheng; Sun, Xiuyun; Shen, Jinyou; Wang, Lianjun

    2017-01-01

    Highlights: • A complete ·OH-mediated degradation pathway of flutriafol is proposed. • Computational approach is effective to reveal the favorable transformation process. • The electrochemical experiments well verify the theoretical results. - Abstract: Flutriafol is one of the widely used triazole fungicides in global pesticides market, and its degradation mechanisms are important to develop powerful technologies to remove it. Insight into the kinetics and mechanisms of ·OH-mediated mineralization of flutriafol have been obtained using quantum chemical calculation and electrochemical experiment methods. The complete ·OH-mediated degradation pathway of flutriafol was proposed by density functional theory (DFT) simulation and the potential energy surface was mapped out for possible reactions. On the basis of DFT calculations, the optimal ·OH-mediated mineralization mechanism of flutriafol was revealed, and a series of intermediates were observed accumulated in the degradation process, most significance among which were (2-fluorophenyl) (4-fluorophenyl)-Methanone, phenol, dihydroxybenzenes, benzoquinones, muconic acids, maleic acids, oxalic acids and formic acid. To give deeper insight into the ·OH-mediated reaction mechanism, the electrostatic potential (ESP) and average local ionization energy (ALIE) analysis were conducted for o-benzoquinone and p-benzoquinone. The proposed mechanism was further validated by electrochemical experiments at TiO_2-NTs/SnO_2-Sb/PbO_2 anode. The main intermediates were identified and quantified by experimental method, indicating that the proposed ·OH-mediated degradation mechanism derived from DFT calculations was feasible. These detailed findings could be instrumental for a comprehensive understanding of the ·OH-mediated mineralization mechanism of flutriafol and the similar contaminants.

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

    Science.gov (United States)

    Gawęda, Łukasz; Kokoszka, Andrzej

    2014-05-01

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

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

    Science.gov (United States)

    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 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.

  5. Theory of mind deficits partly mediate impaired social decision-making in schizophrenia.

    Science.gov (United States)

    Yang, Liuqing; Li, Peifu; Mao, Haiying; Wang, Huiling; Shu, Chang; Bliksted, Vibeke; Zhou, Yuan

    2017-05-05

    Using paradigms from game theory, researchers have reported abnormal decision-making in social context in patients with schizophrenia. However, less is known about the underpinnings of the impairment. This study aimed to test whether theory of mind (ToM) deficits and/or neurocognitive dysfunctions mediate impaired social decision-making in patients with schizophrenia. We compared thirty-five patients with schizophrenia to thirty-eight matched healthy controls with regard to social decision-making using the mini Ultimatum Game (mini UG), a paradigm from game theory. Additionally, we assessed ToM using the Theory of Mind Picture Stories Task, a mental state attribution task, and assessed neurocognition using the Brief Assessment of Cognition in Schizophrenia. Mediation analyses were performed on the data. In contrast to the behavioral pattern of healthy controls in the mini UG, the patients with schizophrenia significantly accepted more disadvantageous offers and rejected more advantageous offers, and showed reduced sensitivity to the fairness-related context changes in the mini UG. Impaired ToM and neurocognition were also found in the patients. Mediation analyses indicated that ToM but not neurocognition partially mediated the group differences on the disadvantageous and advantageous offers in the mini UG. Patients with schizophrenia exhibited impaired social decision-making. This impairment can be partly explained by their ToM deficits rather than neurocognitive deficits. However, the exact nature of the ToM deficits that mediate impaired social decision-making needs to be identified in future.

  6. Ultraviolet Radiation and the Slug Transcription Factor Induce Pro inflammatory and Immunomodulatory Mediator Expression in Melanocytes

    International Nuclear Information System (INIS)

    Shirley, S. H.; Kusewitt, D. F.; Grimm, E. A.

    2012-01-01

    Despite extensive investigation, the precise contribution of the ultraviolet radiation (UVR) component of sunlight to melanoma etiology remains unclear. UVR induces keratinocytes to secrete pro inflammatory and immunomodulatory mediators that promote inflammation and skin tumor development; expression of the slug transcription factor in keratinocytes is required for maximal production of these mediators. In the present studies we examined the possibility that UVR-exposed melanocytes also produce pro inflammatory mediators and that Slug is important in this process. Micro array studies revealed that both UVR exposure and Slug overexpression altered transcription of a variety of pro inflammatory mediators by normal human melanocytes; some of these mediators are also known to stimulate melanocyte growth and migration. There was little overlap in the spectra of cytokines produced by the two stimuli. However IL-20 was similarly induced by both stimuli and the NFκB pathway appeared to be important in both circumstances. Further exploration of UVR-induced and Slug-dependent pathways of cytokine induction in melanocytes may reveal novel targets for melanoma therapy.

  7. Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

    KAUST Repository

    Ferreira, Ari J S

    2014-06-12

    Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world\\'s oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

  8. Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

    KAUST Repository

    Ferreira, Ari J S; Siam, Rania; Setubal, Joã o C; Moustafa, Ahmed; Sayed, Ahmed; Chambergo, Felipe S; Dawe, Adam S; Ghazy, Mohamed A; Sharaf, Hazem; Ouf, Amged; Alam, Intikhab; Abdel-Haleem, Alyaa M; Lehvä slaiho, Heikki; Ramadan, Eman; Antunes, André ; Stingl, Ulrich; Archer, John A.C.; Jankovic, Boris R; Sogin, Mitchell; Bajic, Vladimir B.; El-Dorry, Hamza

    2014-01-01

    Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

  9. Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

    Directory of Open Access Journals (Sweden)

    Ari J S Ferreira

    Full Text Available Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

  10. Does Food Insecurity Affect Parental Characteristics and Child Behavior? Testing Mediation Effects

    OpenAIRE

    Huang, Jin; Oshima, Karen M. Matta; Kim, Youngmi

    2010-01-01

    Using two waves of data from the Child Development Supplement in the Panel Study of Income Dynamics, this study investigates whether parental characteristics (parenting stress, parental warmth, psychological distress, and parent’s self-esteem) mediate household food insecurity’s relations with child behavior problems. Fixed-effects analyses examine data from a low-income sample of 416 children from 249 households. This study finds that parenting stress mediates the effects of food insecurity ...

  11. Sources of sport confidence, imagery type and performance among competitive athletes: the mediating role of sports confidence.

    Science.gov (United States)

    Levy, A R; Perry, J; Nicholls, A R; Larkin, D; Davies, J

    2015-01-01

    This study explored the mediating role of sport confidence upon (1) sources of sport confidence-performance relationship and (2) imagery-performance relationship. Participants were 157 competitive athletes who completed state measures of confidence level/sources, imagery type and performance within one hour after competition. Among the current sample, confirmatory factor analysis revealed appropriate support for the nine-factor SSCQ and the five-factor SIQ. Mediational analysis revealed that sport confidence had a mediating influence upon the achievement source of confidence-performance relationship. In addition, both cognitive and motivational imagery types were found to be important sources of confidence, as sport confidence mediated imagery type- performance relationship. Findings indicated that athletes who construed confidence from their own achievements and report multiple images on a more frequent basis are likely to benefit from enhanced levels of state sport confidence and subsequent performance.

  12. Body image mediates the effect of cancer-related stigmatization on depression

    DEFF Research Database (Denmark)

    Esser, Peter; Mehnert, Anja; Johansen, Christoffer

    2018-01-01

    OBJECTIVE: Because cancer-related stigmatization is prevalent but difficult to change, research on its impact on psychological burden and respective intervening variables is needed. Therefore, we investigated the effect of stigmatization on depressive symptomatology and whether body image mediates...... this relationship. METHODS: This bicentric study assessed patients of 4 major tumor entities. We measured stigmatization (SIS-D), depressive symptomatology (PHQ-9), and body image (FKB-20). Applying multiple mediator analyses, we calculated the total effect of stigmatization on depressive symptomatology...

  13. Evidence that emotion mediates social attention in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Emily J Bethell

    Full Text Available BACKGROUND: Recent work on non-human primates indicates that the allocation of social attention is mediated by characteristics of the attending animal, such as social status and genotype, as well as by the value of the target to which attention is directed. Studies of humans indicate that an individual's emotion state also plays a crucial role in mediating their social attention; for example, individuals look for longer towards aggressive faces when they are feeling more anxious, and this bias leads to increased negative arousal and distraction from other ongoing tasks. To our knowledge, no studies have tested for an effect of emotion state on allocation of social attention in any non-human species. METHODOLOGY: We presented captive adult male rhesus macaques with pairs of adult male conspecific face images - one with an aggressive expression, one with a neutral expression - and recorded gaze towards these images. Each animal was tested twice, once during a putatively stressful condition (i.e. following a veterinary health check, and once during a neutral (or potentially positive condition (i.e. a period of environmental enrichment. Initial analyses revealed that behavioural indicators of anxiety and stress were significantly higher after the health check than during enrichment, indicating that the former caused a negative shift in emotional state. PRINCIPLE FINDINGS: The macaques showed initial vigilance for aggressive faces across both conditions, but subsequent responses differed between conditions. Following the health check, initial vigilance was followed by rapid and sustained avoidance of aggressive faces. By contrast, during the period of enrichment, the macaques showed sustained attention towards the same aggressive faces. CONCLUSIONS/SIGNIFICANCE: These data provide, to our knowledge, the first evidence that shifts in emotion state mediate social attention towards and away from facial cues of emotion in a non-human animal. This work

  14. Mediation Analysis Demonstrates That Trans-eQTLs Are Often Explained by Cis-Mediation: A Genome-Wide Analysis among 1,800 South Asians

    Science.gov (United States)

    Pierce, Brandon L.; Tong, Lin; Chen, Lin S.; Rahaman, Ronald; Argos, Maria; Jasmine, Farzana; Roy, Shantanu; Paul-Brutus, Rachelle; Westra, Harm-Jan; Franke, Lude; Esko, Tonu; Zaman, Rakibuz; Islam, Tariqul; Rahman, Mahfuzar; Baron, John A.; Kibriya, Muhammad G.; Ahsan, Habibul

    2014-01-01

    A large fraction of human genes are regulated by genetic variation near the transcribed sequence (cis-eQTL, expression quantitative trait locus), and many cis-eQTLs have implications for human disease. Less is known regarding the effects of genetic variation on expression of distant genes (trans-eQTLs) and their biological mechanisms. In this work, we use genome-wide data on SNPs and array-based expression measures from mononuclear cells obtained from a population-based cohort of 1,799 Bangladeshi individuals to characterize cis- and trans-eQTLs and determine if observed trans-eQTL associations are mediated by expression of transcripts in cis with the SNPs showing trans-association, using Sobel tests of mediation. We observed 434 independent trans-eQTL associations at a false-discovery rate of 0.05, and 189 of these trans-eQTLs were also cis-eQTLs (enrichment Pmediator based on Sobel Pmediation signals in two European cohorts, and while only 7 trans-eQTL associations were present in one or both cohorts, 6 showed evidence of cis-mediation. Analyses of simulated data show that complete mediation will be observed as partial mediation in the presence of mediator measurement error or imperfect LD between measured and causal variants. Our data demonstrates that trans-associations can become significantly stronger or switch directions after adjusting for a potential mediator. Using simulated data, we demonstrate that this phenomenon is expected in the presence of strong cis-trans confounding and when the measured cis-transcript is correlated with the true (unmeasured) mediator. In conclusion, by applying mediation analysis to eQTL data, we show that a substantial fraction of observed trans-eQTL associations can be explained by cis-mediation. Future studies should focus on understanding the mechanisms underlying widespread cis-mediation and their relevance to disease biology, as well as using mediation analysis to improve eQTL discovery. PMID:25474530

  15. How Teacher Emotional Support Motivates Students: The Mediating Roles of Perceived Peer Relatedness, Autonomy Support, and Competence

    Science.gov (United States)

    Ruzek, Erik A.; Hafen, Christopher A.; Allen, Joseph P.; Gregory, Anne; Mikami, Amori Yee; Pianta, Robert C.

    2016-01-01

    Multilevel mediation analyses test whether students' mid-year reports of classroom experiences of autonomy, relatedness with peers, and competence mediate associations between early in the school year emotionally-supportive teacher-student interactions (independently observed) and student-reported academic year changes in mastery motivation and…

  16. The reciprocal relationship between daily fatigue and catastrophizing following cancer treatment: Affect and physical activity as potential mediators.

    Science.gov (United States)

    Müller, Fabiola; Stephenson, Ellen; DeLongis, Anita; Smink, Ans; Van Ginkel, Robert J; Tuinman, Marrit A; Hagedoorn, Mariët

    2018-03-01

    Fatigue is a distressing symptom many cancer patients experience even after completion of treatment. Although theory and empirical evidence indicate that negative cognitions perpetuate fatigue after completion of treatment, insight into how this process unfolds in daily life is limited. This study used an intensive longitudinal design to investigate the reciprocal relationship between catastrophizing and fatigue in daily life and whether affective and behavioral processes mediate these relationships. Post-treatment colorectal cancer patients (n = 101) completed daily diaries (14 days, 3 times daily) regarding their fatigue, catastrophizing, positive and negative affect, and physical activity. Multilevel modeling was applied to investigate within-person associations within days. Analyses revealed a positive reciprocal relationship between fatigue and catastrophizing throughout the day. That is, high levels of catastrophizing were associated with increases in fatigue within patients. In turn, but to a lesser extent, high levels of fatigue predicted increases in catastrophizing at the next assessment. Low positive affect and high negative affect mediated the effect of catastrophizing on increases in fatigue. Only negative affect mediated the reverse relationship. Physical activity did not mediate either relationship. This study provides evidence for a mutually reinforcing relationship between catastrophizing and fatigue in daily life, which might explain the perpetuation of fatigue after completion of cancer treatment. Fatigue-specific cognitive behavior therapy could be improved by educating patients about this daily reciprocal relationship, train them to quickly replace catastrophizing thoughts in daily life, and help them to cope with affective changes induced by fatigue. Copyright © 2017 John Wiley & Sons, Ltd.

  17. The formation of group norms in computer-mediated communication

    NARCIS (Netherlands)

    Postmes, T; Spears, R; Lea, M

    The formation of group norms in computer-mediated communication (CMC) was examined among students who used e-mail as part of a course. A network analysis of group structures revealed that (a) content and form of communication is normative, group norms defining communication patterns within groups,

  18. Deciphering the Cryptic Genome: Genome-wide Analyses of the Rice Pathogen Fusarium fujikuroi Reveal Complex Regulation of Secondary Metabolism and Novel Metabolites

    Science.gov (United States)

    Studt, Lena; Niehaus, Eva-Maria; Espino, Jose J.; Huß, Kathleen; Michielse, Caroline B.; Albermann, Sabine; Wagner, Dominik; Bergner, Sonja V.; Connolly, Lanelle R.; Fischer, Andreas; Reuter, Gunter; Kleigrewe, Karin; Bald, Till; Wingfield, Brenda D.; Ophir, Ron; Freeman, Stanley; Hippler, Michael; Smith, Kristina M.; Brown, Daren W.; Proctor, Robert H.; Münsterkötter, Martin; Freitag, Michael; Humpf, Hans-Ulrich; Güldener, Ulrich; Tudzynski, Bettina

    2013-01-01

    The fungus Fusarium fujikuroi causes “bakanae” disease of rice due to its ability to produce gibberellins (GAs), but it is also known for producing harmful mycotoxins. However, the genetic capacity for the whole arsenal of natural compounds and their role in the fungus' interaction with rice remained unknown. Here, we present a high-quality genome sequence of F. fujikuroi that was assembled into 12 scaffolds corresponding to the 12 chromosomes described for the fungus. We used the genome sequence along with ChIP-seq, transcriptome, proteome, and HPLC-FTMS-based metabolome analyses to identify the potential secondary metabolite biosynthetic gene clusters and to examine their regulation in response to nitrogen availability and plant signals. The results indicate that expression of most but not all gene clusters correlate with proteome and ChIP-seq data. Comparison of the F. fujikuroi genome to those of six other fusaria revealed that only a small number of gene clusters are conserved among these species, thus providing new insights into the divergence of secondary metabolism in the genus Fusarium. Noteworthy, GA biosynthetic genes are present in some related species, but GA biosynthesis is limited to F. fujikuroi, suggesting that this provides a selective advantage during infection of the preferred host plant rice. Among the genome sequences analyzed, one cluster that includes a polyketide synthase gene (PKS19) and another that includes a non-ribosomal peptide synthetase gene (NRPS31) are unique to F. fujikuroi. The metabolites derived from these clusters were identified by HPLC-FTMS-based analyses of engineered F. fujikuroi strains overexpressing cluster genes. In planta expression studies suggest a specific role for the PKS19-derived product during rice infection. Thus, our results indicate that combined comparative genomics and genome-wide experimental analyses identified novel genes and secondary metabolites that contribute to the evolutionary success of F

  19. Mediation Analysis in a Latent Growth Curve Modeling Framework

    Science.gov (United States)

    von Soest, Tilmann; Hagtvet, Knut A.

    2011-01-01

    This article presents several longitudinal mediation models in the framework of latent growth curve modeling and provides a detailed account of how such models can be constructed. Logical and statistical challenges that might arise when such analyses are conducted are also discussed. Specifically, we discuss how the initial status (intercept) and…

  20. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

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

  1. Diet and stable isotope analyses reveal the feeding ecology of the orangeback squid Sthenoteuthis pteropus (Steenstrup 1855 (Mollusca, Ommastrephidae in the eastern tropical Atlantic.

    Directory of Open Access Journals (Sweden)

    Véronique Merten

    Full Text Available In the eastern tropical Atlantic, the orangeback flying squid Sthenoteuthis pteropus (Steenstrup 1855 (Cephalopoda, Ommastrephidae is a dominant species of the epipelagic nekton community. This carnivore squid has a short lifespan and is one of the fastest-growing squids. In this study, we characterise the role of S. pteropus in the pelagic food web of the eastern tropical Atlantic by investigating its diet and the dynamics of its feeding habits throughout its ontogeny and migration. During three expeditions in the eastern tropical Atlantic in 2015, 129 specimens were caught by hand jigging. Stomach content analyses (via visual identification and DNA barcoding were combined with stable isotope data (∂15N and ∂13C of muscle tissue to describe diet, feeding habits and trophic ecology of S. pteropus. Additionally, stable isotope analyses of incremental samples along the squid's gladius-the chitinous spiniform structure supporting the muscles and organs-were carried out to explore possible diet shifts through ontogeny and migration. Our results show that S. pteropus preys mainly on myctophid fishes (e.g. Myctophum asperum, Myctophum nitidulum, Vinciguerria spp., but also on other teleost species, cephalopods (e.g. Enoploteuthidae, Bolitinidae, Ommastrephidae, crustaceans and possibly on gelatinous zooplankton as well. The squid shows a highly opportunistic feeding behaviour that includes cannibalism. Our study indicates that the trophic position of S. pteropus may increase by approximately one trophic level from a mantle length of 15 cm to 47 cm. The reconstructed isotope-based feeding chronologies of the gladii revealed high intra- and inter-individual variability in the squid's trophic position and foraging area. These findings are not revealed by diet or muscle tissue stable isotope analysis. This suggests a variable and complex life history involving individual variation and migration. The role of S. pteropus in transferring energy and

  2. Diet and stable isotope analyses reveal the feeding ecology of the orangeback squid Sthenoteuthis pteropus (Steenstrup 1855) (Mollusca, Ommastrephidae) in the eastern tropical Atlantic.

    Science.gov (United States)

    Merten, Véronique; Christiansen, Bernd; Javidpour, Jamileh; Piatkowski, Uwe; Puebla, Oscar; Gasca, Rebeca; Hoving, Henk-Jan T

    2017-01-01

    In the eastern tropical Atlantic, the orangeback flying squid Sthenoteuthis pteropus (Steenstrup 1855) (Cephalopoda, Ommastrephidae) is a dominant species of the epipelagic nekton community. This carnivore squid has a short lifespan and is one of the fastest-growing squids. In this study, we characterise the role of S. pteropus in the pelagic food web of the eastern tropical Atlantic by investigating its diet and the dynamics of its feeding habits throughout its ontogeny and migration. During three expeditions in the eastern tropical Atlantic in 2015, 129 specimens were caught by hand jigging. Stomach content analyses (via visual identification and DNA barcoding) were combined with stable isotope data (∂15N and ∂13C) of muscle tissue to describe diet, feeding habits and trophic ecology of S. pteropus. Additionally, stable isotope analyses of incremental samples along the squid's gladius-the chitinous spiniform structure supporting the muscles and organs-were carried out to explore possible diet shifts through ontogeny and migration. Our results show that S. pteropus preys mainly on myctophid fishes (e.g. Myctophum asperum, Myctophum nitidulum, Vinciguerria spp.), but also on other teleost species, cephalopods (e.g. Enoploteuthidae, Bolitinidae, Ommastrephidae), crustaceans and possibly on gelatinous zooplankton as well. The squid shows a highly opportunistic feeding behaviour that includes cannibalism. Our study indicates that the trophic position of S. pteropus may increase by approximately one trophic level from a mantle length of 15 cm to 47 cm. The reconstructed isotope-based feeding chronologies of the gladii revealed high intra- and inter-individual variability in the squid's trophic position and foraging area. These findings are not revealed by diet or muscle tissue stable isotope analysis. This suggests a variable and complex life history involving individual variation and migration. The role of S. pteropus in transferring energy and nutrients from

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

    Science.gov (United States)

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

    2007-01-01

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

  4. Organizational strategies mediate nonverbal memory impairment in obsessive-compulsive disorder.

    Science.gov (United States)

    Savage, C R; Baer, L; Keuthen, N J; Brown, H D; Rauch, S L; Jenike, M A

    1999-04-01

    Previous neuropsychological studies of obsessive-compulsive disorder (OCD) have indicated impaired executive functioning and nonverbal memory. The extent to which impaired executive functioning impacts nonverbal memory has not been established. The current study investigated the mediating effects of organizational strategies used when copying a figure on subsequent nonverbal memory for that figure. We examined neuropsychological performance in 20 unmedicated subjects with OCD and 20 matched normal control subjects. Subjects were administered the Rey-Osterrieth Complex Figure Test (RCFT) and neuropsychological tests assessing various aspects of executive function. OCD subjects differed significantly from healthy control subjects in the organizational strategies used to copy the RCFT figure, and they recalled significantly less information on both immediate and delayed testing. Multiple regression analyses indicated that group differences in immediate percent recall were significantly mediated by copy organizational strategies. Further exploratory analyses indicated that organizational problems in OCD may be related to difficulties shifting mental and/or spatial set. Immediate nonverbal memory problems in OCD subjects were mediated by impaired organizational strategies used during the initial copy of the RCFT figure. Thus, the primary deficit was one affecting executive function, which then had a secondary effect on immediate memory. These findings are consistent with current theories proposing frontal-striatal system dysfunction in OCD.

  5. Mediating Effects of Social Support on Quality of Life for Parents of Adults with Autism

    Science.gov (United States)

    Marsack, Christina N.; Samuel, Preethy S.

    2017-01-01

    The aim of this study was to examine the mediating effect of formal and informal social support on the relationship of caregiver burden and quality of life (QOL), using a sample of 320 parents (aged 50 or older) of adult children with autism spectrum disorder (ASD). Multiple linear regression and mediation analyses indicated that caregiver burden…

  6. The development of CotA mediator cocktail system for dyes decolorization.

    Science.gov (United States)

    Luo, S; Xie, T; Liu, Z; Sun, F; Wang, G

    2018-05-01

    The increasing use of dyes leads to serious environmental concerns, it is significant to explore eco-friendly and economic approaches for dye decolorization. This study aimed to develop mediator cocktail (AS and ABTS) for enhancing the capability of laccase-mediator system in the removal of dyes. By mediator screening, the mediators of ABTS and AS (ABTS, 2, 2'-azino-bis-(3-ethylbenzothiazo-thiazoline-6-sulphonic acid); AS, acetosyringone) were combined for dyes decolorization. The Box-Behnken Design and response surface analysis was performed to optimize experiment conditions. Comparing the CotA-ABTS-AS cocktail system with CotA-single mediator system showed that the coupling of ABTS and AS could increase the decolorization rate 15 times higher, save a third of the cost and shorten the reaction time by 50%. In addition, our studies revealed that sequential oxidation may occur in CotA-ABTS-AS system. Compared with CotA laccase-single mediator system, the CotA-ABTS-AS cocktail system showed advantages including higher efficiency, lower cost and shorter reaction time. This was the first report on the dyes decolorization by laccase mediator cocktail system. These results paved the curb for the application of laccase mediator system in various industrial processes. © 2018 The Society for Applied Microbiology.

  7. Nostalgia-Evoked Inspiration: Mediating Mechanisms and Motivational Implications.

    Science.gov (United States)

    Stephan, Elena; Sedikides, Constantine; Wildschut, Tim; Cheung, Wing-Yee; Routledge, Clay; Arndt, Jamie

    2015-10-01

    Six studies examined the nostalgia-inspiration link and its motivational implications. In Study 1, nostalgia proneness was positively associated with inspiration frequency and intensity. In Studies 2 and 3, the recollection of nostalgic (vs. ordinary) experiences increased both general inspiration and specific inspiration to engage in exploratory activities. In Study 4, serial mediational analyses supported a model in which nostalgia increases social connectedness, which subsequently fosters self-esteem, which then boosts inspiration. In Study 5, a rigorous evaluation of this serial mediational model (with a novel nostalgia induction controlling for positive affect) reinforced the idea that nostalgia-elicited social connectedness increases self-esteem, which then heightens inspiration. Study 6 extended the serial mediational model by demonstrating that nostalgia-evoked inspiration predicts goal pursuit (intentions to pursue an important goal). Nostalgia spawns inspiration via social connectedness and attendant self-esteem. In turn, nostalgia-evoked inspiration bolsters motivation. © 2015 by the Society for Personality and Social Psychology, Inc.

  8. Substrate mediated enzyme prodrug therapy.

    Directory of Open Access Journals (Sweden)

    Betina Fejerskov

    Full Text Available In this report, we detail Substrate Mediated Enzyme Prodrug Therapy (SMEPT as a novel approach in drug delivery which relies on enzyme-functionalized cell culture substrates to achieve a localized conversion of benign prodrug(s into active therapeutics with subsequent delivery to adhering cells or adjacent tissues. For proof-of-concept SMEPT, we use surface adhered micro-structured physical hydrogels based on poly(vinyl alcohol, β-glucuronidase enzyme and glucuronide prodrugs. We demonstrate enzymatic activity mediated by the assembled hydrogel samples and illustrate arms of control over rate of release of model fluorescent cargo. SMEPT was not impaired by adhering cells and afforded facile time - and dose - dependent uptake of the in situ generated fluorescent cargo by hepatic cells, HepG2. With the use of a glucuronide derivative of an anticancer drug, SN-38, SMEPT afforded a decrease in cell viability to a level similar to that achieved using parent drug. Finally, dose response was achieved using SMEPT and administration of judiciously chosen concentration of SN-38 glucuronide prodrug thus revealing external control over drug delivery using drug eluting surface. We believe that this highly adaptable concept will find use in diverse biomedical applications, specifically surface mediated drug delivery and tissue engineering.

  9. Self-regulatory processes mediate the intention-behavior relation for adherence and exercise behaviors.

    Science.gov (United States)

    de Bruin, Marijn; Sheeran, Paschal; Kok, Gerjo; Hiemstra, Anneke; Prins, Jan M; Hospers, Harm J; van Breukelen, Gerard J P

    2012-11-01

    Understanding the gap between people's intentions and actual health behavior is an important issue in health psychology. Our aim in this study was to investigate whether self-regulatory processes (monitoring goal progress and responding to discrepancies) mediate the intention-behavior relation in relation to HIV medication adherence (Study 1) and intensive exercise behavior (Study 2). In Study 1, questionnaire and electronically monitored adherence data were collected at baseline and 3 months later from patients in the control arm of an HIV-adherence intervention study. In Study 2, questionnaire data was collected at 3 time points 6-weeks apart in a cohort study of physical activity. Complete data at all time points were obtained from 51 HIV-infected patients and 499 intensive exercise participants. Intentions were good predictors of behavior and explained 25 to 30% of the variance. Self-regulatory processes explained an additional 11% (Study 1) and 6% (Study 2) of variance in behavior on top of intentions. Regression and bootstrap analyses revealed at least partial, and possibly full, mediation of the intention-behavior relation by self-regulatory processes. The present studies indicate that self-regulatory processes may explain how intentions drive behavior. Future tests, using different health behaviors and experimental designs, could firmly establish whether self-regulatory processes complement current health behavior theories and should become routine targets for intervention. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  10. Effects and mediators of psychosocial work characteristics on somatic symptoms six years later: Prospective findings from the Mannheim Industrial Cohort Studies (MICS).

    Science.gov (United States)

    Herr, Raphael M; Li, Jian; Loerbroks, Adrian; Angerer, Peter; Siegrist, Johannes; Fischer, Joachim E

    2017-07-01

    Ample evidence documented the adverse health effects of work stressors, and recent research has increasingly focused on somatic symptoms which are very common and costly. Prospective evidence is however sparse and yielded mixed findings. Furthermore, there is reason to assume that depression and anxiety might mediate the effects of adverse psychosocial work conditions on somatic symptoms. This study aimed to investigate longitudinal effects of work stressors on somatic symptoms and the potential mediation by anxiety and/or depression. Six year follow-up data from 352 individuals - free of potentially stress-related chronic disease - were utilized. Somatic symptoms were assessed by 19 items of an established list of complaints at baseline and follow-up. The effort-reward-imbalance (ERI) model measured adverse psychosocial work conditions and over-commitment (OC). Linear regressions adjusted for socio-demographics, social status, lifestyle, and baseline symptoms estimated the effects of the ERI ratio, effort, reward, OC, and the ERI ratio×OC interaction on somatic symptoms six years later. Furthermore, single and multiple mediation by anxiety and/or depression was investigated. There was a strong longitudinal effect of the ERI ratio, as well as of its subcomponents, and OC on somatic symptoms (all Bs≥|0.49|; p-values ≤0.004). Moreover, the ERI ratio×OC interaction was significant (p-value=0.047). Multiple mediation analyses revealed especially anxiety to mediate the effect of work stressors on somatic symptoms (Sobel test=0.007). Adverse psychosocial work conditions seem to longitudinally affect somatic symptoms, potentially moderated by OC, and mediated by anxiety. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Intercultural Mediation

    OpenAIRE

    Dragos Marian Radulescu; Denisa Mitrut

    2012-01-01

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

  12. Mediation analysis with multiple versions of the mediator.

    Science.gov (United States)

    Vanderweele, Tyler J

    2012-05-01

    The causal inference literature has provided definitions of direct and indirect effects based on counterfactuals that generalize the approach found in the social science literature. However, these definitions presuppose well-defined hypothetical interventions on the mediator. In many settings, there may be multiple ways to fix the mediator to a particular value, and these various hypothetical interventions may have very different implications for the outcome of interest. In this paper, we consider mediation analysis when multiple versions of the mediator are present. Specifically, we consider the problem of attempting to decompose a total effect of an exposure on an outcome into the portion through the intermediate and the portion through other pathways. We consider the setting in which there are multiple versions of the mediator but the investigator has access only to data on the particular measurement, not information on which version of the mediator may have brought that value about. We show that the quantity that is estimated as a natural indirect effect using only the available data does indeed have an interpretation as a particular type of mediated effect; however, the quantity estimated as a natural direct effect, in fact, captures both a true direct effect and an effect of the exposure on the outcome mediated through the effect of the version of the mediator that is not captured by the mediator measurement. The results are illustrated using 2 examples from the literature, one in which the versions of the mediator are unknown and another in which the mediator itself has been dichotomized.

  13. Two conserved modules of Schizosaccharomyces pombe Mediator regulate distinct cellular pathways

    DEFF Research Database (Denmark)

    Linder, Tomas; Rasmussen, Nina; Samuelsen, Camilla O

    2008-01-01

    Mediator is an evolutionary conserved coregulator complex required for transcription of almost all RNA polymerase II-dependent genes. The Schizosaccharomyces pombe Mediator consists of two dissociable components-a core complex organized into a head and middle domain as well as the Cdk8 regulatory...... subcomplex. In this work we describe a functional characterization of the S. pombe Mediator. We report the identification of the S. pombe Med20 head subunit and the isolation of ts alleles of the core head subunit encoding med17+. Biochemical analysis of med8(ts), med17(ts), Deltamed18, Deltamed20...... and Deltamed27 alleles revealed a stepwise head domain molecular architecture. Phenotypical analysis of Cdk8 and head module alleles including expression profiling classified the Mediator mutant alleles into one of two groups. Cdk8 module mutants flocculate due to overexpression of adhesive cell...

  14. Urban Songlines as Mediator

    DEFF Research Database (Denmark)

    Corlin, Anne

    2016-01-01

    The aim of this paper is to present an investigation of the method The Urban Songlines Book and how it works as a mediator for mapping the experienced space. The method contains a combination of aerial maps, photographs, and interviews as a way to understand the respondent´s use, relations...... and experiences of their neighborhood and the city. Through a presentation of the origin of the method, a description of the conducted study, and an analysis of the process in relation to theories about participatory design, social design, ANT and architectural sociology, the paper reveals how this method...

  15. The integrated model of sport confidence: a canonical correlation and mediational analysis.

    Science.gov (United States)

    Koehn, Stefan; Pearce, Alan J; Morris, Tony

    2013-12-01

    The main purpose of the study was to examine crucial parts of Vealey's (2001) integrated framework hypothesizing that sport confidence is a mediating variable between sources of sport confidence (including achievement, self-regulation, and social climate) and athletes' affect in competition. The sample consisted of 386 athletes, who completed the Sources of Sport Confidence Questionnaire, Trait Sport Confidence Inventory, and Dispositional Flow Scale-2. Canonical correlation analysis revealed a confidence-achievement dimension underlying flow. Bias-corrected bootstrap confidence intervals in AMOS 20.0 were used in examining mediation effects between source domains and dispositional flow. Results showed that sport confidence partially mediated the relationship between achievement and self-regulation domains and flow, whereas no significant mediation was found for social climate. On a subscale level, full mediation models emerged for achievement and flow dimensions of challenge-skills balance, clear goals, and concentration on the task at hand.

  16. mediation: R Package for Causal Mediation Analysis

    Directory of Open Access Journals (Sweden)

    Dustin Tingley

    2014-09-01

    Full Text Available In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting such an analysis. The package is organized into two distinct approaches. Using the model-based approach, researchers can estimate causal mediation effects and conduct sensitivity analysis under the standard research design. Furthermore, the design-based approach provides several analysis tools that are applicable under different experimental designs. This approach requires weaker assumptions than the model-based approach. We also implement a statistical method for dealing with multiple (causally dependent mediators, which are often encountered in practice. Finally, the package also offers a methodology for assessing causal mediation in the presence of treatment noncompliance, a common problem in randomized trials.

  17. The mediating role of metacognitive variables in the relationship between Thought-Action Fusion and obsessive-compulsive symptomatology

    Directory of Open Access Journals (Sweden)

    Paula Odriozola-González

    2016-07-01

    Full Text Available Diverse studies support the central role of Thought-Action Fusion (TAF and other metacognitive variables in the understanding of obsessive-compulsive disorder (OCD symptomatology. However, a more detailed study of the involvement of these variables is needed. This article seeks to assess the possible mediating role of the factors of the Metacognitions Questionnaire (MCQ in the relationship between TAF and OCD symptoms both in clinical and non-clinical samples. A cross-sectional design was used in which 120 participants, divided into three groups (two clinical and one non-clinical, completed the questionnaires assessing the constructs of interest. The mediational findings generally supported the proposed mediation model. Specifically, the mediational analyses focused on negative beliefs and the need to control (metacognitive factors of the MCQ showed that MCQ Negative beliefs mediated the effects of TAF-Total and TAF factors (except for the TAF-Moral on OCD symptomatology in the OCD group. The MCQ Need to control was non-significant as a mediator of the relationships between TAF and OCD. However, it was observed that this mediation approached significance, with considerable effect sizes. In the clinical-control group, the analyses showed that MCQ Negative beliefs mediated the effects of TAF-Likelihood-Oneself on OCD symptoms. In the remaining group, neither MCQ Negative beliefs nor MCQ Need to control were found to be significant mediators. It is generally concluded that certain beliefs, such as TAF, can evolve toward more complex metacognitive beliefs, which ultimately lead to the development of OCD symptoms.

  18. Elaborating on Internet addiction and cyberchondria – relationships, direct and mediated effects

    Directory of Open Access Journals (Sweden)

    Eliza Ivanova

    2014-09-01

    Full Text Available The present paper focuses on the effects of personality traits on the levels of Internet addiction and cyberchondria and their consequent effects on well-being. For the purposes of the research, mediation analyses were carried out, clarifying the influence of personality traits on well-being mediated by Internet addiction, cyberchondria and anxiety aroused by online health information seeking. It was established that Neuroticism leads to decreased well-being through the mediating influence of health anxiety, escalation and persistence of health concerns. Health anxiety is a mediator in the relationship between Openness to Experience and well-being. It was established that low levels of Agreeableness and Conscientiousness, and high levels of Openness, and Neuroticism, influence Internet addiction, which in turn leads to decreased well-being. Furthermore, we established the mediated influence of Internet addiction on the tendency for cyberchondria and health anxiety through using the Internet for health information and judgment biases.

  19. The mediation of environmental assessment’s influence

    DEFF Research Database (Denmark)

    Cashmore, Matthew Asa; Axelsson, Anna

    2013-01-01

    that power was intimately involved in mediating the influence of the policy EA approach, in both positive (enabling) and negative (constraining) ways. It is suggested that the policy EA approach was ultimately a manifestation of a corporate strategy to maintain the powerful position of the World Bank......-date in the context of EA — political power. Using a tripartite analytical framework, a comparative analysis of the influence and significance of power in mediating environmental policy integration is undertaken. Power is analysed, albeit partially, through an exploration of institutions that underpin social order...... the concepts of strategy and intentionality in theorising how and why EA tools are employed, succeed and fail; and secondly, reflect on the reasons why power has received such limited attention to-date in EA scholarship....

  20. Sex differences in the mediators of functional disability in Major Depressive Disorder.

    Science.gov (United States)

    Carmona, Nicole E; Subramaniapillai, Mehala; Mansur, Rodrigo B; Cha, Danielle S; Lee, Yena; Fus, Dominika; McIntyre, Roger S

    2018-01-01

    The aim of this study was to investigate sex differences in discrete domains of psychopathology as mediators of functional disability among individuals with Major Depressive Disorder (MDD). Adults (ages 18-65) with moderate-to-severe MDD (n = 100) and age-, sex-, and education-matched healthy controls (HC; n = 100) participated in a clinical trial validating the THINC-integrated tool, a newly developed cognitive assessment tool for patients with MDD. Variables assessed as possible mediators included depression symptom severity, anxiety symptoms, sleep disturbance, perceived cognitive deficits, and objective cognitive performance. Functional disability was assessed using the total score on the Sheehan Disability Scale. Separate mediation analyses were conducted for men and women. No significant differences were detected between men and women on the assessed domains of psychopathology or functional disability (ps > 0.05). However, the mediation analyses demonstrated different patterns with respect to determinants of functional disability in MDD between men and women. Functional disability was mediated by anxiety (95% CI: -3.17, -0.28) and sleep disturbance (95% CI: -0.69, -0.05) among men and by depressive symptom severity (95% CI: -7.82, -0.32) among women. These preliminary results instantiate the need to dimensionalize psychopathology in MDD. Our results at least in part support the hypothesis that, consistent with the sex differences in the prevalence and illness presentation of MDD, determinants of functional outcomes also differ between men and women, underscoring the need to consider sex differences in order to improve functional outcomes in the treatment of MDD. Copyright © 2017. Published by Elsevier Ltd.

  1. mediation: R package for causal mediation analysis

    OpenAIRE

    Tingley, Dustin; Yamamoto, Teppei; Hirose, Kentaro; Keele, Luke; Imai, Kosuke

    2012-01-01

    In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting su...

  2. Improving quality-of-life outcomes for patients with cancer through mediating effects of depressive symptoms and functional status: a three-path mediation model.

    Science.gov (United States)

    Hsu, Mei-Chi; Tu, Chun-Hsien

    2014-09-01

    To test a hypothetical three-path mediation model evaluating the effects of functional status and depressive symptoms on the relationship between fatigue and quality of life in patients with cancer on the basis of the Theory of Unpleasant Symptoms. Patients with cancer often experience two or more concurrent, interrelated, mutually influential symptoms. Multiple unpleasant symptoms that have been proposed as mediating variables affecting quality of life in a model proposed in recent cancer studies are scanty. This study was a cross-sectional, descriptive, correlational design. Three hundred and twenty-six patients with cancer from oncology clinics were recruited in Taiwan between 2010-2011. Mediation models were tested and confirmed by applying structural modelling using Analysis of Moment Structures and the joint significance test. Fatigue affects patient quality of life directly or indirectly through functional status and depressive symptoms. These two mediating variables exhibited direct effects on quality of life. A path analysis approach revealed that 47·28 and 67·70% of the total effects of functional status and depressive symptoms, respectively, on the quality-of-life mediation models are attributable to 29·6 and 44·7% of the total effects between fatigue and quality of life, which mediated through two mediators, respectively. Quality of life may be enhanced by simultaneously improving physiological and psychological factors. An understanding of mediating effects is valuable in nursing care of patients with cancer, particularly in the early phase of treatment or in newly diagnosed stages I-III or recently treated patients with cancer in different disease stages. © 2013 John Wiley & Sons Ltd.

  3. Self-Stigma Mediates the Impact of Insight on Current Suicide Ideation in Suicide Attempters with Schizophrenia: Results of a Moderated Mediation Approach.

    Science.gov (United States)

    Lien, Yin-Ju; Chang, Hsin-An; Kao, Yu-Chen; Tzeng, Nian-Sheng; Yeh, Chin-Bin; Loh, Ching-Hui

    2017-09-04

    This study examined the relationships among insight, self-stigma, self-esteem, hope, quality of life, and suicidal behavior in individuals diagnosed as having schizophrenia. Hypotheses concerning mediating and moderating effects were examined. A total of 170 community-dwelling patients with schizophrenia participated in the study. The results revealed a negative association between insight and suicide ideation, which was partially mediated by self-stigma. Moreover, this indirect link was stronger among patients with suicide attempts than among those without attempts. We discuss the implications of these results for preventing or reducing the considerable risks of suicide in this population. © 2017 The American Association of Suicidology.

  4. STAT6: its role in interleukin 4-mediated biological functions.

    Science.gov (United States)

    Takeda, K; Kishimoto, T; Akira, S

    1997-05-01

    Interleukin (IL) 4 is known to be a cytokine which plays a central role in the regulation of immune response. Studies on cytokine signal transduction have clarified the mechanism by which IL4 exerts its functions. Two cytoplasmic proteins, signal transducer and activator of transcription (STAT) 6 and IL4-induced phosphotyrosine substrate/insulin receptor substrate 2 (4PS/IRS2), are activated in IL4 signal transduction. Recent studies from STAT6-deficient mice have revealed the essential role of STAT6 in IL4-mediated biological actions. In addition, STAT6 has also been demonstrated to be important for the functions mediated by IL13, which is related to IL4. IL4 and IL13 have been shown to induce the production of IgE, which is a major mediator in an allergic response. These findings indicate that STAT6 activation is involved in IL4- and IL13-mediated disorders such as allergy.

  5. Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1

    Energy Technology Data Exchange (ETDEWEB)

    Pejchal, Robert; Walker, Laura M.; Stanfield, Robyn L.; Phogat, Sanjay K.; Koff, Wayne C.; Poignard, Pascal; Burton, Dennis R.; Wilson, Ian A. (Scripps); (IAVI)

    2010-11-15

    Development of an effective vaccine against HIV-1 will likely require elicitation of broad and potent neutralizing antibodies against the trimeric surface envelope glycoprotein (Env). Monoclonal antibodies (mAbs) PG9 and PG16 neutralize {approx}80% of HIV-1 isolates across all clades with extraordinary potency and target novel epitopes preferentially expressed on Env trimers. As these neutralization properties are ideal for a vaccine-elicited antibody response to HIV-1, their structural basis was investigated. The crystal structure of the antigen-binding fragment (Fab) of PG16 at 2.5 {angstrom} resolution revealed its unusually long, 28-residue, complementarity determining region (CDR) H3 forms a unique, stable subdomain that towers above the antibody surface. A 7-residue 'specificity loop' on the 'hammerhead' subdomain was identified that, when transplanted from PG16 to PG9 and vice versa, accounted for differences in the fine specificity and neutralization of these two mAbs. The PG16 electron density maps also revealed that a CDR H3 tyrosine was sulfated, which was confirmed for both PG9 (doubly) and PG16 (singly) by mass spectral analysis. We further showed that tyrosine sulfation plays a role in binding and neutralization. An N-linked glycan modification is observed in the variable light chain, but not required for antigen recognition. Further, the crystal structure of the PG9 light chain at 3.0 {angstrom} facilitated homology modeling to support the presence of these unusual features in PG9. Thus, PG9 and PG16 use unique structural features to mediate potent neutralization of HIV-1 that may be of utility in antibody engineering and for high-affinity recognition of a variety of therapeutic targets.

  6. Lifelong Learning in Artistic Context Mediated by Advanced Technologies

    Science.gov (United States)

    Ferrari, Mirella

    2016-01-01

    This research starts by analysing the current state of artistic heritage in Italy and studying some examples in Europe: we try to investigate the scope of non-formal learning in artistic context, mediated by advanced technology. The framework within which we have placed our investigation is that of lifelong learning and lifedeep learning. The…

  7. Articular chondrocyte network mediated by gap junctions: role in metabolic cartilage homeostasis

    Science.gov (United States)

    Mayan, Maria D; Gago-Fuentes, Raquel; Carpintero-Fernandez, Paula; Fernandez-Puente, Patricia; Filgueira-Fernandez, Purificacion; Goyanes, Noa; Valiunas, Virginijus; Brink, Peter R; Goldberg, Gary S; Blanco, Francisco J

    2017-01-01

    Objective This study investigated whether chondrocytes within the cartilage matrix have the capacity to communicate through intercellular connections mediated by voltage-gated gap junction (GJ) channels. Methods Frozen cartilage samples were used for immunofluorescence and immunohistochemistry assays. Samples were embedded in cacodylate buffer before dehydration for scanning electron microscopy. Co-immunoprecipitation experiments and mass spectrometry (MS) were performed to identify proteins that interact with the C-terminal end of Cx43. GJ communication was studied through in situ electroporation, electrophysiology and dye injection experiments. A transwell layered culture system and MS were used to identify and quantify transferred amino acids. Results Microscopic images revealed the presence of multiple cellular projections connecting chondrocytes within the matrix. These projections were between 5 and 150 μm in length. MS data analysis indicated that the C-terminus of Cx43 interacts with several cytoskeletal proteins implicated in Cx trafficking and GJ assembly, including α-tubulin and β-tubulin, actin, and vinculin. Electrophysiology experiments demonstrated that 12-mer oligonucleotides could be transferred between chondrocytes within 12 min after injection. Glucose was homogeneously distributed within 22 and 35 min. No transfer was detected when glucose was electroporated into A549 cells, which have no GJs. Transwell layered culture systems coupled with MS analysis revealed connexins can mediate the transfer of L-lysine and L-arginine between chondrocytes. Conclusions This study reveals that intercellular connections between chondrocytes contain GJs that play a key role in cell-cell communication and a metabolic function by exchange of nutrients including glucose and essential amino acids. A three-dimensional cellular network mediated through GJs might mediate metabolic and physiological homeostasis to maintain cartilage tissue. PMID:24225059

  8. Molecular architecture of the yeast Mediator complex

    Science.gov (United States)

    Robinson, Philip J; Trnka, Michael J; Pellarin, Riccardo; Greenberg, Charles H; Bushnell, David A; Davis, Ralph; Burlingame, Alma L; Sali, Andrej; Kornberg, Roger D

    2015-01-01

    The 21-subunit Mediator complex transduces regulatory information from enhancers to promoters, and performs an essential role in the initiation of transcription in all eukaryotes. Structural information on two-thirds of the complex has been limited to coarse subunit mapping onto 2-D images from electron micrographs. We have performed chemical cross-linking and mass spectrometry, and combined the results with information from X-ray crystallography, homology modeling, and cryo-electron microscopy by an integrative modeling approach to determine a 3-D model of the entire Mediator complex. The approach is validated by the use of X-ray crystal structures as internal controls and by consistency with previous results from electron microscopy and yeast two-hybrid screens. The model shows the locations and orientations of all Mediator subunits, as well as subunit interfaces and some secondary structural elements. Segments of 20–40 amino acid residues are placed with an average precision of 20 Å. The model reveals roles of individual subunits in the organization of the complex. DOI: http://dx.doi.org/10.7554/eLife.08719.001 PMID:26402457

  9. Examination of the Relationship between Psychosocial Mediators and Intervention Effects in It’s Your Game: An Effective HIV/STI/Pregnancy Prevention Intervention for Middle School Students

    Directory of Open Access Journals (Sweden)

    Elizabeth Baumler

    2012-01-01

    Full Text Available A set of mediation analyses were carried out in this study using data from It’s Your Game. . .Keep It Real (IYG, a successful HIV/STI/pregnancy prevention program. The IYG study evaluated a skill and normbased. HIV/STI/pregnancy prevention program that was implemented from 2004 to 2007 among 907 urban low-income middle school youth in Houston, TX, USA. Analyses were carried out to investigate the degree to which a set of proposed psychosocial measures of behavioral knowledge, perceived self-efficacy, behavioral, and normative beliefs, and perceived risky situations, all targeted by the intervention, mediated the intervention’s effectiveness in reducing initiation of sex. The mediation process was assessed by examining the significance and size of the estimated effects from the mediating pathways. The findings from this study provide evidence that the majority of the psychosocial mediators targeted by the IYG intervention are indeed related to the desired behavior and provide evidence that the conceptual theory underlying the targeted psychosocial mediators in the intervention is appropriate. Two of the psychosocial mediators significantly mediated the intervention effect, knowledge of STI signs and symptoms and refusal self-efficacy. This study suggests that the underlying causal mechanisms of action of these interventions are complex and warrant further analyses.

  10. A case of non-regenerative immune-mediated anemia treated by ...

    African Journals Online (AJOL)

    A 12-year-old female Shih Tzu dog was referred with diarrhea. Hematological examination indicated severe nonregenerative anemia. Bone marrow aspiration smears and core biopsy specimens revealed normal bone marrow. Based on those results, non-regenerative immune mediated anemia was diagnosed. The dog ...

  11. Studies on nonsense mediated decay reveal novel therapeutic options for genetic diseases.

    Science.gov (United States)

    Bashyam, Murali D

    2009-01-01

    Scientific breakthroughs have often led to commercially viable patents mainly in the field of engineering. Commercialization in the field of medicine has been restricted mostly to machinery and engineering on the one hand and therapeutic drugs for common chronic ailments such as cough, cold, headache, etc, on the other. Sequencing of the human genome has attracted the attention of pharmaceutical companies and now biotechnology has become a goldmine for commercialization of products and processes. Recent advances in our understanding of basic biological processes have resulted in the opening of new avenues for treatment of human genetic diseases, especially single gene disorders. A significant proportion of human genetic disorders have been shown to be caused due to degradation of transcripts for specific genes through a process called nonsense mediated decay (NMD). The modulation of NMD provides a viable therapeutic option for treatment of several genetic disorders and therefore has been a good prospect for patenting and commercialization. In this review the molecular basis for NMD and attempts to treat genetic diseases which result from NMD are discussed.

  12. Comparison of 26 sphingomonad genomes reveals diverse environmental adaptations and biodegradative capabilities

    DEFF Research Database (Denmark)

    Aylward, Frank O.; McDonald, Bradon R.; Adams, Sandra M.

    2013-01-01

    to the genus Sphingobium. Our pan-genomic analysis of sphingomonads reveals numerous species-specific open reading frames (ORFs) but few signatures of genus-specific cores. The organization and coding potential of the sphingomonad genomes appear to be highly variable, and plasmid-mediated gene transfer...... and chromosome-plasmid recombination, together with prophage- and transposon-mediated rearrangements, appear to play prominent roles in the genome evolution of this group. We find that many of the sphingomonad genomes encode numerous oxygenases and glycoside hydrolases, which are likely responsible...... a basis for understanding the ecological strategies employed by sphingomonads and their role in environmental nutrient cycling....

  13. What carries a mediation process? Configural analysis of mediation.

    Science.gov (United States)

    von Eye, Alexander; Mun, Eun Young; Mair, Patrick

    2009-09-01

    Mediation is a process that links a predictor and a criterion via a mediator variable. Mediation can be full or partial. This well-established definition operates at the level of variables even if they are categorical. In this article, two new approaches to the analysis of mediation are proposed. Both of these approaches focus on the analysis of categorical variables. The first involves mediation analysis at the level of configurations instead of variables. Thus, mediation can be incorporated into the arsenal of methods of analysis for person-oriented research. Second, it is proposed that Configural Frequency Analysis (CFA) can be used for both exploration and confirmation of mediation relationships among categorical variables. The implications of using CFA are first that mediation hypotheses can be tested at the level of individual configurations instead of variables. Second, this approach leaves the door open for different types of mediation processes to exist within the same set. Using a data example, it is illustrated that aggregate-level analysis can overlook mediation processes that operate at the level of individual configurations.

  14. Optimizing the photon selection of the CMS Single-Photon search for Supersymmetry using multivariate analyses

    CERN Document Server

    Lange, Johannes

    2014-01-01

    The purpose of this thesis is to improve the photon selection of the CMS SinglePhoton search for Supersymmetry by using multivariate analyses.The Single-Photon search aims to find Supersymmetry (SUSY) in data taken by theCompact Muon Solenoid (CMS) detector at the Large Hadron Collider located atthe research center CERN. SUSY is an extension of the standard model of particlephysics. The search is designed for a general gauge mediation scenario, which describes the gauge mediated SUSY breaking. The analysis uses final states with jets,at least one photon and missing transverse energy. A data-driven prediction of themultijet background is performed for the analysis. For this purpose, photon candidates have to be classified into two selections.In this thesis the usage of multivariate analyses for the photon candidate classification is studied. The methods used are Fisher Discriminant, Boosted Decision Treesand Artificial Neural Networks. Their performance is evaluated with respect to different aspects impor...

  15. Bulk-mediated surface diffusion: non-Markovian desorption dynamics

    International Nuclear Information System (INIS)

    Revelli, Jorge A; Budde, Carlos E; Prato, Domingo; Wio, Horacio S

    2005-01-01

    Here we analyse the dynamics of adsorbed molecules within the bulk-mediated surface diffusion framework, when the particle's desorption mechanism is characterized by a non-Markovian process, while the particle's adsorption as well as its motion in the bulk is governed by Markovian dynamics. We study the diffusion of particles in both semi-infinite and finite cubic lattices, analysing the conditional probability to find the system on the reference absorptive plane as well as the surface dispersion as functions of time. The results are compared with known Markovian cases showing the differences that can be exploited to distinguish between Markovian and non-Markovian desorption mechanisms in experimental situations

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

    Science.gov (United States)

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

    2015-01-01

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

  17. The Nexus of Ethical Leadership, Job Performance, and Turnover Intention: The Mediating Role of Job Satisfaction

    Directory of Open Access Journals (Sweden)

    Imran Shafique

    2018-03-01

    Full Text Available This study aims to examine the impact of ethical leadership on employees' job satisfaction, job performance, and turnover intention. A conceptual framework is developed which integrates job satisfaction as a mediating mechanism in explaining the nexus among ethical leadership, employee job performance, and turnover intention. The proposed model is tested by using the data collected from a sample (n = 196 of tourist companies in Pakistan. The results reveal that ethical leadership has a positive effect on employees' job satisfaction, job performance and negative effect on employees' turnover intentions. Further, job satisfaction mediates the effect of ethical leadership on employees' job performance and turnover intentions. The findings recommend that the demonstration of ethical leadership behaviours by managers at the workplace increases the likelihood of employees' job satisfaction and performance, while reducing their intention to leave the job. This study elucidates that, in Pakistani tourism sector, ethical leadership plays a key role in achieving performance goals. Future research could analyse the said nexus in different sectors and across different cultures while considering other measures of individual performance. The originality of this study is theorizing as well as empirically testing the intervening mechanism of job satisfaction in probing the linkages among ethical leadership, job performance, and turnover intention in Pakistani workplace context.

  18. Negative thinking as a coping strategy mediator of pain and internalizing symptoms in adolescents with sickle cell disease.

    Science.gov (United States)

    Barakat, Lamia P; Schwartz, Lisa A; Simon, Katherine; Radcliffe, Jerilynn

    2007-06-01

    The objective of this study was to examine the role of coping strategies, specifically negative thinking, in mediating the association of pain with symptoms of anxiety and depression in adolescents with sickle cell disease. Fifty-two 12-18-year-old adolescents with sickle cell disease completed a daily pain diary and paper-and-pencil measures of pain, pain coping, depression and anxiety. Symptoms of depression and anxiety were within the non-clinical range. Preliminary analyses indicated that lower family income was associated with higher reports of pain and negative thinking. Mediation regression analyses supported negative thinking as mediating the association of: (1) pain intensity with depression, and (2) pain interference with daily activities with anxiety. Findings highlight negative thinking as a factor compromising adolescents' adaptation to sickle cell pain; however, further investigation is required to determine the mediating influence of pain coping. Associations for lower income emphasize the multiple risk factors experienced by many of these adolescents.

  19. Allergen immunotherapy for IgE-mediated food allergy

    DEFF Research Database (Denmark)

    Nurmatov, Ulugbek; Dhami, S; Arasi, S.

    2017-01-01

    Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness...... economic analyses. Conclusions: AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic...... adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT....

  20. Genome size analyses of Pucciniales reveal the largest fungal genomes.

    Science.gov (United States)

    Tavares, Sílvia; Ramos, Ana Paula; Pires, Ana Sofia; Azinheira, Helena G; Caldeirinha, Patrícia; Link, Tobias; Abranches, Rita; Silva, Maria do Céu; Voegele, Ralf T; Loureiro, João; Talhinhas, Pedro

    2014-01-01

    Rust fungi (Basidiomycota, Pucciniales) are biotrophic plant pathogens which exhibit diverse complexities in their life cycles and host ranges. The completion of genome sequencing of a few rust fungi has revealed the occurrence of large genomes. Sequencing efforts for other rust fungi have been hampered by uncertainty concerning their genome sizes. Flow cytometry was recently applied to estimate the genome size of a few rust fungi, and confirmed the occurrence of large genomes in this order (averaging 225.3 Mbp, while the average for Basidiomycota was 49.9 Mbp and was 37.7 Mbp for all fungi). In this work, we have used an innovative and simple approach to simultaneously isolate nuclei from the rust and its host plant in order to estimate the genome size of 30 rust species by flow cytometry. Genome sizes varied over 10-fold, from 70 to 893 Mbp, with an average genome size value of 380.2 Mbp. Compared to the genome sizes of over 1800 fungi, Gymnosporangium confusum possesses the largest fungal genome ever reported (893.2 Mbp). Moreover, even the smallest rust genome determined in this study is larger than the vast majority of fungal genomes (94%). The average genome size of the Pucciniales is now of 305.5 Mbp, while the average Basidiomycota genome size has shifted to 70.4 Mbp and the average for all fungi reached 44.2 Mbp. Despite the fact that no correlation could be drawn between the genome sizes, the phylogenomics or the life cycle of rust fungi, it is interesting to note that rusts with Fabaceae hosts present genomes clearly larger than those with Poaceae hosts. Although this study comprises only a small fraction of the more than 7000 rust species described, it seems already evident that the Pucciniales represent a group where genome size expansion could be a common characteristic. This is in sharp contrast to sister taxa, placing this order in a relevant position in fungal genomics research.

  1. Metabolic profiling reveals ethylene mediated metabolic changes and a coordinated adaptive mechanism of 'Jonagold' apple to low oxygen stress.

    Science.gov (United States)

    Bekele, Elias A; Beshir, Wasiye F; Hertog, Maarten L A T M; Nicolai, Bart M; Geeraerd, Annemie H

    2015-11-01

    Apples are predominantly stored in controlled atmosphere (CA) storage to delay ripening and prolong their storage life. Profiling the dynamics of metabolic changes during ripening and CA storage is vital for understanding the governing molecular mechanism. In this study, the dynamics of the primary metabolism of 'Jonagold' apples during ripening in regular air (RA) storage and initiation of CA storage was profiled. 1-Methylcyclopropene (1-MCP) was exploited to block ethylene receptors and to get insight into ethylene mediated metabolic changes during ripening of the fruit and in response to hypoxic stress. Metabolic changes were quantified in glycolysis, the tricarboxylic acid (TCA) cycle, the Yang cycle and synthesis of the main amino acids branching from these metabolic pathways. Partial least square discriminant analysis of the metabolic profiles of 1-MCP treated and control apples revealed a metabolic divergence in ethylene, organic acid, sugar and amino acid metabolism. During RA storage at 18°C, most amino acids were higher in 1-MCP treated apples, whereas 1-aminocyclopropane-1-carboxylic acid (ACC) was higher in the control apples. The initial response of the fruit to CA initiation was accompanied by an increase of alanine, succinate and glutamate, but a decline in aspartate. Furthermore, alanine and succinate accumulated to higher levels in control apples than 1-MCP treated apples. The observed metabolic changes in these interlinked metabolites may indicate a coordinated adaptive strategy to maximize energy production. © 2015 Scandinavian Plant Physiology Society.

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

    Science.gov (United States)

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

    2013-06-01

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

  3. Does Competence Mediate the Associations between Puberty and Internalizing or Externalizing Problems in Adolescent Girls

    Science.gov (United States)

    Negriff, Sonya; Hillman, Jennifer, B.; Dorn, Lorah D.

    2011-01-01

    Purpose To examine separate mediational models linking a) menarcheal status or b) pubertal timing to internalizing and externalizing problems through competence. Method Cross-sectional analyses of 262 adolescent girls (11–17 years; M=14.93, SD=2.17) enrolled in a longitudinal study examining the association of psychological functioning and smoking with reproductive and bone health. Measures of menarcheal status (pre/post), pubertal timing (early, on-time, or late), internalizing and externalizing behavior, and perceived competence (parent and adolescent report) were obtained. Structural Equation Modeling was used for analyses. Results Perceived competence was found to fully mediate the association between menarcheal status and parent report of internalizing and externalizing problems. For adolescent report, there was a full mediation effect for internalizing problems but a partial mediation effect for externalizing problems. Being menarcheal was related to lower competence which was related to higher internalizing and externalizing problems. Models including pubertal timing were not significant. Conclusions Perceived competence is important in understanding the associations between menarcheal status and internalizing and externalizing problems. Interventions targeting competence, particularly in post-menarcheal girls, may reduce or prevent problem behaviors. PMID:21939864

  4. Polyethylene Glycol Mediated Colorectal Cancer Chemoprevention: Roles of Epidermal Growth Factor Receptor and Snail

    Science.gov (United States)

    Wali, Ramesh K.; Kunte, Dhananjay P.; Koetsier, Jennifer L.; Bissonnette, Marc; Roy, Hemant K.

    2008-01-01

    Polyethylene glycol (PEG) is a clinically widely used agent with profound chemopreventive properties in experimental colon carcinogenesis. We previously reported that Snail/β-catenin signaling may mediate the suppression of epithelial proliferation by PEG, although the upstream events remain unclear. We report herein the role of epidermal growth factor receptor (EGFR), a known mediator of Snail and overepressed in ~80% of human colorectal cancers (CRC), on PEG-mediated anti-proliferative and hence anti-neoplastic effects in azoxymethane (AOM)-rats and HT-29 colon cancer cells. AOM-rats were randomized to either standard diet or one with 10% PEG 3350 and euthanized 8 weeks later. The colonic samples were subjected to immunohistochemical or Western blot analyses. PEG decreased mucosal EGFR by 60% (pPEG effects were obtained in HT-29 cells. PEG suppressed EGFR protein via lysosmal degradation with no change in mRNA levels. To show that EGFR antagonism per se was responsible for the antiproliferative effect, we inhibited EGFR by either pre-treating cells with gefitinib or stably transfecting with EGFR-shRNA and measured the effect of PEG on proliferation. In either case PEG effect was blunted suggesting a vital role of EGFR. Flow cytometric analysis revealed that EGFR-shRNA cells, besides having reduced membrane EGFR also expressed low Snail levels (40%), corroborating a strong association. Furthermore, in EGFR silenced cells PEG effect on EGFR or Snail was muted, similar to that on proliferation. In conclusion, we show that EGFR is the proximate membrane signaling molecule through which PEG initiates antiproliferative activity with Snail/β-catenin pathway playing the central intermediary function. PMID:18790788

  5. Polyethylene glycol-mediated colorectal cancer chemoprevention: roles of epidermal growth factor receptor and Snail.

    Science.gov (United States)

    Wali, Ramesh K; Kunte, Dhananjay P; Koetsier, Jennifer L; Bissonnette, Marc; Roy, Hemant K

    2008-09-01

    Polyethylene glycol (PEG) is a clinically widely used agent with profound chemopreventive properties in experimental colon carcinogenesis. We reported previously that Snail/beta-catenin signaling may mediate the suppression of epithelial proliferation by PEG, although the upstream events remain unclear. We report herein the role of epidermal growth factor receptor (EGFR), a known mediator of Snail and overexpressed in approximately 80% of human colorectal cancers, on PEG-mediated antiproliferative and hence antineoplastic effects in azoxymethane (AOM) rats and HT-29 colon cancer cells. AOM rats were randomized to either standard diet or one with 10% PEG-3350 and euthanized 8 weeks later. The colonic samples were subjected to immunohistochemical or Western blot analyses. PEG decreased mucosal EGFR by 60% (P PEG effects were obtained in HT-29 cells. PEG suppressed EGFR protein via lysosmal degradation with no change in mRNA levels. To show that EGFR antagonism per se was responsible for the antiproliferative effect, we inhibited EGFR by either pretreating cells with gefitinib or stably transfecting with EGFR-short hairpin RNA and measured the effect of PEG on proliferation. In either case, PEG effect was blunted, suggesting a vital role of EGFR. Flow cytometric analysis revealed that EGFR-short hairpin RNA cells, besides having reduced membrane EGFR, also expressed low Snail levels (40%), corroborating a strong association. Furthermore, in EGFR silenced cells, PEG effect on EGFR or Snail was muted, similar to that on proliferation. In conclusion, we show that EGFR is the proximate membrane signaling molecule through which PEG initiates antiproliferative activity with Snail/beta-catenin pathway playing the central intermediary function.

  6. Bellona and hydrogen - the role of mediation in technical change

    International Nuclear Information System (INIS)

    Kristiansen, Beate

    2001-01-01

    The energy production and consumption is a major contributor to our environmental problems. The energy carrier hydrogen can be a part of the solution. In the thesis the Bellona Foundation's role in the process of technical change towards utilisation of hydrogen in Norway is investigated. Its role is analysed through the concept of mediation, which is based on seeing technical change as a social process. Mediators connect, or build bridges between, different actors, as well as between different types of knowledge. They establish new kinds of links and create new arenas of interaction for previously separated units. In addition, or through their work, they translate knowledge from one context or domain to another. They are also processing, interpreting and combining knowledge in new ways. Mediators bring together people with different competencies, and orchestrate their efforts often on a consensus basis. Bellona combines the different kinds of mediations, to influence the process of technical change at various levels and steps. They mediate mainly within the industry and between the industrial- and governmental domain. To some degree they also mediate between the experts and the public. But the direct contact with the public seems to be more or less absent in their hydrogen work. It seems like Bellona's mediator role fills an open space in the realm of technology policy making. Environmental oriented NGOs will perform or combine various mediating roles differently. To be able to make socially appropriate and sustainable technical change, probably other actors than the established traditional ones should be more involved. The possibilities for public participation should be strengthened, as well as the possibilities for mediation. (Author)

  7. Aptamer-mediated indirect quantum dot labeling and fluorescent imaging of target proteins in living cells

    International Nuclear Information System (INIS)

    Liu, Jianbo; Zhang, Pengfei; Yang, Xiaohai; Wang, Kemin; Guo, Qiuping; Huang, Jin; Li, Wei

    2014-01-01

    Protein labeling for dynamic living cell imaging plays a significant role in basic biological research, as well as in clinical diagnostics and therapeutics. We have developed a novel strategy in which the dynamic visualization of proteins within living cells is achieved by using aptamers as mediators for indirect protein labeling of quantum dots (QDs). With this strategy, the target protein angiogenin was successfully labeled with fluorescent QDs in a minor intactness model, which was mediated by the aptamer AL6-B. Subsequent living cell imaging analyses indicated that the QDs nanoprobes were selectively bound to human umbilical vein endothelial cells, gradually internalized into the cytoplasm, and mostly localized in the lysosome organelle, indicating that the labeled protein retained high activity. Compared with traditional direct protein labeling methods, the proposed aptamer-mediated strategy is simple, inexpensive, and provides a highly selective, stable, and intact labeling platform that has shown great promise for future biomedical labeling and intracellular protein dynamic analyses. (paper)

  8. The relationship between pain, disability, guilt and acceptance in low back pain: a mediation analysis.

    Science.gov (United States)

    Serbic, Danijela; Pincus, Tamar

    2017-08-01

    Pain-related guilt is a common yet unexplored psychological factor in low back pain (LBP). It has recently been linked to greater depression, anxiety and disability in LBP, hence an understanding of how it can be managed in the presence of pain and disability is necessary. Since acceptance of pain has been shown to be associated with improved outcomes in chronic pain, we examined whether it might also help reduce guilt in people with LBP. To this end, a series of mediation analyses were conducted on data from 287 patients with chronic LBP, in which acceptance of pain was tested as a mediator of the relationship between pain/disability and guilt. Results showed that acceptance of pain reduced the impact of pain/disability on pain-related guilt in all mediation analyses. Pain-related guilt might be a potential target for acceptance based interventions, thus this relationship should be further tested using longitudinal designs.

  9. Network-directed cis-mediator analysis of normal prostate tissue expression profiles reveals downstream regulatory associations of prostate cancer susceptibility loci.

    Science.gov (United States)

    Larson, Nicholas B; McDonnell, Shannon K; Fogarty, Zach; Larson, Melissa C; Cheville, John; Riska, Shaun; Baheti, Saurabh; Weber, Alexandra M; Nair, Asha A; Wang, Liang; O'Brien, Daniel; Davila, Jaime; Schaid, Daniel J; Thibodeau, Stephen N

    2017-10-17

    Large-scale genome-wide association studies have identified multiple single-nucleotide polymorphisms associated with risk of prostate cancer. Many of these genetic variants are presumed to be regulatory in nature; however, follow-up expression quantitative trait loci (eQTL) association studies have to-date been restricted largely to cis -acting associations due to study limitations. While trans -eQTL scans suffer from high testing dimensionality, recent evidence indicates most trans -eQTL associations are mediated by cis -regulated genes, such as transcription factors. Leveraging a data-driven gene co-expression network, we conducted a comprehensive cis -mediator analysis using RNA-Seq data from 471 normal prostate tissue samples to identify downstream regulatory associations of previously identified prostate cancer risk variants. We discovered multiple trans -eQTL associations that were significantly mediated by cis -regulated transcripts, four of which involved risk locus 17q12, proximal transcription factor HNF1B , and target trans -genes with known HNF response elements ( MIA2 , SRC , SEMA6A , KIF12 ). We additionally identified evidence of cis -acting down-regulation of MSMB via rs10993994 corresponding to reduced co-expression of NDRG1 . The majority of these cis -mediator relationships demonstrated trans -eQTL replicability in 87 prostate tissue samples from the Gene-Tissue Expression Project. These findings provide further biological context to known risk loci and outline new hypotheses for investigation into the etiology of prostate cancer.

  10. Comparative Transcriptome Analyses Reveal Potential Mechanisms of Enhanced Drought Tolerance in Transgenic Salvia Miltiorrhiza Plants Expressing AtDREB1A from Arabidopsis.

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    Wei, Tao; Deng, Kejun; Wang, Hongbin; Zhang, Lipeng; Wang, Chunguo; Song, Wenqin; Zhang, Yong; Chen, Chengbin

    2018-03-12

    In our previous study, drought-resistant transgenic plants of Salvia miltiorrhiza were produced via overexpression of the transcription factor AtDREB1A. To unravel the molecular mechanisms underpinning elevated drought tolerance in transgenic plants, in the present study we compared the global transcriptional profiles of wild-type (WT) and AtDREB1A -expressing transgenic plants using RNA-sequencing (RNA-seq). Using cluster analysis, we identified 3904 differentially expressed genes (DEGs). Compared with WT plants, 423 unigenes were up-regulated in pRD29A::AtDREB1A-31 before drought treatment, while 936 were down-regulated and 1580 and 1313 unigenes were up- and down-regulated after six days of drought. COG analysis revealed that the 'signal transduction mechanisms' category was highly enriched among these DEGs both before and after drought stress. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation, DEGs associated with "ribosome", "plant hormone signal transduction", photosynthesis", "plant-pathogen interaction", "glycolysis/gluconeogenesis" and "carbon fixation" are hypothesized to perform major functions in drought resistance in AtDREB1A -expressing transgenic plants. Furthermore, the number of DEGs associated with different transcription factors increased significantly after drought stress, especially the AP2/ERF, bZIP and MYB protein families. Taken together, this study substantially expands the transcriptomic information for S. miltiorrhiza and provides valuable clues for elucidating the mechanism of AtDREB1A-mediated drought tolerance in transgenic plants.

  11. Comparative Transcriptome Analyses Reveal Potential Mechanisms of Enhanced Drought Tolerance in Transgenic Salvia Miltiorrhiza Plants Expressing AtDREB1A from Arabidopsis

    Directory of Open Access Journals (Sweden)

    Tao Wei

    2018-03-01

    Full Text Available In our previous study, drought-resistant transgenic plants of Salvia miltiorrhiza were produced via overexpression of the transcription factor AtDREB1A. To unravel the molecular mechanisms underpinning elevated drought tolerance in transgenic plants, in the present study we compared the global transcriptional profiles of wild-type (WT and AtDREB1A-expressing transgenic plants using RNA-sequencing (RNA-seq. Using cluster analysis, we identified 3904 differentially expressed genes (DEGs. Compared with WT plants, 423 unigenes were up-regulated in pRD29A::AtDREB1A-31 before drought treatment, while 936 were down-regulated and 1580 and 1313 unigenes were up- and down-regulated after six days of drought. COG analysis revealed that the ‘signal transduction mechanisms’ category was highly enriched among these DEGs both before and after drought stress. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG annotation, DEGs associated with “ribosome”, “plant hormone signal transduction”, photosynthesis”, “plant-pathogen interaction”, “glycolysis/gluconeogenesis” and “carbon fixation” are hypothesized to perform major functions in drought resistance in AtDREB1A-expressing transgenic plants. Furthermore, the number of DEGs associated with different transcription factors increased significantly after drought stress, especially the AP2/ERF, bZIP and MYB protein families. Taken together, this study substantially expands the transcriptomic information for S. miltiorrhiza and provides valuable clues for elucidating the mechanism of AtDREB1A-mediated drought tolerance in transgenic plants.

  12. Childhood abuse and late-life depression: Mediating effects of psychosocial factors for early- and late-onset depression.

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    Wielaard, Ilse; Hoyer, Mathijs; Rhebergen, Didi; Stek, Max L; Comijs, Hannie C

    2018-03-01

    Childhood abuse makes people vulnerable to developing depression, even in late life. Psychosocial factors that are common in late life, such as loneliness or lack of a partner, may explain this association. Our aim was to investigate whether the association between childhood abuse and depression in older adults can be explained by psychosocial factors. Cross-sectional data were derived from the Netherlands Study of Depression in Older Persons (aged 60-93), including 132 without lifetime depression, 242 persons with an early-onset depression (Childhood abuse (yes/no) and a frequency-based childhood abuse index were included. Multinomial regression and multivariable mediation analyses were used to examine the association between childhood abuse and the onset of depression, and the influence of loneliness, social network, and partner status. Multinomial regression analyses showed a significant association between childhood abuse and the childhood abuse index with early- and late-onset depression. Multivariable mediation analyses showed that the association between childhood abuse and early-onset depression was partly mediated by social network size and loneliness. This was particularly present for emotional neglect and psychological abuse, but not for physical and sexual abuse. No psychosocial mediators were found for the association between childhood abuse and late-onset depression. A smaller social network and feelings of loneliness mediate the association between childhood abuse and early-onset depression in older adults. Our findings show the importance of detecting childhood abuse as well as the age at depression onset and mapping of relevant psychosocial factors in the treatment of late-life depression. Copyright © 2018 John Wiley & Sons, Ltd.

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

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    Irena Lavrnja

    2015-01-01

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

  14. Transcriptome and membrane fatty acid analyses reveal different strategies for responding to permeating and non-permeating solutes in the bacterium Sphingomonas wittichii

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    Johnson David R

    2011-11-01

    opposite effect and decreased after perturbation with PEG8000. Conclusions A combination of growth assays, transcriptome profiling, and membrane fatty acid analyses revealed that permeating and non-permeating solutes trigger different adaptive responses in strain RW1, suggesting these solutes affect cells in fundamentally different ways. Future work is now needed that connects these responses with the responses observed in more realistic scenarios of soil desiccation.

  15. Does multitasking mediate the relationships between episodic memory, attention, executive functions and apathetic manifestations in traumatic brain injury?

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    Arnould, Annabelle; Rochat, Lucien; Dromer, Emilie; Azouvi, Philippe; Van der Linden, Martial

    2018-03-01

    Apathy is frequently described in patients with traumatic brain injury (TBI); its negative consequences particularly affect functional independence. Among apathetic manifestations, lack of initiative and lack of interest have mainly been associated with cognitive impairments. However, few studies have been conducted to precisely identify the underlying cognitive processes. Our aims were (1) to determine the best predictor of apathy from among several cognitive processes, including episodic memory and attention/executive mechanisms and multitasking, and (2) to examine to what extent multitasking could mediate the relationships between specific cognitive processes and lack of initiative/interest. Seventy participants (34 patients with TBI matched with 36 control participants) were given a questionnaire to assess anxio-depressive symptoms, four tasks to assess specific cognitive processes, and one task to assess real-life multitasking. Participants' relatives completed an apathy questionnaire. Multitasking, as assessed by the number of goals not achieved, was the only significant predictor of apathetic manifestations. In addition, the mediation analyses revealed that multitasking performance mediated the relationships between verbal episodic memory and lack of initiative/interest, whereas executive and attentional functions were only indirectly related to lack of initiative/interest due to their significant impacts on multitasking. These results shed new light on the aetiology of apathetic manifestations in patients with TBI, indicating how specific cognitive deficits are expressed in real-life multitasking, and consequently, how they may lead to the development and/or maintenance of apathetic manifestations. © 2016 The British Psychological Society.

  16. Child/Adolescent’s ADHD and Parenting Stress: The Mediating Role of Family Impact and Conduct Problems

    Science.gov (United States)

    Muñoz-Silva, Alicia; Lago-Urbano, Rocio; Sanchez-Garcia, Manuel; Carmona-Márquez, José

    2017-01-01

    Objective: The demands of parenting are usually associated with some stress, and elevated levels of stress may affect the parent–child relationships and parenting practices. This is especially the case of families where children have special needs conditions or disorders, like Attention Deficit Hyperactivity Disorder (ADHD). Method: This study examined parenting stress among mothers of children and adolescents with ADHD. The sample comprised 126 mothers of girls (36; 29%) and boys (90; 71%) aged 6–17 years old. Results: Mothers reported their own stress levels as well as the children and adolescents’ variables (severity of their ADHD symptoms, conduct, and emotional problems) and family–contextual variables (negative impact on family’s social life, impact on couple relationship, and perceived social support). Hierarchical multiple regression showed that (a) negative impact on social life and conduct problems were the strongest predictors of mother’s stress. Bootstrap mediation analyses revealed that (b) the association between child and adolescent’s ADHD and parenting stress was mediated by children’s conduct problems and by negative impact on family’s social life, and not by children’s emotional problems nor by mother’s perceived social support. The mediation analysis also suggested (c) a pathway from child/adolescent’s ADHD through children’s conduct problems and then through their negative impact on family’s social life to mother’s parenting stress. Conclusion: These results suggest that both child/adolescent’s and family factors should be considered in the designing of interventions for reducing parenting stress in families of children and adolescents with ADHD. PMID:29312090

  17. Child/Adolescent’s ADHD and Parenting Stress: The Mediating Role of Family Impact and Conduct Problems

    Directory of Open Access Journals (Sweden)

    Alicia Muñoz-Silva

    2017-12-01

    Full Text Available Objective: The demands of parenting are usually associated with some stress, and elevated levels of stress may affect the parent–child relationships and parenting practices. This is especially the case of families where children have special needs conditions or disorders, like Attention Deficit Hyperactivity Disorder (ADHD.Method: This study examined parenting stress among mothers of children and adolescents with ADHD. The sample comprised 126 mothers of girls (36; 29% and boys (90; 71% aged 6–17 years old.Results: Mothers reported their own stress levels as well as the children and adolescents’ variables (severity of their ADHD symptoms, conduct, and emotional problems and family–contextual variables (negative impact on family’s social life, impact on couple relationship, and perceived social support. Hierarchical multiple regression showed that (a negative impact on social life and conduct problems were the strongest predictors of mother’s stress. Bootstrap mediation analyses revealed that (b the association between child and adolescent’s ADHD and parenting stress was mediated by children’s conduct problems and by negative impact on family’s social life, and not by children’s emotional problems nor by mother’s perceived social support. The mediation analysis also suggested (c a pathway from child/adolescent’s ADHD through children’s conduct problems and then through their negative impact on family’s social life to mother’s parenting stress.Conclusion: These results suggest that both child/adolescent’s and family factors should be considered in the designing of interventions for reducing parenting stress in families of children and adolescents with ADHD.

  18. Structure of a Complete Mediator-RNA Polymerase II Pre-Initiation Complex.

    Science.gov (United States)

    Robinson, Philip J; Trnka, Michael J; Bushnell, David A; Davis, Ralph E; Mattei, Pierre-Jean; Burlingame, Alma L; Kornberg, Roger D

    2016-09-08

    A complete, 52-protein, 2.5 million dalton, Mediator-RNA polymerase II pre-initiation complex (Med-PIC) was assembled and analyzed by cryo-electron microscopy and by chemical cross-linking and mass spectrometry. The resulting complete Med-PIC structure reveals two components of functional significance, absent from previous structures, a protein kinase complex and the Mediator-activator interaction region. It thereby shows how the kinase and its target, the C-terminal domain of the polymerase, control Med-PIC interaction and transcription. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. The "Romsås in Motion" community intervention: program exposure and psychosocial mediated relationships to change in stages of change in physical activity

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    Jenum Anne

    2007-04-01

    Full Text Available Abstract Background Conducting process evaluations of health promoting interventions, and measuring the effectiveness of specific intervention components, may help in the understanding of program failure or success. The purposes of the present study were to examine adults' exposure to and involvement in specific components of a three year long pseudo-experimental community-based physical activity intervention, and to examine the relationship between such exposure and participation and changes in stages of change in physical activity and psychosocial mediators. Methods 1497 persons in the intervention group attended the baseline survey in 2000 (50.6% and 1204 (80.4 of baseline attendees provided data on the outcome variables of the present study. In 2003, 1089 were still living in the area, and were re-invited to follow-up assessments. Current analyses are based on the 603 persons (mean age 49 ± 10 years who provided baseline and follow-up data for the current purposes (56.6% follow-up rate. Process data, stages of change in physical activity, and potential psychosocial mediators of change in physical activity were assessed by questionnaires. The theory-based intervention was composed of communication, physical activity, environmental and participatory components. Data were analysed using frequency and descriptive statistics, Chi-square and t-tests, and regression analyses. Results Exposure and participation rates in the various intervention components varied greatly (1.5–92.7%. Participation in walking groups and aerobic exercise groups, as well as having seen the "Walk the stairs"-poster were significantly and positively related to change in stages of change in physical activity (β = .12, p = .011; β = .211, p Conclusion Findings revealed that particular intervention components, such as participation in physical activity groups, were more strongly related to forward transition in stages of change in physical activity than others. These

  20. Positive affect, negative affect, stress, and social support as mediators of the forgiveness-health relationship.

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    Green, Michelle; Decourville, Nancy; Sadava, Stanley

    2012-01-01

    Structural equation modeling was used to test a model in which positive affect, negative affect, perceived stress, and social support were hypothesized to mediate the relationship between forgiveness and mental and physical health. Six hundred and twenty-three undergraduates completed a battery of self-report measures. Results of the analyses indicated that the forgiveness-health relation was mediated by positive affect, negative affect, stress, and the interrelationship between negative affect and stress. There was limited support for social suppor