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Sample records for internally mediated developmental

  1. Male-mediated developmental toxicity

    Directory of Open Access Journals (Sweden)

    Diana Anderson

    2014-02-01

    Full Text Available Male-mediated developmental toxicity has been of concern for many years. The public became aware of male-mediated developmental toxicity in the early 1990s when it was reported that men working at Sellafield might be causing leukemia in their children. Human and animal studies have contributed to our current understanding of male-mediated effects. Animal studies in the 1980s and 1990s suggested that genetic damage after radiation and chemical exposure might be transmitted to offspring. With the increasing understanding that there is histone retention and modification, protamine incorporation into the chromatin and DNA methylation in mature sperm and that spermatozoal RNA transcripts can play important roles in the epigenetic state of sperm, heritable studies began to be viewed differently. Recent reports using molecular approaches have demonstrated that DNA damage can be transmitted to babies from smoking fathers, and expanded simple tandem repeats minisatellite mutations were found in the germline of fathers who were exposed to radiation from the Chernobyl nuclear power plant disaster. In epidemiological studies, it is possible to clarify whether damage is transmitted to the sons after exposure of the fathers. Paternally transmitted damage to the offspring is now recognized as a complex issue with genetic as well as epigenetic components.

  2. Male-mediated developmental toxicity

    International Nuclear Information System (INIS)

    Anderson, Diana

    2005-01-01

    In recent years, the public has become more aware that exposure of males to certain agents can adversely affect their offspring and cause infertility and cancer. The hazards associated with exposure to ionising radiation have been recognised for nearly a century, but interest was aroused when a cluster of leukaemia cases was identified in young children living in Seascale, close to the nuclear processing plant at Sellafield in West Cumbria. There was a civil court case on behalf of two of the alleged victims of paternal irradiation at Seascale against British Nuclear Fuels. The case foundered on 'the balance of probabilities'. Nevertheless, there was support for paternal exposure from Japanese experimental X-ray studies in mice. The tumours were clearly heritable as shown by F2 transmission. Also, effects of a relatively non-toxic dose of radiation (1Gy) on cell proliferation transmitted to the embryo were manifested in the germ line of adult male mice even after two generations. In addition in humans, smoking fathers appear to give rise to tumours in the F 1 generation. Using rodent models, developmental abnormalities/congenital malformations and tumours can be studied after exposure of males in an extended dominant lethal assay and congenital malformations can be determined which have similar manifestations in humans. The foetuses can also be investigated for skeletal malformations and litters can be allowed to develop to adulthood when tumours, if present, can be observed. Karyotype analysis can be performed on foetuses and adult offspring to determine if induced genetic damage can be transmitted. Using this study design, cyclophosphamide, 1,3-butadiene and urethane have been examined and each compound produced positive responses: cyclophosphamide in all endpoints examined, 1,3-butadiene in some and urethane only produced liver tumours in F 1 male offspring. This suggests the endpoints are determined by independent genetic events. The results from heritable

  3. 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.

  4. Glucocorticoids as mediators of developmental programming effects.

    Science.gov (United States)

    Khulan, Batbayar; Drake, Amanda J

    2012-10-01

    Epidemiological evidence suggests that exposure to an adverse environment in early life is associated with an increased risk of cardio-metabolic and behavioral disorders in adulthood, a phenomenon termed 'early life programming'. One major hypothesis for early life programming is fetal glucocorticoid overexposure. In animal studies, prenatal glucocorticoid excess as a consequence of maternal stress or through exogenous administration to the mother or fetus is associated with programming effects on cardiovascular and metabolic systems and on the brain. These effects can be transmitted to subsequent generations. Studies in humans provide some evidence that prenatal glucocorticoid exposure may exert similar programming effects on glucose/insulin homeostasis, blood pressure and neurodevelopment. The mechanisms by which glucocorticoids mediate these effects are unclear but may include a role for epigenetic modifications. This review discusses the evidence for glucocorticoid programming in animal models and in humans. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Regional Organisations and International Mediation: The ...

    African Journals Online (AJOL)

    Regional Organisations and International Mediation: The Effectiveness of Insider Mediators. ... During the last two decades of the twentieth century, the world witnessed an increasing number of regional conflict management efforts undertaken by regional inter-governmental organisations. There are therefore strong reasons ...

  6. Developmental environment mediates male seminal protein investment in Drosophila melanogaster.

    Science.gov (United States)

    Wigby, Stuart; Perry, Jennifer C; Kim, Yon-Hee; Sirot, Laura K

    2016-03-01

    Males of many species fine-tune their ejaculates in response to sperm competition risk. Resource availability and the number of competitors during development can also strongly influence sperm production. However, despite the key role of seminal proteins in mediating reproductive processes, it is unclear whether seminal protein investment is dependent on the developmental environment.We manipulated the developmental environment of Drosophila melanogaster by rearing flies at low and high density. As expected, this resulted in large and small (i.e. high and low condition) adult phenotypes, respectively.As predicted, large males produced more of two key seminal proteins, sex peptide (SP) and ovulin, and were more successful at obtaining matings with both virgin and previously mated females. However, there was only a weak and non-significant trend for large males to transfer more absolute quantities of SP at mating, and thus, small males ejaculated proportionally more of their stored accessory gland SP resources.Males transferred more receptivity-inhibiting SP to large females. Despite this, large females remated more quickly than small females and thus responded to their developmental environment over and above the quantity of SP they received.The results are consistent with two non-mutually exclusive hypotheses. First, flies might respond to condition-dependent reproductive opportunities, with (i) small males investing heavily in ejaculates when mating opportunities arise and large males strategically partitioning SP resources and (ii) small females remating at reduced rates because they have higher mating costs or need to replenish sperm less often.Second, flies may be primed by their larval environment to deal with similar adult population densities, with (i) males perceiving high density as signalling increased competition, leading small males to invest proportionally more SP resources at mating and (ii) females perceiving high density as signalling abundant

  7. Characteristics of international websites with information on developmental disabilities.

    Science.gov (United States)

    Reichow, Brian; Gelbar, Nicholas W; Mouradjian, Keri; Shefcyk, Allison; Smith, Isaac C

    2014-10-01

    The Internet often serves as a primary resource for individuals seeking health-related information, and a large and growing number of websites contain information related to developmental disabilities. This paper presents the results of an international evaluation of the characteristics and content of the top 10 ranked results (i.e., not including sponsored results - pay-per-click) returned when one of five terms related to developmental disabilities (i.e., ADHD, autism, down syndrome, learning disability, intellectual disability) was entered into one of six country specific Google online search engines (i.e., Australia (https://www.google.com.au), Canada (https://www.google.ca), Ireland (https://www.google.ie), New Zealand (https://www.google.co.nz), the United Kingdom (https://www.google.co.uk), and the United States (https://www.google.com)) on October 22, 2013. Collectively, we found that international consumers of websites related to developmental disabilities will encounter different websites with differing content and terminology, and should be critical consumers to ensure they locate the information they are seeking. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Parental verbal abuse and the mediating role of self-criticism in adult internalizing disorders.

    Science.gov (United States)

    Sachs-Ericsson, Natalie; Verona, Edelyn; Joiner, Thomas; Preacher, Kristopher J

    2006-07-01

    Researchers (e.g., [Gibb, B.E., 2002. Childhood maltreatment and negative cognitive styles. A quantitative and qualitative review. Clinical Psychology Review, 22 (2), 223-246]; [Rose, D.T., Abramson, L.Y., 1992. Developmental predictors of depressive cognitive styles: developmental perspectives on depression. In Cicchetti, D., Toth, S.L. (Eds.), Developmental Perspectives on Depression. Rochester symposium on developmental psychopathology, vol. 4, pp. 323-349]) have proposed that when childhood abuse is verbal (rather than sexual or physical), the child is more likely to develop a negative self-schema because the negative self-cognitions are directly supplied to the child by the abuser (e.g., "you are stupid"). In a test of this theory in adult participants, and drawing on the National Comorbidity Survey (NCS) (N=5877), we investigate the mediating role of current levels of self-criticism on the relationship between retrospective reports of parental verbal abuse, as well as sexual and physical abuse, and adult internalizing symptoms. We found self-criticism, but not dependency traits, to fully mediate the relationship between childhood verbal abuse perpetrated by parents and internalizing (depression, anxiety) symptoms. On the other hand, self-criticism was only a partial mediator of the relationship between the other types of abuse and internalizing symptoms. The NCS data is cross-sectional, which limits any firm conclusions regarding causality. While these results are suggestive that self-criticism is a mediator of the relationship between abuse and internalizing symptoms, longitudinal data are necessary to help rule out alternative explanations. Results of this study suggest that childhood abuse experiences, and in particular verbal abuse, may confer risk for internalizing disorders in part because verbal abuse influences the development of a self-critical style.

  9. Developmental Pathways in Juvenile Externalizing and Internalizing Problems

    Science.gov (United States)

    Loeber, Rolf; Burke, Jeffrey D.

    2011-01-01

    This article summarizes the empirical studies showing pathways in the development of externalizing and delinquent behaviors. Pathways are defined as the orderly temporal development between more than two problem behaviors. The paper addresses the following questions: (1) What are the developmental pathways between different diagnoses of Disruptive…

  10. Adaptive developmental plasticity: Compartmentalized responses to environmental cues and corresponding internal signals provide phenotypic flexibility

    NARCIS (Netherlands)

    Mateus, A.R.A.; Marques-Pita, M.; Oostra, V.; Lafuente, E.; Brakefield, P.M.; Zwaan, B.J.; Beldade, P.

    2014-01-01

    Background The environmental regulation of development can result in the production of distinct phenotypes from the same genotype and provide the means for organisms to cope with environmental heterogeneity. The effect of the environment on developmental outcomes is typically mediated by hormonal

  11. Regional Organisations and International Mediation: The ...

    African Journals Online (AJOL)

    Angela

    increasing number of regional conflict management efforts undertaken by ... to study the advantages and disadvantages of mediation efforts by regional ... Elgström is Professor at the Department of Political Science, Lund University,. Sweden. .... partial or full settlement) in 42.1 per cent of cases; the UN achieved success.

  12. 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…

  13. Computer Mediated Communication and University International Students

    Science.gov (United States)

    Robbins, Nancy; Lo, Yen-Hai; Hou, Feng-Heiung; Chou, Tsai-Sheng; Chen, Chin-Hung; Chen, Chao-Chien; Chen, Wen-Chiang; Chen, Yen-Chuan; Wang, Shih-Jen; Huang, Shih-Yu; Lii, Jong-Yiing

    2002-01-01

    The design for this preliminary study was based on the experiences of the international students and faculty members of a small southwest university being surveyed and interviewed. The data collection procedure blends qualitative and quantitative data. A strong consensus was found that supports the study's premise that there is an association…

  14. Internal conversion mediated by specific nuclear motions

    DEFF Research Database (Denmark)

    Klein, Liv Bærenholdt; Sølling, Theis Ivan

    2014-01-01

    the excitation energies, and the excitation in all cases is by a 200 nm photon, the S1 density-of-states in the Franck-Condon region will be high for the more N-alkylated amine. This, according to standard models, should lead to faster internal conversion. The experimental results are in contrast to this...

  15. Module for Interns in Medical Ethics: A Developmental Diegesis.

    Science.gov (United States)

    Mahajan, Rajiv; Goyal, Parmod Kumar; Sidhu, Tanvir Kaur; Kaur, Upinder; Kaur, Sandeep; Gupta, Vitull

    2017-12-01

    Media report is rife with incidences of doctor-patients' conflict, and this partly is due to communication gap and unethical practices being adopted by the doctors. Our regular curriculum fails to impart any training in ethical issues in patient care. Imparting training to students in these soft-skills is the need of the hour. To develop a module for interns in medical ethics (MIME) in patient care, validate it and pilot run the module for standardization. After conducting faculty development workshop in curriculum designing and three rounds of Delphi with alumni, a module in medical ethics was developed and peer validated. The questionnaire for pilot run, questionnaire for future use of module delivery and pre- and post-test were also peer validated. The module was delivered to 17 interns as pilot run in the form of 4 days' workshop. After pilot run, the module was standardized to 10 broad topics and 3 days' workshop. The questionnaire for future delivery of module in regular routine was also validated during pilot run. Twenty-five faculty members participated in 1 day faculty development workshop and 59 alumni completed three rounds of Delphi. After peer review by five experts, a module of 11 broad areas was developed and was pilot run on 17 interns. Based on the feedback from pilot run, a standardized, validated 18 h teaching MIME in patient care was developed. Pilot study proves that curriculum innovation in the form of medical ethics training to interns; when as undergraduate students, they actively participate in patient care under supervision will go a long way in inculcating soft skills like ethics, compassion and communication in them.

  16. Developmental Pathways Linking Externalizing Symptoms, Internalizing Symptoms, and Academic Competence to Adolescent Substance Use

    Science.gov (United States)

    Englund, Michelle M.; Siebenbruner, Jessica

    2012-01-01

    This study extends previous research investigating the developmental pathways predicting adolescent alcohol and marijuana use by examining the cascading effects of externalizing and internalizing symptoms and academic competence in the prediction of use and level of use of these substances in adolescence. Participants (N = 191) were drawn from a…

  17. The Mediator complex of Caenorhabditis elegans: insights into the developmental and physiological roles of a conserved transcriptional coregulator.

    Science.gov (United States)

    Grants, Jennifer M; Goh, Grace Y S; Taubert, Stefan

    2015-02-27

    The Mediator multiprotein complex ('Mediator') is an important transcriptional coregulator that is evolutionarily conserved throughout eukaryotes. Although some Mediator subunits are essential for the transcription of all protein-coding genes, others influence the expression of only subsets of genes and participate selectively in cellular signaling pathways. Here, we review the current knowledge of Mediator subunit function in the nematode Caenorhabditis elegans, a metazoan in which established and emerging genetic technologies facilitate the study of developmental and physiological regulation in vivo. In this nematode, unbiased genetic screens have revealed critical roles for Mediator components in core developmental pathways such as epidermal growth factor (EGF) and Wnt/β-catenin signaling. More recently, important roles for C. elegans Mediator subunits have emerged in the regulation of lipid metabolism and of systemic stress responses, engaging conserved transcription factors such as nuclear hormone receptors (NHRs). We emphasize instances where similar functions for individual Mediator subunits exist in mammals, highlighting parallels between Mediator subunit action in nematode development and in human cancer biology. We also discuss a parallel between the association of the Mediator subunit MED12 with several human disorders and the role of its C. elegans ortholog mdt-12 as a regulatory hub that interacts with numerous signaling pathways. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Perceived Parenting Styles Fail to Mediate between Anxiety and Attachment Styles in Adult Siblings of Individuals with Developmental Disabilities

    Science.gov (United States)

    O'Neill, Linda P.; Murray, Lindsay E.

    2016-01-01

    Adult siblings of individuals with developmental disabilities often experience higher levels of anxiety than individuals in the general population. The present study tested whether perceived parenting could mediate the relationship between attachment styles and anxiety in the sibling group compared to a control group. Little association was found…

  19. Unequally redundant RCD1 and SRO1 mediate stress and developmental responses and interact with transcription factors

    NARCIS (Netherlands)

    Jaspers, P.; Blomster, T.; Brosché, M.; Salojärvi, J.; Ahlfors, R.; Vainonen, J.P.; Reddy, R.A.; Immink, G.H.; Angenent, G.C.; Turck, F.; Overmyer, K.; Kangasjärvi, J.

    2009-01-01

    RADICAL-INDUCED CELL DEATH1 (RCD1) is an important regulator of stress and hormonal and developmental responses in Arabidopsis thaliana. Together with its closest homolog, SIMILAR TO RCD-ONE1 (SRO1), it is the only Arabidopsis protein containing the WWE domain, which is known to mediate

  20. Factor Structure, Internal Consistency, and Screening Sensitivity of the GARS-2 in a Developmental Disabilities Sample

    OpenAIRE

    Martin A. Volker; Elissa H. Dua; Christopher Lopata; Marcus L. Thomeer; Jennifer A. Toomey; Audrey M. Smerbeck; Jonathan D. Rodgers; Joshua R. Popkin; Andrew T. Nelson; Gloria K. Lee

    2016-01-01

    The Gilliam Autism Rating Scale-Second Edition (GARS-2) is a widely used screening instrument that assists in the identification and diagnosis of autism. The purpose of this study was to examine the factor structure, internal consistency, and screening sensitivity of the GARS-2 using ratings from special education teaching staff for a sample of 240 individuals with autism or other significant developmental disabilities. Exploratory factor analysis yielded a correlated three-factor solution si...

  1. Peer-Mediated AAC Instruction for Young Children with Autism and other Developmental Disabilities.

    Science.gov (United States)

    Thiemann-Bourque, Kathy

    2012-12-01

    Many young children with developmental disabilities (DD) have significant delays in social, communication, and play skills. For those children learning to use augmentative and alternative communication (.AAC% successful social interactions with peers will require explicit instruction on the same system for both communication partners. Peer-mediated (PM) interventions are recommended best practice based on more than 30 years of research with young children with autism and other DDs. Integrating direct AAC instruction within PM programs to advance social reciprocity in typical preschool routines is a necessary and important next step for young AAC users. In this article, I will summarize the design and outcomes of two PM AAC studies documenting positive social outcomes for preschool children with severe autism. I will also teach } peer partners how to use AAC highlight strategies to recruit peers without disabilities systems (e.g., Picture Exchange Communication System [PECS], Speech Generating Devices [SGDs]), and engineer the preschool classroom for successful AAC communication. I will describe data collection procedures for measuring changes in reciprocal child and peer social communication interactions.

  2. THE EFFECTS OF DEVELOPMENTAL AND RATIONAL SUBCULTURES ON ENTREPRENEURIAL BEHAVIORS: THE MEDIATING ROLE OF PERCEIVED ENVIRONMENTAL UNCERTAINTY

    OpenAIRE

    Irfan Akkoc; Abdullah Caliskan; Omer Turunc

    2012-01-01

    The aim of this study is to investigate the effect of developmental and rational culture on the employees’ entrepreneurial behaviors and the mediating role of the perceived environmental uncertainty on this effect. The relationship between the aforementioned variables is analyzed by using a set of statistical techniques, i.e., factor analysis, regression analysis, and sobel tests. The data used in the analysis is obtained through questionnaires filled out by 651 employees of the private firms...

  3. International medallists' and non-medallists' developmental sport activities - a matched-pairs analysis.

    Science.gov (United States)

    Güllich, Arne

    2017-12-01

    The study examined developmental participation patterns of international top athletes. Pairs of 83 international medallists (including 38 Olympic/World Champions) and 83 non-medallists were matched by sport, age and gender. A questionnaire recorded their volume of organised (coach-led) practice/training in their respective main sport and in other sports through childhood, adolescence and adulthood, and also involvement in non-organised (peer-led) sport activity. Analyses revealed that the medallists started practice/training in their main sport at an older age than non-medallists and accumulated slightly, but significantly less main-sport practice/training through childhood/adolescence. But they participated in more practice/training in other sports, particularly before entering their main sport. The medallists also maintained engagement in other sports over more years and specialised later than the non-medallists. Other sports engaged in were mostly unrelated to an athlete's main sport. The results were robust across different types of sports. The observations are reflected against tenets of the "deliberate practice" and "Developmental Model of Sport Participation" frameworks. Early diversified practice and learning experiences are discussed relative to the expansion of youngsters' potential for future long-term learning. In elite athletes, interaction of sport-specific practice/training with early other-sports participation mostly facilitates long-term attainment of international senior medals.

  4. Predicting developmental changes in internalizing symptoms: examining the interplay between parenting and neuroendocrine stress reactivity.

    Science.gov (United States)

    Kuhlman, Kate R; Olson, Sheryl L; Lopez-Duran, Nestor L

    2014-07-01

    In this study, we examined whether parenting and HPA-axis reactivity during middle childhood predicted increases in internalizing symptoms during the transition to adolescence, and whether HPA-axis reactivity mediated the impact of parenting on internalizing symptoms. The study included 65 children (35 boys) who were assessed at age 5, 7, and 11. Parenting behaviors were assessed via parent report at age 5 and 11. The child's HPA-axis reactivity was measured at age 7 via a stress task. Internalizing symptoms were measured via teacher reports at age 5 and 11. High maternal warmth at age 5 predicted lower internalizing symptoms at age 11. Also, high reported maternal warmth and induction predicted lower HPA-axis reactivity. Additionally, greater HPA-axis reactivity at age 7 was associated with greater increases in internalizing symptoms from age 5 to 11. Finally, the association between age 5 maternal warmth and age 11 internalizing symptoms was partially mediated by lower cortisol in response to the stress task. Thus, parenting behaviors in early development may influence the physiological stress response system and therefore buffer the development of internalizing symptoms during preadolescence when risk for disorder onset is high. © 2013 Wiley Periodicals, Inc.

  5. K-Cl Cotransporter 2-mediated Cl- Extrusion Determines Developmental Stage-dependent Impact of Propofol Anesthesia on Dendritic Spines.

    Science.gov (United States)

    Puskarjov, Martin; Fiumelli, Hubert; Briner, Adrian; Bodogan, Timea; Demeter, Kornel; Lacoh, Claudia-Marvine; Mavrovic, Martina; Blaesse, Peter; Kaila, Kai; Vutskits, Laszlo

    2017-05-01

    General anesthetics potentiating γ-aminobutyric acid (GABA)-mediated signaling are known to induce a persistent decrement in excitatory synapse number in the cerebral cortex when applied during early postnatal development, while an opposite action is produced at later stages. Here, the authors test the hypothesis that the effect of general anesthetics on synaptogenesis depends upon the efficacy of GABA receptor type A (GABAA)-mediated inhibition controlled by the developmental up-regulation of the potassium-chloride (K-Cl) cotransporter 2 (KCC2). In utero electroporation of KCC2 was used to prematurely increase the efficacy of (GABAA)-mediated inhibition in layer 2/3 pyramidal neurons in the immature rat somatosensory cortex. Parallel experiments with expression of the inward-rectifier potassium channel Kir2.1 were done to reduce intrinsic neuronal excitability. The effects of these genetic manipulations (n = 3 to 4 animals per experimental group) were evaluated using iontophoretic injection of Lucifer Yellow (n = 8 to 12 cells per animal). The total number of spines analyzed per group ranged between 907 and 3,371. The authors found a robust effect of the developmental up-regulation of KCC2-mediated Cl transport on the age-dependent action of propofol on dendritic spines. Premature expression of KCC2, unlike expression of a transport-inactive KCC2 variant, prevented a propofol-induced decrease in spine density. In line with a reduction in neuronal excitability, the above result was qualitatively replicated by overexpression of Kir2.1. The KCC2-dependent developmental increase in the efficacy of GABAA-mediated inhibition is a major determinant of the age-dependent actions of propofol on dendritic spinogenesis.

  6. The developmental outcomes of P0-mediated ARGONAUTE destabilization in tomato.

    Science.gov (United States)

    Hendelman, Anat; Kravchik, Michael; Stav, Ran; Zik, Moriyah; Lugassi, Nitsan; Arazi, Tzahi

    2013-01-01

    The plant protein ARGONAUTE1 (AGO1) functions in multiple RNA-silencing pathways, including those of microRNAs, key regulators of growth and development. Genetic analysis of ago1 mutants with informative defects has provided valuable insights into AGO1's biological functions. Tomato encodes two AGO1 homologs (SlAGO1s), but mutants have not been described to date. To analyze SlAGO1s' involvement in development, we confirmed that both undergo decay in the presence of the Polerovirus silencing suppressor P0 and produce a transgenic responder line (OP:P0HA) that, upon transactivation, expresses P0 C-terminally fused to a hemagglutinin (HA) tag (P0HA) and destabilizes SlAGO1s at the site of expression. By crossing OP:P0HA with a battery of driver lines, constitutive as well as organ- and stage-specific SlAGO1 downregulation was induced in the F1 progeny. Activated plants exhibited various developmental phenotypes that partially overlapped with those of Arabidopsis ago1 mutants. Plants that constitutively expressed P0HA had reduced SlAGO1 levels and increased accumulation of miRNA targets, indicating compromised SlAGO1-mediated silencing. Consistent with this, they exhibited pleiotropic morphological defects and their growth was arrested post-germination. Transactivation of P0HA in young leaf and floral organ primordia dramatically modified corresponding organ morphology, including the radialization of leaflets, petals and anthers, suggesting that SlAGO1s' activities are required for normal lateral organ development and polarity. Overall, our results suggest that the OP:P0HA responder line can serve as a valuable tool to suppress SlAGO1 silencing pathways in tomato. The suppression of additional SlAGOs by P0HA and its contribution to the observed phenotypes awaits investigation.

  7. Developmental Origins of Biological Explanations: The case of infants' internal property bias.

    Science.gov (United States)

    Taborda-Osorio, Hernando; Cheries, Erik W

    2017-10-01

    People's explanations about the biological world are heavily biased toward internal, non-obvious properties. Adults and children as young as 5 years of age find internal properties more causally central than external features for explaining general biological processes and category membership. In this paper, we describe how this 'internal property bias' may be grounded in two different developmental precursors observed in studies with infants: (1) an early understanding of biological agency that is apparent in infants' reasoning about animals, and (2) the acquisition of kind-based representations that distinguish between essential and accidental properties, spanning from animals to artifacts. We argue that these precursors may support the progressive construction of the notion of biological kinds and explanations during childhood. Shortly after their first year of life, infants seem to represent the internal properties of animates as more central and identity-determining that external properties. Over time, this skeletal notion of biological kinds is integrated into diverse explanations about kind membership and biological processes, with an increasingly better understanding of the causal role of internal properties.

  8. Perceived Parenting Styles Fail to Mediate Between Anxiety and Attachment Styles in Adult Siblings of Individuals with Developmental Disabilities.

    Science.gov (United States)

    O'Neill, Linda P; Murray, Lindsay E

    2016-09-01

    Adult siblings of individuals with developmental disabilities often experience higher levels of anxiety than individuals in the general population. The present study tested whether perceived parenting could mediate the relationship between attachment styles and anxiety in the sibling group compared to a control group. Little association was found between perceived parenting and attachment styles or anxiety for the siblings but there were robust and expected findings for the control. Adult attachment-related-anxiety was a significant unique predictor of anxiety in the sibling group but there was no mediational role for perceived parenting. Conversely, the majority of parenting styles significantly mediated the relationship between attachment and anxiety in the control. Implications for the atypical findings in the sibling group are discussed.

  9. Cultural Mediation. The Usefulness of Selected Concepts of Developmental Psychology for Coaching and Mentoring Relations

    OpenAIRE

    Smorczewska, Barbara

    2013-01-01

    Some developmental psychological concepts, such as L. S. Vygotsky’s zone of proximal development or H. R. Schaffer’s joint involvement episodes, gave a new perspective in perceiving the process of teaching and development, by providing very detailed characteristics of the situation of acquiring competence in social relations. The mentioned concepts are based on a belief in the developmental potential of humans, and they perceive teaching as future-oriented. These assumptions are also characte...

  10. Description of a developmental criterion-referenced assessment for promoting competence in internal medicine residents.

    Science.gov (United States)

    Varney, Andrew; Todd, Christine; Hingle, Susan; Clark, Michael

    2009-09-01

    End-of- rotation global evaluations can be subjective, produce inflated grades, lack interrater reliability, and offer information that lacks value. This article outlines the generation of a unique developmental criterion-referenced assessment that applies adult learning theory and the learner, manager, teacher model, and represents an innovative application to the American Board of Internal Medicine (ABIM) 9-point scale. We describe the process used by Southern Illinois University School of Medicine to develop rotation-specific, criterion-based evaluation anchors that evolved into an effective faculty development exercise. The intervention gave faculty a clearer understanding of the 6 Accreditation Council for Graduate Medical Education competencies, each rotation's educational goals, and how rotation design affects meaningful work-based assessment. We also describe easily attainable successes in evaluation design and pitfalls that other institutions may be able to avoid. Shifting the evaluation emphasis on the residents' development of competence has made the expectations of rotation faculty more transparent, has facilitated conversations between program director and residents, and has improved the specificity of the tool for feedback. Our findings showed the new approach reduced grade inflation compared with the ABIM end-of-rotation global evaluation form. We offer the new developmental criterion-referenced assessment as a unique application of the competences to the ABIM 9-point scale as a transferable model for improving the validity and reliability of resident evaluations across graduate medical education programs.

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

    Science.gov (United States)

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

    2007-11-01

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

  12. Maternal Immune-Mediated Conditions, Autism Spectrum Disorders, and Developmental Delay

    Science.gov (United States)

    Lyall, Kristen; Ashwood, Paul; Van de Water, Judy; Hertz-Picciotto, Irva

    2014-01-01

    The maternal immune system may play a role in offspring neurodevelopment. We examined whether maternal autoimmune disease, asthma, and allergy were associated with child autism spectrum disorder (ASD) and developmental delay without autism (DD) using 560 ASD cases, 391 typically developing controls, and 168 DD cases from the CHildhood Autism Risk…

  13. Perceptions of Services and Resources as Mediators of Depression among Parents of Children with Developmental Disabilities.

    Science.gov (United States)

    Herman, Sandra E.; Marcenko, Maureen O.

    1997-01-01

    This study examined effects of resource perceptions and respite use in a theoretical model of adaptation with 72 parents of children with developmental disabilities. Amount and quality of respite services indirectly affected parental depression. Both quality and respite use were related to helpfulness of the parent's social network. The strongest…

  14. Factor Structure, Internal Consistency, and Screening Sensitivity of the GARS-2 in a Developmental Disabilities Sample

    Directory of Open Access Journals (Sweden)

    Martin A. Volker

    2016-01-01

    Full Text Available The Gilliam Autism Rating Scale-Second Edition (GARS-2 is a widely used screening instrument that assists in the identification and diagnosis of autism. The purpose of this study was to examine the factor structure, internal consistency, and screening sensitivity of the GARS-2 using ratings from special education teaching staff for a sample of 240 individuals with autism or other significant developmental disabilities. Exploratory factor analysis yielded a correlated three-factor solution similar to that found in 2005 by Lecavalier for the original GARS. Though the three factors appeared to be reasonably consistent with the intended constructs of the three GARS-2 subscales, the analysis indicated that more than a third of the GARS-2 items were assigned to the wrong subscale. Internal consistency estimates met or exceeded standards for screening and were generally higher than those in previous studies. Screening sensitivity was .65 and specificity was .81 for the Autism Index using a cut score of 85. Based on these findings, recommendations are made for instrument revision.

  15. Developmental trajectories and longitudinal mediation effects of self-esteem, peer attachment, child maltreatment and depression on early adolescents.

    Science.gov (United States)

    Ju, Soyoung; Lee, Yanghee

    2018-02-01

    The purpose of this study is to identify the developmental trajectories of peer attachment, self-esteem, depression, and child maltreatment, and to understand the longitudinal mediation effects that peer attachment and self-esteem have on the influence of perceived abuse on early adolescent depression. This study uses Year 1 to Year 5 data of the 4th grader panel of the Korea Youth Panel Survey (KYPS) and utilizes a multivariate latent growth model to analyze the main variables in the applicable data between 5th (i.e., Year 2) and 8th (i.e., Year 5) grades. The results indicate that from the 5th to the 8th grade, the degree of abuse and depression increases while self-esteem gradually decreases with slowly lowering peer attachment. A significant distribution of the initial values and the rate of change were present for all main variables of the study, confirming individual differences in time wise changes. Further, more exposure to abuse correlated with a decrease in self-esteem, while an increase in self-esteem greatly reduced depression. The initial value of self-esteem showed a partial mediation effect, whereas the rate of change indicated a full mediation effect with a significant longitudinal mediation effect. More experience of abuse during early adolescence indicated a lower degree of peer attachment, and a higher peer attachment was related to decreased depression. A significant partial mediation effect was present for both the initial value and the rate of change of peer attachment, and a longitudinal mediation effect was present. This study confirmed that self-esteem in early adolescents is an important protective factor that can greatly reduce the degree of depression, and suggests continuous interventions conducted to increase self-esteem in adolescence. Furthermore, by determining that peer attachment decreases the degree of depression in children at risk, the study emphasizes the healing aspect of adolescent peer attachment. Copyright © 2017 Elsevier

  16. Conceptualising International Peace Mediation - Bring Back the Law

    OpenAIRE

    Higgins, Noelle; Daly, Brenda

    2011-01-01

    Mediation has been acknowledged and utilised for a number of decades as an effective method of alternative dispute resolution in a variety of areas of law, including family law, commercial law and medical law. A uniform, standardised framework exists within legal discourse which clearly identifies and categorises three main styles of mediation as facilitative, evaluative and transformative mediation. In the post-Cold War period, mediation has also emerged as an important resolution tool in ar...

  17. Cultural Mediation. The Usefulness of Selected Concepts of Developmental Psychology for Coaching and Mentoring Relations

    Directory of Open Access Journals (Sweden)

    Barbara Smorczewska

    2013-09-01

    Full Text Available Some developmental psychological concepts, such as L. S. Vygotsky’s zone of proximal development or H. R. Schaffer’s joint involvement episodes, gave a new perspective in perceiving the process of teaching and development, by providing very detailed characteristics of the situation of acquiring competence in social relations. The mentioned concepts are based on a belief in the developmental potential of humans, and they perceive teaching as future-oriented. These assumptions are also characteristic for coaching and mentoring which are nowadays becoming more and more popular forms of development in work places; hence an attempt to find some analogy between them. The prepared comparison contributes to extending the theoretical bases of “development cooperation relations,” as coaching and mentoring are jointly referred to.

  18. Parental dysphoria and children's internalizing symptoms: marital conflict styles as mediators of risk.

    Science.gov (United States)

    Du Rocher Schudlich, Tina D; Cummings, E Mark

    2003-01-01

    Parents' marital conflict styles were investigated as mediators in the associations between parental dysphoria and children's internalizing symptoms. A community sample of 267 children, ages 8 to 16, participated with their parents. Behavioral observations were made of parents' interactions during marital conflict resolution tasks. Questionnaires assessed parents' dysphoria and children's internalizing problems. Structural equation modeling indicated that marital discord, in particular, depressive conflict styles, mediated the relationship between parental dysphoria and children's internalizing problems. Furthermore, whereas for dysphoric mothers, depressive conflict styles partially mediated the links with children's internalizing, for fathers, depressive conflict styles fully mediated the links. Destructive and constructive marital conflict were associated with parental dysphoria (positively and negatively, respectively) but did not mediate the relations with children's internalizing.

  19. International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes.

    Science.gov (United States)

    Bal-Price, Anna; Crofton, Kevin M; Leist, Marcel; Allen, Sandra; Arand, Michael; Buetler, Timo; Delrue, Nathalie; FitzGerald, Rex E; Hartung, Thomas; Heinonen, Tuula; Hogberg, Helena; Bennekou, Susanne Hougaard; Lichtensteiger, Walter; Oggier, Daniela; Paparella, Martin; Axelstad, Marta; Piersma, Aldert; Rached, Eva; Schilter, Benoît; Schmuck, Gabriele; Stoppini, Luc; Tongiorgi, Enrico; Tiramani, Manuela; Monnet-Tschudi, Florianne; Wilks, Martin F; Ylikomi, Timo; Fritsche, Ellen

    2015-02-01

    A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.

  20. The impact of parenting styles on children developmental outcome: The role of academic self-concept as a mediator.

    Science.gov (United States)

    Sangawi, Hoshiar; Adams, John; Reissland, Nadja

    2016-08-23

    Although the importance of parenting styles directly influencing child development is well established, fewer studied have examined whether parenting styles also affect children's behavioural problems indirectly, mediated through children's academic self-concept (ASC). We examined direct and shared effects of parenting styles on behavioural problems of 199 Kurdish primary school children with a mean age of 11 years 7 months (range 11 years 5 months to 12 years 3 months). Questionnaires measured parenting styles (child version of Alabama Parenting Questionnaire), assessed children's ASC (Myself-As-Learner Scale) and identified children's behavioural problems with the Strengths and Difficulties Questionnaire (SDQ). PROCESS analysis was used to perform the mediation analysis. The results revealed that positive and negative parenting composites are indirectly related to children's internalising behaviour problems. In addition, ASC partially mediated the relationship between the negative parenting composite and prosocial behaviour. However, the mediation analysis did not show the expected indirect effect of parenting styles on externalising problems as being mediated via ASC. Hence, we argue that the ASC serves as a significant mediator in the relationship between parenting styles with prosocial behaviour and internalising problems. © 2016 International Union of Psychological Science.

  1. Developmental expression of Manduca shade, the P450 mediating the final step in molting hormone synthesis

    DEFF Research Database (Denmark)

    Rewitz, Kim; Rybczynski, Robert; Warren, James T.

    2006-01-01

    body and epidermis with very low expression in the prothoracic gland and nervous system. Developmental variations in E20MO enzymatic activity are almost perfectly correlated with comparable changes in the gene expression of Msshd in the fat body and midgut during the fifth instar and the beginning...... gene shade (shd; CYP314A1) that encodes the E20MO in the tobacco hornworm, Manduca sexta. Manduca Shd (MsShd) mediates the conversion of E to 20E when expressed in Drosophila S2 cells. In accord with the central dogma, the data show that Msshd is expressed mainly in the midgut, Malpighian tubules, fat...... of pupal-adult development. The results indicate three successive and overlapping peaks of expression in the fat body, midgut and Malpighian tubules, respectively, during the fifth larval instar. The data suggest that precise tissue-specific transcriptional regulation controls the levels, and thereby...

  2. Enhanced excitatory input to MCH neurons during developmental period of high food intake is mediated by GABA

    Science.gov (United States)

    Li, Ying; van den Pol, Anthony N.

    2010-01-01

    In contrast to the local axons of GABA neurons of the cortex and hippocampus, lateral hypothalamic neurons containing melanin concentrating hormone (MCH) and GABA send long axons throughout the brain and play key roles in energy homeostasis and mental status. In adults, MCH neurons maintain a hyperpolarized membrane potential and most of the synaptic input is inhibitory. In contrast, we found that developing MCH neurons received substantially more excitatory synaptic input. Based on gramicidicin-perforated patch recordings in hypothalamic slices from MCH-GFP transgenic mice, we found that GABA was the primary excitatory synaptic transmitter in embryonic and neonatal ages up to postnatal day 10. Surprisingly, glutamate assumed only a minor excitatory role, if any. GABA plays a complex role in developing MCH neurons, with its actions conditionally dependent on a number of factors. GABA depolarization could lead to an increase in spikes either independently or in summation with other depolarizing stimuli, or alternately, depending on the relative timing of other depolarizing events, could lead to shunting inhibition. The developmental shift from depolarizing to hyperpolarizing occurred later in the dendrites than in the cell body. Early GABA depolarization was based on a Cl− dependent inward current. An interesting secondary depolarization in mature neurons that followed an initial hyperpolarization was based on a bicarbonate mechanism. Thus during the early developmental period when food consumption is high, MCH neurons are more depolarized than in the adult, and an increased level of excitatory synaptic input to these orexigenic cells is mediated by GABA. PMID:19955372

  3. Enhanced excitatory input to melanin concentrating hormone neurons during developmental period of high food intake is mediated by GABA.

    Science.gov (United States)

    Li, Ying; van den Pol, Anthony N

    2009-12-02

    In contrast to the local axons of GABA neurons of the cortex and hippocampus, lateral hypothalamic neurons containing melanin concentrating hormone (MCH) and GABA send long axons throughout the brain and play key roles in energy homeostasis and mental status. In adults, MCH neurons maintain a hyperpolarized membrane potential and most of the synaptic input is inhibitory. In contrast, we found that developing MCH neurons received substantially more excitatory synaptic input. Based on gramicidin-perforated patch recordings in hypothalamic slices from MCH-green fluorescent protein transgenic mice, we found that GABA was the primary excitatory synaptic transmitter in embryonic and neonatal ages up to postnatal day 10. Surprisingly, glutamate assumed only a minor excitatory role, if any. GABA plays a complex role in developing MCH neurons, with its actions conditionally dependent on a number of factors. GABA depolarization could lead to an increase in spikes either independently or in summation with other depolarizing stimuli, or alternately, depending on the relative timing of other depolarizing events, could lead to shunting inhibition. The developmental shift from depolarizing to hyperpolarizing occurred later in the dendrites than in the cell body. Early GABA depolarization was based on a Cl(-)-dependent inward current. An interesting secondary depolarization in mature neurons that followed an initial hyperpolarization was based on a bicarbonate mechanism. Thus during the early developmental period when food consumption is high, MCH neurons are more depolarized than in the adult, and an increased level of excitatory synaptic input to these orexigenic cells is mediated by GABA.

  4. Global Processing Speed as a Mediator of Developmental Changes in Children's Auditory Memory Span

    Science.gov (United States)

    Ferguson, A.N.; Bowey, J.A.

    2005-01-01

    This study examined the role of global processing speed in mediating age increases in auditory memory span in 5- to 13-year-olds. Children were tested on measures of memory span, processing speed, single-word speech rate, phonological sensitivity, and vocabulary. Structural equation modeling supported a model in which age-associated increases in…

  5. Peer Rejection and Internalizing Behavior: The Mediating Role of Peer Victimization in Preschool.

    Science.gov (United States)

    Metin Aslan, Özge

    2018-05-23

    The author examined the relationship among peer rejection, peer victimization, and internalizing behaviors. The author hypothesized that physical and relational victimization would have a different indirect effect on the relationship between peer rejection and internalizing behaviors. Participants were 94 preschool children (37 girls; average age 49.97 months) from two university preschools located in the northern part of the United States. The results indicated that internalizing behaviors predicted the mediating variables only regarding relational victimization. Relational victimization indirectly affected the association between peer rejection and internalizing behaviors. The study provides evidence of the mediating effect of victimization behaviors on the relationship among peer rejection, victimization, and internalizing behaviors.

  6. A novel ecdysone receptor mediates steroid-regulated developmental events during the mid-third instar of Drosophila.

    Directory of Open Access Journals (Sweden)

    Benjamin F B Costantino

    2008-06-01

    Full Text Available The larval salivary gland of Drosophila melanogaster synthesizes and secretes glue glycoproteins that cement developing animals to a solid surface during metamorphosis. The steroid hormone 20-hydroxyecdysone (20E is an essential signaling molecule that modulates most of the physiological functions of the larval gland. At the end of larval development, it is known that 20E--signaling through a nuclear receptor heterodimer consisting of EcR and USP--induces the early and late puffing cascade of the polytene chromosomes and causes the exocytosis of stored glue granules into the lumen of the gland. It has also been reported that an earlier pulse of hormone induces the temporally and spatially specific transcriptional activation of the glue genes; however, the receptor responsible for triggering this response has not been characterized. Here we show that the coordinated expression of the glue genes midway through the third instar is mediated by 20E acting to induce genes of the Broad Complex (BRC through a receptor that is not an EcR/USP heterodimer. This result is novel because it demonstrates for the first time that at least some 20E-mediated, mid-larval, developmental responses are controlled by an uncharacterized receptor that does not contain an RXR-like component.

  7. AMPA receptor mediated excitotoxicity in neocortical neurons is developmentally regulated and dependent upon receptor desensitization

    DEFF Research Database (Denmark)

    Jensen, J B; Schousboe, A; Pickering, D S

    1998-01-01

    with a fast and rapidly desensitizing response, this could explain the relatively low toxicity produced by 500 microM AMPA. This was investigated by blocking AMPA receptor desensitization with cyclothiazide. Using a lower concentration (25 microM) of AMPA, addition of 50 microM cyclothiazide increased...... the AMPA induced excitotoxicity in cultured cortical neurons at all DIV except for DIV 2. This combination of AMPA + cyclothiazide yielded 77% cell death for DIV 12 cultures. In contrast to the results observed with 500 microM AMPA, the neurotoxicity mediated directly by AMPA receptors when desensitization...

  8. Dynamics of Receptor-Mediated Nanoparticle Internalization into Endothelial Cells

    Science.gov (United States)

    Gonzalez-Rodriguez, David; Barakat, Abdul I.

    2015-01-01

    Nanoparticles offer a promising medical tool for targeted drug delivery, for example to treat inflamed endothelial cells during the development of atherosclerosis. To inform the design of such therapeutic strategies, we develop a computational model of nanoparticle internalization into endothelial cells, where internalization is driven by receptor-ligand binding and limited by the deformation of the cell membrane and cytoplasm. We specifically consider the case of nanoparticles targeted against ICAM-1 receptors, of relevance for treating atherosclerosis. The model computes the kinetics of the internalization process, the dynamics of binding, and the distribution of stresses exerted between the nanoparticle and the cell membrane. The model predicts the existence of an optimal nanoparticle size for fastest internalization, consistent with experimental observations, as well as the role of bond characteristics, local cell mechanical properties, and external forces in the nanoparticle internalization process. PMID:25901833

  9. Developmental endothelial locus-1 modulates platelet-monocyte interactions and instant blood-mediated inflammatory reaction in islet transplantation.

    Science.gov (United States)

    Kourtzelis, Ioannis; Kotlabova, Klara; Lim, Jong-Hyung; Mitroulis, Ioannis; Ferreira, Anaisa; Chen, Lan-Sun; Gercken, Bettina; Steffen, Anja; Kemter, Elisabeth; Klotzsche-von Ameln, Anne; Waskow, Claudia; Hosur, Kavita; Chatzigeorgiou, Antonios; Ludwig, Barbara; Wolf, Eckhard; Hajishengallis, George; Chavakis, Triantafyllos

    2016-04-01

    Platelet-monocyte interactions are strongly implicated in thrombo-inflammatory injury by actively contributing to intravascular inflammation, leukocyte recruitment to inflamed sites, and the amplification of the procoagulant response. Instant blood-mediated inflammatory reaction (IBMIR) represents thrombo-inflammatory injury elicited upon pancreatic islet transplantation (islet-Tx), thereby dramatically affecting transplant survival and function. Developmental endothelial locus-1 (Del-1) is a functionally versatile endothelial cell-derived homeostatic factor with anti-inflammatory properties, but its potential role in IBMIR has not been previously addressed. Here, we establish Del-1 as a novel inhibitor of IBMIR using a whole blood-islet model and a syngeneic murine transplantation model. Indeed, Del-1 pre-treatment of blood before addition of islets diminished coagulation activation and islet damage as assessed by C-peptide release. Consistently, intraportal islet-Tx in transgenic mice with endothelial cell-specific overexpression of Del-1 resulted in a marked decrease of monocytes and platelet-monocyte aggregates in the transplanted tissues, relative to those in wild-type recipients. Mechanistically, Del-1 decreased platelet-monocyte aggregate formation, by specifically blocking the interaction between monocyte Mac-1-integrin and platelet GPIb. Our findings reveal a hitherto unknown role of Del-1 in the regulation of platelet-monocyte interplay and the subsequent heterotypic aggregate formation in the context of IBMIR. Therefore, Del-1 may represent a novel approach to prevent or mitigate the adverse reactions mediated through thrombo-inflammatory pathways in islet-Tx and perhaps other inflammatory disorders involving platelet-leukocyte aggregate formation.

  10. Interaction and developmental activation of two neuroendocrine systems that regulate light-mediated skin pigmentation.

    Science.gov (United States)

    Bertolesi, Gabriel E; Song, Yi N; Atkinson-Leadbeater, Karen; Yang, Jung-Lynn J; McFarlane, Sarah

    2017-07-01

    Lower vertebrates use rapid light-regulated changes in skin colour for camouflage (background adaptation) or during circadian variation in irradiance levels. Two neuroendocrine systems, the eye/alpha-melanocyte-stimulating hormone (α-MSH) and the pineal complex/melatonin circuits, regulate the process through their respective dispersion and aggregation of pigment granules (melanosomes) in skin melanophores. During development, Xenopus laevis tadpoles raised on a black background or in the dark perceive less light sensed by the eye and darken in response to increased α-MSH secretion. As embryogenesis proceeds, the pineal complex/melatonin circuit becomes the dominant regulator in the dark and induces lightening of the skin of larvae. The eye/α-MSH circuit continues to mediate darkening of embryos on a black background, but we propose the circuit is shut down in complete darkness in part by melatonin acting on receptors expressed by pituitary cells to inhibit the expression of pomc, the precursor of α-MSH. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Predator mediated selection and the impact of developmental stage on viability in wood frog tadpoles (Rana sylvatica

    Directory of Open Access Journals (Sweden)

    Calsbeek Ryan

    2011-12-01

    Full Text Available Abstract Background Complex life histories require adaptation of a single organism for multiple ecological niches. Transitions between life stages, however, may expose individuals to an increased risk of mortality, as the process of metamorphosis typically includes developmental stages that function relatively poorly in both the pre- and post-metamorphic habitat. We studied predator-mediated selection on tadpoles of the wood frog, Rana sylvatica, to identify this hypothesized period of differential predation risk and estimate its ontogenetic onset. We reared tadpoles in replicated mesocosms in the presence of the larval odonate Anax junius, a known tadpole predator. Results The probability of tadpole survival increased with increasing age and size, but declined steeply at the point in development where hind limbs began to erupt from the body wall. Selection gradient analyses indicate that natural selection favored tadpoles with short, deep tail fins. Tadpoles resorb their tails as they progress toward metamorphosis, which may have led to the observed decrease in survivorship. Path models revealed that selection acted directly on tail morphology, rather than through its indirect influence on swimming performance. Conclusions This is consistent with the hypothesis that tail morphology influences predation rates by reducing the probability a predator strikes the head or body.

  12. A Bacterial Parasite Effector Mediates Insect Vector Attraction in Host Plants Independently of Developmental Changes

    Science.gov (United States)

    Orlovskis, Zigmunds; Hogenhout, Saskia A.

    2016-01-01

    Parasites can take over their hosts and trigger dramatic changes in host appearance and behavior that are typically interpreted as extended phenotypes that promote parasite survival and fitness. For example, Toxoplasma gondii is thought to manipulate the behaviors of infected rodents to aid transmission to cats and parasitic trematodes of the genus Ribeiroia alter limb development in their amphibian hosts to facilitate predation of the latter by birds. Plant parasites and pathogens also reprogram host development and morphology. However, whereas some parasite-induced morphological alterations may have a direct benefit to the fitness of the parasite and may therefore be adaptive, other host alterations may be side effects of parasite infections having no adaptive effects on parasite fitness. Phytoplasma parasites of plants often induce the development of leaf-like flowers (phyllody) in their host plants, and we previously found that the phytoplasma effector SAP54 generates these leaf-like flowers via the degradation of plant MADS-box transcription factors (MTFs), which regulate all major aspects of development in plants. Leafhoppers prefer to reproduce on phytoplasma-infected and SAP54-trangenic plants leading to the hypothesis that leafhopper vectors are attracted to plants with leaf-like flowers. Surprisingly, here we show that leafhopper attraction occurs independently of the presence of leaf-like flowers. First, the leafhoppers were also attracted to SAP54 transgenic plants without leaf-like flowers and to single leaves of these plants. Moreover, leafhoppers were not attracted to leaf-like flowers of MTF-mutant plants without the presence of SAP54. Thus, the primary role of SAP54 is to attract leafhopper vectors, which spread the phytoplasmas, and the generation of leaf-like flowers may be secondary or a side effect of the SAP54-mediated degradation of MTFs. PMID:27446117

  13. Self-objectification, weight bias internalization, and binge eating in young women: Testing a mediational model.

    Science.gov (United States)

    Mehak, Adrienne; Friedman, Aliza; Cassin, Stephanie E

    2018-03-01

    Self-objectification and weight bias internalization are two internalization processes that are positively correlated with binge eating among young women. However, the mechanisms underlying these relationships are understudied. Consistent with objectification theory, this study examined appearance anxiety and body shame as mediators between self-objectification, weight bias internalization and binge eating. Female undergraduates (N=102) completed self-report measures of self-objectification, weight bias internalization, appearance anxiety, body shame, and binge eating. Results indicated that women who self-objectified and internalized negative weight-related attitudes reported greater binge eating (r s =.43 and r s =.57, respectively) and these associations were mediated by the combined effects of body shame and appearance anxiety. The contrast between the two mediators was also significant, such that body shame emerged as a stronger mediator within both mediational models. Results demonstrated that these internalization processes contribute to negative affect in young women, which may in turn lead to binge eating. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Megalin binds and mediates cellular internalization of folate binding protein

    DEFF Research Database (Denmark)

    Birn, Henrik; Zhai, Xiaoyue; Holm, Jan

    2005-01-01

    Folate is an essential vitamin involved in a number of biological processes. High affinity folate binding proteins (FBPs) exist both as glycosylphosphatidylinositol-linked, membrane associated folate binding proteins and as soluble FBPs in plasma and some secretory fluids such as milk, saliva...... to express high levels of megalin, is inhibitable by excess unlabeled FBP and by receptor associated protein, a known inhibitor of binding to megalin. Immortalized rat yolk sac cells, representing an established model for studying megalin-mediated uptake, reveal (125)I-labeled FBP uptake which is inhibited...

  15. Attributional style as a mediator between parental abuse risk and child internalizing symptomatology.

    Science.gov (United States)

    Rodriguez, Christina M

    2006-05-01

    This study examined a model wherein children's attributional style mediates the relationship between parental physical child-abuse risk and children's internalizing problems. Using structural equation modeling, three indices of abuse risk were selected (child abuse potential, physical discipline use, and dysfunctional parenting style) and two indices of children's internalizing problems (depression and anxiety). The sample included 75 parent-child dyads, in which parents reported on their abuse risk and children independently completed measures of depressive and anxious symptomatology and a measure on their attributional style. Findings supported the model that children's attributional style for positive events (but not negative events) partially mediated the relationship between abuse risk and internalizing symptoms, with significant direct and indirect effects of abuse risk on internalizing symptomatology. Future directions to continue evaluating additional mediators and other possible contextual variables are discussed.

  16. Comparison in stress of caring mothers of children with developmental, external and internal disorders and normal children

    Directory of Open Access Journals (Sweden)

    Narges Zamani

    2017-06-01

    Full Text Available However, having a baby brings positive emotions such as happiness, sense of maturity and proud, parenting's issue could cause high level of stress and child's characteristics was a detrimental factor which can effect on parent's stress, so the aim of this research was comparison of stress of caring in mothers of children with developmental, external, and internal disorders and normal children. The study population included all mothers of children with developmental, emotional, and disruptive behavior disorders, and mothers with normal children in Hamadan (a city in Iran. 240 mothers (4 groups include 60 mothers were chosen based on simple random sampling. Family inventory of life events and changes Mc Cubbin, Patterson & Wilson was used for assessing participants. The results showed that maternal stress in mothers with children who have diagnosis of disruptive behavior disorders were significantly more than of mothers of children with developmental disorders, emotional and mothers of normal children. The present study showed that disruptive behavior disorders in children have a greater impact on their mothers. So, we suggest approved psychological interventions for helping mothers of children with psychological problems, particularly children with external disorders.

  17. Coping, perceived stress, and job satisfaction among medical interns: The mediating effect of mindfulness

    Directory of Open Access Journals (Sweden)

    M Vinothkumar

    2016-01-01

    Full Text Available Background: Past research studies on the exploration of attributes to the stress of doctors/medical interns were reported more often than the types of coping strategies, healthy practices to strengthen their internal resources to deal effectively with the stressful situations. Objectives: The present study was conducted to find such internal resource – “mindfulness” as a mediator of coping, perceived stress, and job satisfaction among medical interns. Methods: A cross-sectional descriptive study comprised 120 medical interns forms from various medical colleges in Mangalore were recruited and completed the assessment on mindfulness, cognitive-emotive regulation, coping strategies, perceived stress, and job satisfaction from doctoral interns were collected. Results: Initial correlation analysis results indicate that adaptive coping strategies significantly associate with greater mindfulness and less perceived stress. In turn, mindfulness is negatively correlated with nonadaptive coping strategies and perceived. Job satisfaction showed no significant relationship with any of the other variables. Mediational models indicate that the relationship between adaptive coping strategies and perceived stress was significantly mediated by mindfulness. Furthermore, partial mediation between nonadaptive strategies and perceived stress through mindfulness indicates that respondents reported a high level of nonadaptive strategy experience and a lower level of mindfulness can be counterproductive as they encourage the ineffective way to deal with the stresses. Conclusion: The implication of the results were discussed with suggesting a possible intervention to improve the adaptive strategies and mindfulness among the medical interns.

  18. Coping, perceived stress, and job satisfaction among medical interns: The mediating effect of mindfulness.

    Science.gov (United States)

    Vinothkumar, M; Arathi, A; Joseph, Merin; Nayana, Prasad; Jishma, E Joshy; Sahana, U

    2016-01-01

    Past research studies on the exploration of attributes to the stress of doctors/medical interns were reported more often than the types of coping strategies, healthy practices to strengthen their internal resources to deal effectively with the stressful situations. The present study was conducted to find such internal resource - "mindfulness" as a mediator of coping, perceived stress, and job satisfaction among medical interns. A cross-sectional descriptive study comprised 120 medical interns forms from various medical colleges in Mangalore were recruited and completed the assessment on mindfulness, cognitive-emotive regulation, coping strategies, perceived stress, and job satisfaction from doctoral interns were collected. Initial correlation analysis results indicate that adaptive coping strategies significantly associate with greater mindfulness and less perceived stress. In turn, mindfulness is negatively correlated with nonadaptive coping strategies and perceived. Job satisfaction showed no significant relationship with any of the other variables. Mediational models indicate that the relationship between adaptive coping strategies and perceived stress was significantly mediated by mindfulness. Furthermore, partial mediation between nonadaptive strategies and perceived stress through mindfulness indicates that respondents reported a high level of nonadaptive strategy experience and a lower level of mindfulness can be counterproductive as they encourage the ineffective way to deal with the stresses. The implication of the results were discussed with suggesting a possible intervention to improve the adaptive strategies and mindfulness among the medical interns.

  19. Conditional Mediation of Absorptive Capacity and Environment in International Entrepreneurial Orientation of Family Businesses.

    Science.gov (United States)

    Hernández-Perlines, Felipe; Xu, Wenkai

    2018-01-01

    This study analyzes the effect of conditional mediation of environment-absorptive capacity in international entrepreneurial orientation of family businesses. Results involve data from 218 Spanish family businesses, analyzed with SmartPLS 3.2.7 software. This paper presents a relevant contribution both to the academic field and the performance of family firms, helping to understand the process of transforming international entrepreneurial orientation into a better international performance through absorptive capacity while family businesses invest their efforts in aligning international entrepreneurial orientation and absorptive capacity with international results, bearing in mind the positive moderator effect of environment. The most relevant contribution of this work is to integrate in the same model the mediating effect of the absorption capacity and the moderating effect of the environment: the effect of the international entrepreneurial orientation on the international performance of family businesses improves with the mediation of the absorptive capacity (the variability of international performance goes from 32.5 to 40.6%) and the moderation of the environment (to variability of international performance goes from 40.6 to 45.3%).

  20. Role of the beta1-integrin cytoplasmic tail in mediating invasin-promoted internalization of Yersinia

    DEFF Research Database (Denmark)

    Gustavsson, Anna; Armulik, Annika; Brakebusch, Cord

    2002-01-01

    Invasin of Yersinia pseudotuberculosis binds to beta1-integrins on host cells and triggers internalization of the bacterium. To elucidate the mechanism behind the beta1-integrin-mediated internalization of Yersinia, a beta1-integrin-deficient cell line, GD25, transfected with wild-type beta1A, beta......1B or different mutants of the beta1A subunit was used. Both beta1A and beta1B bound to invasin-expressing bacteria, but only beta1A was able to mediate internalization of the bacteria. The cytoplasmic region of beta1A, differing from beta1B, contains two NPXY motifs surrounding a double threonine...... noted that cells affected in bacterial internalization exhibited reduced spreading capability when seeded onto invasin, suggesting a correlation between the internalization of invasin-expressing bacteria and invasin-induced spreading. Likewise, integrins defective in forming peripheral focal complex...

  1. 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

  2. K-Cl Cotransporter 2–mediated Cl− Extrusion Determines Developmental Stage–dependent Impact of Propofol Anesthesia on Dendritic Spines

    KAUST Repository

    Puskarjov, Martin; Fiumelli, Hubert; Briner, Adrian; Bodogan, Timea; Demeter, Kornel; Lacoh, Claudia Marvine; Mavrovic, Martina; Blaesse, Peter; Kaila, Kai; Vutskits, Laszlo

    2017-01-01

    Background: General anesthetics potentiating γ-aminobutyric acid (GABA)-mediated signaling are known to induce a persistent decrement in excitatory synapse number in the cerebral cortex when applied during early postnatal development, while an opposite action is produced at later stages. Here, the authors test the hypothesis that the effect of general anesthetics on synaptogenesis depends upon the efficacy of GABA receptor type A (GABA A)-mediated inhibition controlled by the developmental up-regulation of the potassium-chloride (K-Cl) cotransporter 2 (KCC2). Methods: In utero electroporation of KCC2 was used to prematurely increase the efficacy of (GABA A)-mediated inhibition in layer 2/3 pyramidal neurons in the immature rat somatosensory cortex. Parallel experiments with expression of the inward-rectifier potassium channel Kir2.1 were done to reduce intrinsic neuronal excitability. The effects of these genetic manipulations (n = 3 to 4 animals per experimental group) were evaluated using iontophoretic injection of Lucifer Yellow (n = 8 to 12 cells per animal). The total number of spines analyzed per group ranged between 907 and 3,371. Results: The authors found a robust effect of the developmental up-regulation of KCC2-mediated Cl - transport on the age-dependent action of propofol on dendritic spines. Premature expression of KCC2, unlike expression of a transport-inactive KCC2 variant, prevented a propofol-induced decrease in spine density. In line with a reduction in neuronal excitability, the above result was qualitatively replicated by overexpression of Kir2.1. Conclusions: The KCC2-dependent developmental increase in the efficacy of GABA A -mediated inhibition is a major determinant of the age-dependent actions of propofol on dendritic spinogenesis.

  3. K-Cl Cotransporter 2–mediated Cl− Extrusion Determines Developmental Stage–dependent Impact of Propofol Anesthesia on Dendritic Spines

    KAUST Repository

    Puskarjov, Martin

    2017-03-16

    Background: General anesthetics potentiating γ-aminobutyric acid (GABA)-mediated signaling are known to induce a persistent decrement in excitatory synapse number in the cerebral cortex when applied during early postnatal development, while an opposite action is produced at later stages. Here, the authors test the hypothesis that the effect of general anesthetics on synaptogenesis depends upon the efficacy of GABA receptor type A (GABA A)-mediated inhibition controlled by the developmental up-regulation of the potassium-chloride (K-Cl) cotransporter 2 (KCC2). Methods: In utero electroporation of KCC2 was used to prematurely increase the efficacy of (GABA A)-mediated inhibition in layer 2/3 pyramidal neurons in the immature rat somatosensory cortex. Parallel experiments with expression of the inward-rectifier potassium channel Kir2.1 were done to reduce intrinsic neuronal excitability. The effects of these genetic manipulations (n = 3 to 4 animals per experimental group) were evaluated using iontophoretic injection of Lucifer Yellow (n = 8 to 12 cells per animal). The total number of spines analyzed per group ranged between 907 and 3,371. Results: The authors found a robust effect of the developmental up-regulation of KCC2-mediated Cl - transport on the age-dependent action of propofol on dendritic spines. Premature expression of KCC2, unlike expression of a transport-inactive KCC2 variant, prevented a propofol-induced decrease in spine density. In line with a reduction in neuronal excitability, the above result was qualitatively replicated by overexpression of Kir2.1. Conclusions: The KCC2-dependent developmental increase in the efficacy of GABA A -mediated inhibition is a major determinant of the age-dependent actions of propofol on dendritic spinogenesis.

  4. Developmental Scaffolding

    DEFF Research Database (Denmark)

    Giorgi, Franco; Bruni, Luis Emilio

    2015-01-01

    . Within the developmental hierarchy, each module yields an inter-level relationship that makes it possible for the scaffolding to mediate the production of selectable variations. Awide range of genetic, cellular and morphological mechanisms allows the scaffolding to integrate these modular variations...... to the complexity of sign recognition proper of a cellular community. In this semiotic perspective, the apparent goal directness of any developmental strategy should no longer be accounted for by a predetermined genetic program, but by the gradual definition of the relationships selected amongst the ones...

  5. Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses.

    Science.gov (United States)

    Tay, Matthew Zirui; Liu, Pinghuang; Williams, LaTonya D; McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T; Dennison, S Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S Munir; Moody, M Anthony; Hope, Thomas J; Haynes, Barton F; Tomaras, Georgia D

    2016-08-01

    Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine

  6. [The Mediating Role of Parenting Self-Efficacy on Parenting Stress and Quality of Life in Parents of Young Children With Developmental Delay].

    Science.gov (United States)

    Sun, Yi; Wu, Wei-Wen; Lin, Kuan-Chia; Chen, Jo-Lin

    2016-10-01

    Previous studies indicate that parents of developmentally delayed children have higher parenting stress (PS) and lower quality of life (QoL) than parents of healthy children. Parenting self-efficacy (PSE) may mediate the effects of PS on the QoL of parents. The present study explores the mediating role of PSE between PS and the QoL of parents of developmentally delayed children and compares the differences in several variables between fathers and mothers. A cross-sectional research design was used to study a sample of 70 parent dyads. Instruments used were the Basic Information Form, Parenting Stress Index Short Form (PSI-SF), Parenting Self-efficacy Scale (PSE Scale), and World Health Organization Quality of Life-BREF Taiwan version (WHOQOL-BREF). (1) Participants had a moderate level of QoL, PS, and PSE. (2) The PS of participants was significantly and negatively correlated with both QoL and PSE while their PSE was significantly and positively correlated with QoL. (3) The PSE of the fathers completely mediated the effects of PS on their QoL (p accounting for 62.2% of observed variation, while the PSE of the mothers partially mediated the effects of PS on their QoL (p accounting for 59.5% of observed variation. PSE was identified as the mediator between PS and QoL in both fathers and mothers. The PSE of the fathers completely mediated the effect of PS on QoL, while the PSE of the mothers partially mediated the effect of PS on QoL. Further research that explores the factors that affect the QoL of parents and then uses the results to develop interventions to enhance the PSE of parents, especially fathers, is recommended.

  7. Evidence for shear stress-mediated dilation of the internal carotid artery in humans

    DEFF Research Database (Denmark)

    Carter, Howard Henry; Atkinson, Ceri L; Heinonen, Ilkka H A

    2016-01-01

    -mediated dilation of larger conduit arteries in humans. There was a strong association between change in shear and diameter of the internal carotid (r=0.68; Ptime in humans, that shear stress is an important stimulus for hypercapnic vasodilation of the internal carotid...... increases carotid shear stress, a known stimulus to vasodilation in other conduit arteries. To explore the hypothesis that shear stress contributes to hypercapnic internal carotid dilation in humans, temporal changes in internal and common carotid shear rate and diameter, along with changes in middle.......01) carotids. Diameter also increased (Ptime course is associated with shear...

  8. Abstracts of the 11th International Conference on Developmental Coordination Disorder (DCD11

    Directory of Open Access Journals (Sweden)

    DCD11 Congress Delegates

    2015-06-01

    Full Text Available CD11 – Developmental coordination disorder and other neurodevelopmental disorders: a focus on comorbidity; Toulouse, France, July 2-4, 2015 Comorbidity refers to the presence of two or more disorders in the same person (especially DCD, dyslexia and attention deficit hyperactivity disorder in terms of developmental disorders. There has been growing interest in the presence of comorbidity in persons with neurodevelopmental disorders. Many recent studies suggest that up to half of all individuals diagnosed with a psychiatric or neurodevelopmental disorder have more than one condition. Comorbidity not only impacts patient outcomes but can also create a significant strain on both family and school life. It can also complicate diagnosis and healthcare organization. The 11th congress on DCD aimed to address some of the important issues surrounding comorbidity in neurodevelopmental disorders. Three main topics were covered during oral and poster presentations: (1 assessment and diagnostic criteria, (2 underlying processes, causal factors, and prognostic markers, and (3 intervention and management of DCD and associated disorders.

  9. l-Ergothioneine improves the developmental potential of in vitro sheep embryos without influencing OCTN1-mediated cross-membrane transcript expression.

    Science.gov (United States)

    Mishra, A; Reddy, I J; Dhali, A; Javvaji, P K

    2018-04-02

    SummaryThe objective of the study was to investigate the effect of l-ergothioneine (l-erg) (5 mM or 10 mM) supplementation in maturation medium on the developmental potential and OCTN1-dependant l-erg-mediated (10 mM) change in mRNA abundance of apoptotic (Bcl2, Bax, Casp3 and PCNA) and antioxidant (GPx, SOD1, SOD2 and CAT) genes in sheep oocytes and developmental stages of embryos produced in vitro. Oocytes matured with l-erg (10 mM) reduced their embryo toxicity by decreasing intracellular ROS and increasing intracellular GSH in matured oocytes that in turn improved developmental potential, resulting in significantly (P l-erg without change in maturation rate. l-Erg (10 mM) treatment did not influence the mRNA abundance of the majority of apoptotic and antioxidant genes studied in the matured oocytes and developmental stages of embryo. A gene expression study found that the SLC22A4 gene that encodes OCTN1, an integral membrane protein and specific transporter of l-erg was not expressed in oocytes and developmental stages of embryos. Therefore it was concluded from the study that although there was improvement in the developmental potential of sheep embryos by l-erg supplementation in maturation medium, there was no change in the expression of the majority of the genes studied due to the absence of the SLC22A4 gene in oocytes and embryos that encode OCTN1, which is responsible for transportation of l-erg across the membrane to alter gene expression.

  10. Potential pest transfer mediated by international ornamental plant trade.

    Science.gov (United States)

    Patoka, Jiří; Bláha, Martin; Kalous, Lukáš; Vrabec, Vladimír; Buřič, Miloš; Kouba, Antonín

    2016-05-25

    In recent years, the keeping of ornamental freshwater animals and plants in garden ponds has been growing in popularity. Water hyacinth (Eichhornia crassipes) is one of the preferred macrophytes seasonally imported mainly from South-eastern Asia throughout the world. This constitutes a secondary introduction inasmuch as the species is native to South America. Although many assemblages of aquatic invertebrates have been described as associated with this plant in the wild, there has been no research focused on their potential introduction via the international plant trade. We examined 216 specimens of water hyacinths imported for ornamental purposes from Indonesia into the Czech Republic. Numerous meio- and macroinvertebrates belonging to at least 39 species were captured. On the total number of individuals, the highest prevalence was of Tubulinea and Rotifera. Most of these were still alive and vital, including a caterpillar of the Indo-Australian invasive moth Spodoptera litura. Water hyacinths are usually placed into outdoor ponds immediately after import, which facilitates the release of non-target alien species. The present paper aims to draw attention to "hitchhikers" associated with the ornamental trade.

  11. The role of empowerment in youth development: a study of sociopolitical control as mediator of ecological systems' influence on developmental outcomes.

    Science.gov (United States)

    Christens, Brian D; Peterson, N Andrew

    2012-05-01

    Empowerment has become an influential concept and theoretical framework for social policy and practice. Still, relatively little is known about the roles that empowerment plays in the ecology of human development, particularly among young people. This article reports results of a study of psychological empowerment among young people, using data from 629 high school students (65.8% female; 96.5% non-white). Using a path analysis, we examined the role of perceived sociopolitical control--an indicator of the intrapersonal component of psychological empowerment--as a mediator between ecological support systems and developmental outcomes. Findings confirmed that social support in family, peer, and school settings, and family cohesion positively predict self-esteem and perceived school importance, which, in turn, have protective effects on psychological symptoms, violent behaviors and substance use. Sociopolitical control was found to mediate the relationships between ecological supports and risk factors and developmental outcomes, leading to the conclusion that perceived efficacy in the sociopolitical domain, and youth empowerment, more generally, should be considered as core elements of the ecology of human development. Policy and practice aimed at promoting positive developmental outcomes and preventing risk behaviors should take their relationship to sociopolitical control into account.

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

    Science.gov (United States)

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

    2014-01-01

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

  13. Styles of International Mediation in Peace Processes Between States and Terrorist Organizations

    Science.gov (United States)

    2016-06-01

    NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS Approved for public release; distribution is unlimited STYLES OF...Office of Management and Budget, Paperwork Reduction Project (0704-0188) Washington, DC 20503. 1. AGENCY USE ONLY (Leave blank) 2. REPORT DATE...June 2016 3. REPORT TYPE AND DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE STYLES OF INTERNATIONAL MEDIATION IN PEACE PROCESSES BETWEEN

  14. Interpersonal Mediators Linking Acculturation Stressors to Subsequent Internalizing Symptoms and Self-Esteem in Latino Adolescents

    Science.gov (United States)

    Smokowski, Paul Richard; Bacallao, Martica; Buchanan, Rachel Lee

    2009-01-01

    The specific aim of this study was to examine pathways leading to internalizing symptoms and self-esteem in Latino adolescents. Adolescent feelings of interpersonal humiliation, family conflict and commitment, and friendships with peers were investigated as potential mediators linking acculturation stress to subsequent adolescent self-esteem and…

  15. Maternal Warmth and Early Adolescents' Internalizing Symptoms and Externalizing Behavior: Mediation via Emotional Insecurity

    Science.gov (United States)

    Alegre, Albert; Benson, Mark J.; Pérez-Escoda, Núria

    2014-01-01

    This study examines the relation between maternal warmth and the internalizing and externalizing problems of early adolescents, and the potential mediation of this relation by emotional insecurity. The hypotheses for the study derive from Cummings and Davies' theory of emotional security. The current study extends the theory to security processes…

  16. Mediators of the Associations between Externalizing Behaviors and Internalizing Symptoms in Late Childhood and Early Adolescence

    Science.gov (United States)

    Yong, Minglee; Fleming, Charles B.; McCarty, Carolyn A.; Catalano, Richard F.

    2014-01-01

    This study tests the predictive associations between externalizing behaviors and internalizing symptoms and examines the mediating roles of social competence, parent-child conflicts, and academic achievement. Using youth-, parent-, and teacher-reported longitudinal data on a sample of 523 boys and 460 girls from late childhood to early…

  17. Peer Relationships and Internalizing Problems in Adolescents: Mediating Role of Self-Esteem

    Science.gov (United States)

    Bosacki, Sandra; Dane, Andrew; Marini, Zopito

    2007-01-01

    This study examined whether self-esteem mediated the association between peer relationships and internalizing problems (i.e., depression and social anxiety). A total of 7290 (3756 girls) adolescents (ages 13-18 years) completed self-report measures of peer relationships, including direct and indirect victimization, social isolation, friendship…

  18. Meeting report on the 3rd International Congress on Developmental Origins of Health and Disease (DOHaD).

    Science.gov (United States)

    Gillman, Matthew W; Barker, David; Bier, Dennis; Cagampang, Felino; Challis, John; Fall, Caroline; Godfrey, Keith; Gluckman, Peter; Hanson, Mark; Kuh, Diana; Nathanielsz, Peter; Nestel, Penelope; Thornburg, Kent L

    2007-05-01

    Developmental origins of health and disease (DOHaD) focuses on the earliest stages of human development, and provides a novel paradigm to complement other strategies for lifelong prevention of common chronic health conditions. The 3 International Congress on DOHaD, held in 2005, retained the most popular features from the first two biannual Congresses, while adding a number of innovations, including increased emphasis on implications of DOHaD for the developing world; programs for trainees and young investigators; and new perspectives, including developmental plasticity, influences of social hierarchies, effects of prematurity, and populations in transition. Emerging areas of science included, first, the controversial role of infant weight gain in predicting adult obesity, diabetes, and cardiovascular disease. Second, in the era of epidemic obesity, paying attention to the over-nourished fetus is as important as investigating the growth retarded one. Third, environmental toxins appear to have abroad range of long-lasting effects on the developing human. Fourth, epigenetic mechanisms could unite several strands of human and animal observations, and explain how genetically identical individuals raised in similar postnatal environments can nonetheless develop widely differing phenotypes. Improving the environment to which an individual is exposed during development may be as important as any other public health effort to enhance population health world wide.

  19. From Discrimination to Internalized Mental Illness Stigma: The Mediating Roles of Anticipated Discrimination and Anticipated Stigma

    Science.gov (United States)

    Quinn, Diane M.; Williams, Michelle K.; Weisz, Bradley M.

    2015-01-01

    Objective Internalizing mental illness stigma is related to poorer well-being, but less is known about the factors that predict levels of internalized stigma. This study explored how experiences of discrimination relate to greater anticipation of discrimination and devaluation in the future, and how anticipation of stigma, in turn predicts greater stigma internalization. Method Participants were 105 adults with mental illness who self-reported their experiences of discrimination based on their mental illness, their anticipation of discrimination and social devaluation from others in the future, and their level of internalized stigma. Participants were approached in several locations and completed surveys on laptop computers. Results Correlational analyses indicated that more experiences of discrimination due to one’s mental illness were related to increased anticipated discrimination in the future, increased anticipated social stigma from others, and greater internalized stigma. Multiple serial mediator analyses showed that the effect of experiences of discrimination on internalized stigma was fully mediated by increased anticipated discrimination and anticipated stigma. Conclusion and Implications for Practice Experiences of discrimination over the lifetime may influence not only how much future discrimination people with mental illness are concerned with but also how much they internalize negative feelings about the self. Mental health professionals may need to address concerns with future discrimination and devaluation in order to decrease internalized stigma. PMID:25844910

  20. From discrimination to internalized mental illness stigma: The mediating roles of anticipated discrimination and anticipated stigma.

    Science.gov (United States)

    Quinn, Diane M; Williams, Michelle K; Weisz, Bradley M

    2015-06-01

    Internalizing mental illness stigma is related to poorer well-being, but less is known about the factors that predict levels of internalized stigma. This study explored how experiences of discrimination relate to greater anticipation of discrimination and devaluation in the future and how anticipation of stigma in turn predicts greater stigma internalization. Participants were 105 adults with mental illness who self-reported their experiences of discrimination based on their mental illness, their anticipation of discrimination and social devaluation from others in the future, and their level of internalized stigma. Participants were approached in several locations and completed surveys on laptop computers. Correlational analyses indicated that more experiences of discrimination due to one's mental illness were related to increased anticipated discrimination in the future, increased anticipated social stigma from others, and greater internalized stigma. Multiple serial mediator analyses showed that the effect of experiences of discrimination on internalized stigma was fully mediated by increased anticipated discrimination and anticipated stigma. Experiences of discrimination over one's lifetime may influence not only how much future discrimination people with mental illness are concerned with but also how much they internalize negative feelings about the self. Mental health professionals may need to address concerns with future discrimination and devaluation in order to decrease internalized stigma. (c) 2015 APA, all rights reserved).

  1. Parental discipline behaviours and beliefs about their child: associations with child internalizing and mediation relationships.

    Science.gov (United States)

    Laskey, B J; Cartwright-Hatton, S

    2009-09-01

    Internalizing disorders of childhood are a common and disabling problem, with sufferers at increased risk of subsequent psychiatric morbidity. Several studies have found associations between parenting styles and children's internalizing, although few have considered the role of parental discipline. Parental discipline style may exert an effect on children's internalizing symptoms. Anxiety and depression are reliably found to run in families and parental anxiety has been shown to effect parenting behaviour. This study set out to examine the links between parental anxiety, parental discipline style and child internalizing symptoms. Eighty-eight parents of children aged 4-10 years were recruited through primary schools. All parents completed questionnaires including measures relating to: adult anxiety (State-Trait Anxiety Inventory - Trait version, Penn State Worry Questionnaire), parental depression (Beck Depression Inventory - Fastscreen), parental discipline (The Parenting Scale), parenting-related attributions (Parenting Attitudes, Beliefs and Cognitions Scale) and child psychological morbidity (Child Behaviour Checklist 4-18 version). Significant correlations were found between both parental anxiety and child internalizing symptoms with ineffective discipline and negative beliefs about parenting. Particularly strong correlations were found between parental anxiety and child internalizing symptoms with harsh discipline. Parents of anxious/withdrawn children were more likely to hold negative beliefs about their child. The link between parental anxiety and child internalizing symptoms was mediated by harsh discipline. The link between parental anxiety and harsh discipline was mediated by parental beliefs about the child. Discipline style may be an important factor in the relationship between parent anxiety and child internalizing symptoms.

  2. Social Support as a Mediator between Internalized Stigma and Coping Behaviors of Individuals with Substance Abuse Issues

    Science.gov (United States)

    Chou, Chih-Chin; Robb, Jayci Lynn; Clay, Matthew Christopher; Chronister, Julie Ann

    2013-01-01

    In this study, 51 individuals from online substance abuse support groups were surveyed to investigate the mediating role of social support on the relationship between internalized stigma and coping. Regression and bootstrapping were conducted to perform mediation analysis. Findings suggest that social support mediates the negative impact of…

  3. Charting the Road to Competence: Developmental Milestones for Internal Medicine Residency Training

    Science.gov (United States)

    Green, Michael L.; Aagaard, Eva M.; Caverzagie, Kelly J.; Chick, Davoren A.; Holmboe, Eric; Kane, Gregory; Smith, Cynthia D.; Iobst, William

    2009-01-01

    Background The Accreditation Council for Graduate Medical Education (ACGME) Outcome Project requires that residency program directors objectively document that their residents achieve competence in 6 general dimensions of practice. Intervention In November 2007, the American Board of Internal Medicine (ABIM) and the ACGME initiated the development of milestones for internal medicine residency training. ABIM and ACGME convened a 33-member milestones task force made up of program directors, experts in evaluation and quality, and representatives of internal medicine stakeholder organizations. This article reports on the development process and the resulting list of proposed milestones for each ACGME competency. Outcomes The task force adopted the Dreyfus model of skill acquisition as a framework the internal medicine milestones, and calibrated the milestones with the expectation that residents achieve, at a minimum, the “competency” level in the 5-step progression by the completion of residency. The task force also developed general recommendations for strategies to evaluate the milestones. Discussion The milestones resulting from this effort will promote competency-based resident education in internal medicine, and will allow program directors to track the progress of residents and inform decisions regarding promotion and readiness for independent practice. In addition, the milestones may guide curriculum development, suggest specific assessment strategies, provide benchmarks for resident self-directed assessment-seeking, and assist remediation by facilitating identification of specific deficits. Finally, by making explicit the profession's expectations for graduates and providing a degree of national standardization in evaluation, the milestones may improve public accountability for residency training. PMID:21975701

  4. Internalized Transphobia, Resilience, and Mental Health: Applying the Psychological Mediation Framework to Italian Transgender Individuals

    Directory of Open Access Journals (Sweden)

    Cristiano Scandurra

    2018-03-01

    Full Text Available Transgender and gender nonconforming (TGNC people are a highly-stigmatized population. For this reason, they might internalize society’s normative gender attitudes and develop negative mental health outcomes. As an extension of the minority stress model, the psychological mediation framework sheds light on psychological processes through which anti-transgender discrimination might affect mental health. Within this framework, the current study aimed at assessing in 149 TGNC Italian individuals the role of internalized transphobia as a mediator between anti-transgender discrimination and mental health, considering resilience as the individual-level coping mechanism buffering this relationship. The results suggest that both indicators of internalized transphobia (i.e., shame and alienation mediate the relationship between anti-transgender discrimination and depression, while only alienation mediates the relationship between anti-transgender discrimination and anxiety. Furthermore, the results suggest that the indirect relation between anti-transgender discrimination and anxiety through alienation is conditional on low and moderate levels of resilience. Findings have important implications for clinical practice and psycho-social interventions to reduce stigma and stress caused by interpersonal and individual stigma.

  5. Internalized Transphobia, Resilience, and Mental Health: Applying the Psychological Mediation Framework to Italian Transgender Individuals

    Science.gov (United States)

    Bochicchio, Vincenzo; Amodeo, Anna Lisa; Esposito, Concetta; Valerio, Paolo; Maldonato, Nelson Mauro; Bacchini, Dario; Vitelli, Roberto

    2018-01-01

    Transgender and gender nonconforming (TGNC) people are a highly-stigmatized population. For this reason, they might internalize society’s normative gender attitudes and develop negative mental health outcomes. As an extension of the minority stress model, the psychological mediation framework sheds light on psychological processes through which anti-transgender discrimination might affect mental health. Within this framework, the current study aimed at assessing in 149 TGNC Italian individuals the role of internalized transphobia as a mediator between anti-transgender discrimination and mental health, considering resilience as the individual-level coping mechanism buffering this relationship. The results suggest that both indicators of internalized transphobia (i.e., shame and alienation) mediate the relationship between anti-transgender discrimination and depression, while only alienation mediates the relationship between anti-transgender discrimination and anxiety. Furthermore, the results suggest that the indirect relation between anti-transgender discrimination and anxiety through alienation is conditional on low and moderate levels of resilience. Findings have important implications for clinical practice and psycho-social interventions to reduce stigma and stress caused by interpersonal and individual stigma. PMID:29534023

  6. Developmental and Behavioral Performance of Internationally Adopted Preschoolers: A Pilot Study

    Science.gov (United States)

    Jacobs, Emma; Miller, Laurie C.; Tirella, Linda G.

    2010-01-01

    Most international adoptees (IA) have rapid catch-up of the delays common at arrival. However, it is not known whether development at arrival predicts later abilities or school readiness. Therefore, we comprehensively evaluated language, fine motor, visual reception (VR), executive function (EF), attention (ATT), and sensory skills (SS) in IA…

  7. Receptor-mediated internalization of [3H]-neurotensin in synaptosomal preparations from rat neostriatum.

    Science.gov (United States)

    Nguyen, Ha Minh Ky; Cahill, Catherine M; McPherson, Peter S; Beaudet, Alain

    2002-06-01

    Following its binding to somatodendritic receptors, the neuropeptide neurotensin (NT) internalizes via a clathrin-mediated process. In the present study, we investigated whether NT also internalizes presynaptically using synaptosomes from rat neostriatum, a region in which NT1 receptors are virtually all presynaptic. Binding of [(3)H]-NT to striatal synaptosomes in the presence of levocabastine to block NT2 receptors is specific, saturable, and has NT1 binding properties. A significant fraction of the bound radioactivity is resistant to hypertonic acid wash indicating that it is internalized. Internalization of [(3)H]-NT, like that of [(125)I]-transferrin, is blocked by sucrose and low temperature, consistent with endocytosis occurring via a clathrin-dependent pathway. However, contrary to what was reported at the somatodendritic level, neither [(3)H]-NT nor [(125)I]-transferrin internalization in synaptosomes is sensitive to the endocytosis inhibitor phenylarsine oxide. Moreover, treatment of synaptosomes with monensin, which prevents internalized receptors from recycling to the plasma membrane, reduces [(3)H]-NT binding and internalization, suggesting that presynaptic NT1 receptors, in contrast to somatodendritic ones, are recycled back to the plasma membrane. Taken together, these results suggest that NT internalizes in nerve terminals via an endocytic pathway that is related to, but is mechanistically distinct from that responsible for NT internalization in nerve cell bodies.

  8. Attention to Language in Day Care Attending Children: A Mediating Factor in the Developmental Effects of Otitis Media.

    Science.gov (United States)

    Feagans, Lynne V.; And Others

    Three ways in which otitis media may affect development of hearing are explored. First, developmental effects may be due to illness in general; second, otitis media may cause fluctuating hearing loss which may lead to deficits in language in many areas; and, third, fluctuating hearing loss may have only a temporary effect on the acquisition of…

  9. Executive Functioning Mediates the Effect of Behavioral Problems on Depression in Mothers of Children with Developmental Disabilities

    Science.gov (United States)

    Chan, Wai; Smith, Leann E.; Greenberg, Jan S.; Hong, Jinkuk; Mailick, Marsha R.

    2017-01-01

    The present investigation explored long-term relationships of behavioral symptoms of adolescents and adults with developmental disabilities with the mental health of their mothers. Fragile X premutation carrier mothers of an adolescent or adult child with fragile X syndrome (n = 95), and mothers of a grown child with autism (n = 213) were…

  10. Locus of Control Fails to Mediate between Stress and Anxiety and Depression in Parents of Children with a Developmental Disorder

    Science.gov (United States)

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

    2007-01-01

    Stress, anxiety and depression are raised amongst parents of children with a developmental disorder. However, the processes by which stress leads to depression and anxiety are poorly understood. In a cross-sectional survey, levels of parental stress, depression and anxiety were compared between parents of children with an autistic disorder,…

  11. Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates later-life Notch1-mediated T cell development and leukemogenesis

    International Nuclear Information System (INIS)

    Ahrenhoerster, Lori S.; Leuthner, Tess C.; Tate, Everett R.; Lakatos, Peter A.; Laiosa, Michael D.

    2015-01-01

    Over half of T cell acute lymphoblastic leukemia (T-ALL) patients have activating mutations in the Notch gene. Moreover, the contaminant 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is a known carcinogen that mediates its toxicity through the aryl hydrocarbon receptor (AHR), and crosstalk between activated AHR and Notch signaling pathways has previously been observed. Given the importance of Notch signaling in thymocyte development and T-ALL disease progression, we hypothesized that the activated AHR potentiates disease initiation and progression in an in vivo model of Notch1-induced thymoma. This hypothesis was tested utilizing adult and developmental exposure paradigms to TCDD in mice expressing a constitutively active Notch1 transgene (Notch ICN-TG ). Following exposure of adult Notch ICN-TG mice to a single high dose of TCDD, we observed a significant increase in the efficiency of CD8 thymocyte generation. We next exposed pregnant mice to 3 μg/kg of TCDD throughout gestation and lactation to elucidate effects of developmental AHR activation on later-life T cell development and T-ALL-like thymoma susceptibility induced by Notch1. We found that the vehicle-exposed Notch ICN-TG offspring have a peripheral T cell pool heavily biased toward the CD4 lineage, while TCDD-exposed Notch ICN-TG offspring were biased toward the CD8 lineage. Furthermore, while the vehicle-exposed NotchICN-TG mice showed increased splenomegaly and B to T cell ratios indicative of disease, mice developmentally exposed to TCDD were largely protected from disease. These studies support a model where developmental AHR activation attenuates later-life Notch1-dependent impacts on thymocyte development and disease progression. - Highlights: • Adult mice exposed to 30 μg/kg TCDD have higher efficiency of CD8 thymocyte generation. • Mice carrying a constitutively active Notch transgene were exposed to 3 μg/kg TCDD throughout development. • Progression of Notch-induced thymoma was different in

  12. Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates later-life Notch1-mediated T cell development and leukemogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ahrenhoerster, Lori S.; Leuthner, Tess C.; Tate, Everett R.; Lakatos, Peter A.; Laiosa, Michael D., E-mail: laiosa@uwm.edu

    2015-03-01

    Over half of T cell acute lymphoblastic leukemia (T-ALL) patients have activating mutations in the Notch gene. Moreover, the contaminant 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is a known carcinogen that mediates its toxicity through the aryl hydrocarbon receptor (AHR), and crosstalk between activated AHR and Notch signaling pathways has previously been observed. Given the importance of Notch signaling in thymocyte development and T-ALL disease progression, we hypothesized that the activated AHR potentiates disease initiation and progression in an in vivo model of Notch1-induced thymoma. This hypothesis was tested utilizing adult and developmental exposure paradigms to TCDD in mice expressing a constitutively active Notch1 transgene (Notch{sup ICN-TG}). Following exposure of adult Notch{sup ICN-TG} mice to a single high dose of TCDD, we observed a significant increase in the efficiency of CD8 thymocyte generation. We next exposed pregnant mice to 3 μg/kg of TCDD throughout gestation and lactation to elucidate effects of developmental AHR activation on later-life T cell development and T-ALL-like thymoma susceptibility induced by Notch1. We found that the vehicle-exposed Notch{sup ICN-TG} offspring have a peripheral T cell pool heavily biased toward the CD4 lineage, while TCDD-exposed Notch{sup ICN-TG} offspring were biased toward the CD8 lineage. Furthermore, while the vehicle-exposed NotchICN-TG mice showed increased splenomegaly and B to T cell ratios indicative of disease, mice developmentally exposed to TCDD were largely protected from disease. These studies support a model where developmental AHR activation attenuates later-life Notch1-dependent impacts on thymocyte development and disease progression. - Highlights: • Adult mice exposed to 30 μg/kg TCDD have higher efficiency of CD8 thymocyte generation. • Mice carrying a constitutively active Notch transgene were exposed to 3 μg/kg TCDD throughout development. • Progression of Notch

  13. Crosslinguistic Developmental Consistency in the Composition of Toddlers’ Internal State Vocabulary: Evidence from Four Languages

    Directory of Open Access Journals (Sweden)

    Susanne Kristen

    2014-01-01

    Full Text Available Mental state language, emerging in the second and third years of life in typically developing children, is one of the first signs of an explicit psychological understanding. While mental state vocabulary may serve a variety of conversational functions in discourse and thus might not always indicate psychological comprehension, there is evidence for genuine references to mental states (desires, knowledge, beliefs, and emotions early in development across languages. This present study presents parental questionnaire data on the composition of 297 toddler-aged (30-to 32-month-olds children’s internal state vocabulary in four languages: Italian, German, English, and French. The results demonstrated that across languages expressions for physiological states (e.g., hungry and tired were among the most varied, while children’s vocabulary for cognitive entities (e.g., know and think proved to be least varied. Further, consistent with studies on children’s comprehension of these concepts, across languages children’s mastery of volition terms (e.g., like to do and want preceded their mastery of cognition terms. These findings confirm the cross-linguistic consistency of children’s emerging expression of abstract psychological concepts.

  14. Gender nonconformity and mental health among lesbian, gay, and bisexual adults: Homophobic stigmatization and internalized homophobia as mediators.

    Science.gov (United States)

    Van Beusekom, Gabriël; Bos, Henny Mw; Kuyper, Lisette; Overbeek, Geertjan; Sandfort, Theo Gm

    2016-04-01

    We assessed among a sample of 724 Dutch lesbian, gay, and bisexual-identified adults ( M age  = 31.42) whether experiences with homophobic stigmatization and internalized homophobia simultaneously mediated the relation of gender nonconformity with mental health. Results indicated that homophobic stigmatization and internalized homophobia partially mediated the relation between gender nonconformity and mental health. Gender nonconformity was related to more mental health problems via increased experiences with homophobic stigmatization and to less mental health problems because of reduced levels of internalized homophobia. However, the mediated relation of gender nonconformity with mental health via homophobic stigmatization was only significant for men.

  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. COPING AS A MEDIATOR OF INTERNALIZED HOMOPHOBIA AND PSYCHOLOGICAL DISTRESS AMONG YOUNG ADULT SEXUAL MINORITY WOMEN.

    Science.gov (United States)

    Kaysen, Debra; Kulesza, Magdalena; Balsam, Kimberly F; Rhew, Isaac C; Blayney, Jessica A; Lehavot, Keren; Hughes, Tonda L

    2014-09-01

    Sexual minorities have higher rates of depression and anxiety than their heterosexual counterparts. This elevated risk of psychological distress has generally been hypothesized to be a result of the effects of discrimination including internalized negative beliefs about sexual minorities. However, little research has examined the role of various types of coping in mediating between internalized homophobia and mental health. We tested the direct relationship between internalized homophobia and psychological distress and evaluated general and sexual minority-specific coping strategies as potential mediators using structural equation modeling. Data are from a national sample of 1,099 young adult sexual minority women who were on average 20.86 ( SD = 2.12) years old, participating in a study on mental health and substance use. The model demonstrated acceptable fit, χ 2 (83) = 402.9, p homophobia and psychological distress, sexual minority-specific coping did not. Our findings support previous studies that have demonstrated the impact of internalized homophobia on psychological distress as well as the role of coping as a protective/risk factor in this relationship.

  17. The peer review process for awarding funds to international science research consortia: a qualitative developmental evaluation.

    Science.gov (United States)

    Gregorius, Stefanie; Dean, Laura; Cole, Donald C; Bates, Imelda

    2017-01-01

    Background:  Evaluating applications for multi-national, multi-disciplinary, dual-purpose research consortia is highly complex. There has been little research on the peer review process for evaluating grant applications and almost none on how applications for multi-national consortia are reviewed. Overseas development investments are increasingly being channelled into international science consortia to generate high-quality research while simultaneously strengthening multi-disciplinary research capacity. We need a better understanding of how such decisions are made and their effectiveness. Methods:  An award-making institution planned to fund 10 UK-Africa research consortia. Over two annual rounds, 34 out of 78 eligible applications were shortlisted and reviewed by at least five external reviewers before final selections were made by a face-to-face panel. We used an innovative approach involving structured, overt observations of award-making panel meetings and semi-structured interviews with panel members to explore how assessment criteria concerning research quality and capacity strengthening were applied during the peer review process. Data were coded and analysed using pre-designed matrices which incorporated categories relating to the assessment criteria. Results:  In general the process was rigorous and well-managed. However, lack of clarity about differential weighting of criteria and variations in the panel's understanding of research capacity strengthening resulted in some inconsistencies in use of the assessment criteria. Using the same panel for both rounds had advantages, in that during the second round consensus was achieved more quickly and the panel had increased focus on development aspects. Conclusion:  Grant assessment panels for such complex research applications need to have topic- and context-specific expertise. They must also understand research capacity issues and have a flexible but equitable and transparent approach. This study has

  18. Health-related quality of life in fathers of children with or without developmental disability: the mediating effect of parental stress.

    Science.gov (United States)

    Huang, Yu-Ping; Chang, Ming-yuh; Chi, Yu-Lin; Lai, Fei-Chen

    2014-02-01

    The aims of this study were to compare parental stress and health-related quality of life (HRQOL) between Taiwanese fathers of children with and without developmental disabilities (DDs) and to examine the mediating effect of parental stress on the association between having a child with DD and paternal HRQOL within Chinese culture. This cross-sectional, prospective, unmatched case-control study included 206 fathers of children with DDs and 207 fathers of healthy children. HRQOL was assessed by the SF-36 short-form questionnaire, and parental stress was assessed by the Chinese version Parental Stress Scale. Fathers of children with DDs experienced poorer mental and physical HRQOL and higher parental stress than fathers of healthy children. Parental stress acted as a complete mediator for paternal physical HRQOL, while parental stress had a partial mediating effect on the relationship between having a child with DD and paternal mental HRQOL. Having a child with DD also directly affected paternal mental HRQOL. Fathers of children with DDs should be monitored for parental stress and HRQOL, and interventions should be provided to empower them with the knowledge and skills to reduce their stress and to enhance their HRQOL.

  19. International Mediation and Negotiating Positions of Cyprus' Regional Conflict After the 1974 Turkish Invasion. Obstacles and Prospects to a Settlement

    National Research Council Canada - National Science Library

    Alexopoulos, Konstantinos

    2000-01-01

    ... communities on the island have played serious roles in the maintenance of the conflict. The thesis illustrates the weakness of the international mediation effort and the obstacles to a settlement...

  20. Internal ribosomal entry site-mediated translation is important for rhythmic PERIOD1 expression.

    Directory of Open Access Journals (Sweden)

    Kyung-Ha Lee

    Full Text Available The mouse PERIOD1 (mPER1 plays an important role in the maintenance of circadian rhythm. Translation of mPer1 is directed by both a cap-dependent process and cap-independent translation mediated by an internal ribosomal entry site (IRES in the 5' untranslated region (UTR. Here, we compared mPer1 IRES activity with other cellular IRESs. We also found critical region in mPer1 5'UTR for heterogeneous nuclear ribonucleoprotein Q (HNRNPQ binding. Deletion of HNRNPQ binding region markedly decreased IRES activity and disrupted rhythmicity. A mathematical model also suggests that rhythmic IRES-dependent translation is a key process in mPER1 oscillation. The IRES-mediated translation of mPer1 will help define the post-transcriptional regulation of the core clock genes.

  1. Hypoxia Decreases Invasin-Mediated Yersinia enterocolitica Internalization into Caco-2 Cells.

    Science.gov (United States)

    Zeitouni, Nathalie E; Dersch, Petra; Naim, Hassan Y; von Köckritz-Blickwede, Maren

    2016-01-01

    Yersinia enterocolitica is a major cause of human yersiniosis, with enterocolitis being a typical manifestation. These bacteria can cross the intestinal mucosa, and invade eukaryotic cells by binding to host β1 integrins, a process mediated by the bacterial effector protein invasin. This study examines the role of hypoxia on the internalization of Y. enterocolitica into intestinal epithelial cells, since the gastrointestinal tract has been shown to be physiologically deficient in oxygen levels (hypoxic), especially in cases of infection and inflammation. We show that hypoxic pre-incubation of Caco-2 cells resulted in significantly decreased bacterial internalization compared to cells grown under normoxia. This phenotype was absent after functionally blocking host β1 integrins as well as upon infection with an invasin-deficient Y. enterocolitica strain. Furthermore, downstream phosphorylation of the focal adhesion kinase was also reduced under hypoxia after infection. In good correlation to these data, cells grown under hypoxia showed decreased protein levels of β1 integrins at the apical cell surface whereas the total protein level of the hypoxia inducible factor (HIF-1) alpha was elevated. Furthermore, treatment of cells with the HIF-1 α stabilizer dimethyloxalylglycine (DMOG) also reduced invasion and decreased β1 integrin protein levels compared to control cells, indicating a potential role for HIF-1α in this process. These results suggest that hypoxia decreases invasin-integrin-mediated internalization of Y. enterocolitica into intestinal epithelial cells by reducing cell surface localization of host β1 integrins.

  2. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

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

  3. Board members’ contribution to strategy: The mediating role of board internal processes

    Directory of Open Access Journals (Sweden)

    Carmen Barroso-Castro

    2017-05-01

    Full Text Available This study aims to explore what directors do on the board, to what extent the processes occurring in the board allow the sharing and integrating of the existing knowledge, thus facilitating the board members’ contributions to strategy. We adopt the view that the internal board processes increase the impact of the cognitive resources on board performance. Using survey data from 200 large Spanish companies we demonstrate that directors’ level of knowledge of the firm and board job-related diversity positively influence the degree of the board's strategic involvement. Additionally, the internal processes that take place within the board – particularly Cognitive Conflict, the Critical and Independent Approach and the Comprehensive Discussion Process – influence the board's strategic involvement and play a partial mediating role on the aforementioned relationships. However, our results show no evidence for a positive relationship between Board Meeting Dynamics and the board's strategic involvement.

  4. Shear-mediated dilation of the internal carotid artery occurs independent of hypercapnia

    DEFF Research Database (Denmark)

    Hoiland, Ryan L; Smith, Kurt J; Carter, Howard Henry

    2017-01-01

    preceded increases in diameter in both transient (time: 16.8 ± 13.2 vs. 59.4 ± 60.3 s, P time: 18.2 ± 14.2 vs. 110.3 ± 79.6 s, P dilation was positively correlated with shear rate area under the curve in the transient (r2 = 0.44, P ...Evidence for shear stress as a regulator of carotid artery dilation in response to increased arterial CO2 was recently demonstrated in humans during sustained elevations in CO2 (hypercapnia); however, the relative contributions of CO2 and shear stress to this response remains unclear. We examined...... the hypothesis that, after a 30-s transient increase in arterial CO2 tension and consequent increase in internal carotid artery shear stress, internal carotid artery diameter would increase, indicating shear-mediated dilation, in the absence of concurrent hypercapnia. In 27 healthy participants, partial...

  5. Amphetamine activates Rho GTPase signaling to mediate dopamine transporter internalization and acute behavioral effects of amphetamine

    Science.gov (United States)

    Wheeler, David S.; Underhill, Suzanne M.; Stolz, Donna B.; Murdoch, Geoffrey H.; Thiels, Edda; Romero, Guillermo; Amara, Susan G.

    2015-01-01

    Acute amphetamine (AMPH) exposure elevates extracellular dopamine through a variety of mechanisms that include inhibition of dopamine reuptake, depletion of vesicular stores, and facilitation of dopamine efflux across the plasma membrane. Recent work has shown that the DAT substrate AMPH, unlike cocaine and other nontransported blockers, can also stimulate endocytosis of the plasma membrane dopamine transporter (DAT). Here, we show that when AMPH enters the cytoplasm it rapidly stimulates DAT internalization through a dynamin-dependent, clathrin-independent process. This effect, which can be observed in transfected cells, cultured dopamine neurons, and midbrain slices, is mediated by activation of the small GTPase RhoA. Inhibition of RhoA activity with C3 exotoxin or a dominant-negative RhoA blocks AMPH-induced DAT internalization. These actions depend on AMPH entry into the cell and are blocked by the DAT inhibitor cocaine. AMPH also stimulates cAMP accumulation and PKA-dependent inactivation of RhoA, thus providing a mechanism whereby PKA- and RhoA-dependent signaling pathways can interact to regulate the timing and robustness of AMPH’s effects on DAT internalization. Consistent with this model, the activation of D1/D5 receptors that couple to PKA in dopamine neurons antagonizes RhoA activation, DAT internalization, and hyperlocomotion observed in mice after AMPH treatment. These observations support the existence of an unanticipated intracellular target that mediates the effects of AMPH on RhoA and cAMP signaling and suggest new pathways to target to disrupt AMPH action. PMID:26553986

  6. Using Peer-Mediated Literacy-Based Behavioral Interventions to Increase First Aid Safety Skills in Students With Developmental Disabilities.

    Science.gov (United States)

    Kearney, Kelly B; Brady, Michael P; Hall, Kalynn; Honsberger, Toby

    2017-08-01

    Many adolescents with developmental disabilities do not learn the safety skills needed to maintain physical well-being in domestic and community environments. Literacy-based behavioral interventions (LBBIs) that combine print, pictures, and behavioral rehearsal are effective for promoting acquisition and maintenance of self-care skills, but have not been investigated as safety skill intervention. Also, LBBIs have primarily been implemented by teachers and other professionals. In this study, a peer partner was taught to deliver an LBBI story to students so they would learn to perform a basic first aid routine: cleaning and dressing a wound. Results showed that students' accuracy with the first aid routine increased after a peer delivered the LBBI instructional package, and maintained after the peer stopped delivering it. This study demonstrates the effectiveness of the LBBI instructional package for teaching first aid safety skills, and extends previous research showing the efficacy of peers in delivering this intervention.

  7. Relative political and value proximity in mediated public diplomacy: The effect of state-level homophily on international frame building

    NARCIS (Netherlands)

    Sheafer, T.; Shenhav, S.R.; Takens, J.H.; van Atteveldt, W.H.

    2014-01-01

    This article applies the homophily thesis to public diplomacy and offers an empirical examination of a country's success in its mediated public diplomacy efforts. It analyzes international frame building, the process of creating or changing media frames in the international communications arena, by

  8. B Cell Receptor-Mediated Internalization of Salmonella: A Novel Pathway for Autonomous B Cell Activation and Antibody Production

    NARCIS (Netherlands)

    Souwer, Yuri; Griekspoor, Alexander; Jorritsma, Tineke; de Wit, Jelle; Janssen, Hans; Neefjes, Jacques; van Ham, S. Marieke

    2009-01-01

    The present paradigm is that primary B cells are nonphagocytosing cells. In this study, we demonstrate that human primary B cells are able to internalize bacteria when the bacteria are recognized by the BCR. BCR-mediated internalization of Salmonella typhimurium results in B cell differentiation and

  9. Chinese International Students' Social Connectedness, Social and Academic Adaptation: The Mediating Role of Global Competence

    Science.gov (United States)

    Meng, Qian; Zhu, Chang; Cao, Chun

    2018-01-01

    This study examined global competence of Chinese international students sojourning in a non-Anglophone European country as a mediator between foreign language proficiency (i.e., English and local language) and social and academic adaptation, and social connectedness in international community. A sample of 206 Chinese students in Belgium responded…

  10. Internalized stigma and quality of life domains among people with mental illness: the mediating role of self-esteem.

    Science.gov (United States)

    Oliveira, Sandra E H; Carvalho, Helena; Esteves, Francisco

    2016-01-01

    People with mental illness who internalize stigma often experience reduced self-esteem and impaired quality of life (QOL). To propose a theoretical model in which self-esteem mediates the effects of internalized stigma on the multidimensional domains comprising QOL. In 403 inpatients and outpatients (DSM-IV, American Psychiatric Association, 1994), from hospital-based and community mental health facilities, self-report measures of internalized stigma (ISMI), self-esteem (RSES) and QOL (WHOQOL-Bref) were administrated. Structural equation modeling results supported the proposed model. Self-esteem fully mediated the relation between internalized stigma and the physical and the social relationships domains, and partially mediated the relationship between internalized stigma and psychological, environment and level of independence QOL domains. Such results provided empirical support and shed light upon previous research. Specifically the results emphasize the mediating role that self-esteem plays in the degree to which internalized stigma exerts a negative effect on specific QOL domains. Self-esteem appears to be a core element in reducing the negative effects of internalized stigma on aspects of QOL among people with mental illness. These findings suggest there is a crucial impact regarding clinical mental health interventions along with important theoretical implications.

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

    Science.gov (United States)

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

    2016-07-01

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

  12. Quality of life among adolescents with sickle cell disease: Mediation of pain by internalizing symptoms and parenting stress

    Directory of Open Access Journals (Sweden)

    Daniel Lauren C

    2008-08-01

    Full Text Available Abstract Background This study aimed to clarify associations between pain, psychological adjustment, and family functioning with health-related quality of life (HRQOL in a sample of adolescents with sickle cell disease (SCD utilizing teen- and parent-report. Methods Forty-two adolescents (between the ages of 12 and 18 with SCD and their primary caregivers completed paper-and-pencil measures of pain, teen's psychological adjustment, and HRQOL. In addition, primary caregivers completed a measure of disease-related parenting stress. Medical file review established disease severity. Results Pearson correlations identified significant inverse associations of pain frequency with physical and psychosocial domains of HRQOL as rated by the teen and primary caregiver. Generally, internalizing symptoms (i.e. anxiety and depression and disease-related parenting stress were also significantly correlated with lower HRQOL. Examination of possible mediator models via a series of regression analyses confirmed that disease-related parenting stress served as a mediator between pain frequency and physical and psychosocial HRQOL. Less consistent were findings for mediation models involving internalizing symptoms. For these, parent-rated teen depression and teen anxiety served as mediators of the association of pain frequency and HRQOL. Conclusion Results are consistent with extant literature that suggests the association of pain and HRQOL and identify concomitant pain variables of internalizing symptoms and family variables as mediators. Efforts to improve HRQOL should aim to address internalizing symptoms associated with pain as well as parenting stress in the context of SCD management.

  13. Intelligence Tests with Higher G-Loadings Show Higher Correlations with Body Symmetry: Evidence for a General Fitness Factor Mediated by Developmental Stability

    Science.gov (United States)

    Prokosch, M.D.; Yeo, R.A.; Miller, G.F.

    2005-01-01

    Just as body symmetry reveals developmental stability at the morphological level, general intelligence may reveal developmental stability at the level of brain development and cognitive functioning. These two forms of developmental stability may overlap by tapping into a ''general fitness factor.'' If so, then intellectual tests with higher…

  14. Multilevel risk factors and developmental assets for internalizing symptoms and self-esteem in disadvantaged adolescents: modeling longitudinal trajectories from the Rural Adaptation Project.

    Science.gov (United States)

    Smokowski, Paul R; Guo, Shenyang; Rose, Roderick; Evans, Caroline B R; Cotter, Katie L; Bacallao, Martica

    2014-11-01

    The current study filled significant gaps in our knowledge of developmental psychopathology by examining the influence of multilevel risk factors and developmental assets on longitudinal trajectories of internalizing symptoms and self-esteem in an exceptionally culturally diverse sample of rural adolescents. Integrating ecological and social capital theories, we explored if positive microsystem transactions are associated with self-esteem while negative microsystem transactions increase the chances of internalizing problems. Data came from the Rural Adaptation Project, a 5-year longitudinal panel study of more than 4,000 middle school students from 28 public schools in two rural, disadvantaged counties in North Carolina. Three-level hierarchical linear modeling models were estimated to predict internalizing symptoms (e.g., depression, anxiety) and self-esteem. Relative to other students, risk for internalizing problems and low self-esteem was elevated for aggressive adolescents, students who were hassled or bullied at school, and those who were rejected by peers or in conflict with their parents. Internalizing problems were also more common among adolescents from socioeconomically disadvantaged families and neighborhoods, among those in schools with more suspensions, in students who reported being pressured by peers, and in youth who required more teacher support. It is likely that these experiences left adolescents disengaged from developing social capital from ecological microsystems (e.g., family, school, peers). On the positive side, support from parents and friends and optimism about the future were key assets associated with lower internalizing symptoms and higher self-esteem. Self-esteem was also positively related to religious orientation, school satisfaction, and future optimism. These variables show active engagement with ecological microsystems. The implications and limitations were discussed.

  15. Parental bonds and body dissatisfaction in a clinical sample: The mediating roles of attachment anxiety and media internalization.

    Science.gov (United States)

    Grenon, Renee; Tasca, Giorgio A; Maxwell, Hilary; Balfour, Louise; Proulx, Genevieve; Bissada, Hany

    2016-12-01

    We evaluated an attachment theory model in which mother and father care were hypothesized to be indirectly related to body dissatisfaction mediated by attachment anxiety and media internalization. Participants were 232 women diagnosed with an eating disorder who completed a retrospective measure of parental bonds, and measures of attachment anxiety, media internalization, and body image. Mother care was negatively associated with body dissatisfaction, suggesting that recollection of mothers as less caring was directly related to poorer body image. Lower father care, was indirectly associated with greater body dissatisfaction mediated by higher attachment anxiety and higher media internalization. That is, women with an eating disorder who recollected fathers as less caring had higher attachment anxiety, which was related to greater internalizing of media-related thin ideals, that in turn was associated with poorer body image. Mothers and fathers may impact body dissatisfaction by differing mechanisms in clinical samples. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. The Mediation Effects of Dysfunctional Beliefs and Emotional Regulation on Children's Perceived Parental Conflict and Internalizing and Externalizing Problems

    Science.gov (United States)

    Lee, Ji-yeon; Wesbecher, Kristen; Lee, Mihwa; Lee, Jeeyon

    2015-01-01

    The purpose of this study was to examine the mediational effects of dysfunctional beliefs and difficulties in emotional regulation on children's perception of interparental conflict and subsequent internalizing and externalizing problems. The participants in this study were 335 fifth grade elementary school students in Korea. We hypothesized that…

  17. Big Five Personality Traits and Eating Attitudes in Intensively Training Dancers: The Mediating Role of Internalized Thinness Norms

    Directory of Open Access Journals (Sweden)

    Stéphanie Scoffier-Mériaux, Charlène Falzon, Peter Lewton-Brain, Edith Filaire, Fabienne d’Arripe-Longueville

    2015-09-01

    Full Text Available Dancers are at high risk of developing disordered eating attitudes, notably because of internalized thinness norms. Although the big five personality traits have been shown to be associated with eating attitudes in daily life, in dancers where eating issues and thinness norms internalization could be salient little is known about these associations and the role of the internalization of thinness norms in this relationship. The main objectives of this study were thus to examine the relationships between the personality traits defined in the big five model and the self-regulation of eating attitudes, and to assess the role of internalized thinness norms in this association. The study included 180 intensively training dancers with an average age of 15.6 years (SD = 2.8. Dancers completed questionnaires measuring the big five personality traits, internalization of thinness norms and self-regulation of eating attitudes in sport. Bootstrapped mediation analyses showed that neuroticism was negatively associated with self-regulation of eating attitudes, both directly and indirectly through the mediating role of internalized thinness norms. This study suggested that: (a neuroticism is a vulnerability factor for self-regulation of eating attitudes in dancers, as already evidenced in the general population, and (b the internalization of thinness norms is a pathway through which neuroticism affects self-regulation of eating attitudes. The big five model is therefore partially related to the internalization of thinness norms and eating attitudes in dancers.

  18. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui [Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang (China); Teng, Weiping, E-mail: twpendocrine@yahoo.com.cn [Liaoning Provincial Key Laboratory of Endocrine Diseases, the First Hospital of China Medical University, Shenyang (China); Chen, Jie, E-mail: chenjie@mail.cmu.edu.cn [Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang (China)

    2013-09-01

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  19. Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

    International Nuclear Information System (INIS)

    Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui; Teng, Weiping; Chen, Jie

    2013-01-01

    Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

  20. Causal Mediation in Educational Research: An Illustration Using International Assessment Data

    Science.gov (United States)

    Caro, Daniel H.

    2015-01-01

    This paper applies the causal mediation framework proposed by Kosuke Imai and colleagues (Imai, Keele, & Tingley, 2010) to educational research by examining the causal mediating role of early literacy activities in parental education influences on reading performance. The paper argues that the study of causal mediation is particularly relevant…

  1. Regulated internalization of NMDA receptors drives PKD1-mediated suppression of the activity of residual cell-surface NMDA receptors.

    Science.gov (United States)

    Fang, Xiao-Qian; Qiao, Haifa; Groveman, Bradley R; Feng, Shuang; Pflueger, Melissa; Xin, Wen-Kuan; Ali, Mohammad K; Lin, Shuang-Xiu; Xu, Jindong; Duclot, Florian; Kabbaj, Mohamed; Wang, Wei; Ding, Xin-Sheng; Santiago-Sim, Teresa; Jiang, Xing-Hong; Salter, Michael W; Yu, Xian-Min

    2015-11-19

    Constitutive and regulated internalization of cell surface proteins has been extensively investigated. The regulated internalization has been characterized as a principal mechanism for removing cell-surface receptors from the plasma membrane, and signaling to downstream targets of receptors. However, so far it is still not known whether the functional properties of remaining (non-internalized) receptor/channels may be regulated by internalization of the same class of receptor/channels. The N-methyl-D-aspartate receptor (NMDAR) is a principal subtype of glutamate-gated ion channel and plays key roles in neuronal plasticity and memory functions. NMDARs are well-known to undergo two types of regulated internalization - homologous and heterologous, which can be induced by high NMDA/glycine and DHPG, respectively. In the present work, we investigated effects of regulated NMDAR internalization on the activity of residual cell-surface NMDARs and neuronal functions. In electrophysiological experiments we discovered that the regulated internalization of NMDARs not only reduced the number of cell surface NMDARs but also caused an inhibition of the activity of remaining (non-internalized) surface NMDARs. In biochemical experiments we identified that this functional inhibition of remaining surface NMDARs was mediated by increased serine phosphorylation of surface NMDARs, resulting from the activation of protein kinase D1 (PKD1). Knockdown of PKD1 did not affect NMDAR internalization but prevented the phosphorylation and inhibition of remaining surface NMDARs and NMDAR-mediated synaptic functions. These data demonstrate a novel concept that regulated internalization of cell surface NMDARs not only reduces the number of NMDARs on the cell surface but also causes an inhibition of the activity of remaining surface NMDARs through intracellular signaling pathway(s). Furthermore, modulating the activity of remaining surface receptors may be an effective approach for treating receptor

  2. Low functional programming of renal AT{sub 2}R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

    Energy Technology Data Exchange (ETDEWEB)

    Ao, Ying [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071 (China); Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Li, Bin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Yang, Shuailong; Xia, Liping; Wu, Yong [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Wang, Linlong [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); He, Zheng [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071 (China)

    2015-09-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT{sub 2}R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT{sub 1a}R)/AT{sub 2}R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT{sub 2}R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT{sub 2}R might mediate the developmental origin of adult glomerulosclerosis. - Highlights: • Prenatal caffeine exposure induces glomerulosclerosis in adult offspring. • Prenatal caffeine

  3. Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

    International Nuclear Information System (INIS)

    Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

    2015-01-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT 2 R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT 1a R)/AT 2 R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT 2 R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT 2 R might mediate the developmental origin of adult glomerulosclerosis. - Highlights: • Prenatal caffeine exposure induces glomerulosclerosis in adult offspring. • Prenatal caffeine exposure inhibits

  4. Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure.

    Science.gov (United States)

    Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

    2015-09-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT2R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT1aR)/AT2R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT2R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT2R might mediate the developmental origin of adult glomerulosclerosis. Copyright © 2015. Published by Elsevier Inc.

  5. Internalized weight bias mediates the relationship between depressive symptoms and disordered eating behavior among women who think they are overweight.

    Science.gov (United States)

    Sienko, Rachel M; Saules, Karen K; Carr, Meagan M

    2016-08-01

    This study tested the potential mediating role of Internalized Weight Bias (IWB) in the relationship between depressive symptoms (DEP-SX) and disordered eating behavior. In particular, we hypothesized that IWB may be an intervening variable in the well documented association between depression and disordered eating. College women (N=172) who were taking undergraduate psychology courses and who endorsed thinking they were overweight completed the Patient Health Questionnaire depression screener (PHQ-9), the Weight Bias Internalization Scale (WBIS), and the Eating Disorder Examination Questionnaire (EDE-Q). Bootstrapping mediation analyses were conducted to explore the relationships between these variables. IWB was significantly correlated with eating disorder symptoms and DEP-SX, but not Body Mass Index. Mediation analyses supported a model in which IWB mediated the relationship between DEP-SX and disordered eating behavior. Results indicate that individuals with elevated DEP-SX may be likely to internalize weight bias, which may in turn lead to maladaptive approaches to eating and weight control, regardless of one's actual weight status. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Testing inferences in developmental evolution: the forensic evidence principle.

    Science.gov (United States)

    Larsson, Hans C E; Wagner, Günter P

    2012-09-01

    Developmental evolution (DE) examines the influence of developmental mechanisms on biological evolution. Here we consider the question: "what is the evidence that allows us to decide whether a certain developmental scenario for an evolutionary change is in fact "correct" or at least falsifiable?" We argue that the comparative method linked with what we call the "forensic evidence principle" (FEP) is sufficient to conduct rigorous tests of DE scenarios. The FEP states that different genetically mediated developmental causes of an evolutionary transformation will leave different signatures in the development of the derived character. Although similar inference rules have been used in practically every empirical science, we expand this approach here in two ways: (1) we justify the validity of this principle with reference to a well-known result from mathematical physics, known as the symmetry principle, and (2) propose a specific form of the FEP for DE: given two or more developmental explanations for a certain evolutionary event, say an evolutionary novelty, then the evidence discriminating between these hypotheses will be found in the most proximal internal drivers of the derived character. Hence, a detailed description of the ancestral and derived states, and their most proximal developmental drivers are necessary to discriminate between various evolutionary developmental hypotheses. We discuss how this stepwise order of testing is necessary, establishes a formal test, and how skipping this order of examination may violate a more accurate examination of DE. We illustrate the approach with an example from avian digit evolution. © 2012 Wiley Periodicals, Inc.

  7. Big Five Personality Traits and Eating Attitudes in Intensively Training Dancers: The Mediating Role of Internalized Thinness Norms.

    Science.gov (United States)

    Scoffier-Mériaux, Stéphanie; Falzon, Charlène; Lewton-Brain, Peter; Filaire, Edith; d'Arripe-Longueville, Fabienne

    2015-09-01

    Dancers are at high risk of developing disordered eating attitudes, notably because of internalized thinness norms. Although the big five personality traits have been shown to be associated with eating attitudes in daily life, in dancers where eating issues and thinness norms internalization could be salient little is known about these associations and the role of the internalization of thinness norms in this relationship. The main objectives of this study were thus to examine the relationships between the personality traits defined in the big five model and the self-regulation of eating attitudes, and to assess the role of internalized thinness norms in this association. The study included 180 intensively training dancers with an average age of 15.6 years (SD = 2.8). Dancers completed questionnaires measuring the big five personality traits, internalization of thinness norms and self-regulation of eating attitudes in sport. Bootstrapped mediation analyses showed that neuroticism was negatively associated with self-regulation of eating attitudes, both directly and indirectly through the mediating role of internalized thinness norms. This study suggested that: (a) neuroticism is a vulnerability factor for self-regulation of eating attitudes in dancers, as already evidenced in the general population, and (b) the internalization of thinness norms is a pathway through which neuroticism affects self-regulation of eating attitudes. The big five model is therefore partially related to the internalization of thinness norms and eating attitudes in dancers. Key pointsThe big five model relates to the internalization of thinness norms and eating attitudes in dancers.Neuroticism is negatively related to the self-regulation of eating attitudes.The internalization of thinness norms is correlated to the relationship between neuroticism and self-regulation of eating attitudes.

  8. 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

  9. A La autoantigen homologue is required for the internal ribosome entry site mediated translation of giardiavirus.

    Directory of Open Access Journals (Sweden)

    Srinivas Garlapati

    2011-03-01

    Full Text Available Translation of Giardiavirus (GLV mRNA is initiated at an internal ribosome entry site (IRES in the viral transcript. The IRES localizes to a downstream portion of 5' untranslated region (UTR and a part of the early downstream coding region of the transcript. Recent studies indicated that the IRES does not require a pre-initiation complex to initiate translation but may directly recruit the small ribosome subunit with the help of a number of trans-activating protein factors. A La autoantigen homologue in the viral host Giardia lamblia, GlLa, was proposed as one of the potential trans-activating factors based on its specific binding to GLV-IRES in vitro. In this study, we further elucidated the functional role of GlLa in GLV-IRES mediated translation in Giardia by knocking down GlLa with antisense morpholino oligo, which resulted in a reduction of GLV-IRES activity by 40%. An over-expression of GlLa in Giardia moderately stimulated GLV-IRES activity by 20%. A yeast inhibitory RNA (IRNA, known to bind mammalian and yeast La autoantigen and inhibit Poliovirus and Hepatitis C virus IRES activities in vitro and in vivo, was also found to bind to GlLa protein in vitro and inhibited GLV-IRES function in vivo. The C-terminal domain of La autoantigen interferes with the dimerization of La and inhibits its function. An over-expression of the C-terminal domain (200-348aa of GlLa in Giardia showed a dominant-negative effect on GLV-IRES activity, suggesting a potential inhibition of GlLa dimerization. HA tagged GlLa protein was detected mainly in the cytoplasm of Giardia, thus supporting a primary role of GlLa in translation initiation in Giardiavirus.

  10. 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...

  11. Role of Host Type IA Phosphoinositide 3-Kinase Pathway Components in Invasin-Mediated Internalization of Yersinia enterocolitica.

    Science.gov (United States)

    Dowd, Georgina C; Bhalla, Manmeet; Kean, Bernard; Thomas, Rowan; Ireton, Keith

    2016-06-01

    Many bacterial pathogens subvert mammalian type IA phosphoinositide 3-kinase (PI3K) in order to induce their internalization into host cells. How PI3K promotes internalization is not well understood. Also unclear is whether type IA PI3K affects different pathogens through similar or distinct mechanisms. Here, we performed an RNA interference (RNAi)-based screen to identify components of the type IA PI3K pathway involved in invasin-mediated entry of Yersinia enterocolitica, an enteropathogen that causes enteritis and lymphadenitis. The 69 genes targeted encode known upstream regulators or downstream effectors of PI3K. A similar RNAi screen was previously performed with the food-borne bacterium Listeria monocytogenes The results of the screen with Y. enterocolitica indicate that at least nine members of the PI3K pathway are needed for invasin-mediated entry. Several of these proteins, including centaurin-α1, Dock180, focal adhesion kinase (FAK), Grp1, LL5α, LL5β, and PLD2 (phospholipase D2), were recruited to sites of entry. In addition, centaurin-α1, FAK, PLD2, and mTOR were required for remodeling of the actin cytoskeleton during entry. Six of the human proteins affecting invasin-dependent internalization also promote InlB-mediated entry of L. monocytogenes Our results identify several host proteins that mediate invasin-induced effects on the actin cytoskeleton and indicate that a subset of PI3K pathway components promote internalization of both Y. enterocolitica and L. monocytogenes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  12. Disentangling the Sleep-Pain Relationship in Pediatric Chronic Pain: The Mediating Role of Internalizing Mental Health Symptoms

    Directory of Open Access Journals (Sweden)

    Maria Pavlova

    2017-01-01

    Full Text Available Background. Pediatric chronic pain often emerges in adolescence and cooccurs with internalizing mental health issues and sleep impairments. Emerging evidence suggests that sleep problems may precede the onset of chronic pain as well as anxiety and depression. Studies conducted in pediatric populations with pain-related chronic illnesses suggest that internalizing mental health symptoms may mediate the sleep-pain relationship; however, this has not been examined in youth with primary pain disorders. Objective. To examine whether anxiety and depressive symptoms mediated relationships between sleep quality and pain outcomes among youth with chronic pain. Methods. Participants included 147 youth (66.7% female aged 8–18 years who were referred to a tertiary-level chronic pain program. At intake, the youth completed psychometrically sound measures of sleep quality, pain intensity, pain interference, and anxiety and depressive symptoms. Results. As hypothesized, poor sleep quality was associated with increased pain intensity and pain interference, and anxiety and depressive symptoms mediated these sleep-pain relationships. Discussion. For youth with chronic pain, poor sleep quality may worsen pain through alterations in mood and anxiety; however, prospective research using objective measures is needed. Future research should examine whether targeting sleep and internalizing mental health symptoms in treatments improve pain outcomes in these youth.

  13. Sociopolitical analysis of the role of mediating of international organizations in conflicts at Burundi and Uganda

    Directory of Open Access Journals (Sweden)

    Alexandre Cesar Cunha Leite

    2016-06-01

    Full Text Available This article aims to discuss the effectiveness of the mediator role of the United Nations and the African Union on conflict resolution in the cases of Burundi and Uganda. The argument is that this mediating role influenced considerably in the negotiations since it realized a ceasefire in hostilities between the warring parties and the establishment of more significant agreements on pending issues. For this discussion, we attempted to describe the processes of successful mediation in recent decades in Africa, based on the cases as mentioned above, whose similar methods of resolution could achieve positive results. Finally, we evaluated the effectiveness of UN mediator in the field of maintenance and promotion of peace, emphasizing their strategies on reducing violence on the ground and in the protection of civilians.

  14. Internal wave-mediated shading causes frequent vertical migrations in fishes

    KAUST Repository

    Kaartvedt, Stein; Klevjer, TA; Aksnes, Dag L.

    2012-01-01

    We provide evidence that internal waves cause frequent vertical migrations (FVM) in fishes. Acoustic data from the Benguela Current revealed that pelagic scattering layers of fish below ~140 m moved in opposite phases to internal waves, ascending

  15. A new adjustable parallel drill guide for internal fixation of femoral neck fracture: a developmental and experimental study

    OpenAIRE

    Yuenyongviwat, Varah; Tuntarattanapong, Pakjai; Tangtrakulwanich, Boonsin

    2016-01-01

    Background Internal fixation is one treatment for femoral neck fracture. Some devices and techniques reported improved accuracy and decreased fluoroscopic time. However, these are not widely used nowadays due to the lack of available special instruments and techniques. To improve the surgical procedure, the authors designed a new adjustable drill guide and tested the efficacy of the device. Methods The authors developed a new adjustable drill guide for cannulated screw guide wire insertion fo...

  16. “Intellectual developmental disorders”: reflections on the international consensus document for redefining “mental retardation-intellectual disability” in ICD-11

    Science.gov (United States)

    Bertelli, Marco O.; Munir, Kerim; Harris, James; Salvador-Carulla, Luis

    2016-01-01

    Purpose The debate as to whether intellectual disability (ID) should be conceptualized as a health condition or as a disability has intensified as the revision of World Health Organization’s (WHO’s) International Classification of Diseases (ICD) is being finalized. Defining ID as a health condition is central to retaining it in ICD, with significant implications for health policy and access to health services. The purpose of this paper is to include some reflections on the consensus document produced by the first WHO Working Group on the Classification of MR (WHO WG-MR) and on the process that was followed to realize it. The consensus report was the basis for the development of official recommendations sent to the WHO Advisory Group for ICD-11. Design/methodology/approach A mixed qualitative approach was followed in a series of meetings leading to the final consensus report submitted to the WHO Advisory group. These recommendations combined prior expert knowledge with available evidence; a nominal approach was followed throughout with face-to-face conferences. Findings The WG recommended a synonym set (“synset”) ontological approach to the conceptualisation of this health condition underlying a clinical rationale for its diagnosis. It proposed replacing MR with Intellectual Developmental Disorders (IDD) in ICD-11, defined as “a group of developmental conditions characterized by a significant impairment of cognitive functions, which are associated with limitations of learning, adaptive behaviour and skills”. The WG further advised that IDD be included under the parent category of neurodevelopmental disorders, that current distinctions (mild, moderate, severe and profound) be continued as severity qualifiers, and that problem behaviours removed from its core classification structure and instead described as associated features. Originality/value Within the ID/IDD synset two different names combine distinct aspects under a single construct that describes

  17. Male Asian international students' perceived racial discrimination, masculine identity, and subjective masculinity stress: a moderated mediation model.

    Science.gov (United States)

    Wong, Y Joel; Tsai, Pei-Chun; Liu, Tao; Zhu, Qingqing; Wei, Meifen

    2014-10-01

    This study examined male Asian international college students' perceptions of racial discrimination, subjective masculinity stress, centrality of masculine identity, and psychological distress by testing a moderated mediation model. Participants were 160 male Asian international college students from 2 large public universities. Participants' perceived racial discrimination was positively related to their subjective masculinity stress only at high (but not low) levels of masculine identity centrality. Additionally, subjective masculinity stress was positively related to psychological distress, although this association was stronger among those who reported high levels of masculine identity centrality. The authors also detected a moderated mediation effect in which subjective masculinity stress mediated the relationship between perceived racial discrimination and psychological distress only at high (but not low) levels of masculine identity centrality. These findings contribute to the counseling psychology literature by highlighting the connections between race- and gender-related stressors as well as the relevance of masculine identity to an understanding of men's mental health. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  18. On the integration developmental characteristics as a form of international policy in the context of modern globalization processes

    Directory of Open Access Journals (Sweden)

    Bostan Sergii Ivanovich

    2014-12-01

    Full Text Available Under globalization of the world community, there are new opportunities and potential threats to the current system of international relations, collective security and geopolitical development of different regions. Integration and regionalization, consolidation and separatism entered upon the agenda of the political present. The integration process becomes one of the variations of peaceful and mutually beneficial solution to the question of the globalization influence of uneven development of the world regions, the fight against global problems of humanity, discrimination and intolerance, spread the values of democracy, rights, freedom and equality.

  19. Internalization as a mediator of the relationship between conformity to masculine norms and body image attitudes and behaviors among young men in Sweden, US, UK, and Australia.

    Science.gov (United States)

    Franko, Debra L; Fuller-Tyszkiewicz, Matthew; Rodgers, Rachel F; Holmqvist Gattario, Kristina; Frisén, Ann; Diedrichs, Phillippa C; Ricciardelli, Lina A; Yager, Zali; Smolak, Linda; Thompson-Brenner, Heather; Shingleton, Rebecca M

    2015-09-01

    We examined whether internalization of sociocultural body ideals mediated the relationship between conformity to masculine norms and drive for muscularity, leanness, and thinness in a sample of males from Sweden, US, UK, and Australia. Over six hundred young men [n=142 (Sweden); n=192 (US); n=141 (UK); n=160 (Australia)] completed an online survey that included assessments of masculine role norms, body image, and internalization of sociocultural body ideals. Path analyses confirmed internalization as a mediator between greater conformity to masculine norms and body image measures (drive for thinness, desire for leanness, and desire for muscularity) across the sample. However, significant cross-country differences in the strength of these mediation effects were found. Mediation effects among US, Australian, and Swedish males were comparable, whereas these effects were weaker in the UK sample. Findings confirmed the importance of internalization of sociocultural body ideals in the tested models. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Family income, parental education and internalizing and externalizing psychopathology among 2-3-year-old Chinese children: the mediator effect of parent-child conflict.

    Science.gov (United States)

    Zhang, Xiao

    2014-02-01

    Using a sample of 156 Chinese children aged 2-3 years and their parents, this study examined the effects of socio-economic status, specifically family income and parental education, on the children's internalizing and externalizing psychopathology and whether these effects were mediated by mother-child and father-child conflict. Results indicated that family income, maternal education and paternal education all negatively predicted externalizing symptoms. Income also negatively predicted internalizing symptoms among boys but not girls. Maternal education negatively predicted internalizing symptoms among girls but not boys. The effects of income on psychopathology were fully mediated by mother-child and father-child conflict. In contrast, the effects of education were not mediated or only partially mediated by conflict. Findings are discussed in the framework of the family stress model. © 2013 International Union of Psychological Science.

  1. Identification, characterization and developmental expression of Halloween genes encoding P450 enzymes mediating ecdysone biosynthesis in the tobacco hornworm, Manduca sexta

    DEFF Research Database (Denmark)

    Rewitz, Kim; Rybczynski, Robert; Warren, James T.

    2006-01-01

    this work to the tobacco hornworm Manduca sexta, an established model for endocrinological and developmental studies. cDNA clones were obtained for three Manduca orthologs of CYP306A1 (phantom; phm, the 25-hydroxylase), CYP302A1 (disembodied; dib, the 22-hydroxylase) and CYP315A1 (shadow; sad, the 2...... in the developmentally varying steroidogenic capacities of the prothoracic glands during the fifth instar. The consistent expression of the Halloween genes confirms the importance of the prothoracic glands in pupal-adult development. These studies establish Manduca as an excellent model for examining the regulation...

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

    Science.gov (United States)

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

    2014-10-01

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

  3. IGF-1 deficiency in a critical period early in life influences the vascular aging phenotype in mice by altering miRNA-mediated post-transcriptional gene regulation: implications for the developmental origins of health and disease hypothesis.

    Science.gov (United States)

    Tarantini, Stefano; Giles, Cory B; Wren, Jonathan D; Ashpole, Nicole M; Valcarcel-Ares, M Noa; Wei, Jeanne Y; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna

    2016-08-01

    Epidemiological findings support the concept of Developmental Origins of Health and Disease, suggesting that early-life hormonal influences during a sensitive period of development have a fundamental impact on vascular health later in life. The endocrine changes that occur during development are highly conserved across mammalian species and include dramatic increases in circulating IGF-1 levels during adolescence. The present study was designed to characterize the effect of developmental IGF-1 deficiency on the vascular aging phenotype. To achieve that goal, early-onset endocrine IGF-1 deficiency was induced in mice by knockdown of IGF-1 in the liver using Cre-lox technology (Igf1 f/f mice crossed with mice expressing albumin-driven Cre recombinase). This model exhibits low-circulating IGF-1 levels during the peripubertal phase of development, which is critical for the biology of aging. Due to the emergence of miRNAs as important regulators of the vascular aging phenotype, the effect of early-life IGF-1 deficiency on miRNA expression profile in the aorta was examined in animals at 27 months of age. We found that developmental IGF-1 deficiency elicits persisting late-life changes in miRNA expression in the vasculature, which significantly differed from those in mice with adult-onset IGF-1 deficiency (TBG-Cre-AAV8-mediated knockdown of IGF-1 at 5 month of age in Igf1 f/f mice). Using a novel computational approach, we identified miRNA target genes that are co-expressed with IGF-1 and associate with aging and vascular pathophysiology. We found that among the predicted targets, the expression of multiple extracellular matrix-related genes, including collagen-encoding genes, were downregulated in mice with developmental IGF-1 deficiency. Collectively, IGF-1 deficiency during a critical period during early in life results in persistent changes in post-transcriptional miRNA-mediated control of genes critical targets for vascular health, which likely contribute to the

  4. Mediators for internalizing problems in adolescents of parents with chronic medical condition

    NARCIS (Netherlands)

    Sieh, D.S.; Oort, F.J.; Visser-Meily, J.M.A.; Meijer, A.M.

    2014-01-01

    Parents’ chronic medical condition (CMC) is related to internalizing problem behavior in adolescents. Following the transactional stress and coping (TSC) model of Hocking and Lochman, our study examines whether the effect of illness and demographic parameters on the child’s internalizing problems is

  5. The Effect of Internal Marketing on Organizational Commitment: Job Involvement and Job Satisfaction as Mediators

    Science.gov (United States)

    Ting, Shueh-Chin

    2011-01-01

    Purpose: After reviewing previous research, this study found that few school or educational studies have simultaneously explored both internal marketing and organizational commitment, and of those that have, only direct effects were examined. This study clarifies the relationship between school organization's internal marketing and teachers'…

  6. Internalized Homophobia as a Partial Mediator between Homophobic Bullying and Self-Esteem among Sexual Minority Youths in Quebec (Canada)

    Science.gov (United States)

    Blais, Martin; Gervais, Jesse; Hébert, Martine

    2016-01-01

    Verbal/psychological homophobic bullying is widespread among sexual minority youths. Homophobic bullying has been associated with both high internalized homophobia and low self-esteem. The objectives were to document verbal/psychological homophobic bullying among sexual minority youths and to model the relationships between homophobic bullying, internalized homophobia and self-esteem. Method: A community sample of 300 sexual minority youths aged 14 to 22 years old was used. A structural equations model was tested using a nonlinear, robust estimator implemented in Mplus. The model postulated that homophobic bullying impacts self-esteem both directly and indirectly, via internalized homophobia. Results: 60.7% of the sample reported at least on form of verbal/psychological homophobic bullying. The model explained 29% of the variance of self-esteem, 19.6% of the variance of internalized homophobia and 5.3% of the verbal/psychological homophobic bullying. The model suggests that the relationship between verbal/psychological homophobic bullying and self-esteem is partially mediated by internalized homophobia. Conclusion: Our results underscore the importance of initiatives to prevent homophobic bullying in order to prevent its negative effects on well-being of sexual minority youths. PMID:24714888

  7. Cryptococcus neoformans Is Internalized by Receptor-Mediated or ‘Triggered’ Phagocytosis, Dependent on Actin Recruitment

    Science.gov (United States)

    Guerra, Caroline Rezende; Seabra, Sergio Henrique; de Souza, Wanderley; Rozental, Sonia

    2014-01-01

    Cryptococcosis by the encapsulated yeast Cryptococcus neoformans affects mostly immunocompromised individuals and is a frequent neurological complication in AIDS patients. Recent studies support the idea that intracellular survival of Cryptococcus yeast cells is important for the pathogenesis of cryptococcosis. However, the initial steps of Cryptococcus internalization by host cells remain poorly understood. Here, we investigate the mechanism of Cryptococcus neoformans phagocytosis by peritoneal macrophages using confocal and electron microscopy techniques, as well as flow cytometry quantification, evaluating the importance of fungal capsule production and of host cell cytoskeletal elements for fungal phagocytosis. Electron microscopy analyses revealed that capsular and acapsular strains of C. neoformans are internalized by macrophages via both ‘zipper’ (receptor-mediated) and ‘trigger’ (membrane ruffle-dependent) phagocytosis mechanisms. Actin filaments surrounded phagosomes of capsular and acapsular yeasts, and the actin depolymerizing drugs cytochalasin D and latrunculin B inhibited yeast internalization and actin recruitment to the phagosome area. In contrast, nocodazole and paclitaxel, inhibitors of microtubule dynamics decreased internalization but did not prevent actin recruitment to the site of phagocytosis. Our results show that different uptake mechanisms, dependent on both actin and tubulin dynamics occur during yeast internalization by macrophages, and that capsule production does not affect the mode of Cryptococcus uptake by host cells. PMID:24586631

  8. A new adjustable parallel drill guide for internal fixation of femoral neck fracture: a developmental and experimental study.

    Science.gov (United States)

    Yuenyongviwat, Varah; Tuntarattanapong, Pakjai; Tangtrakulwanich, Boonsin

    2016-01-11

    Internal fixation is one treatment for femoral neck fracture. Some devices and techniques reported improved accuracy and decreased fluoroscopic time. However, these are not widely used nowadays due to the lack of available special instruments and techniques. To improve the surgical procedure, the authors designed a new adjustable drill guide and tested the efficacy of the device. The authors developed a new adjustable drill guide for cannulated screw guide wire insertion for multiple screw fixation. Eight orthopaedic surgeons performed the experimental study to evaluate the efficacy of this device. Each surgeon performed guide wire insertion for multiple screw fixation in six synthetic femurs: three times with the new device and three times with the conventional technique. The fluoroscopic time, operative time and surgeon satisfaction were evaluated. In the operations with the new adjustable drill guide, the fluoroscopic and operative times were significantly lower than the operations with the conventional technique (p level of satisfaction of this device was also statistically significantly better (p = 0.02) than the conventional technique. The fluoroscopic and operative times with the new adjustable drill guide were reduced for multiple screw fixation of femoral neck fracture and the satisfaction of the surgeons was good.

  9. 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.

  10. Developmental Immunotoxicity

    Science.gov (United States)

    Animal models suggest that the immature immune system is more susceptible to xenobiotics than the fully mature system, and sequelae of developmental immunotoxicant exposure may be persistent well into adulthood. Immune maturation may be delayed by xenobiotic exposure and recover...

  11. Internalization Mediation towards the Relationship between Entrepreneurial Action and Individual Performance for the Next Generation of Family Companies in Surabaya

    Directory of Open Access Journals (Sweden)

    Carolina Novi Mustikarini

    2017-06-01

    Full Text Available This study  examined the effect of entrepreneurial action for the performance of the next generation using the sample of students who joined the Family Business Community. In this study, there is a high contribution given by the role of entrepreneurship education in preparing the next generation in the family business. In addition, entrepreneurship education is considered possible through the process of internalization of the leaning process that is going on. For example, it is noted that entrepreneurial action can have a significant effect on the performance of the organization. In the context of the family business and entrepreneurial education at the University of Ciputra, both variables (entrepreneurial action and individual performance are necessary to be tested and therefore, the researcher finds it possible to cary out a research that is supposed to have a contribution to the family business. This study uses a hierarchical regression analysis, to test the stages of the mediation process. The results showed that most of relationships mediate internalization Entrepreneurial Action and Individual Performance.

  12. Common Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Epitopes Mediate Multiple Routes for Internalization and Function

    Science.gov (United States)

    DeVay, Rachel M.; Yamamoto, Lynn; Shelton, David L.; Liang, Hong

    2015-01-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a soluble protein that directs membrane-bound receptors to lysosomes for degradation. In the most studied example of this, PCSK9 binding leads to the degradation of low density lipoprotein receptor (LDLR), significantly affecting circulating LDL-C levels. The mechanism mediating this degradation, however, is not completely understood. We show here that LDLR facilitates PCSK9 interactions with amyloid precursor like protein 2 (APLP2) at neutral pH leading to PCSK9 internalization, although direct binding between PCSK9 and LDLR is not required. Moreover, binding to APLP2 or LDLR is independently sufficient for PCSK9 endocytosis in hepatocytes, while LDL can compete with APLP2 for PCSK9 binding to indirectly mediate PCSK9 endocytosis. Finally, we show that APLP2 and LDLR are also required for the degradation of another PCSK9 target, APOER2, necessitating a general role for LDLR and APLP2 in PCSK9 function. Together, these findings provide evidence that PCSK9 has at least two endocytic epitopes that are utilized by a variety of internalization mechanisms and clarifies how PCSK9 may direct proteins to lysosomes. PMID:25905719

  13. Identification of phenylalanine 346 in the rat growth hormone receptor as being critical for ligand-mediated internalization and down-regulation

    DEFF Research Database (Denmark)

    Allevato, G; Billestrup, N; Goujon, L

    1995-01-01

    The functional significance of growth hormone (GH) receptor (GHR) internalization is unknown; therefore, we have analyzed domains and individual amino acids in the cytoplasmic region of the rat GHR required for ligand-mediated receptor internalization, receptor down-regulation, and transcriptiona...

  14. Trust in Effective International Business Cooperation: Mediating Effect of Work Engagement

    Directory of Open Access Journals (Sweden)

    Małgorzata Chrupała-Pniak

    2017-06-01

    Full Text Available Objective: This study aims to analyse the relationships between relational competence and its trust-building processes with individuals’ traits considered as psychological antecedents of inter-organizational relationships (IORs, outcomes. We hypothesize that organizational trust-building competence, situational trust, trust propensity, and autonomous motivation of cooperating teams and their managers influence IORs outcomes through work engagement of cooperating people. Research Design & Methods: We addressed 210 managers and 982 employees responsible for inter-organizational cooperation from medium and big companies. As explanatory model we adopted the job resources-demands (JR-D model. Correlation, regression, mediation analyses with bootstrapping, and structural equations modelling (SEM were used. Findings: Our analyses confirmed positive role of both organizational competences and psychological states of individuals, as valuable mediators in translating the potential of personal traits of teams and managers into IORs outcomes. Implications & Recommendations: As both psychological variables of people responsible for the course of IORs and relational competences of organizations play a vital role in reaching outcomes in IORs attention should be paid simultaneously to both aspects. Our findings highlight the necessity for interdisciplinary research in the field of IORs. Contribution & Value Added: We expose the multilevel and multifactor character of relationships between the antecedents of firms success in IORs, with the use of relationships theory in organization science, and theories proposed by psychology of work and organization.

  15. Children with Internalizing Problems and Peer Problems : Risk Factors, Treatment Effectiveness, Moderation, and Mediation

    NARCIS (Netherlands)

    Mulder, Saskia

    2014-01-01

    In this dissertation, internalizing and peer problems in children around the age of twelve were examined. These children were all about to make the transition to secondary school, or had just made that transition. The dissertation reports on four studies. First, we examined the extent to which the

  16. The developmental effects of media-ideal internalization and self-objectification processes on adolescents' negative body-feelings, dietary restraint, and binge eating.

    Science.gov (United States)

    Dakanalis, Antonios; Carrà, Giuseppe; Calogero, Rachel; Fida, Roberta; Clerici, Massimo; Zanetti, Maria Assunta; Riva, Giuseppe

    2015-08-01

    Despite accumulated experimental evidence of the negative effects of exposure to media-idealized images, the degree to which body image, and eating related disturbances are caused by media portrayals of gendered beauty ideals remains controversial. On the basis of the most up-to-date meta-analysis of experimental studies indicating that media-idealized images have the most harmful and substantial impact on vulnerable individuals regardless of gender (i.e., "internalizers" and "self-objectifiers"), the current longitudinal study examined the direct and mediated links posited in objectification theory among media-ideal internalization, self-objectification, shame and anxiety surrounding the body and appearance, dietary restraint, and binge eating. Data collected from 685 adolescents aged between 14 and 15 at baseline (47 % males), who were interviewed and completed standardized measures annually over a 3-year period, were analyzed using a structural equation modeling approach. Results indicated that media-ideal internalization predicted later thinking and scrutinizing of one's body from an external observer's standpoint (or self-objectification), which then predicted later negative emotional experiences related to one's body and appearance. In turn, these negative emotional experiences predicted subsequent dietary restraint and binge eating, and each of these core features of eating disorders influenced each other. Differences in the strength of these associations across gender were not observed, and all indirect effects were significant. The study provides valuable information about how the cultural values embodied by gendered beauty ideals negatively influence adolescents' feelings, thoughts and behaviors regarding their own body, and on the complex processes involved in disordered eating. Practical implications are discussed.

  17. Internalized mental illness stigma and subjective well-being: The mediating role of psychological well-being.

    Science.gov (United States)

    Pérez-Garín, Daniel; Molero, Fernando; Bos, Arjan E R

    2015-08-30

    This study examines the relationships between internalized stigma, psychological well-being, and subjective well-being in a sample of people with mental illness. We conducted a cross-sectional study with 213 outpatients from the Spanish public social care network. The results showed that (a) internalized stigma was significantly negatively correlated with psychological well-being and subjective well-being (affect balance and life satisfaction) (all correlations are significant with at least pstigma on affect balance and life satisfaction was mediated by psychological well-being. The component of internalized stigma most consistently associated with both types of well-being was alienation (life satisfaction: B=-0.35, p=0.001; affect balance: B=-0.38, p=0.001). These findings should be confirmed in future longitudinal or experimental research. On the basis of these results we recommend that interventions to combat self-stigma aim to reduce feelings of alienation and improve self-acceptance and other aspects of positive psychological functioning. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Internal wave-mediated shading causes frequent vertical migrations in fishes

    KAUST Repository

    Kaartvedt, Stein

    2012-04-25

    We provide evidence that internal waves cause frequent vertical migrations (FVM) in fishes. Acoustic data from the Benguela Current revealed that pelagic scattering layers of fish below ~140 m moved in opposite phases to internal waves, ascending ~20 m towards the wave trough and descending from the wave crest. At the trough, the downward displacement of upper waters and the upward migration of fish created an overlapping zone. Near-bottom fish correspondingly left the benthic boundary zone at the wave trough, ascending into an acoustic scattering layer likely consisting of zooplankton and then descending to the benthic boundary zone at the wave crest. We suggest that this vertical fish migration is a response to fluctuations in light intensity of 3 to 4 orders of magnitude caused by shading from a turbid surface layer that had chlorophyll a values of 3 to 4 mg m−3 and varied in thickness from ~15 to 50 m at a temporal scale corresponding to the internal wave period (30 min). This migration frequency thus is much higher than that of the common and widespread light-associated diel vertical migration. Vertical movements affect prey encounters, growth, and survival. We hypothesize that FVM increase the likelihood of prey encounters and the time for safe visual foraging among planktivorous fish, thereby contributing to efficient trophic transfer in major upwelling areas.

  19. Developmental delay

    Science.gov (United States)

    Nutrition support is essential for the care of the child with developmental delay. After a thorough evaluation, an individualized intervention plan that accounts for the child’s nutrition status, feeding ability, and medical condition may be determined. Nutrition assessments may be performed at leas...

  20. Developmental Work

    DEFF Research Database (Denmark)

    Møller, Niels; Hvid, Helge; Kristensen, Tage Søndergaard

    2003-01-01

    Human Deveoplment and Working Life - Work for Welfare explores whether the development of human resources at company level can improve individuals' quality of life, companies' possibilities of development, and welfare and democracy in society. Chapter two discuss the concept "developmental work...

  1. "Thinking About Arrows" : Modeling the associations between inadequate parenting, mentalizing, and dissociation. Commentary on "The developmental roots of dissociation: A multiple mediation analysis" (Schimmenti, 2017)

    NARCIS (Netherlands)

    Garofalo, C.; Velotti, Patrizia

    In an article published in Psychoanalytic Psychology, Schimmenti (2017) reported an empirical study whose results were interpreted as supporting the trauma model of dissociation and suggested that alexithymia and deficits in theory of mind might mediate the relation between emotional neglect and

  2. Thin-Ideal Internalization and Comparison Process as Mediators of Social Influence and Psychological Functioning in the Development of Disturbed Eating Habits in Croatian College Females

    Directory of Open Access Journals (Sweden)

    Alessandra Pokrajac-Bulian

    2008-12-01

    Full Text Available This study examined the role of internalization and comparison as mediators of relationships between socio-cultural pressures to be thin, psychological factors, restrictive and bulimic behaviours in college females. Participants were 262 Croatian college females (mean age = 21.22 ± 1.47 years who completed self-report questionnaires. Regression analysis was used to test a model in which internalization and social comparison mediated the impact of socio-cultural pressure (parents and peers dieting, teasing, pressure to be thin, media influences, self-esteem, anxiety, depression, and perfectionism in restrictive and bulimic behaviours. Internalization is a significant mediator of the relationships between all predictors included in this research and disturbed eating habits. Social comparison is relevant as a mediator between social influence, negative affect, self-esteem, perfectionism and restrictive behaviour but does not mediate bulimic behaviour. These findings could be seful in understanding processes that may predispose young women to develop eating dysfunctions and indicate the need for prevention programs that incorporate formative influences and processes such as internalization of societal norms and comparison in the construction of therapeutic strategies.

  3. dbl-1/TGF-β and daf-12/NHR Signaling Mediate Cell-Nonautonomous Effects of daf-16/FOXO on Starvation-Induced Developmental Arrest.

    Directory of Open Access Journals (Sweden)

    Rebecca E W Kaplan

    2015-12-01

    Full Text Available Nutrient availability has profound influence on development. In the nematode C. elegans, nutrient availability governs post-embryonic development. L1-stage larvae remain in a state of developmental arrest after hatching until they feed. This "L1 arrest" (or "L1 diapause" is associated with increased stress resistance, supporting starvation survival. Loss of the transcription factor daf-16/FOXO, an effector of insulin/IGF signaling, results in arrest-defective and starvation-sensitive phenotypes. We show that daf-16/FOXO regulates L1 arrest cell-nonautonomously, suggesting that insulin/IGF signaling regulates at least one additional signaling pathway. We used mRNA-seq to identify candidate signaling molecules affected by daf-16/FOXO during L1 arrest. dbl-1/TGF-β, a ligand for the Sma/Mab pathway, daf-12/NHR and daf-36/oxygenase, an upstream component of the daf-12 steroid hormone signaling pathway, were up-regulated during L1 arrest in a daf-16/FOXO mutant. Using genetic epistasis analysis, we show that dbl-1/TGF-β and daf-12/NHR steroid hormone signaling pathways are required for the daf-16/FOXO arrest-defective phenotype, suggesting that daf-16/FOXO represses dbl-1/TGF-β, daf-12/NHR and daf-36/oxygenase. The dbl-1/TGF-β and daf-12/NHR pathways have not previously been shown to affect L1 development, but we found that disruption of these pathways delayed L1 development in fed larvae, consistent with these pathways promoting development in starved daf-16/FOXO mutants. Though the dbl-1/TGF-β and daf-12/NHR pathways are epistatic to daf-16/FOXO for the arrest-defective phenotype, disruption of these pathways does not suppress starvation sensitivity of daf-16/FOXO mutants. This observation uncouples starvation survival from developmental arrest, indicating that DAF-16/FOXO targets distinct effectors for each phenotype and revealing that inappropriate development during starvation does not cause the early demise of daf-16/FOXO mutants. Overall

  4. dbl-1/TGF-β and daf-12/NHR Signaling Mediate Cell-Nonautonomous Effects of daf-16/FOXO on Starvation-Induced Developmental Arrest.

    Science.gov (United States)

    Kaplan, Rebecca E W; Chen, Yutao; Moore, Brad T; Jordan, James M; Maxwell, Colin S; Schindler, Adam J; Baugh, L Ryan

    2015-12-01

    Nutrient availability has profound influence on development. In the nematode C. elegans, nutrient availability governs post-embryonic development. L1-stage larvae remain in a state of developmental arrest after hatching until they feed. This "L1 arrest" (or "L1 diapause") is associated with increased stress resistance, supporting starvation survival. Loss of the transcription factor daf-16/FOXO, an effector of insulin/IGF signaling, results in arrest-defective and starvation-sensitive phenotypes. We show that daf-16/FOXO regulates L1 arrest cell-nonautonomously, suggesting that insulin/IGF signaling regulates at least one additional signaling pathway. We used mRNA-seq to identify candidate signaling molecules affected by daf-16/FOXO during L1 arrest. dbl-1/TGF-β, a ligand for the Sma/Mab pathway, daf-12/NHR and daf-36/oxygenase, an upstream component of the daf-12 steroid hormone signaling pathway, were up-regulated during L1 arrest in a daf-16/FOXO mutant. Using genetic epistasis analysis, we show that dbl-1/TGF-β and daf-12/NHR steroid hormone signaling pathways are required for the daf-16/FOXO arrest-defective phenotype, suggesting that daf-16/FOXO represses dbl-1/TGF-β, daf-12/NHR and daf-36/oxygenase. The dbl-1/TGF-β and daf-12/NHR pathways have not previously been shown to affect L1 development, but we found that disruption of these pathways delayed L1 development in fed larvae, consistent with these pathways promoting development in starved daf-16/FOXO mutants. Though the dbl-1/TGF-β and daf-12/NHR pathways are epistatic to daf-16/FOXO for the arrest-defective phenotype, disruption of these pathways does not suppress starvation sensitivity of daf-16/FOXO mutants. This observation uncouples starvation survival from developmental arrest, indicating that DAF-16/FOXO targets distinct effectors for each phenotype and revealing that inappropriate development during starvation does not cause the early demise of daf-16/FOXO mutants. Overall, this study shows

  5. The relationship between internalized stigma and quality of life among people with mental illness: are self-esteem and sense of coherence sequential mediators?

    Science.gov (United States)

    Świtaj, Piotr; Grygiel, Paweł; Chrostek, Anna; Nowak, Izabela; Wciórka, Jacek; Anczewska, Marta

    2017-09-01

    To elucidate the mechanism through which internalized stigma reduces the quality of life (QoL) of people with mental illness by exploring the mediating roles of self-esteem and sense of coherence (SOC). A cross-sectional analysis of 229 patients diagnosed with schizophrenia or affective disorders was undertaken to test a sequential mediation model assuming that more severe internalized stigma is related to lower self-esteem, which is associated with weaker SOC, which in turn relates to worse QoL. The proposed model was supported by the data. A sequential indirect effect from internalized stigma to QoL via self-esteem and SOC turned out to be significant [beta = -0.06, SE = 0.02; 95% CI (-0.11, -0.03)]. Support was also found for simple mediation models with either self-esteem or SOC as single mediators between internalized stigma and QoL. Self-esteem and SOC are personal resources that should be considered as potential targets of interventions aiming to prevent the harmful consequences of internalized stigma for the QoL of people receiving psychiatric treatment.

  6. Adaptor Protein Complex-2 (AP-2) and Epsin-1 Mediate Protease-activated Receptor-1 Internalization via Phosphorylation- and Ubiquitination-dependent Sorting Signals*

    Science.gov (United States)

    Chen, Buxin; Dores, Michael R.; Grimsey, Neil; Canto, Isabel; Barker, Breann L.; Trejo, JoAnn

    2011-01-01

    Signaling by protease-activated receptor-1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, is regulated by desensitization and internalization. PAR1 desensitization is mediated by β-arrestins, like most classic GPCRs. In contrast, internalization of PAR1 occurs through a clathrin- and dynamin-dependent pathway independent of β-arrestins. PAR1 displays two modes of internalization. Constitutive internalization of unactivated PAR1 is mediated by the clathrin adaptor protein complex-2 (AP-2), where the μ2-adaptin subunit binds directly to a tyrosine-based motif localized within the receptor C-tail domain. However, AP-2 depletion only partially inhibits agonist-induced internalization of PAR1, suggesting a function for other clathrin adaptors in this process. Here, we now report that AP-2 and epsin-1 are both critical mediators of agonist-stimulated PAR1 internalization. We show that ubiquitination of PAR1 and the ubiquitin-interacting motifs of epsin-1 are required for epsin-1-dependent internalization of activated PAR1. In addition, activation of PAR1 promotes epsin-1 de-ubiquitination, which may increase its endocytic adaptor activity to facilitate receptor internalization. AP-2 also regulates activated PAR1 internalization via recognition of distal C-tail phosphorylation sites rather than the canonical tyrosine-based motif. Thus, AP-2 and epsin-1 are both required to promote efficient internalization of activated PAR1 and recognize discrete receptor sorting signals. This study defines a new pathway for internalization of mammalian GPCRs. PMID:21965661

  7. In vivo [3H]spiperone binding: evidence for accumulation in corpus striatum by agonist-mediated receptor internalization

    International Nuclear Information System (INIS)

    Chugani, D.C.; Ackermann, R.F.; Phelps, M.E.

    1988-01-01

    The processes of receptor internalization and recycling have been well-documented for receptors for hormones, growth factors, lysosomal enzymes, and cellular substrates. Evidence also exists that these processes also occur for beta-adrenergic, muscarinic cholinergic, and delta-opiate receptors in frog erythrocytes or cultured nervous tissue. In this study, evidence is presented that agonist-mediated receptor internalization and recycling occurs at the dopamine receptor in rat corpus striatum. First, the in vivo binding of the dopamine antagonist [3H]spiperone was increased by both electrical stimulation and pharmacologically induced increases of dopamine release. Conversely, depletion of dopamine with reserpine decreased in vivo [3H]spiperone binding, but the same reserpine treatment did not alter its in vitro binding. Second, the rate of dissociation of [3H]spiperone from microsomal membranes prepared from rat striatum following in vivo binding was fivefold slower than its dissociation following in vitro equilibrium binding. Mild detergent treatment, employed to disrupt endocytic vesicle membranes, increased the rate of dissociation of in vivo bound [3H]spiperone from microsomal membranes to values not significantly different from its in vitro bound dissociation rate. Third, treatment of rats with chloroquine, a drug that prevents receptor recycling but not internalization, prior to [3H]spiperone injection resulted in a selective increase of in vivo [3H]spiperone binding in the light microsome membranes. The existence of mechanisms that rapidly alter the number of neurotransmitter receptors at synapses provides dynamic regulation of receptors in response to varied acute stimulation states

  8. Characterizations of the α1-adrenoceptor subtypes mediating contractions of the human internal anal sphincter.

    Science.gov (United States)

    Owaki, Hiroyuki; Sadahiro, Sotaro; Takaki, Miyako

    2015-04-01

    Human internal anal sphincter (IAS) is contracted by α1-adrenoceptor stimulation and thus α1-adrenoceptor agonists may be useful in treating fecal incontinence. This study characterizes the contribution of α1-adrenoceptor subtypes in contraction of human IAS and to investigate the age-related risk of patients with fecal incontinence. IAS and inferior mesenteric artery (IMA), as a predictor of systemic arterial pressure, were obtained from 11 patients. Both muscle strips were assessed by isometric-contraction experiments using phenylephrine, further in IAS, in the presence of various subtype selective α1-adrenoceptor antagonists. Immunohistochemistry and gene expression studies were performed in the same samples. The mean pEC50 values with SEM of phenylephrine in IAS (6.30 ± 0.13) were higher than those of IMA (5.60 ± 0.10). Furthermore, the age-related pEC50 change of IAS was observed between age IAS, rightward shift of the concentration-response curves of phenylephrine was observed with three α1-adrenoceptor antagonists. Each pKB value of silodosin, BMY-7378 and prazosin was 9.36 ± 0.53, 7.28 ± 0.20 and 8.89 ± 0.12, respectively. These pKB values and gene expression studies indicated that α1A-adrenoceptor subtypes predominantly contributed to human IAS contraction. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  9. Internalized stigma and quality of life among persons with severe mental illness: the mediating roles of self-esteem and hope.

    Science.gov (United States)

    Mashiach-Eizenberg, Michal; Hasson-Ohayon, Ilanit; Yanos, Philip T; Lysaker, Paul H; Roe, David

    2013-06-30

    Research has revealed the negative consequences of internalized stigma among people with serious mental illness (SMI), including reductions in self-esteem and hope. The purpose of the present study was to investigate the relation between internalized stigma and subjective quality of life (QoL) by examining the mediating role of self-esteem and hope. Measures of internalized stigma, self-esteem, QoL, and hope were administrated to 179 people who had a SMI. Linear regression analysis and structural equation modeling (SEM) were used to analyze the cross-sectional data. Self-esteem mediated the relation between internalized stigma and hope. In addition, hope partially mediated the relationship between self-esteem and QoL. The findings suggest that the effect of internalized stigma upon hope and QoL may be closely related to levels of self-esteem. This may point to the need for the development of interventions that target internalized stigma as well as self-esteem. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. How accurate is the phenotype? – An analysis of developmental noise in a cotton aphid clone

    Directory of Open Access Journals (Sweden)

    Babbitt Gregory A

    2008-02-01

    Full Text Available Abstract Background The accuracy by which phenotype can be reproduced by genotype potentially is important in determining the stability, environmental sensitivity, and evolvability of morphology and other phenotypic traits. Because two sides of an individual represent independent development of the phenotype under identical genetic and environmental conditions, average body asymmetry (or "fluctuating asymmetry" can estimate the developmental instability of the population. The component of developmental instability not explained by intrapopulational differences in gene or environment (or their interaction can be further defined as internal developmental noise. Surprisingly, developmental noise remains largely unexplored despite its potential influence on our interpretations of developmental stability, canalization, and evolvability. Proponents of fluctuating asymmetry as a bioindicator of environmental or genetic stress, often make the assumption that developmental noise is minimal and, therefore, that phenotype can respond sensitively to the environment. However, biologists still have not measured whether developmental noise actually comprises a significant fraction of the overall environmental response of fluctuating asymmetry observed within a population. Results In a morphometric study designed to partition developmental noise from fluctuating asymmetry in the wing morphology of a monoclonal culture of cotton aphid, Aphis gossipyii, it was discovered that fluctuating asymmetry in the aphid wing was nearly four times higher than in other insect species. Also, developmental noise comprised a surprisingly large fraction (≈ 50% of the overall response of fluctuating asymmetry to a controlled graded temperature environment. Fluctuating asymmetry also correlated negatively with temperature, indicating that environmentally-stimulated changes in developmental instability are mediated mostly by changes in the development time of individuals

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

    Science.gov (United States)

    Marr, Joni; Wilcox, Sara

    2015-01-01

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

  12. Gender-Related Discourses as Mediators in the Association between Internalization of the Thin-Body Ideal and Indicants of Body Dissatisfaction and Disordered Eating

    Science.gov (United States)

    Morrison, Todd G.; Sheahan, Emer E.

    2009-01-01

    This study examined whether the gender-related discourses of self-objectification, self-silencing, and anger suppression mediated the association between internalization of the thin-body ideal and body dissatisfaction and eating pathology. We employed a cross-sectional design to study both university (n = 140) and community (n = 76) samples of…

  13. Mediating Political Action: Internet related Beliefs and Frustrations amongst International Solidarity Campaigns in Britain

    Directory of Open Access Journals (Sweden)

    Veronica Barassi

    2009-05-01

    Full Text Available El terreny de l'activisme en els mitjans de comunicació avui s'associa a internet; s'ha construït sobretot per mitjà de xarxes o plataformes en línia i, a poc a poc, va transformant la manera d'imaginar, experimentar i organitzar l'acció política. Aquest article explora els efectes que tenen les creences i frustracions relacionades amb internet sobre les formes contemporànies d'acció política. Partint del context etnogràfic en què se situen les campanyes de solidaritat internacional i els sindicats britànics, el treball proposa que la relació que mantenen els activistes amb les tecnologies d'internet és complexa i s'insereix en una doble tensió entre l'apoderament i la frustració. Tal com sosté l'article, és mitjançant una exploració etnogràfica d'aquesta tensió que els especialistes poden arribar a entendre més bé els conflictes permanents i les negociacions socials creats arran de les transformacions tecnològico-històriques dels últims quinze anys. The terrain of media activism today has become an internet connected one; one that is primarily constructed through online networks or platforms; one that is gradually transforming the way in which political action is imagined, experienced and organised. The following article explores the effects of internet related beliefs and frustrations on contemporary forms of political action. Drawing from the ethnographic context of international solidarity campaigns and the trade unions in Britain, the paper argues that activists' relationship to internet technologies is a complex one, which is embedded in a double tension of empowerment and frustration. It is by ethnographically exploring this tension, the paper contends, that scholars can gain important insights on the ongoing social conflicts and negotiations created by the techno-historical transformations of the last fifteen years.  El terreno del activismo en los medios de comunicación hoy se asocia a internet; se ha

  14. Mitogen-activated protein kinase signaling pathways promote low-density lipoprotein receptor-related protein 1-mediated internalization of beta-amyloid protein in primary cortical neurons.

    Science.gov (United States)

    Yang, Wei-Na; Ma, Kai-Ge; Qian, Yi-Hua; Zhang, Jian-Shui; Feng, Gai-Feng; Shi, Li-Li; Zhang, Zhi-Chao; Liu, Zhao-Hui

    2015-07-01

    Mounting evidence suggests that the pathological hallmarks of Alzheimer's disease (AD) are caused by the intraneuronal accumulation of beta-amyloid protein (Aβ). Reuptake of extracellular Aβ is believed to contribute significantly to the intraneuronal Aβ pool in the early stages of AD. Published reports have claimed that the low-density lipoprotein receptor-related protein 1 (LRP1) mediates Aβ1-42 uptake and lysosomal trafficking in GT1-7 neuronal cells and mouse embryonic fibroblast non-neuronal cells. However, there is no direct evidence supporting the role of LRP1 in Aβ internalization in primary neurons. Our recent study indicated that p38 MAPK and ERK1/2 signaling pathways are involved in regulating α7 nicotinic acetylcholine receptor (α7nAChR)-mediated Aβ1-42 uptake in SH-SY5Y cells. This study was designed to explore the regulation of MAPK signaling pathways on LRP1-mediatedinternalization in neurons. We found that extracellular Aβ1-42 oligomers could be internalized into endosomes/lysosomes and mitochondria in cortical neurons. Aβ1-42 and LRP1 were also found co-localized in neurons during Aβ1-42 internalization, and they could form Aβ1-42-LRP1 complex. Knockdown of LRP1 expression significantly decreased neuronal Aβ1-42 internalization. Finally, we identified that p38 MAPK and ERK1/2 signaling pathways regulated the internalization of Aβ1-42 via LRP1. Therefore, these results demonstrated that LRP1, p38 MAPK and ERK1/2 mediated the internalization of Aβ1-42 in neurons and provided evidence that blockade of LRP1 or inhibitions of MAPK signaling pathways might be a potential approach to lowering brain Aβ levels and served a potential therapeutic target for AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Overvaluation of shape and weight as a mediator between self-esteem and weight bias internalization among patients with binge eating disorder.

    Science.gov (United States)

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

    2014-04-01

    This study aimed to evaluate the roles of self-esteem and overvaluation of shape and weight in accounting for the internalization of weight bias among patients with binge eating disorder (BED) and obesity. Two hundred forty-five treatment-seeking individuals with BED and obesity were evaluated with diagnostic and semi-structured interviews and completed the Weight Bias Internalization Scale (WBIS) and the Rosenberg Self-Esteem Scale (RSE). Correlations and bootstrapping mediation analyses were computed to evaluate the relationships among self-esteem, overvaluation of shape/weight, and weight bias internalization. The effects of body mass index (BMI) and binge-eating frequency were also tested. Significant correlations emerged between WBIS, RSE, and overvaluation of shape and weight. BMI did not correlate with any measure, and binge-eating frequency only correlated with overvaluation. Mediation analyses provided support for the hypothesis that overvaluation of shape and weight mediates the relationship between self-esteem and weight bias internalization. These findings provide support to the proposed model that self-esteem and overvaluation of shape and weight contribute to weight bias internalization among patients with BED, which holds implications for clinical efforts to address weight bias and associated eating and weight-related psychopathology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Distinct CPT-induced deaths in lung cancer cells caused by clathrin-mediated internalization of CP micelles

    Science.gov (United States)

    Liu, Yu-Sheng; Cheng, Ru-You; Lo, Yu-Lun; Hsu, Chin; Chen, Su-Hwei; Chiu, Chien-Chih; Wang, Li-Fang

    2016-02-01

    We previously synthesized a chondroitin sulfate-graft-poly(ε-caprolactone) copolymer (H-CP) with a high content of poly(ε-caprolactone) (18.7 mol%), which self-assembled in water into a rod-like micelle to encapsulate hydrophobic camptothecin (CPT) in the core (micelle/CPT) for tumor-targeted drug delivery. As a result of the recognition of the micelle by CD44, the micelle/CPT entered CRL-5802 cells efficiently and released CPT efficaciously, resulting in higher tumor suppression than commercial CPT-11. In this study, H1299 cells were found to have a higher CD44 expression than CRL-5802 cells. However, the lower CD44-expressing CRL-5802 cells had a higher percentage of cell death and higher cellular uptake of the micelle/CPT than the higher CD44-expressing H1299 cells. Examination of the internalization pathway of the micelle/CPT in the presence of different endocytic chemical inhibitors showed that the CRL-5802 cells involved clathrin-mediated endocytosis, which was not found in the H1299 cells. Analysis of the cell cycle of the two cell lines exposed to the micelle/CPT revealed that the CRL-5802 cells arrested mainly in the S phase and the H1299 cells arrested mainly in the G2-M phase. A consistent result was also found in the evaluation of γ-H2AX expression, which was about three-fold higher in the CRL-5802 cells than in the H1299 cells. A near-infrared dye, IR780, was encapsulated into the micelle to observe the in vivo biodistribution of the micelle/IR780 in tumor-bearing mice. The CRL-5802 tumor showed a higher fluorescence intensity than the H1299 tumor at any tracing time after 1 h. Thus we tentatively concluded that CRL-5802 cells utilized the clathrin-mediated internalization pathway and arrested in the S phase on exposure to the micelle/CPT; all are possible reasons for the better therapeutic outcome in CRL-5802 cells than in H1299 cells.We previously synthesized a chondroitin sulfate-graft-poly(ε-caprolactone) copolymer (H-CP) with a high content of

  17. Developmental Programming: Impact of Gestational Steroid and Metabolic Milieus on Mediators of Insulin Sensitivity in Prenatal Testosterone-Treated Female Sheep.

    Science.gov (United States)

    Puttabyatappa, Muraly; Andriessen, Victoria; Mesquitta, Makeda; Zeng, Lixia; Pennathur, Subramaniam; Padmanabhan, Vasantha

    2017-09-01

    Prenatal testosterone (T) excess in sheep leads to peripheral insulin resistance (IR), reduced adipocyte size, and tissue-specific changes, with liver and muscle but not adipose tissue being insulin resistant. To determine the basis for the tissue-specific differences in insulin sensitivity, we assessed changes in negative (inflammation, oxidative stress, and lipotoxicity) and positive mediators (adiponectin and antioxidants) of insulin sensitivity in the liver, muscle, and adipose tissues of control and prenatal T-treated sheep. Because T excess leads to maternal hyperinsulinemia, fetal hyperandrogenism, and functional hyperandrogenism and IR in their female offspring, prenatal and postnatal interventions with antiandrogen, flutamide, and the insulin sensitizer rosiglitazone were used to parse out the contribution of androgenic and metabolic pathways in programming and maintaining these defects. Results showed that (1) peripheral IR in prenatal T-treated female sheep is related to increases in triglycerides and 3-nitrotyrosine, which appear to override the increase in high-molecular-weight adiponectin; (2) liver IR is a function of the increase in oxidative stress (3-nitrotyrosine) and lipotoxicity; (3) muscle IR is related to lipotoxicity; and (4) the insulin-sensitive status of visceral adipose tissue appears to be a function of the increase in antioxidants that likely overrides the increase in proinflammatory cytokines, macrophages, and oxidative stress. Prenatal and postnatal intervention with either antiandrogen or insulin sensitizer had partial effects in preventing or ameliorating the prenatal T-induced changes in mediators of insulin sensitivity, suggesting that both pathways are critical for the programming and maintenance of the prenatal T-induced changes and point to potential involvement of estrogenic pathways. Copyright © 2017 Endocrine Society.

  18. Mechanisms for the Negative Effects of Internalized HIV-Related Stigma on Antiretroviral Therapy Adherence in Women: The Mediating Roles of Social Isolation and Depression.

    Science.gov (United States)

    Turan, Bulent; Smith, Whitney; Cohen, Mardge H; Wilson, Tracey E; Adimora, Adaora A; Merenstein, Daniel; Adedimeji, Adebola; Wentz, Eryka L; Foster, Antonina G; Metsch, Lisa; Tien, Phyllis C; Weiser, Sheri D; Turan, Janet M

    2016-06-01

    Internalization of HIV-related stigma may inhibit a person's ability to manage HIV disease through adherence to treatment regimens. Studies, mainly with white men, have suggested an association between internalized stigma and suboptimal adherence to antiretroviral therapy (ART). However, there is a scarcity of research with women of different racial/ethnic backgrounds and on mediating mechanisms in the association between internalized stigma and ART adherence. The Women's Interagency HIV Study (WIHS) is a multicenter cohort study. Women living with HIV complete interviewer-administered questionnaires semiannually. Cross-sectional analyses for the current article included 1168 women on ART for whom data on medication adherence were available from their last study visit between April 2013 and March 2014, when the internalized stigma measure was initially introduced. The association between internalized stigma and self-reported suboptimal ART adherence was significant for those in racial/ethnic minority groups (AOR = 0.69, P = 0.009, 95% CI: 0.52 to 0.91), but not for non-Hispanic whites (AOR = 2.15, P = 0.19, 95% CI: 0.69 to 6.73). Depressive symptoms, loneliness, and low perceived social support mediated the association between internalized stigma and suboptimal adherence in the whole sample, as well as in the subsample of minority participants. In serial mediation models, internalized stigma predicted less-perceived social support (or higher loneliness), which in turn predicted more depressive symptoms, which in turn predicted suboptimal medication adherence. Findings suggest that interconnected psychosocial mechanisms affect ART adherence, and that improvements in adherence may require multifaceted interventions addressing both mental health and interpersonal factors, especially for minority women.

  19. NIDCAP and developmental care

    Directory of Open Access Journals (Sweden)

    Dominique Haumont

    2014-06-01

    Full Text Available Perinatal mortality in very low birth weight infants has dramatically decreased during the last decades. However, 15-25% of these infants will show neurodevelopmental impairment later on. The aim of implementing early developmental care (EDC, emerged as a new field in neonatology, is to create an intervention program designed to provide support for optimal neurobehavioral development during this highly vulnerable period of brain growth. The theoretical framework, which underlies the approach, is supported by research in different scientific fields, including neuroscience, psychology, medicine and nursing. EDC utilizes a range of medical and nursing interventions that aim to decrease the stress of preterm neonates in neonatal intensive care units (NICUs. The Neonatal Individualized Developmental Care Assessment Program (NIDCAP is an integrated and holistic form of family-centered developmental care. Changing the traditional NICU towards an EDC-NICU includes training nursing and medical staff, investing in their quality and most importantly keeping parents in proximity to the infants. The new challenge of modern neonatology is to restore the mother-infant dyad applying “couplet care” starting at birth until discharge. Most of the European NICUs apply some elements of EDC, but it is more consistent in northern Europe. The development of NIDCAP training centers in Europe demonstrates the evolution of care. It is likely that future research and intervention programs will optimize our practices. Developmental care could prove to be an important recent step in improving outcome in extremely preterm neonates. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  20. Receptor-mediated endocytosis of polypeptide hormones is a regulated process: inhibition of [125I]iodoinsulin internalization in hypoinsulinemic diabetes of rat and man

    International Nuclear Information System (INIS)

    Carpentier, J.L.; Robert, A.; Grunberger, G.; van Obberghen, E.; Freychet, P.; Orci, L.; Gorden, P.

    1986-01-01

    Much data suggest that receptor-mediated endocytosis is regulated in states of hormone excess. Thus, in hyperinsulinemic states there is an accelerated loss of cell surface insulin receptors. In the present experiments we addressed this question in hypoinsulinemic states, in which insulin binding to cell surface receptors is generally increased. In hepatocytes obtained from hypoinsulinemic streptozotocin-induced diabetic rats, [ 125 I]iodoglucagon internalization was increased, while at the same time [ 125 I]iodoinsulin internalization was decreased. The defect in [ 125 I]iodoinsulin internalization was corrected by insulin treatment of the animal. In peripheral blood monocytes from patients with type I insulinopenic diabetes, internalization of [ 125 I]iodoinsulin was impaired; this defect was not present in insulin-treated patients. These data in the hypoinsulinemic rat and human diabetes suggest that receptor-mediated endocytosis is regulated in states of insulin deficiency as well as insulin excess. Delayed or reduced internalization of the insulin-receptor complex could amplify the muted signal caused by deficient hormone secretion

  1. Follicle-stimulating hormone (FSH) activates extracellular signal-regulated kinase phosphorylation independently of beta-arrestin- and dynamin-mediated FSH receptor internalization

    Science.gov (United States)

    Piketty, Vincent; Kara, Elodie; Guillou, Florian; Reiter, Eric; Crepieux, Pascale

    2006-01-01

    Background The follicle-stimulating hormone receptor (FSH-R) is a seven transmembrane spanning receptor (7TMR) which plays a crucial role in male and female reproduction. Upon FSH stimulation, the FSH-R activates the extracellular signal-regulated kinases (ERK). However, the mechanisms whereby the agonist-stimulated FSH-R activates ERK are poorly understood. In order to activate ERK, some 7 TMRs require beta-arrestin-and dynamin-dependent internalization to occur, whereas some others do not. In the present study, we examined the ability of the FSH-activated FSH-R to induce ERK phosphorylation, in conditions where its beta-arrestin- and dynamin-mediated internalization was impaired. Methods Human embryonic kidney (HEK) 293 cells were transiently transfected with the rat FSH-R. Internalization of the FSH-R was manipulated by co-expression of either a beta-arrestin (319–418) dominant negative peptide, either an inactive dynamin K44A mutant or of wild-type beta-arrestin 1 or 2. The outcomes on the FSH-R internalization were assayed by measuring 125I-FSH binding at the cell surface when compared to internalized 125I-FSH binding. The resulting ERK phosphorylation level was visualized by Western blot analysis. Results In HEK 293 cells, FSH stimulated ERK phosphorylation in a dose-dependent manner. Co-transfection of the beta- arrestin (319–418) construct, or of the dynamin K44A mutant reduced FSH-R internalization in response to FSH, without affecting ERK phosphorylation. Likewise, overexpression of wild-type beta-arrestin 1 or 2 significantly increased the FSH-R internalization level in response to FSH, without altering FSH-induced ERK phosphorylation. Conclusion From these results, we conclude that the FSH-R does not require beta-arrestin- nor dynamin-mediated internalization to initiate ERK phosphorylation in response to FSH. PMID:16787538

  2. Enhancing Research Ethics Review Systems in Egypt: The Focus of an International Training Program Informed by an Ecological Developmental Approach to Enhancing Research Ethics Capacity.

    Science.gov (United States)

    Edwards, Hillary Anne; Hifnawy, Tamer; Silverman, Henry

    2015-12-01

    Recently, training programs in research ethics have been established to enhance individual and institutional capacity in research ethics in the developing world. However, commentators have expressed concern that the efforts of these training programs have placed 'too great an emphasis on guidelines and research ethics review', which will have limited effect on ensuring ethical conduct in research. What is needed instead is a culture of ethical conduct supported by national and institutional commitment to ethical practices that are reinforced by upstream enabling conditions (strong civil society, public accountability, and trust in basic transactional processes), which are in turn influenced by developmental conditions (basic freedoms of political freedoms, economic facilities, social opportunities, transparency guarantees, and protective security). Examining this more inclusive understanding of the determinants of ethical conduct enhances at once both an appreciation of the limitations of current efforts of training programs in research ethics and an understanding of what additional training elements are needed to enable trainees to facilitate national and institutional policy changes that enhance research practices. We apply this developmental model to a training program focused in Egypt to describe examples of such additional training activities. © 2014 John Wiley & Sons Ltd.

  3. Expectations from different perspectives on future work outcome of young adults with intellectual and developmental disabilities

    NARCIS (Netherlands)

    Holwerda, Anja; Brouwer, Sandra; de Boer, Michiel R.; Groothoff, Johan W.; van der Klink, Jac J. L.

    2015-01-01

    Purpose Expectations strongly influence future employment outcomes and social networks seem to mediate employment success of young adults with intellectual and developmental disabilities. The aim of this study is to examine the expectations of young adults with intellectual and developmental

  4. Expectations from Different Perspectives on Future Work Outcome of Young Adults with Intellectual and Developmental Disabilities

    NARCIS (Netherlands)

    Holwerda, A.; Brouwer, S.; de Boer, M.R.; Groothoff, J.W.; van der Klink, J.J.L.

    2015-01-01

    Purpose Expectations strongly influence future employment outcomes and social networks seem to mediate employment success of young adults with intellectual and developmental disabilities. The aim of this study is to examine the expectations of young adults with intellectual and developmental

  5. Expectations from Different Perspectives on Future Work Outcome of Young Adults with Intellectual and Developmental Disabilities

    NARCIS (Netherlands)

    Holwerda, Anja; Brouwer, Sandra; de Boer, Michiel R.; Groothoff, Johan W.; van der Klink, Jac J. L.

    Purpose Expectations strongly influence future employment outcomes and social networks seem to mediate employment success of young adults with intellectual and developmental disabilities. The aim of this study is to examine the expectations of young adults with intellectual and developmental

  6. Developmental dyscalculia.

    Science.gov (United States)

    Kucian, Karin; von Aster, Michael

    2015-01-01

    Numerical skills are essential in our everyday life, and impairments in the development of number processing and calculation have a negative impact on schooling and professional careers. Approximately 3 to 6 % of children are affected from specific disorders of numerical understanding (developmental dyscalculia (DD)). Impaired development of number processing skills in these children is characterized by problems in various aspects of numeracy as well as alterations of brain activation and brain structure. Moreover, DD is assumed to be a very heterogeneous disorder putting special challenges to define homogeneous diagnostic criteria. Finally, interdisciplinary perspectives from psychology, neuroscience and education can contribute to the design for interventions, and although results are still sparse, they are promising and have shown positive effects on behaviour as well as brain function. In the current review, we are going to give an overview about typical and atypical development of numerical abilities at the behavioural and neuronal level. Furthermore, current status and obstacles in the definition and diagnostics of DD are discussed, and finally, relevant points that should be considered to make an intervention as successful as possible are summarized.

  7. 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.

  8. InlB-mediated Listeria monocytogenes internalization requires a balanced phospholipase D activity maintained through phospho-cofilin

    NARCIS (Netherlands)

    Han, Xuelin; Yu, Rentao; Ji, Lei; Zhen, Dongyu; Tao, Sha; Li, Shuai; Sun, Yansong; Huang, Liuyu; Feng, Zhe; Li, Xianping; Han, Gaige; Schmidt, Martina; Han, Li

    Internalization of Listeria monocytogenes into non-phagocytic cells is tightly controlled by host cell actin dynamics and cell membrane alterations. However, knowledge about the impact of phosphatidylcholine cleavage driven by host cell phospholipase D (PLD) on Listeria internalization into

  9. The Mediating Roles of Rejection Sensitivity and Proximal Stress in the Association Between Discrimination and Internalizing Symptoms Among Sexual Minority Women.

    Science.gov (United States)

    Dyar, Christina; Feinstein, Brian A; Eaton, Nicholas R; London, Bonita

    2018-01-01

    The negative impact of discrimination on mental health among lesbian, gay, and bisexual populations has been well documented. However, the possible mediating roles of sexual orientation rejection sensitivity and rejection-based proximal stress in the association between discrimination and internalizing symptoms remain unclear. Rejection-based proximal stress is a subset of proximal stressors that are theorized to arise from concerns about and expectations of sexual orientation-based rejection and discrimination. Drawing on minority stress theory, we tested potential mediating effects using indirect effects structural equation modeling in a sample of 300 sexual minority women. Results indicated that the indirect effect of discrimination on internalizing symptoms (a latent variable indicated by depression and anxiety symptoms) through sexual orientation rejection sensitivity and rejection-based proximal stress (a latent variable indicated by preoccupation with stigma, concealment motivation, and difficulty developing a positive sexual identity) was significant. Additionally, the indirect effects of discrimination on rejection-based proximal stress through sexual orientation rejection sensitivity and of sexual orientation rejection sensitivity on internalizing symptoms through rejection-based proximal stress were also significant. These findings indicate that sexual orientation rejection sensitivity plays an important role in contributing to rejection-based proximal stress and internalizing symptoms among sexual minority women.

  10. Preadoption adversities and postadoption mediators of mental health and school outcomes among international, foster, and private adoptees in the United States.

    Science.gov (United States)

    Harwood, Robin; Feng, Xin; Yu, Stella

    2013-06-01

    Adopted children are a heterogeneous group, varying along numerous factors, including type of adoption (international, foster, private), length of exposure to preadoption adversities as indexed by age of adoption, history of preadoption maltreatment, and prenatal substance exposure. Yet, we know little about how these adversity factors are mediated by quality of postadoption parent-child relationships and/or the presence of special health care needs to produce specific child outcomes across different groups of U.S. adopted children. This study uses structural equation modeling to analyze cross-sectional data from the National Survey of Adoptive Parents to investigate differences in outcomes among three groups of U.S. adopted children: international, foster, and private. SEM results indicate that compared with privately adopted children, (a) children adopted from the foster care system were more likely to be identified with special health care needs, and (b) internationally adopted children showed on average poorer school performance as indexed by math and reading. Analyses yielded both direct and indirect paths between preadoption adversities and child outcomes, with the majority of associations mediated or partially mediated by quality of parent-child relationships and/or special health care needs status. The results of these analyses highlight the heterogeneity among different groups of adopted children within the United States and also underline the important mediating roles that the quality of parent-child relationship and children's special health care needs status have on adopted children's selected mental health and academic outcomes. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  11. Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by μ-opioid receptor internalization

    Science.gov (United States)

    Chen, Wenling; Marvizón, Juan Carlos G.

    2009-01-01

    The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using μ-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hindpaw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hindpaw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected Complete Freund's Adjuvant (CFA) in the hindpaw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hindpaw. These results show that acute inflammation, but not chronic inflammation, induce segmental opioid release in the spinal cord that involves supraspinal signals. PMID:19298846

  12. Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by mu-opioid receptor internalization.

    Science.gov (United States)

    Chen, W; Marvizón, J C G

    2009-06-16

    The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using mu-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hind paw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hind paw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected complete Freund's adjuvant (CFA) in the hind paw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hind paw. These results show that acute inflammation, but not chronic inflammation, induces segmental opioid release in the spinal cord that involves supraspinal signals.

  13. C-terminal of human histamine H1 receptors regulates their agonist-induced clathrin-mediated internalization and G-protein signaling.

    Science.gov (United States)

    Hishinuma, Shigeru; Nozawa, Hiroki; Akatsu, Chizuru; Shoji, Masaru

    2016-11-01

    It has been suggested that the agonist-induced internalization of G-protein-coupled receptors from the cell surface into intracellular compartments regulates cellular responsiveness. We previously reported that G q/11 -protein-coupled human histamine H 1 receptors internalized via clathrin-dependent mechanisms upon stimulation with histamine. However, the molecular determinants of H 1 receptors responsible for agonist-induced internalization remain unclear. In this study, we evaluated the roles of the intracellular C-terminal of human histamine H 1 receptors tagged with hemagglutinin (HA) at the N-terminal in histamine-induced internalization in Chinese hamster ovary cells. The histamine-induced internalization was evaluated by the receptor binding assay with [ 3 H]mepyramine and confocal immunofluorescence microscopy with an anti-HA antibody. We found that histamine-induced internalization was inhibited under hypertonic conditions or by pitstop, a clathrin terminal domain inhibitor, but not by filipin or nystatin, disruptors of the caveolar structure and function. The histamine-induced internalization was also inhibited by truncation of a single amino acid, Ser487, located at the end of the intracellular C-terminal of H 1 receptors, but not by its mutation to alanine. In contrast, the receptor-G-protein coupling, which was evaluated by histamine-induced accumulation of [ 3 H]inositol phosphates, was potentiated by truncation of Ser487, but was lost by its mutation to alanine. These results suggest that the intracellular C-terminal of human H 1 receptors, which only comprises 17 amino acids (Cys471-Ser487), plays crucial roles in both clathrin-dependent internalization of H 1 receptors and G-protein signaling, in which truncation of Ser487 and its mutation to alanine are revealed to result in biased signaling toward activation of G-proteins and clathrin-mediated internalization, respectively. © 2016 International Society for Neurochemistry.

  14. Heterologous activation of protein kinase C stimulates phosphorylation of delta-opioid receptor at serine 344, resulting in beta-arrestin- and clathrin-mediated receptor internalization

    DEFF Research Database (Denmark)

    Xiang, B; Yu, G H; Guo, J

    2001-01-01

    The purpose of the current study is to investigate the effect of opioid-independent, heterologous activation of protein kinase C (PKC) on the responsiveness of opioid receptor and the underlying molecular mechanisms. Our result showed that removing the C terminus of delta opioid receptor (DOR......) containing six Ser/Thr residues abolished both DPDPE- and phorbol 12-myristate 13-acetate (PMA)-induced DOR phosphorylation. The phosphorylation levels of DOR mutants T352A, T353A, and T358A/T361A/S363S were comparable to that of the wild-type DOR, whereas S344G substitution blocked PMA-induced receptor......, and ionomycin resulted in DOR internalization that required phosphorylation of Ser-344. Expression of dominant negative beta-arrestin and hypertonic sucrose treatment blocked PMA-induced DOR internalization, suggesting that PKC mediates DOR internalization via a beta-arrestin- and clathrin-dependent mechanism...

  15. 7-11-year-old children show an advantage for matching and recognizing the internal features of familiar faces: evidence against a developmental shift.

    Science.gov (United States)

    Bonner, Lesley; Burton, Mike

    2004-08-01

    Adults are better at recognizing familiar faces from the internal facial features (eyes, nose, mouth) than from the external facial features (hair, face outline). However, previous research suggests that this "internal advantage" does not appear until relatively late in childhood, and some studies suggest that children rely on external features to recognize all faces, whether familiar or not. We use a matching task to examine face processing in 7-8- and 10-11-year-old children. We use a design in which all face stimuli can be used as familiar items (for participants who are classmates) and unfamiliar items (for participants from a different school). Using this design, we find an internal feature advantage for matching familiar faces, for both groups of children. The same children were then shown the external and internal features of their classmates and were asked to name or otherwise identify them. Again, both age groups identified more of their classmates correctly from the internal than the external features. This is the first time an internal advantage has been reported in this age group. Results suggest that children as young as 7 process faces in the same way as do adults, and that once procedural difficulties are overcome, the standard effects of familiarity are observed.

  16. Activatory and Inhibitory Fcγ Receptors Augment Rituximab-mediated Internalization of CD20 Independent of Signaling via the Cytoplasmic Domain*

    Science.gov (United States)

    Vaughan, Andrew T.; Chan, Claude H. T.; Klein, Christian; Glennie, Martin J.; Beers, Stephen A.; Cragg, Mark S.

    2015-01-01

    Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes. PMID:25568316

  17. Cumulative Risk and Adolescent's Internalizing and Externalizing Problems: The Mediating Roles of Maternal Responsiveness and Self-Regulation

    Science.gov (United States)

    Doan, Stacey N.; Fuller-Rowell, Thomas E.; Evans, Gary W.

    2012-01-01

    The purpose of the present study was to examine longitudinal associations among maternal responsiveness, self-regulation, and behavioral adjustment in adolescents. The authors used structural equation modeling to test a model that demonstrates that the effects of early cumulative risk on behavioral problems is mediated by maternal responsiveness…

  18. Perceived Support and Internalizing Symptoms in African American Adolescents: Self-Esteem and Ethnic Identity as Mediators

    Science.gov (United States)

    Gaylord-Harden, Noni K.; Ragsdale, Brian L.; Mandara, Jelani; Richards, Maryse H.; Petersen, Anne C.

    2007-01-01

    Existing research leaves a gap in explaining why African American adolescents do not exhibit more anxiety and depression than other youth, at the same time that they experience more contextual risk factors. The current study examined the roles of social support as well as possible mediators self-esteem and ethnic identity (sense of belonging to…

  19. Catastrophizing and internal pain control as mediators of outcome in the multidisciplinary treatment of chronic low back pain.

    NARCIS (Netherlands)

    Spinhoven, P.; Kuile, M. ter; Kole-Snijders, A.M.J.; Hutten Mansfeld, M.; Ouden, D.J. den; Vlaeyen, J.W.S.

    2004-01-01

    The aim of the present study was to examine (a) whether a cognitive-behavioral treatment (differentially) affects pain coping and cognition; and (b) whether changes in pain coping and cognition during treatment mediate treatment outcome. Participants in this randomized clinical trial were 148

  20. Herpes simplex virus internalization into epithelial cells requires Na+/H+ exchangers and p21-activated kinases but neither clathrin- nor caveolin-mediated endocytosis.

    Science.gov (United States)

    Devadas, Deepika; Koithan, Thalea; Diestel, Randi; Prank, Ute; Sodeik, Beate; Döhner, Katinka

    2014-11-01

    Herpes simplex virus 1 (HSV-1) is an alphaherpesvirus that has been reported to infect some epithelial cell types by fusion at the plasma membrane but others by endocytosis. To determine the molecular mechanisms of productive HSV-1 cell entry, we perturbed key endocytosis host factors using specific inhibitors, RNA interference (RNAi), or overexpression of dominant negative proteins and investigated their effects on HSV-1 infection in the permissive epithelial cell lines Vero, HeLa, HEp-2, and PtK2. HSV-1 internalization required neither endosomal acidification nor clathrin- or caveolin-mediated endocytosis. In contrast, HSV-1 gene expression and internalization were significantly reduced after treatment with 5-(N-ethyl-N-isopropyl)amiloride (EIPA). EIPA blocks the activity of Na(+)/H(+) exchangers, which are plasma membrane proteins implicated in all forms of macropinocytosis. HSV-1 internalization furthermore required the function of p21-activated kinases that contribute to macropinosome formation. However, in contrast to some forms of macropinocytosis, HSV-1 did not enlist the activities of protein kinase C (PKC), tyrosine kinases, C-terminal binding protein 1, or dynamin to activate its internalization. These data suggest that HSV-1 depends on Na(+)/H(+) exchangers and p21-activated kinases either for macropinocytosis or for local actin rearrangements required for fusion at the plasma membrane or subsequent passage through the actin cortex underneath the plasma membrane. After initial replication in epithelial cells, herpes simplex viruses (HSVs) establish latent infections in neurons innervating these regions. Upon primary infection and reactivation from latency, HSVs cause many human skin and neurological diseases, particularly in immunocompromised hosts, despite the availability of effective antiviral drugs. Many viruses use macropinocytosis for virus internalization, and many host factors mediating this entry route have been identified, although the

  1. Internalized homophobia as a partial mediator between homophobic bullying and self-esteem among youths of sexual minorities in Quebec (Canada).

    Science.gov (United States)

    Blais, Martin; Gervais, Jesse; Hébert, Martine

    2014-03-01

    Verbal/psychological homophobic bullying is widespread among youths of sexual minorities. Homophobic bullying has been associated with both high internalized homophobia and low self-esteem. The objectives were to document verbal/psychological homophobic bullying among youths of sexual minorities and model the relationships between homophobic bullying, internalized homophobia and self-esteem. A community sample of 300 youths of sexual minorities aged 14 to 22 years old was used. A structural equation model was tested using a nonlinear, robust estimator implemented in Mplus. The model postulated that homophobic bullying impacts self-esteem both directly and indirectly, via internalized homophobia. 60.7% of the sample reported at least one form of verbal/psychological homophobic bullying. The model explained 29% of the variance of self-esteem, 19.6% of the variance of internalized homophobia and 5.3% of the verbal/psychological homophobic bullying. The model suggests that the relationship between verbal/psychological homophobic bullying and self-esteem is partially mediated by internalized homophobia. The results underscore the importance of initiatives to prevent homophobic bullying in order to prevent its negative effects on the well-being of youths of sexual minorities.

  2. Internalized homophobia as a partial mediator between homophobic bullying and self-esteem among youths of sexual minorities in Quebec (Canada

    Directory of Open Access Journals (Sweden)

    Martin Blais

    2014-03-01

    Full Text Available Verbal/psychological homophobic bullying is widespread among youths of sexual minorities. Homophobic bullying has been associated with both high internalized homophobia and low self-esteem. The objectives were to document verbal/psychological homophobic bullying among youths of sexual minorities and model the relationships between homophobic bullying, internalized homophobia and self-esteem. A community sample of 300 youths of sexual minorities aged 14 to 22 years old was used. A structural equation model was tested using a nonlinear, robust estimator implemented in Mplus. The model postulated that homophobic bullying impacts self-esteem both directly and indirectly, via internalized homophobia. 60.7% of the sample reported at least one form of verbal/psychological homophobic bullying. The model explained 29% of the variance of self-esteem, 19.6% of the variance of internalized homophobia and 5.3% of the verbal/psychological homophobic bullying. The model suggests that the relationship between verbal/psychological homophobic bullying and self-esteem is partially mediated by internalized homophobia. The results underscore the importance of initiatives to prevent homophobic bullying in order to prevent its negative effects on the well-being of youths of sexual minorities.

  3. Defining the Locus of Developmental Differences in Children's Causal Reasoning

    Science.gov (United States)

    Siegler, Robert S.

    1975-01-01

    Five experiments were performed in the area of children's causal reasoning to validate a previously reported developmental difference, to examine the role of a possible mediating mechanism, and to test a number of competing theoretical interpretations. (GO)

  4. Associations of Timing of Sexual Orientation Developmental Milestones and Other Sexual Minority Stressors with Internalizing Mental Health Symptoms Among Sexual Minority Young Adults.

    Science.gov (United States)

    Katz-Wise, Sabra L; Rosario, Margaret; Calzo, Jerel P; Scherer, Emily A; Sarda, Vishnudas; Austin, S Bryn

    2017-07-01

    Sexual minorities (mostly heterosexual, bisexual, lesbian/gay) are more likely than heterosexuals to have adverse mental health, which may be related to minority stress. We used longitudinal data from 1461 sexual minority women and men, aged 22-30 years, from Wave 2010 of the Growing Up Today Study, to examine associations between sexual minority stressors and mental health. We hypothesized that sexual minority stressors (earlier timing of sexual orientation developmental milestones categorized into early adolescence, middle adolescence, late adolescence/young adulthood; greater sexual orientation mobility; more bullying victimization) would be positively associated with mental health outcomes (depressive and anxious symptoms). Linear regression models stratified by gender and sexual orientation were fit via generalized estimating equations and controlled for age and race/ethnicity. Models were fit for each stressor predicting each mental health outcome. Reaching sexual minority milestones in early versus middle adolescence was associated with greater depressive and anxious symptoms among lesbians and gay men. Reaching sexual minority milestones in late adolescence/young adulthood versus middle adolescence was associated with greater depressive symptoms among lesbians, but fewer depressive and anxious symptoms among gay men. Greater sexual orientation mobility was associated with greater depressive symptoms among mostly heterosexual women. More bullying victimization was associated with greater depressive symptoms among bisexual women and with greater anxious symptoms among mostly heterosexual women. Sexual minority stressors are associated with adverse mental health among some sexual minority young adults. More research is needed to understand what may be protecting some subgroups from the mental health effects of sexual minority stressors.

  5. International

    International Nuclear Information System (INIS)

    Anon.

    1997-01-01

    This rubric reports on 10 short notes about international economical facts about nuclear power: Electricite de France (EdF) and its assistance and management contracts with Eastern Europe countries (Poland, Hungary, Bulgaria); Transnuclear Inc. company (a 100% Cogema daughter company) acquired the US Vectra Technologies company; the construction of the Khumo nuclear power plant in Northern Korea plays in favour of the reconciliation between Northern and Southern Korea; the delivery of two VVER 1000 Russian reactors to China; the enforcement of the cooperation agreement between Euratom and Argentina; Japan requested for the financing of a Russian fast breeder reactor; Russia has planned to sell a floating barge-type nuclear power plant to Indonesia; the control of the Swedish reactor vessels of Sydkraft AB company committed to Tractebel (Belgium); the renewal of the nuclear cooperation agreement between Swiss and USA; the call for bids from the Turkish TEAS electric power company for the building of the Akkuyu nuclear power plant answered by three candidates: Atomic Energy of Canada Limited (AECL), Westinghouse (US) and the French-German NPI company. (J.S.)

  6. Internalization of U.S. female beauty standards as a mediator of the relationship between Mexican American women's acculturation and body dissatisfaction.

    Science.gov (United States)

    Poloskov, Elizabeth; Tracey, Terence J G

    2013-09-01

    The relationships among acculturation, internalization of U.S. sociocultural standards of female beauty, and body dissatisfaction were examined in a sample of 211 Mexican American college women. Structural equation modeling was used to identify the paths among these three factors. Results demonstrated that there are two distinct types of body dissatisfaction: global evaluations and composite site-specific evaluations. The relationships between acculturation toward dominant U.S. culture and both types of body dissatisfaction were found to be fully mediated by internalization of U.S. standards of female beauty. There were no relationships between Mexican orientation and any of the study variables. The results from this study imply that it is important for therapists working with Mexican American female clients to assess the client's level of acculturation, examine the cultural (U.S. and Mexican) messages the client receives, and explore how these messages impact her body image. Copyright © 2013. Published by Elsevier Ltd.

  7. The effect of phonon-mediated charge transfer and internal proximity effect on the properties of multigap cuprate superconductors

    International Nuclear Information System (INIS)

    Kresin, V.Z.; Wolf, S.A.; Deutscher, G.

    1992-01-01

    The theoretical model capable of calculating the superconducting properties (e.g. Tc, energy gaps, etc) of materials such as Y 1 Ba 2 Cu 3 O 7 which consist of two conducting subsystem (planes and chains) is developed. The system is characterized by two energies gaps. The interplay of two channels (phonon-mediated processes and the intrinsic proximity effect) inducing the superconducting state in the chains is studied. The proximity effect combined with the phonon-mediated channel appears to be favorable for superconductivity. The theory describes the effect of the oxygen ordering on Tc and the induced gap and allows us to explain a number of experiments including the plateau in Tc versus oxygen, the large residual microwave losses, zero-bias anomalies and the temperature dependence of the penetration depth. (orig.)

  8. HER2 monoclonal antibodies that do not interfere with receptor heterodimerization-mediated signaling induce effective internalization and represent valuable components for rational antibody-drug conjugate design.

    Science.gov (United States)

    de Goeij, Bart E C G; Peipp, Matthias; de Haij, Simone; van den Brink, Edward N; Kellner, Christian; Riedl, Thilo; de Jong, Rob; Vink, Tom; Strumane, Kristin; Bleeker, Wim K; Parren, Paul W H I

    2014-01-01

    The human epidermal growth factor receptor (HER)2 provides an excellent target for selective delivery of cytotoxic drugs to tumor cells by antibody-drug conjugates (ADC) as has been clinically validated by ado-trastuzumab emtansine (Kadcyla(TM)). While selecting a suitable antibody for an ADC approach often takes specificity and efficient antibody-target complex internalization into account, the characteristics of the optimal antibody candidate remain poorly understood. We studied a large panel of human HER2 antibodies to identify the characteristics that make them most suitable for an ADC approach. As a model toxin, amenable to in vitro high-throughput screening, we employed Pseudomonas exotoxin A (ETA') fused to an anti-kappa light chain domain antibody. Cytotoxicity induced by HER2 antibodies, which were thus non-covalently linked to ETA', was assessed for high and low HER2 expressing tumor cell lines and correlated with internalization and downmodulation of HER2 antibody-target complexes. Our results demonstrate that HER2 antibodies that do not inhibit heterodimerization of HER2 with related ErbB receptors internalize more efficiently and show greater ETA'-mediated cytotoxicity than antibodies that do inhibit such heterodimerization. Moreover, stimulation with ErbB ligand significantly enhanced ADC-mediated tumor kill by antibodies that do not inhibit HER2 heterodimerization. This suggests that the formation of HER2/ErbB-heterodimers enhances ADC internalization and subsequent killing of tumor cells. Our study indicates that selecting HER2 ADCs that allow piggybacking of HER2 onto other ErbB receptors provides an attractive strategy for increasing ADC delivery and tumor cell killing capacity to both high and low HER2 expressing tumor cells.

  9. Internalization of titanium dioxide nanoparticles by glial cells is given at short times and is mainly mediated by actin reorganization-dependent endocytosis.

    Science.gov (United States)

    Huerta-García, Elizabeth; Márquez-Ramírez, Sandra Gissela; Ramos-Godinez, María Del Pilar; López-Saavedra, Alejandro; Herrera, Luis Alonso; Parra, Alberto; Alfaro-Moreno, Ernesto; Gómez, Erika Olivia; López-Marure, Rebeca

    2015-12-01

    Many nanoparticles (NPs) have toxic effects on multiple cell lines. This toxicity is assumed to be related to their accumulation within cells. However, the process of internalization of NPs has not yet been fully characterized. In this study, the cellular uptake, accumulation, and localization of titanium dioxide nanoparticles (TiO2 NPs) in rat (C6) and human (U373) glial cells were analyzed using time-lapse microscopy (TLM) and transmission electron microscopy (TEM). Cytochalasin D (Cyt-D) was used to evaluate whether the internalization process depends of actin reorganization. To determine whether the NP uptake is mediated by phagocytosis or macropinocytosis, nitroblue tetrazolium (NBT) reduction was measured and the 5-(N-ethyl-N-isopropyl)-amiloride was used. Expression of proteins involved with endocytosis and exocytosis such as caveolin-1 (Cav-1) and cysteine string proteins (CSPs) was also determined using flow cytometry. TiO2 NPs were taken up by both cell types, were bound to cellular membranes and were internalized at very short times after exposure (C6, 30 min; U373, 2h). During the uptake process, the formation of pseudopodia and intracellular vesicles was observed, indicating that this process was mediated by endocytosis. No specific localization of TiO2 NPs into particular organelles was found: in contrast, they were primarily localized into large vesicles in the cytoplasm. Internalization of TiO2 NPs was strongly inhibited by Cyt-D in both cells and by amiloride in U373 cells; besides, the observed endocytosis was not associated with NBT reduction in either cell type, indicating that macropinocytosis is the main process of internalization in U373 cells. In addition, increases in the expression of Cav-1 protein and CSPs were observed. In conclusion, glial cells are able to internalize TiO2 NPs by a constitutive endocytic mechanism which may be associated with their strong cytotoxic effect in these cells; therefore, TiO2 NPs internalization and their

  10. PGE2 mediates EGFR internalization and nuclear translocation via caveolin endocytosis promoting its transcriptional activity and proliferation in human NSCLC cells.

    Science.gov (United States)

    Bazzani, Lorenzo; Donnini, Sandra; Giachetti, Antonio; Christofori, Gerhard; Ziche, Marina

    2018-03-13

    Prostaglandin E 2 (PGE 2 ) contributes to tumor progression by promoting cancer cell growth, invasion and by creating a favorable pro-tumor microenvironment. PGE 2 has been reported to transactivate and internalize into the nucleus receptor tyrosine kinases such as Epidermal growth factor receptor (EGFR), thereby supporting tumor progression. Here we demonstrate that in non-small cell lung carcinoma (NSCLC) cells, PGE 2 induces EGFR nuclear translocation via different dynamin-dependent endocytic pathways, promotes the formation of an EGFR-STAT3 complex, affects nuclear EGFR target gene expression and mediates tumor cell proliferation. Indeed, we find that PGE 2 induces EGFR internalization and consequent nuclear import through Clathrin- and Caveolin-mediated endocytosis and through the interaction of EGFR with Importin β1. Within the nucleus, EGFR forms a complex with STAT3, an event blocked by ablation of Clathrin Heavy Chain or Caveolin-1. The combination of EGF and PGE 2 prolongs nuclear EGFR transcriptional activity manifested by the upregulation of CCND1 , PTGS2 , MYC and NOS2 mRNA levels and potentiates nuclear EGFR-induced NSCLC cell proliferation. Additionally, NSCLC patients with high expression of a nuclear EGFR gene signature display shorter survival times than those with low expression, thus showing a putative correlation between nuclear EGFR and poor prognosis in NSCLC. Together, our findings indicate a complex mechanism underlying PGE 2 -induced EGF/EGFR signaling and transcriptional control, which plays a key role in cancer progression.

  11. A serial mediation model testing early adversity, self-concept clarity, and thin-ideal internalization as predictors of body dissatisfaction.

    Science.gov (United States)

    Vartanian, Lenny R; Froreich, Franzisca V; Smyth, Joshua M

    2016-12-01

    This study examined the associations among early family adversity (e.g., family violence, neglect), self-concept clarity (i.e., having a clear and coherent sense of one's own personal identity), thin-ideal internalization, and body dissatisfaction. Female university students in Australia (n=323) and adult female community members in the United States (n=371) completed self-report measures of the relevant constructs. In both samples, serial mediation analysis revealed that early family adversity was negatively associated with self-concept clarity, self-concept clarity was negatively associated with thin-ideal internalization, and thin-ideal internalization was positively associated with body dissatisfaction. These findings suggest that early adverse experiences might impair individuals' self-concept clarity, and that low self-concept clarity might increase the risk of internalization of the thin ideal (as a means of defining the self) and consequently body dissatisfaction. These findings also suggest possible avenues for prevention and intervention efforts. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. The Domain of Developmental Psychopathology.

    Science.gov (United States)

    Sroufe, L. Alan; Rutter, Michael

    1984-01-01

    Describes how developmental psychopathology differs from related disciplines, including abnormal psychology, psychiatry, clinical child psychology, and developmental psychology. Points out propositions underlying a developmental perspective and discusses implications for research in developmental psychopathology. (Author/RH)

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

    Science.gov (United States)

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

    2018-05-01

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

  14. [The role of parental support in the relationship between homophobic bullying, internalized homophobia and psychological distress among sexual-minority youths (SMY): a moderated mediation approach].

    Science.gov (United States)

    Bergeron, Félix-Antoine; Blais, Martin; Hébert, Martine

    Introduction Sexual-minority youths (SMY) report high rates of psychological distress such as depression, anxiety and suicidal ideation (Burton, Marshal, Chisolm, Sucato et Friedman, 2013; Williams & Chapman, 2011). Several studies confirm that the poor mental health outcomes are partly related to their high likelihood of experiencing homophobic victimization (Blais, Gervais, Boucher, Hébert & Lavoie, 2013; Taylor & Peter, 2011; Hughes, McCabe, Wilsnack, West & Boyd, 2010; Chamberland, Richard & Bernier, 2013). Whereas the development of a positive sexual minority identity is crucial for the mental health of SMY (Chamberland, Richard & Chevrier, 2011; Rosario, Schrimshaw & Hunter, 2011; Luhtanen, 2002), the victimization they experience put them at risk of internalizing societal homophobia and heterosexism (Meyer, 2003; Hatzenbuehler, 2009). It is important to identify variables that may influence the impact of distal and proximal factors that impact SMY's mental health.Objectives The objectives of this paper are 1) to document different forms of homophobic victimization experienced by SMY, according to gender and age, and 2) to test the potential moderating effect of parental support in the relationship between homophobic victimization, internalized homophobia and psychological distress.Method Data come from 228 SMY aged 14 to 22 years old recruited through online means as part of the Quebec Youth's Romantic Relationships Survey. The impact of homophobic victimization, parental support, and internalized homophobia on psychological distress is explored by a linear regression model including moderated mediation effects.Results Results show the relationship between homophobic victimization and psychological distress as well as indirect significant relationship through internalized homophobia. The moderated mediation analysis also confirms the moderating role of parental support in the relationship between homophobic victimization and psychological distress. Thus

  15. Prenatal Internal Locus of Control Is Positively Associated with Offspring IQ, Mediated through Parenting Behavior, Prenatal Lifestyle and Social Circumstances

    Directory of Open Access Journals (Sweden)

    Jean Golding

    2017-08-01

    Full Text Available Locus of control (LOC is a measure that identifies the likelihood as to whether an individual considers what happens to him is largely a matter of luck or fate (known as externally oriented or whether it is something that the individual can influence (internality. Here we have used data collected as part of the Avon Longitudinal Study of Parents and Children (ALSPAC to determine the associations between the mothers’ LOC orientation before the birth of the child and her child’s cognition measured at age 8. Using results from 6801 children we show that maternal internal LOC is associated with increased ability in offspring IQ, as measured using the WISC, with children of internally oriented mothers having an advantage of approximately 7 IQ points at age 8. As a sensitivity analysis we used the IQ test results of a sample of 986 preschool children tested using the WPSSI at age 4. A similar advantage was found among the offspring of the internally oriented mothers. We investigated mechanistic explanations for these results firstly by determining the extent to which three separate sets of factors known to be influenced by the LOC orientation might explain these findings. We showed that (a perinatal life-style exposures, (b parenting attitudes and strategies and (c socio-economic circumstances, largely explain the mechanism through which the internality of the mother influences the cognition of the child. Similar effects were found using the smaller sample tested at age 4. The results indicate that efforts made to foster internality in adolescents and young adults prior to parenthood may result in improvements in the cognitive development of the next generation. Intervention studies are urgently needed.

  16. Prenatal Internal Locus of Control Is Positively Associated with Offspring IQ, Mediated through Parenting Behavior, Prenatal Lifestyle and Social Circumstances.

    Science.gov (United States)

    Golding, Jean; Gregory, Steven; Ellis, Genette L; Iles-Caven, Yasmin; Nowicki, Stephen

    2017-01-01

    Locus of control (LOC) is a measure that identifies the likelihood as to whether an individual considers what happens to him is largely a matter of luck or fate (known as externally oriented) or whether it is something that the individual can influence (internality). Here we have used data collected as part of the Avon Longitudinal Study of Parents and Children (ALSPAC) to determine the associations between the mothers' LOC orientation before the birth of the child and her child's cognition measured at age 8. Using results from 6801 children we show that maternal internal LOC is associated with increased ability in offspring IQ, as measured using the WISC, with children of internally oriented mothers having an advantage of approximately 7 IQ points at age 8. As a sensitivity analysis we used the IQ test results of a sample of 986 preschool children tested using the WPSSI at age 4. A similar advantage was found among the offspring of the internally oriented mothers. We investigated mechanistic explanations for these results firstly by determining the extent to which three separate sets of factors known to be influenced by the LOC orientation might explain these findings. We showed that (a) perinatal life-style exposures, (b) parenting attitudes and strategies and (c) socio-economic circumstances, largely explain the mechanism through which the internality of the mother influences the cognition of the child. Similar effects were found using the smaller sample tested at age 4. The results indicate that efforts made to foster internality in adolescents and young adults prior to parenthood may result in improvements in the cognitive development of the next generation. Intervention studies are urgently needed.

  17. Size-dependent internalization of particles via the pathways of clathrin-and caveolae-mediated endocytosis

    NARCIS (Netherlands)

    Rejman, J; Oberle, [No Value; Zuhorn, IS; Hoekstra, D

    2004-01-01

    Non-phagocytic eukaryotic cells can internalize particles <1 mum in size, encompassing pathogens, liposomes for drug delivery or lipoplexes applied in gene delivery. In the present study, we have investigated the effect of particle size on the pathway of entry and subsequent intracellular fate in

  18. Activatory and inhibitory Fcγ receptors augment rituximab-mediated internalization of CD20 independent of signaling via the cytoplasmic domain.

    Science.gov (United States)

    Vaughan, Andrew T; Chan, Claude H T; Klein, Christian; Glennie, Martin J; Beers, Stephen A; Cragg, Mark S

    2015-02-27

    Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Developmental immunotoxicity testing of 4-methyl anisole.

    Science.gov (United States)

    Tonk, Elisa C M; Verhoef, Aart; Gremmer, Eric R; van Loveren, Henk; Piersma, Aldert H

    2015-07-01

    The developmental immunotoxicity of 4-methyl anisole (4MA) was investigated in the rat. Four study designs were used, with either premating or post-weaning onset of exposure, continued to postnatal day 50, and with or without additional oral gavage of pups from postnatal day 10 onward. Reduced litter size (benchmark dose lower confidence limit (BMDL) 80mg/kg bw/day) was the most sensitive developmental parameter, with pup relative organ weight effects observed at similar BMDLs, in the absence of maternal toxicity. Eosinophil numbers were reduced at lower doses (BMDL 16mg/kg bw/day). KLH challenge resulted in increased IL-13 and TNF-α responses, and variably reduced IgG production (BMDL 27mg/kg bw/day). T4 levels were reduced by 11% at maximum with a BMDL of 73mg/kg bw/day. Differences between exposure cohorts were limited and were considered to be without biological significance. This study shows that 4MA induces developmental immunotoxicity at doses below those inducing developmental and general toxicity. These observations being independent of the study designs applied suggest that the post-weaning period, included in all designs, is the most relevant sensitive period for inducing 4MA mediated developmental immunotoxicity. Moreover, this study stresses the importance of including developmental immunotoxicity testing by default in regulatory toxicology. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. How Does Stigma Affect People Living with HIV? The Mediating Roles of Internalized and Anticipated HIV Stigma in the Effects of Perceived Community Stigma on Health and Psychosocial Outcomes.

    Science.gov (United States)

    Turan, Bulent; Budhwani, Henna; Fazeli, Pariya L; Browning, Wesley R; Raper, James L; Mugavero, Michael J; Turan, Janet M

    2017-01-01

    Few researchers have attempted to examine the mechanisms through which HIV-related stigma in the community is processed and experienced at an individual level by people living with HIV. We examined how the effects of perceived HIV stigma in the community on health outcomes for people living with HIV are mediated by internalized stigma and anticipated stigma. Participants (N = 203) from an HIV clinic completed self-report measures and their clinical data were obtained from medical records. Results suggested that the association between perceived community stigma and affective, cognitive, and mental health outcomes (self-esteem, depressive symptoms, avoidance coping, self-blame) are mediated by internalized stigma. Furthermore, a serial mediation model suggested that perceived community stigma leads to internalized stigma, which leads to anticipated community stigma, which in turn leads to lower medication adherence. The associations between perceived community stigma and interpersonal outcomes (social support, trust in physicians) were mediated by internalized stigma and anticipated stigma, again in a serial fashion (perceived community stigma leads to internalized stigma, which leads to anticipated stigma, which in turn leads to interpersonal outcomes). These results suggest that perceived HIV-related stigma in the community may cause people living with HIV to internalize stigma and anticipate stigmatizing experiences, resulting in adverse health and psychosocial outcomes-information that can be used to shape interventions.

  1. How Does Stigma Affect People Living with HIV? The Mediating Roles of Internalized and Anticipated HIV Stigma in the Effects of Perceived Community Stigma on Health and Psychosocial Outcomes

    Science.gov (United States)

    Budhwani, Henna; Fazeli, Pariya L.; Browning, Wesley R.; Raper, James L.; Mugavero, Michael J.; Turan, Janet M.

    2016-01-01

    Few researchers have attempted to examine the mechanisms through which HIV-related stigma in the community is processed and experienced at an individual level by people living with HIV. We examined how the effects of perceived HIV stigma in the community on health outcomes for people living with HIV are mediated by internalized stigma and anticipated stigma. Participants (N = 203) from an HIV clinic completed self-report measures and their clinical data were obtained from medical records. Results suggested that the association between perceived community stigma and affective, cognitive, and mental health outcomes (self-esteem, depressive symptoms, avoidance coping, self-blame) are mediated by internalized stigma. Furthermore, a serial mediation model suggested that perceived community stigma leads to internalized stigma, which leads to anticipated community stigma, which in turn leads to lower medication adherence. The associations between perceived community stigma and interpersonal outcomes (social support, trust in physicians) were mediated by internalized stigma and anticipated stigma, again in a serial fashion (perceived community stigma leads to internalized stigma, which leads to anticipated stigma, which in turn leads to interpersonal outcomes). These results suggest that perceived HIV-related stigma in the community may cause people living with HIV to internalize stigma and anticipate stigmatizing experiences, resulting in adverse health and psychosocial outcomes—information that can be used to shape interventions. PMID:27272742

  2. Protein kinase A-induced internalization of Slack channels from the neuronal membrane occurs by adaptor protein-2/clathrin-mediated endocytosis.

    Science.gov (United States)

    Gururaj, Sushmitha; Evely, Katherine M; Pryce, Kerri D; Li, Jun; Qu, Jun; Bhattacharjee, Arin

    2017-11-24

    The sodium-activated potassium (K Na ) channel Kcnt1 (Slack) is abundantly expressed in nociceptor (pain-sensing) neurons of the dorsal root ganglion (DRG), where they transmit the large outward conductance I KNa and arbitrate membrane excitability. Slack channel expression at the DRG membrane is necessary for their characteristic firing accommodation during maintained stimulation, and reduced membrane channel density causes hyperexcitability. We have previously shown that in a pro-inflammatory state, a decrease in membrane channel expression leading to reduced Slack-mediated I KNa expression underlies DRG neuronal sensitization. An important component of the inflammatory milieu, PKA internalizes Slack channels from the DRG membrane, reduces I KNa , and produces DRG neuronal hyperexcitability when activated in cultured primary DRG neurons. Here, we show that this PKA-induced retrograde trafficking of Slack channels also occurs in intact spinal cord slices and that it is carried out by adaptor protein-2 (AP-2) via clathrin-mediated endocytosis. We provide mass spectrometric and biochemical evidence of an association of native neuronal AP-2 adaptor proteins with Slack channels, facilitated by a dileucine motif housed in the cytoplasmic Slack C terminus that binds AP-2. By creating a competitive peptide blocker of AP-2-Slack binding, we demonstrated that this interaction is essential for clathrin recruitment to the DRG membrane, Slack channel endocytosis, and DRG neuronal hyperexcitability after PKA activation. Together, these findings uncover AP-2 and clathrin as players in Slack channel regulation. Given the significant role of Slack in nociceptive neuronal excitability, the AP-2 clathrin-mediated endocytosis trafficking mechanism may enable targeting of peripheral and possibly, central neuronal sensitization. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Adolescents Who are Less Religious than Their Parents are at Risk for Externalizing and Internalizing Symptoms: The Mediating Role of Parent-Adolescent Relationship Quality

    Science.gov (United States)

    Kim-Spoon, Jungmeen; Longo, Gregory S.; McCullough, Michael E.

    2012-01-01

    Parents generally take pains to insure that their children adopt their own religious beliefs and practices, so what happens psychologically to adolescents who find themselves less religious than their parents? We examined the relationships among parents’ and adolescents’ religiousness, adolescents’ ratings of parent-adolescent relationship quality, and adolescents’ psychological adjustment using data from 322 adolescents and their parents. Adolescent boys who had lower organizational and personal religiousness than their parents, and girls who had lower personal religiousness than their parents, had more internalizing and externalizing psychological symptoms than did adolescents whose religiousness better matched their parents’. The apparent effects of sub-parental religiousness on adolescents’ psychological symptoms were mediated by their intermediate effects on adolescents’ ratings of the quality of their relationships with their parents. These findings identify religious discrepancies between parents and their children as an important influence on the quality of parent-adolescent relationships, with important implications for adolescents’ psychological well-being. PMID:22888785

  4. The Influence of Personal Well-Being on Learning Achievement in University Students Over Time: Mediating or Moderating Effects of Internal and External University Engagement

    Directory of Open Access Journals (Sweden)

    Lu Yu

    2018-01-01

    Full Text Available The current study examined the relationship between students' personal well-being and their learning achievement during university study, and whether such relationship would be mediated or moderated by university engagement. A total of 434 university students from one public university in Hong Kong participated in the study. The participants completed an online survey consisting of personal well-being (cognitive behavioral competence and general positive youth development, university engagement, and learning achievement measures (personal growth, and accumulated GPA as academic achievement at four time points with a 1-year interval. Results showed that personal well-being measured at the beginning of university study positively predicted students' personal growth and academic achievement after 3 years' study. While the internal dimensions of university engagement (academic challenge and learning with peers showed longitudinal significant mediational effect, the external dimensions (experience with faculty and campus environment did not have significant longitudinal moderating effect. Nevertheless, external dimensions of student engagement also showed direct effect on personal growth and academic achievement. The long-standing positive effects of personal well-being on university engagement and subsequently, learning achievement during university years call for more attention to the promotion of holistic development among university students in Hong Kong.

  5. The Influence of Personal Well-Being on Learning Achievement in University Students Over Time: Mediating or Moderating Effects of Internal and External University Engagement

    Science.gov (United States)

    Yu, Lu; Shek, Daniel T. L.; Zhu, Xiaoqin

    2018-01-01

    The current study examined the relationship between students' personal well-being and their learning achievement during university study, and whether such relationship would be mediated or moderated by university engagement. A total of 434 university students from one public university in Hong Kong participated in the study. The participants completed an online survey consisting of personal well-being (cognitive behavioral competence and general positive youth development), university engagement, and learning achievement measures (personal growth, and accumulated GPA as academic achievement) at four time points with a 1-year interval. Results showed that personal well-being measured at the beginning of university study positively predicted students' personal growth and academic achievement after 3 years' study. While the internal dimensions of university engagement (academic challenge and learning with peers) showed longitudinal significant mediational effect, the external dimensions (experience with faculty and campus environment) did not have significant longitudinal moderating effect. Nevertheless, external dimensions of student engagement also showed direct effect on personal growth and academic achievement. The long-standing positive effects of personal well-being on university engagement and subsequently, learning achievement during university years call for more attention to the promotion of holistic development among university students in Hong Kong. PMID:29375421

  6. Identifying intrinsic and extrinsic determinants that regulate internal initiation of translation mediated by the FMR1 5' leader

    Directory of Open Access Journals (Sweden)

    Timmerman Stephanie

    2008-10-01

    Full Text Available Abstract Background Regulating synthesis of the Fragile X gene (FMR1 product, FMRP alters neural plasticity potentially through its role in the microRNA pathway. Cap-dependent translation of the FMR1 mRNA, a process requiring ribosomal scanning through the 5' leader, is likely impeded by the extensive secondary structure generated by the high guanosine/cytosine nucleotide content including the CGG triplet nucleotide repeats in the 5' leader. An alternative mechanism to initiate translation – internal initiation often utilizes secondary structure to recruit the translational machinery. Consequently, studies were undertaken to confirm and extend a previous observation that the FMR1 5' leader contains an internal ribosomal entry site (IRES. Results Cellular transfection of a dicistronic DNA construct containing the FMR1 5' leader inserted into the intercistronic region yielded significant translation of the second cistron, but the FMR1 5' leader was also found to contain a cryptic promoter possibly confounding interpretation of these results. However, transfection of dicistronic and monocistronic RNA ex vivo or in vitro confirmed that the FMR1 5' leader contains an IRES. Moreover, inhibiting cap-dependent translation ex vivo did not affect the expression level of endogenous FMRP indicating a role for IRES-dependent translation of FMR1 mRNA. Analysis of the FMR1 5' leader revealed that the CGG repeats and the 5' end of the leader were vital for internal initiation. Functionally, exposure to potassium chloride or intracellular acidification and addition of polyinosinic:polycytidylic acid as mimics of neural activity and double stranded RNA, respectively, differentially affected FMR1 IRES activity. Conclusion Our results indicate that multiple stimuli influence IRES-dependent translation of the FMR1 mRNA and suggest a functional role for the CGG nucleotide repeats.

  7. Enhancement of internal ribosome entry site-mediated translation and replication of hepatitis C virus by PD98059

    International Nuclear Information System (INIS)

    Murata, Takayuki; Hijikata, Makoto; Shimotohno, Kunitada

    2005-01-01

    Translation initiation of hepatitis C virus (HCV) occurs in an internal ribosome entry site (IRES)-dependent manner. We found that HCV IRES-dependent protein synthesis is enhanced by PD98059, an inhibitor of the extracellular signal-regulated kinase (ERK) signaling pathway, while cellular cap-dependent translation was relatively unaffected by the compound. Treatment of cells with PD98059 allowed for robust HCV replication following cellular incubation with HCV-positive serum. Though the molecular mechanism underlying IRES enhancement remains elusive, PD98059 is a potent accelerator of HCV RNA replication

  8. Policy-relevant behaviours predict heavier drinking and mediate the relationship with age, gender and education status: Analysis from the International Alcohol Control study.

    Science.gov (United States)

    Casswell, Sally; Huckle, Taisia; Wall, Martin; Parker, Karl; Chaiyasong, Surasak; Parry, Charles D H; Viet Cuong, Pham; Gray-Phillip, Gaile; Piazza, Marina

    2018-02-21

    To investigate behaviours related to four alcohol policy variables (policy-relevant behaviours) and demographic variables in relation to typical quantities of alcohol consumed on-premise in six International Alcohol Control study countries. General population surveys with drinkers using a comparable survey instrument and data analysed using path analysis in an overall model and for each country. typical quantities per occasion consumed on-premise; gender, age; years of education, prices paid, time of purchase, time to access alcohol and liking for alcohol advertisements. In the overall model younger people, males and those with fewer years of education consumed larger typical quantities. Overall lower prices paid, later time of purchase and liking for alcohol ads predicted consuming larger typical quantities; this was found in the high-income countries, less consistently in the high-middle-income countries and not in the low middle-income country. Three policy-relevant behaviours (prices paid, time of purchase, liking for alcohol ads) mediated the relationships between age, gender, education and consumption in high-income countries. International Alcohol Control survey data showed a relationship between policy-relevant behaviours and typical quantities consumed and support the likely effect of policy change (trading hours, price and restrictions on marketing) on heavier drinking. The path analysis also revealed policy-relevant behaviours were significant mediating variables between the effect of age, gender and educational status on consumption. However, this relationship is clearest in high-income countries. Further research is required to understand better how circumstances in low-middle-income countries impact effects of policies. © 2018 The Authors Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.

  9. Reproductive and developmental toxicology

    National Research Council Canada - National Science Library

    Gupta, Ramesh C

    2011-01-01

    .... Reproductive and Developmental Toxicology is a comprehensive and authoritative resource providing the latest literature enriched with relevant references describing every aspect of this area of science...

  10. Open Abdomen Therapy with Vacuum and Mesh Mediated Fascial Traction After Aortic Repair: an International Multicentre Study.

    Science.gov (United States)

    Acosta, Stefan; Seternes, Arne; Venermo, Maarit; Vikatmaa, Leena; Sörelius, Karl; Wanhainen, Anders; Svensson, Mats; Djavani, Khatereh; Björck, Martin

    2017-12-01

    Open abdomen therapy may be necessary to prevent or treat abdominal compartment syndrome (ACS). The aim of the study was to analyse the primary delayed fascial closure (PDFC) rate and complications after open abdomen therapy with vacuum and mesh mediated fascial traction (VACM) after aortic repair and to compare outcomes between those treated with open abdomen after primary versus secondary operation. This was a retrospective cohort, multicentre study in Sweden, Finland, and Norway, including consecutive patients treated with open abdomen and VACM after aortic repair at six vascular centres in 2006-2015. The primary endpoint was PDFC rate. Among 191 patients, 155 were men. The median age was 71 years (IQR 66-76). Ruptured abdominal aortic aneurysm (RAAA) occurred in 69.1%. Endovascular/hybrid and open repairs were performed in 49 and 142 patients, respectively. The indications for open abdomen were inability to close the abdomen (62%) at primary operation and ACS (80%) at secondary operation. Duration of open abdomen was 11 days (IQR 7-16) in 157 patients alive at open abdomen termination. The PDFC rate was 91.8%. Open abdomen initiated at primary (N=103), compared with secondary operation (N=88), was associated with less severe initial open abdomen status (p=.006), less intestinal ischaemia (p=.002), shorter duration of open abdomen (p=.007), and less renal replacement therapy (RRT, popen abdomen initiated at primary versus secondary operation. VACM was associated with a high PDFC rate after prolonged open abdomen therapy following aortic repair. Patient outcomes seemed better when open abdomen was initiated at primary, compared with secondary operation but a selection effect is possible. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  11. Evaluation of an Internally Controlled Multiplex Tth Endonuclease Cleavage Loop-Mediated Isothermal Amplification (TEC-LAMP Assay for the Detection of Bacterial Meningitis Pathogens

    Directory of Open Access Journals (Sweden)

    Owen Higgins

    2018-02-01

    Full Text Available Bacterial meningitis infection is a leading global health concern for which rapid and accurate diagnosis is essential to reduce associated morbidity and mortality. Loop-mediated isothermal amplification (LAMP offers an effective low-cost diagnostic approach; however, multiplex LAMP is difficult to achieve, limiting its application. We have developed novel real-time multiplex LAMP technology, TEC-LAMP, using Tth endonuclease IV and a unique LAMP primer/probe. This study evaluates the analytical specificity, limit of detection (LOD and clinical application of an internally controlled multiplex TEC-LAMP assay for detection of leading bacterial meningitis pathogens: Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae. Analytical specificities were established by testing 168 bacterial strains, and LODs were determined using Probit analysis. The TEC-LAMP assay was 100% specific, with LODs for S. pneumoniae, N. meningitidis and H. influenzae of 39.5, 17.3 and 25.9 genome copies per reaction, respectively. Clinical performance was evaluated by testing 65 archived PCR-positive samples. Compared to singleplex real-time PCR, the multiplex TEC-LAMP assay demonstrated diagnostic sensitivity and specificity of 92.3% and 100%, respectively. This is the first report of a single-tube internally controlled multiplex LAMP assay for bacterial meningitis pathogen detection, and the first report of Tth endonuclease IV incorporation into nucleic acid amplification diagnostic technology.

  12. Evaluation of an Internally Controlled Multiplex Tth Endonuclease Cleavage Loop-Mediated Isothermal Amplification (TEC-LAMP) Assay for the Detection of Bacterial Meningitis Pathogens

    Science.gov (United States)

    Clancy, Eoin; Cormican, Martin; Boo, Teck Wee; Cunney, Robert

    2018-01-01

    Bacterial meningitis infection is a leading global health concern for which rapid and accurate diagnosis is essential to reduce associated morbidity and mortality. Loop-mediated isothermal amplification (LAMP) offers an effective low-cost diagnostic approach; however, multiplex LAMP is difficult to achieve, limiting its application. We have developed novel real-time multiplex LAMP technology, TEC-LAMP, using Tth endonuclease IV and a unique LAMP primer/probe. This study evaluates the analytical specificity, limit of detection (LOD) and clinical application of an internally controlled multiplex TEC-LAMP assay for detection of leading bacterial meningitis pathogens: Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae. Analytical specificities were established by testing 168 bacterial strains, and LODs were determined using Probit analysis. The TEC-LAMP assay was 100% specific, with LODs for S. pneumoniae, N. meningitidis and H. influenzae of 39.5, 17.3 and 25.9 genome copies per reaction, respectively. Clinical performance was evaluated by testing 65 archived PCR-positive samples. Compared to singleplex real-time PCR, the multiplex TEC-LAMP assay demonstrated diagnostic sensitivity and specificity of 92.3% and 100%, respectively. This is the first report of a single-tube internally controlled multiplex LAMP assay for bacterial meningitis pathogen detection, and the first report of Tth endonuclease IV incorporation into nucleic acid amplification diagnostic technology. PMID:29425124

  13. Meeting the New Challenges to International Mediation : Report from an international symposium at the Department of Peace and Conflict Research, Uppsala University, Uppsala, Sweden, June 14-16, 2010

    OpenAIRE

    Lindgren, Mathilda; Wallensteen, Peter; Grusell, Helena

    2010-01-01

    The discussions of the Uppsala symposium on Mediation in June 2010 highlighted a number of issues novel either to researchers or to practitioners. The meeting was organized around eight such themes. In short, the discussions showed that there are selections effects which makes the evaluation of success in mediation very difficult (more difficult conflicts get more mediation attempts), and that a biased mediator or mediation mandating actor is not always negative. If a conflict is about the co...

  14. Transnational mediation: a practical approach in the treatment of private international relationships / Mediación transnacional: una aproximación práctica en el ámbito de las relaciones privadas internacionales

    Directory of Open Access Journals (Sweden)

    Carmelo Hernández Ramos

    2015-10-01

    Full Text Available Conflict resolution through mediation, in the course of private international relationships and in the context of multiculturalism, particularly when it involves individuals from other countries or cultures requires robust tools for conflict management and efficient negotiation skills. In the resolution of civil or commercial conflicts and, in general, in the camp of international private mediation, is necessary to know and apply strategies and specific skills to resolve conflicts that must be addressed having in mind his legal aspects, along with his interdisciplinary characteristics and specially his intercultural nature. Why then is good to use mediation as a tool to solve a conflict in this so complex area? Because it aims to solve disputes avoiding lengthy and costly procedures for the persons, which involves the incorporation of conflict management techniques, together with negotiation skills and communication strategies and extrajudicial settlement of disputes raised.

  15. Cavin-1/PTRF alters prostate cancer cell-derived extracellular vesicle content and internalization to attenuate extracellular vesicle-mediated osteoclastogenesis and osteoblast proliferation

    Directory of Open Access Journals (Sweden)

    Kerry L. Inder

    2014-06-01

    Full Text Available Background: Tumour-derived extracellular vesicles (EVs play a role in tumour progression; however, the spectrum of molecular mechanisms regulating EV secretion and cargo selection remain to be fully elucidated. We have reported that cavin-1 expression in prostate cancer PC3 cells reduced the abundance of a subset of EV proteins, concomitant with reduced xenograft tumour growth and metastasis. Methods: We examined the functional outcomes and mechanisms of cavin-1 expression on PC3-derived EVs (PC3-EVs. Results: PC3-EVs were internalized by osteoclast precursor RAW264.7 cells and primary human osteoblasts (hOBs in vitro, stimulating osteoclastogenesis 37-fold and hOB proliferation 1.5-fold, respectively. Strikingly, EVs derived from cavin-1-expressing PC3 cells (cavin-1-PC3-EVs failed to induce multinucleate osteoblasts or hOB proliferation. Cavin-1 was not detected in EVs, indicating an indirect mechanism of action. EV morphology, size and quantity were also not affected by cavin-1 expression, suggesting that cavin-1 modulated EV cargo recruitment rather than release. While cavin-1-EVs had no osteoclastogenic function, they were internalized by RAW264.7 cells but at a reduced efficiency compared to control EVs. EV surface proteins are required for internalization of PC3-EVs by RAW264.7 cells, as proteinase K treatment abolished uptake of both control and cavin-1-PC3-EVs. Removal of sialic acid modifications by neuraminidase treatment increased the amount of control PC3-EVs internalized by RAW264.7 cells, without affecting cavin-1-PC3-EVs. This suggests that cavin-1 expression altered the glycosylation modifications on PC3-EV surface. Finally, cavin-1 expression did not affect EV in vivo tissue targeting as both control and cavin-1-PC3-EVs were predominantly retained in the lung and bone 24 hours after injection into mice. Discussion: Taken together, our results reveal a novel pathway for EV cargo sorting, and highlight the potential of utilizing

  16. Life Span Developmental Approach

    Directory of Open Access Journals (Sweden)

    Ali Eryilmaz

    2011-03-01

    Full Text Available The Life Span Developmental Approach examines development of individuals which occurs from birth to death. Life span developmental approach is a multi-disciplinary approach related with disciplines like psychology, psychiatry, sociology, anthropology and geriatrics that indicates the fact that development is not completed in adulthood, it continues during the life course. Development is a complex process that consists of dying and death. This approach carefully investigates the development of individuals with respect to developmental stages. This developmental approach suggests that scientific disciplines should not explain developmental facts only with age changes. Along with aging, cognitive, biological, and socioemotional development throughout life should also be considered to provide a reasonable and acceptable context, guideposts, and reasonable expectations for the person. There are three important subjects whom life span developmental approach deals with. These are nature vs nurture, continuity vs discontinuity, and change vs stability. Researchers using life span developmental approach gather and produce knowledge on these three most important domains of individual development with their unique scientific methodology.

  17. S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization[S

    Science.gov (United States)

    Lee, Mi-Hye; Appleton, Kathryn M.; El-Shewy, Hesham M.; Sorci-Thomas, Mary G.; Thomas, Michael J.; Lopes-Virella, Maria F.; Luttrell, Louis M.; Hammad, Samar M.; Klein, Richard L.

    2017-01-01

    HDL normally transports about 50–70% of plasma sphingosine 1-phosphate (S1P), and the S1P in HDL reportedly mediates several HDL-associated biological effects and signaling pathways. The HDL receptor, SR-BI, as well as the cell surface receptors for S1P (S1PRs) may be involved partially and/or completely in these HDL-induced processes. Here we investigate the nature of the HDL-stimulated interaction between the HDL receptor, SR-BI, and S1PR1 using a protein-fragment complementation assay and confocal microscopy. In both primary rat aortic vascular smooth muscle cells and HEK293 cells, the S1P content in HDL particles increased intracellular calcium concentration, which was mediated by S1PR1. Mechanistic studies performed in HEK293 cells showed that incubation of cells with HDL led to an increase in the physical interaction between the SR-BI and S1PR1 receptors that mainly occurred on the plasma membrane. Model recombinant HDL (rHDL) particles formed in vitro with S1P incorporated into the particle initiated the internalization of S1PR1, whereas rHDL without supplemented S1P did not, suggesting that S1P transported in HDL can selectively activate S1PR1. In conclusion, these data suggest that S1P in HDL stimulates the transient interaction between SR-BI and S1PRs that can activate S1PRs and induce an elevation in intracellular calcium concentration. PMID:27881715

  18. Pacemaker Therapy in Patients With Neurally Mediated Syncope and Documented Asystole Third International Study on Syncope of Uncertain Etiology (ISSUE-3) A Randomized Trial

    NARCIS (Netherlands)

    Brignole, Michele; Menozzi, Carlo; Moya, Angel; Andresen, Dietrich; Blanc, Jean Jacques; Krahn, Andrew D.; Wieling, Wouter; Beiras, Xulio; Deharo, Jean Claude; Russo, Vitantonio; Tomaino, Marco; Sutton, Richard; Tomaino, M.; Pescoller, F.; Donateo, P.; Oddone, D.; Russo, V.; Pierri, F.; Matino, M. G.; Vitale, E.; Massa, R.; Piccinni, G.; Melissano, D.; Menozzi, C.; Lolli, G.; Gulizia, M.; Francese, M.; Iorfida, M.; Golzio, P.; Gaggioli, G.; Laffi, M.; Rabjoli, F.; Cecchinato, C.; Ungar, A.; Rafanelli, M.; Chisciotti, V.; Morrione, A.; del Rosso, A.; Guernaccia, V.; Palella, M.; D'Agostino, C.; Campana, A.; Brigante, M.; Miracapillo, G.; Addonisio, L.; Proclemer, A.; Facchin, D.; Vado, A.; Knops, R. E.; Dekker, L. R. C.

    2012-01-01

    Background-The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope. Methods and

  19. B-Raf and CRHR1 internalization mediate biphasic ERK1/2 activation by CRH in hippocampal HT22 Cells.

    Science.gov (United States)

    Bonfiglio, Juan J; Inda, Carolina; Senin, Sergio; Maccarrone, Giuseppina; Refojo, Damián; Giacomini, Damiana; Turck, Christoph W; Holsboer, Florian; Arzt, Eduardo; Silberstein, Susana

    2013-03-01

    CRH is a key regulator of neuroendocrine, autonomic, and behavioral response to stress. CRH-stimulated CRH receptor 1 (CRHR1) activates ERK1/2 depending on intracellular context. In a previous work, we demonstrated that CRH activates ERK1/2 in limbic areas of the mouse brain (hippocampus and basolateral amygdala). ERK1/2 is an essential mediator of hippocampal physiological processes including emotional behavior, synaptic plasticity, learning, and memory. To elucidate the molecular mechanisms by which CRH activates ERK1/2 in hippocampal neurons, we used the mouse hippocampal cell line HT22. We document for the first time that ERK1/2 activation in response to CRH is biphasic, involving a first cAMP- and B-Raf-dependent early phase and a second phase that critically depends on CRHR1 internalization and β-arrestin2. By means of mass-spectrometry-based screening, we identified B-Raf-associated proteins that coimmunoprecipitate with endogenous B-Raf after CRHR1 activation. Using molecular and pharmacological tools, the functional impact of selected B-Raf partners in CRH-dependent ERK1/2 activation was dissected. These results indicate that 14-3-3 proteins, protein kinase A, and Rap1, are essential for early CRH-induced ERK1/2 activation, whereas dynamin and vimentin are required for the CRHR1 internalization-dependent phase. Both phases of ERK1/2 activation depend on calcium influx and are affected by calcium/calmodulin-dependent protein kinase II inactivation. Thus, this report describes the dynamics and biphasic nature of ERK1/2 activation downstream neuronal CRHR1 and identifies several new critical components of the CRHR1 signaling machinery that selectively controls the early and late phases of ERK1/2 activation, thus providing new potential therapeutic targets for stress-related disorders.

  20. Anti-HMGCR antibodies as a biomarker for immune-mediated necrotizing myopathies: A history of statins and experience from a large international multi-center study.

    Science.gov (United States)

    Musset, Lucile; Allenbach, Yves; Benveniste, Olivier; Boyer, Olivier; Bossuyt, Xavier; Bentow, Chelsea; Phillips, Joe; Mammen, Andrew; Van Damme, Philip; Westhovens, René; Ghirardello, Anna; Doria, Andrea; Choi, May Y; Fritzler, Marvin J; Schmeling, Heinrike; Muro, Yoshinao; García-De La Torre, Ignacio; Ortiz-Villalvazo, Miguel A; Bizzaro, Nicola; Infantino, Maria; Imbastaro, Tiziana; Peng, Qinglin; Wang, Guochun; Vencovský, Jiří; Klein, Martin; Krystufkova, Olga; Franceschini, Franco; Fredi, Micaela; Hue, Sophie; Belmondo, Thibaut; Danko, Katalin; Mahler, Michael

    2016-10-01

    In an effort to find naturally occurring substances that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), statins were first discovered by Endo in 1972. With the widespread prescription and use of statins to decrease morbidity from myocardial infarction and stroke, it was noted that approximately 5% of all statin users experienced muscle pain and weakness during treatment. In a smaller proportion of patients, the myopathy progressed to severe morbidity marked by proximal weakness and severe muscle wasting. Remarkably, Mammen and colleagues were the first to discover that the molecular target of statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), is an autoantibody target in patients that develop an immune-mediated necrotizing myopathy (IMNM). These observations have been confirmed in a number of studies but, until today, a multi-center, international study of IMNM, related idiopathic inflammatory myopathies (IIM), other auto-inflammatory conditions and controls has not been published. Accordingly, an international, multi-center study investigated the utility of anti-HMGCR antibodies in the diagnosis of statin-associated IMNM in comparison to different forms of IIM and controls. This study included samples from patients with different forms of IIM (n=1250) and patients with other diseases (n=656) that were collected from twelve sites and tested for anti-HMGCR antibodies by ELISA. This study confirmed that anti-HMGCR autoantibodies, when found in conjunction with statin use, characterize a subset of IIM who are older and have necrosis on muscle biopsy. Taken together, the data to date indicates that testing for anti-HMGCR antibodies is important in the differential diagnosis of IIM and might be considered for future classification criteria. Copyright © 2016. Published by Elsevier B.V.

  1. Loop-Mediated Isothermal Amplification for Detection of Endogenous Sad1 Gene in Cotton: An Internal Control for Rapid Onsite GMO Testing.

    Science.gov (United States)

    Singh, Monika; Bhoge, Rajesh K; Randhawa, Gurinderjit

    2018-04-20

    Background : Confirming the integrity of seed samples in powdered form is important priorto conducting a genetically modified organism (GMO) test. Rapid onsite methods may provide a technological solution to check for genetically modified (GM) events at ports of entry. In India, Bt cotton is the commercialized GM crop with four approved GM events; however, 59 GM events have been approved globally. GMO screening is required to test for authorized GM events. The identity and amplifiability of test samples could be ensured first by employing endogenous genes as an internal control. Objective : A rapid onsite detection method was developed for an endogenous reference gene, stearoyl acyl carrier protein desaturase ( Sad1 ) of cotton, employing visual and real-time loop-mediated isothermal amplification (LAMP). Methods : The assays were performed at a constant temperature of 63°C for 30 min for visual LAMP and 62ºC for 40 min for real-time LAMP. Positive amplification was visualized as a change in color from orange to green on addition of SYBR ® Green or detected as real-time amplification curves. Results : Specificity of LAMP assays was confirmed using a set of 10 samples. LOD for visual LAMP was up to 0.1%, detecting 40 target copies, and for real-time LAMP up to 0.05%, detecting 20 target copies. Conclusions : The developed methods could be utilized to confirm the integrity of seed powder prior to conducting a GMO test for specific GM events of cotton. Highlights : LAMP assays for the endogenous Sad1 gene of cotton have been developed to be used as an internal control for onsite GMO testing in cotton.

  2. Pituitary adenylate cyclase 1 receptor internalization and endosomal signaling mediate the pituitary adenylate cyclase activating polypeptide-induced increase in guinea pig cardiac neuron excitability.

    Science.gov (United States)

    Merriam, Laura A; Baran, Caitlin N; Girard, Beatrice M; Hardwick, Jean C; May, Victor; Parsons, Rodney L

    2013-03-06

    After G-protein-coupled receptor activation and signaling at the plasma membrane, the receptor complex is often rapidly internalized via endocytic vesicles for trafficking into various intracellular compartments and pathways. The formation of signaling endosomes is recognized as a mechanism that produces sustained intracellular signals that may be distinct from those generated at the cell surface for cellular responses including growth, differentiation, and survival. Pituitary adenylate cyclase activating polypeptide (PACAP; Adcyap1) is a potent neurotransmitter/neurotrophic peptide and mediates its diverse cellular functions in part through internalization of its cognate G-protein-coupled PAC1 receptor (PAC1R; Adcyap1r1). In the present study, we examined whether PAC1R endocytosis participates in the regulation of neuronal excitability. Although PACAP increased excitability in 90% of guinea pig cardiac neurons, pretreatment with Pitstop 2 or dynasore to inhibit clathrin and dynamin I/II, respectively, suppressed the PACAP effect. Subsequent addition of inhibitor after the PACAP-induced increase in excitability developed gradually attenuated excitability with no changes in action potential properties. Likewise, the PACAP-induced increase in excitability was markedly decreased at ambient temperature. Receptor trafficking studies with GFP-PAC1 cell lines demonstrated the efficacy of Pitstop 2, dynasore, and low temperatures at suppressing PAC1R endocytosis. In contrast, brefeldin A pretreatments to disrupt Golgi vesicle trafficking did not blunt the PACAP effect, and PACAP/PAC1R signaling still increased neuronal cAMP production even with endocytic blockade. Our results demonstrate that PACAP/PAC1R complex endocytosis is a key step for the PACAP modulation of cardiac neuron excitability.

  3. Family Life and Developmental Idealism in Yazd, Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Jalal Abbasi-Shavazi

    2012-03-01

    Full Text Available BACKGROUND This paper is motivated by the theory that developmental idealism has been disseminated globally and has become an international force for family and demographic change. Developmental idealism is a set of cultural beliefs and values about development and how development relates to family and demographic behavior. It holds that modern societies are causal forces producing modern families, that modern families help to produce modern societies, and that modern family change is to be expected. OBJECTIVE We examine the extent to which developmental idealism has been disseminated in Iran. We also investigate predictors of the dissemination of developmental idealism. METHODS We use survey data collected in 2007 from a sample of women in Yazd, a city in Iran. We examine the distribution of developmental idealism in the sample and the multivariate predictors of developmental idealism. RESULTS We find considerable support for the expectation that many elements of developmental idealism have been widely disseminated. Statistically significant majorities associate development with particular family attributes, believe that development causes change in families, believe that fertility reductions and age-at-marriage increases help foster development, and perceive family trends in Iran headed toward modernity. As predicted, parental education, respondent education, and income affect adherence to developmental idealism. CONCLUSIONS Developmental idealism has been widely disseminated in Yazd, Iran and is related to social and demographic factors in predicted ways. COMMENTS Although our data come from only one city, we expect that developmental idealism has been widely distributed in Iran, with important implications for family and demographic behavior.

  4. Rapid authentication of the precious herb saffron by loop-mediated isothermal amplification (LAMP) based on internal transcribed spacer 2 (ITS2) sequence.

    Science.gov (United States)

    Zhao, Mingming; Shi, Yuhua; Wu, Lan; Guo, Licheng; Liu, Wei; Xiong, Chao; Yan, Song; Sun, Wei; Chen, Shilin

    2016-05-05

    Saffron is one of the most expensive species of Chinese herbs and has been subjected to various types of adulteration because of its high price and limited production. The present study introduces a loop-mediated isothermal amplification (LAMP) technique for the differentiation of saffron from its adulterants. This novel technique is sensitive, efficient and simple. Six specific LAMP primers were designed on the basis of the nucleotide sequence of the internal transcribed spacer 2 (ITS2) nuclear ribosomal DNA of Crocus sativus. All LAMP amplifications were performed successfully, and visual detection occurred within 60 min at isothermal conditions of 65 °C. The results indicated that the LAMP primers are accurate and highly specific for the discrimination of saffron from its adulterants. In particular, 10 fg of genomic DNA was determined to be the limit for template accuracy of LAMP in saffron. Thus, the proposed novel, simple, and sensitive LAMP assay is well suited for immediate on-site discrimination of herbal materials. Based on the study, a practical standard operating procedure (SOP) for utilizing the LAMP protocol for herbal authentication is provided.

  5. Positive and negative effects of internalizing on alcohol use problems from childhood to young adulthood: The mediating and suppressing role of externalizing.

    Science.gov (United States)

    Foster, Katherine T; Hicks, Brian M; Zucker, Robert A

    2018-05-01

    A longstanding hypothesis is that some alcohol use problems (AUP) develop and are maintained through the "self-medication" of internalizing (INT; depression and anxiety) problems. However, their high rate of co-occurrence with one another and with externalizing (EXT; antisocial behavior and impulse control) problems obscures any causal association because EXT may account for the INT-AUP link. Using a large community sample, we estimated prospective effects of INT and EXT on AUP via latent cross-lagged mediation panel spanning 14 years from childhood (ages 9-11) to young adulthood (ages 21-23). After adjusting for the cross-lagged, concurrent, and stability effects across factors, INT decreased AUP risk through its direct and indirect effects and increased AUP risk through shared variance with EXT. Between childhood and young adulthood, unique aspects of INT reduced risk for AUP while aspects of INT shared with EXT increased risk for AUP. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  6. Adolescents who are less religious than their parents are at risk for externalizing and internalizing symptoms: the mediating role of parent-adolescent relationship quality.

    Science.gov (United States)

    Kim-Spoon, Jungmeen; Longo, Gregory S; McCullough, Michael E

    2012-08-01

    Parents generally take pains to insure that their children adopt their own religious beliefs and practices, so what happens psychologically to adolescents who find themselves less religious than their parents? We examined the relationships among parents' and adolescents' religiousness, adolescents' ratings of parent-adolescent relationship quality, and adolescents' psychological adjustment using data from 322 adolescents and their parents. Adolescent boys who had lower organizational and personal religiousness than their parents, and girls who had lower personal religiousness than their parents, had more internalizing and externalizing psychological symptoms than did adolescents whose religiousness better matched their parents'. The apparent effects of subparental religiousness on adolescents' psychological symptoms were mediated by their intermediate effects on adolescents' ratings of the quality of their relationships with their parents. These findings identify religious discrepancies between parents and their children as an important influence on the quality of parent-adolescent relationships, with important implications for adolescents' psychological well-being. PsycINFO Database Record (c) 2012 APA, all rights reserved.

  7. Reproductive and developmental toxicology

    National Research Council Canada - National Science Library

    Gupta, Ramesh C

    2011-01-01

    .... With a special focus on placental toxicity, this book is the only available reference to connect the three key risk stages, and is the only resource to include reproductive and developmental toxicity in domestic animals, fish, and wildlife.

  8. Developmental coordination disorder

    Science.gov (United States)

    Developmental coordination disorder can lead to: Learning problems Low self-esteem resulting from poor ability at sports and teasing by other children Repeated injuries Weight gain as a result of not wanting to participate ...

  9. Facts about Developmental Disabilities

    Science.gov (United States)

    ... play, learn, speak, behave, and move (for example, crawling and walking). Children develop at their own pace, ... person’s lifetime. Most developmental disabilities begin before a baby is born, but some can happen after birth ...

  10. Life Span Developmental Approach

    OpenAIRE

    Ali Eryilmaz

    2011-01-01

    The Life Span Developmental Approach examines development of individuals which occurs from birth to death. Life span developmental approach is a multi-disciplinary approach related with disciplines like psychology, psychiatry, sociology, anthropology and geriatrics that indicates the fact that development is not completed in adulthood, it continues during the life course. Development is a complex process that consists of dying and death. This approach carefully investigates the development of...

  11. Transgenerational developmental programming.

    Science.gov (United States)

    Aiken, Catherine E; Ozanne, Susan E

    2014-01-01

    The concept of developmental programming suggests that the early life environment influences offspring characteristics in later life, including the propensity to develop diseases such as the metabolic syndrome. There is now growing evidence that the effects of developmental programming may also manifest in further generations without further suboptimal exposure. This review considers the evidence, primarily from rodent models, for effects persisting to subsequent generations, and evaluates the mechanisms by which developmental programming may be transmitted to further generations. In particular, we focus on the potential role of the intrauterine environment in contributing to a developmentally programmed phenotype in subsequent generations. The literature was systematically searched at http://pubmed.org and http://scholar.google.com to identify published findings regarding transgenerational (F2 and beyond) developmental programming effects in human populations and animal models. Transmission of programming effects is often viewed as a form of epigenetic inheritance, either via the maternal or paternal line. Evidence exists for both germline and somatic inheritance of epigenetic modifications which may be responsible for phenotypic changes in further generations. However, there is increasing evidence for the role of both extra-genomic components of the zygote and the interaction of the developing conceptus with the intrauterine environment in propagating programming effects. The contribution of a suboptimal reproductive tract environment or maternal adaptations to pregnancy may be critical to inheritance of programming effects via the maternal line. As the effects of age exacerbate the programmed metabolic phenotype, advancing maternal age may increase the likelihood of developmental programming effects being transmitted to further generations. We suggest that developmental programming effects could be propagated through the maternal line de novo in generations

  12. Moderators, mediators, and bidirectional relationships in the International Classification of Functioning, Disability and Health (ICF) framework: An empirical investigation using a longitudinal design and Structural Equation Modeling (SEM).

    Science.gov (United States)

    Rouquette, Alexandra; Badley, Elizabeth M; Falissard, Bruno; Dub, Timothée; Leplege, Alain; Coste, Joël

    2015-06-01

    The International Classification of Functioning, Disability and Health (ICF) published in 2001 describes the consequences of health conditions with three components of impairments in body structures or functions, activity limitations and participation restrictions. Two of the new features of the conceptual model were the possibility of feedback effects between each ICF component and the introduction of contextual factors conceptualized as moderators of the relationship between the components. The aim of this longitudinal study is to provide empirical evidence of these two kinds of effect. Structural equation modeling was used to analyze data from a French population-based cohort of 548 patients with knee osteoarthritis recruited between April 2007 and March 2009 and followed for three years. Indicators of the body structure and function, activity and participation components of the ICF were derived from self-administered standardized instruments. The measurement model revealed four separate factors for body structures impairments, body functions impairments, activity limitations and participation restrictions. The classic sequence from body impairments to participation restrictions through activity limitations was found at each assessment time. Longitudinal study of the ICF component relationships showed a feedback pathway indicating that the level of participation restrictions at baseline was predictive of activity limitations three years later. Finally, the moderating role of personal (age, sex, mental health, etc.) and environmental factors (family relationships, mobility device use, etc.) was investigated. Three contextual factors (sex, family relationships and walking stick use) were found to be moderators for the relationship between the body impairments and the activity limitations components. Mental health was found to be a mediating factor of the effect of activity limitations on participation restrictions. Copyright © 2015 Elsevier Ltd. All rights

  13. MEDIATOR18 and MEDIATOR20 confer susceptibility to Fusarium oxysporum in Arabidopsis thaliana

    OpenAIRE

    Fallath, Thorya; Kidd, Brendan N.; Stiller, Jiri; Davoine, Celine; Bj?rklund, Stefan; Manners, John M.; Kazan, Kemal; Schenk, Peer M.

    2017-01-01

    The conserved protein complex known as Mediator conveys transcriptional signals by acting as an intermediary between transcription factors and RNA polymerase II. As a result, Mediator subunits play multiple roles in regulating developmental as well as abiotic and biotic stress pathways. In this report we identify the head domain subunits MEDIATOR18 and MEDIATOR20 as important susceptibility factors for Fusarium oxysporum infection in Arabidopsis thaliana. Mutants of MED18 and MED20 display do...

  14. Reading in developmental prosopagnosia

    DEFF Research Database (Denmark)

    Starrfelt, Randi; Klargaard, Solja K; Petersen, Anders

    2018-01-01

    exposure durations (targeting the word superiority effect), and d) text reading. RESULTS: Participants with developmental prosopagnosia performed strikingly similar to controls across the four reading tasks. Formal analysis revealed a significant dissociation between word and face recognition......, that is, impaired reading in developmental prosopagnosia. METHOD: We tested 10 adults with developmental prosopagnosia and 20 matched controls. All participants completed the Cambridge Face Memory Test, the Cambridge Face Perception test and a Face recognition questionnaire used to quantify everyday face...... recognition experience. Reading was measured in four experimental tasks, testing different levels of letter, word, and text reading: (a) single word reading with words of varying length,(b) vocal response times in single letter and short word naming, (c) recognition of single letters and short words at brief...

  15. The Developmental Work

    DEFF Research Database (Denmark)

    Møller, Niels; Hvid, Helge

    2001-01-01

    AbstractIn the nineties, the concept of the developmental work (DW) has become a significant point of orientation for the actors on Danish labour market. The DW has moved the focus of the labour market from wages and working time towards work and production. For employees, the DW promises...... developmental possibilities, influence and responsibility, but also greater social responsibility for the firm. For firms, the DW promises increased competitiveness and better products. In this paper we present the concept of the DW as one which encourages the development of work, production and organisation...... of the firm and show that the DW is different from mainstream management concepts, as the DW...

  16. How Does Stigma Affect People Living with HIV? The Mediating Roles of Internalized and Anticipated HIV Stigma in the Effects of Perceived Community Stigma on Health and Psychosocial Outcomes

    OpenAIRE

    Turan, Bulent; Budhwani, Henna; Fazeli, Pariya L.; Browning, Wesley R.; Raper, James L.; Mugavero, Michael J.; Turan, Janet M.

    2017-01-01

    Few researchers have attempted to examine the mechanisms through which HIV-related stigma in the community is processed and experienced at an individual level by people living with HIV. We examined how the effects of perceived HIV stigma in the community on health outcomes for people living with HIV are mediated by internalized stigma and anticipated stigma. Participants (N = 203) from an HIV clinic completed self-report measures and their clinical data were obtained from medical records. Res...

  17. Developmental Risk and Young Children's Regulatory Strategies: Predicting Behavior Problems at Age Five

    Science.gov (United States)

    Gerstein, Emily D.; Pedersen y Arbona, Anita; Crnic, Keith A.; Ryu, Ehri; Baker, Bruce L.; Blacher, Jan

    2011-01-01

    Children with early developmental delays are at heightened risk for behavior problems and comorbid psychopathology. This study examined the trajectories of regulatory capabilities and their potentially mediating role in the development of behavior problems for children with and without early developmental delays. A sample of 231 children comprised…

  18. Arguments from Developmental Order.

    Science.gov (United States)

    Stöckle-Schobel, Richard

    2016-01-01

    In this article, I investigate a special type of argument regarding the role of development in theorizing about psychological processes and cognitive capacities. Among the issues that developmental psychologists study, discovering the ontogenetic trajectory of mechanisms or capacities underpinning our cognitive functions ranks highly. The order in which functions are developed or capacities are acquired is a matter of debate between competing psychological theories, and also philosophical conceptions of the mind - getting the role and the significance of the different steps in this order right could be seen as an important virtue of such theories. Thus, a special kind of strategy in arguments between competing philosophical or psychological theories is using developmental order in arguing for or against a given psychological claim. In this article, I will introduce an analysis of arguments from developmental order, which come in two general types: arguments emphasizing the importance of the early cognitive processes and arguments emphasizing the late cognitive processes. I will discuss their role in one of the central tools for evaluating scientific theories, namely in making inferences to the best explanation. I will argue that appeal to developmental order is, by itself, an insufficient criterion for theory choice and has to be part of an argument based on other core explanatory or empirical virtues. I will end by proposing a more concerted study of philosophical issues concerning (cognitive) development, and I will present some topics that also pertain to a full-fledged 'philosophy of development.'

  19. Developmental Education Evaluation Model.

    Science.gov (United States)

    Perry-Miller, Mitzi; And Others

    A developmental education evaluation model designed to be used at a multi-unit urban community college is described. The purpose of the design was to determine the cost effectiveness/worth of programs in order to initiate self-improvement. A needs assessment was conducted by interviewing and taping the responses of students, faculty, staff, and…

  20. Arguments from Developmental Order

    Directory of Open Access Journals (Sweden)

    Richard eStöckle-Schobel

    2016-05-01

    Full Text Available In this article, I investigate a special type of argument regarding the role of development in theorising about psychological processes and cognitive capacities. Among the issues that developmental psychologists study, discovering the ontogenetic trajectory of mechanisms or capacities underpinning our cognitive functions ranks highly. The order in which functions are developed or capacities are acquired is a matter of debate between competing psychological theories, and also philosophical conceptions of the mind – getting the role and the significance of the different steps in this order right could be seen as an important virtue of such theories.Thus, a special kind of strategy in arguments between competing philosophical or psychological theories is using developmental order in arguing for or against a given psychological claim. In this article, I will introduce an analysis of arguments from developmental order, which come in two general types: arguments emphasising the importance of the early cognitive processes and arguments emphasising the late cognitive processes. I will discuss their role in one of the central tools for evaluating scientific theories, namely in making inferences to the best explanation. I will argue that appeal to developmental order is, by itself, an insufficient criterion for theory choice and has to be part of an argument based on other core explanatory or empirical virtues. I will end by proposing a more concerted study of philosophical issues concerning (cognitive development, and I will present some topics that also pertain to a full-fledged ‘philosophy of development’.

  1. Developmental paediatric anaesthetic pharmacology

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing

    2015-01-01

    Safe and effective drug therapy in neonates, infants and children require detailed knowledge about the ontogeny of drug disposition and action as well how these interact with genetics and co-morbidity of children. Recent advances in developmental pharmacology in children follow the increased...

  2. A developmental etiological model for drug abuse in men.

    Science.gov (United States)

    Kendler, Kenneth S; Ohlsson, Henrik; Edwards, Alexis C; Sundquist, Jan; Sundquist, Kristina

    2017-10-01

    We attempt to develop a relatively comprehensive structural model of risk factors for drug abuse (DA) in Swedish men that illustrates developmental and mediational processes. We examined 20 risk factors for DA in 48,369 men undergoing conscription examinations in 1969-70 followed until 2011 when 2.34% (n=1134) of them had DA ascertained in medical, criminal and pharmacy registries. Risk factors were organized into four developmental tiers reflecting i) birth, ii) childhood/early adolescence, iii) late adolescence, and iv) young adulthood. Structural equational model fitting was performed using Mplus. The best fitting model explained 47.8% of the variance in DA. The most prominent predictors, in order, were: early adolescent externalizing behavior, early adult criminal behavior, early adolescent internalizing behavior, early adult unemployment, early adult alcohol use disorder, and late adolescent drug use. Two major inter-connecting pathways emerged reflecting i) genetic/familial risk and ii) family dysfunction and psychosocial adversity. Generated on a first and tested on a second random half of the sample, a model from these variables predicted DA with an ROC area under the curve of 83.6%. Fifty-nine percent of DA cases arose from subjects in the top decile of risk. DA in men is a highly multifactorial syndrome with risk arising from familial-genetic, psychosocial, behavioral and psychological factors acting and interacting over development. Among the multiple predisposing factors for DA, a range of psychosocial adversities, externalizing psychopathology and lack of social constraints in early adulthood are predominant. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Is Season of Birth Related to Developmental Dyslexia?

    Science.gov (United States)

    Donfrancesco, Renato; Iozzino, Roberto; Caruso, Barbara; Ferrante, Laura; Mugnaini, Daniele; Talamo, Alessandra; Miano, Silvia; Dimitri, Andrea; Masi, Gabriele

    2010-01-01

    Different moderators/mediators of risk are involved in developmental dyslexia (DD), but data are inconsistent. We explored the prevalence of season of birth and its association with gender and age of school entry in an Italian sample of dyslexic children compared to an Italian normal control group. The clinical sample included 498 children (345…

  4. The role of developmental plasticity and epigenetics in human health.

    Science.gov (United States)

    Gluckman, Peter D; Hanson, Mark A; Low, Felicia M

    2011-03-01

    Considerable epidemiological, experimental and clinical data have amassed showing that the risk of developing disease in later life is dependent on early life conditions, mainly operating within the normative range of developmental exposures. This relationship reflects plastic responses made by the developing organism as an evolved strategy to cope with immediate or predicted circumstances, to maximize fitness in the context of the range of environments potentially faced. There is now increasing evidence, both in animals and humans, that such developmental plasticity is mediated in part by epigenetic mechanisms. However, recognition of the importance of developmental plasticity as an important factor in influencing later life health-particularly within the medical and public health communities-is low, and we argue that this indifference cannot be sustained in light of the growing understanding of developmental processes and the rapid rise in the prevalence of obesity and metabolic disease globally. Copyright © 2011 Wiley-Liss, Inc.

  5. The effects of early positive parenting and developmental delay status on child emotion dysregulation.

    Science.gov (United States)

    Norona, A N; Baker, B L

    2017-02-01

    Emotion regulation has been identified as a robust predictor of adaptive functioning across a variety of domains (Aldao et al. ). Furthermore, research examining early predictors of competence and deficits in ER suggests that factors internal to the individual (e.g. neuroregulatory reactivity, behavioural traits and cognitive ability) and external to the individual (e.g. caregiving styles and explicit ER training) contribute to the development of ER (Calkins ). Many studies have focused on internal sources or external sources; however, few have studied them simultaneously within one model, especially in studies examining children with developmental delays (DD). Here, we addressed this specific research gap and examined the contributions of one internal factor and one external factor on emotion dysregulation outcomes in middle childhood. Specifically, our current study used structural equation modelling (SEM) to examine prospective, predictive relationships between DD status, positive parenting at age 4 years and child emotion dysregulation at age 7 years. Participants were 151 families in the Collaborative Family Study, a longitudinal study of young children with and without DD. A positive parenting factor was composed of sensitivity and scaffolding scores from mother-child interactions at home and in the research centre at child age 4 years. A child dysregulation factor was composed of a dysregulation code from mother-child interactions and a parent-report measure of ER and lability/negativity at age 7 years. Finally, we tested the hypothesis that positive parenting would mediate the relationship between DD and child dysregulation. Mothers of children with DD exhibited fewer sensitive and scaffolding behaviours compared with mothers of typically developing children, and children with DD were more dysregulated on all measures of ER. SEM revealed that both DD status and early positive parenting predicted emotion dysregulation in middle childhood. Furthermore

  6. Evolutionary and developmental modules.

    Science.gov (United States)

    Lacquaniti, Francesco; Ivanenko, Yuri P; d'Avella, Andrea; Zelik, Karl E; Zago, Myrka

    2013-01-01

    The identification of biological modules at the systems level often follows top-down decomposition of a task goal, or bottom-up decomposition of multidimensional data arrays into basic elements or patterns representing shared features. These approaches traditionally have been applied to mature, fully developed systems. Here we review some results from two other perspectives on modularity, namely the developmental and evolutionary perspective. There is growing evidence that modular units of development were highly preserved and recombined during evolution. We first consider a few examples of modules well identifiable from morphology. Next we consider the more difficult issue of identifying functional developmental modules. We dwell especially on modular control of locomotion to argue that the building blocks used to construct different locomotor behaviors are similar across several animal species, presumably related to ancestral neural networks of command. A recurrent theme from comparative studies is that the developmental addition of new premotor modules underlies the postnatal acquisition and refinement of several different motor behaviors in vertebrates.

  7. The Mediating Roles of Internal Context Variables in the Relationship between Distributed Leadership Perceptions and Continuous Change Behaviours of Public School Teachers

    Science.gov (United States)

    Kondakci, Yasar; Zayim, Merve; Beycioglu, Kadir; Sincar, Mehmet; Ugurlu, Celal T

    2016-01-01

    This study aims at building a theoretical base for continuous change in education and using this base to test the mediating roles of two key contextual variables, knowledge sharing and trust, in the relationship between the distributed leadership perceptions and continuous change behaviours of teachers. Data were collected from 687 public school…

  8. Petro-States - Predatory or Developmental?

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-10-01

    Political attention is increasing on the glaring contradiction in most oil-rich countries between natural abundance and economic and social misery. How can it be that oil is not a blessing, but becomes a curse? Although drawing on economic analysis (Dutch disease), the analytical framework established in this report on Angola and Azerbaijan pays special attention to political and institutional factors and concentrates on the role of the state. Selected variables that are likely to decide whether the petro-states become ''predatory'' or ''developmental'' are studied for both countries. The analysis indicates a danger that oil resources will continue to trickle away instead of trickling down to the benefit of the broader Angolan and Azerbaijani population. Concerted action by international oil companies and the Bretton Woods institutions provides the best hope of moving the present political leadership in Angola and Azerbaijan into a developmental direction. (author)

  9. Petro-States - Predatory or Developmental?

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-10-01

    Political attention is increasing on the glaring contradiction in most oil-rich countries between natural abundance and economic and social misery. How can it be that oil is not a blessing, but becomes a curse? Although drawing on economic analysis (Dutch disease), the analytical framework established in this report on Angola and Azerbaijan pays special attention to political and institutional factors and concentrates on the role of the state. Selected variables that are likely to decide whether the petro-states become ''predatory'' or ''developmental'' are studied for both countries. The analysis indicates a danger that oil resources will continue to trickle away instead of trickling down to the benefit of the broader Angolan and Azerbaijani population. Concerted action by international oil companies and the Bretton Woods institutions provides the best hope of moving the present political leadership in Angola and Azerbaijan into a developmental direction. (author)

  10. [Neuropsychomotor developmental delay: conceptual map, term definitions, uses and limitations].

    Science.gov (United States)

    Dornelas, Lílian de Fátima; Duarte, Neuza Maria de Castro; Magalhães, Lívia de Castro

    2015-01-01

    To retrieve the origin of the term neuropsychomotor developmental delay" (NPMD), its conceptual evolution over time, and to build a conceptual map based on literature review. A literature search was performed in the SciELO Brazil, Web of Science, Science Direct, OneFile (GALE), Pubmed (Medline), Whiley Online, and Springer databases, from January of 1940 to January of 2013, using the following keywords NPMD delay, NPMD retardation, developmental delay, and global developmental delay. A total of 71 articles were selected, which were used to build the conceptual map of the term. Of the 71 references, 55 were international and 16 national. The terms developmental delay and global developmental delay were the most frequently used in the international literature and, in Brazil, delayed NPMD was the most often used. The term developmental delay emerged in the mid 1940s, gaining momentum in the 1990 s. In Brazil, the term delayed NPMD started to be used in the 1980s, and has been frequently cited and published in the literature. Delayed development was a characteristic of 13 morbidities described in 23 references. Regarding the type of use, 19 references were found, with seven forms of use. Among the references, 34 had definitions of the term, and 16 different concepts were identified. Developmental delay is addressed in the international and national literature under different names, various applications, and heterogeneous concepts. Internationally, ways to improve communication between professionals have been indicated, with standardized definition of the term and use in very specific situations up to the fifth year of life, which was not found in Brazilian publications. Copyright © 2014 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  11. The Roles of Family and Teacher Support in Moderating and Mediating Externalized and Internalized Outcomes of Exposure to Community Violence Among Arab and Jewish Adolescents in Israel.

    Science.gov (United States)

    Haj-Yahia, Muhammad M; Leshem, Becky; Guterman, Neil B

    2018-02-01

    The study examined family and teacher support as factors that can protect adolescents from internalized and externalized problems after exposure to community violence (ECV). Self-administered questionnaires were filled out by a sample of 1,832 Arab and Jewish Israeli high school students. The Arab adolescents reported significantly higher levels of community violence victimization, internalized problems, externalized problems, family support, and teacher support than the Jewish adolescents. The girls reported higher levels of internalized problems, and the boys reported higher levels of externalized problems. ECV predicted high levels of internalized and externalized problems, family support predicted low levels of internalized and externalized problems, and teacher support had no predictive role. Path analysis confirmed the significance of the relationships between ECV effects, support variables, and gender. The limitations of the study and implications of the findings for future research and for the development of family care and family intervention programs are discussed.

  12. Topographic processing in developmental prosopagnosia

    DEFF Research Database (Denmark)

    Klargaard, Solja K.; Starrfelt, Randi; Petersen, Anders

    2016-01-01

    deficit in visual processing or visual short-term memory. Interestingly, a classical dissociation could be demonstrated between impaired face memory and preserved topographic memory in two developmental prosopagnosics. We conclude that impairments in topographic memory tend to co-occur with developmental......Anecdotal evidence suggests a relation between impaired spatial (navigational) processing and developmental prosopagnosia. To address this formally, we tested two aspects of topographic processing – that is, perception and memory of mountain landscapes shown from different viewpoints. Participants...

  13. DEVELOPMENTAL TAXONOMY OF CONDUCT DISORDER

    OpenAIRE

    Jelena Kostić; Milkica Nešić; Jasminka Marković; Miodrag Stanković

    2015-01-01

    Conduct disorder is a heterogeneous disorder in terms of etiology, course and prognosis, and currently, there is no singular model that would describe the development of the disorder. The results of empirical research on males confirm this heterogeneity, as they point out to two possible developmental pathways: childhood-onset and adolescentonset type. This paper presents the basic elements of developmental taxonomic theory which argues that there are two different developmental pathways to c...

  14. 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.

  15. Developmental plasticity: Friend or foe?

    Science.gov (United States)

    Michels, Karin B

    2017-01-01

    Developmental plasticity - the concept that adaptation to changing and unfavorable environmental conditions are possible but may come at the price of compromised health potentials - has evolutionary grounding as it facilitates survival but dissents with fundamental evolutionary principles in that it may advance the lesser fit. It is an important cornerstone of the Developmental Origins of Health and Disease (DOHaD). Unlike evolutionary adaptation developmental plasticity may be short-lived and restricted to one or few generations and inheritance is uncertain. Potential mechanisms include epigenetic modifications adopted in utero which may not transmit to the next generation; future insights may allow adjustments of the outcomes of developmental plasticity.

  16. Qualitative methodology in developmental psychology

    DEFF Research Database (Denmark)

    Demuth, Carolin; Mey, Günter

    2015-01-01

    Qualitative methodology presently is gaining increasing recognition in developmental psychology. Although the founders of developmental psychology to a large extent already used qualitative procedures, the field was long dominated by a (post) positivistic quantitative paradigm. The increasing rec...... in qualitative research offers a promising avenue to advance the field in this direction.......Qualitative methodology presently is gaining increasing recognition in developmental psychology. Although the founders of developmental psychology to a large extent already used qualitative procedures, the field was long dominated by a (post) positivistic quantitative paradigm. The increasing...

  17. Building a developmental toxicity ontology.

    Science.gov (United States)

    Baker, Nancy; Boobis, Alan; Burgoon, Lyle; Carney, Edward; Currie, Richard; Fritsche, Ellen; Knudsen, Thomas; Laffont, Madeleine; Piersma, Aldert H; Poole, Alan; Schneider, Steffen; Daston, George

    2018-04-03

    As more information is generated about modes of action for developmental toxicity and more data are generated using high-throughput and high-content technologies, it is becoming necessary to organize that information. This report discussed the need for a systematic representation of knowledge about developmental toxicity (i.e., an ontology) and proposes a method to build one based on knowledge of developmental biology and mode of action/ adverse outcome pathways in developmental toxicity. This report is the result of a consensus working group developing a plan to create an ontology for developmental toxicity that spans multiple levels of biological organization. This report provide a description of some of the challenges in building a developmental toxicity ontology and outlines a proposed methodology to meet those challenges. As the ontology is built on currently available web-based resources, a review of these resources is provided. Case studies on one of the most well-understood morphogens and developmental toxicants, retinoic acid, are presented as examples of how such an ontology might be developed. This report outlines an approach to construct a developmental toxicity ontology. Such an ontology will facilitate computer-based prediction of substances likely to induce human developmental toxicity. © 2018 Wiley Periodicals, Inc.

  18. Personality, biographical characteristics, and job interview success: a longitudinal study of the mediating effects of interviewing self-efficacy and the moderating effects of internal locus of causality.

    Science.gov (United States)

    Tay, Cheryl; Ang, Soon; Van Dyne, Linn

    2006-03-01

    In this study, the authors developed and tested a model of performance in job interviews that examines the mediating role of interviewing self-efficacy (I-SE; job applicants' beliefs about their interviewing capabilities) in linking personality and biographical background with interview success and the moderating role of locus of causality attributions in influencing the relationship between interview success and subsequent I-SE. The authors tested their model (over 5 months' duration) with matched data from 229 graduating seniors, firms, and university records. Hierarchical regression analyses demonstrated I-SE mediated the effects of Extraversion, Conscientiousness, and leadership experience on interview success. Locus of causality attributions for interview outcomes moderated the relationship between interview success and subsequent I-SE. Theoretical and practical implications are discussed.

  19. Developmental immunotoxicology of lead

    International Nuclear Information System (INIS)

    Dietert, Rodney R.; Lee, Ji-Eun; Hussain, Irshad; Piepenbrink, Michael

    2004-01-01

    The heavy metal, lead, is a known developmental immunotoxicant that has been shown to produce immune alterations in humans as well as other species. Unlike many compounds that exert adverse immune effects, lead exposure at low to moderate levels does not produce widespread loss of immune cells. In contrast, changes resulting from lead exposure are subtle at the immune cell population level but, nevertheless, can be functionally dramatic. A hallmark of lead-induced immunotoxicity is a pronounced shift in the balance in T helper cell function toward T helper 2 responses at the expense of T helper 1 functions. This bias alters the nature and range of immune responses that can be produced thereby influencing host susceptibility to various diseases. Immunotoxic responses to lead appear to differ across life stages not only quantitatively with regard to dose response, but also qualitatively in terms of the spectrum of immune alterations. Experimental studies in several lab animal species suggest the latter stages of gestation are a period of considerable sensitivity for lead-induced immunotoxicity. This review describes the basic characteristics of lead-induced immunotoxicity emphasizing experimental animal results. It also provides a framework for the consideration of toxicant exposure effects across life stages. The existence of and probable basis for developmental windows of immune hyper-susceptibility are presented. Finally, the potential for lead to serve as a perinatal risk factor for childhood asthma as well as other diseases is considered

  20. Signaling via ITGB1/FAK and microfilament rearrangement mediates the internalization of Leptospira interrogans in mouse J774A.1 macrophages

    Directory of Open Access Journals (Sweden)

    Zhao Xin

    2015-01-01

    Full Text Available Leptospirosis caused by pathogenic Leptospira species is a worldwide zoonotic 2 infectious disease, but the mechanisms of leptospiral internalization remain poorly understood. Here, we report that mouse J774A.1 macrophages expressed integrin-subfamily proteins (ITGB1, ITGB2 and ITGB3. Antibody blockage and siRNA-based knockdown of ITGB1 decreased the internalization of leptospires into mouse J774A.1 macrophage cells. The internalization required focal adhesion kinase (FAK activation in J774A.1 cells rather than phosphoinositide-3-kinase (PI3K, and microfilament rather than microtubule aggregation during infection. The data indicated that the ITGB1/FAK/microfilament signaling pathway is responsible for leptospiral internalization in mouse macrophages.

  1. Time perspective as a determinant of smoking cessation in four countries: Direct and mediated effects from the International Tobacco Control (ITC) 4-Country Surveys.

    Science.gov (United States)

    Hall, Peter A; Fong, Geoffrey T; Meng, Gang

    2014-07-01

    Future oriented time perspective predicts a number of important health behaviors and outcomes, including smoking cessation. However, it is not known how future orientation exerts its effects on such outcomes, and no large scale cross-national studies have examined the question prospectively. The aim of the current investigation was to examine the relationship between time perspective and success in smoking cessation, and social cognitive mediators of the association. The ITC-4 is a multi-wave, four country survey (Australia, Canada, United States, United Kingdom) of current smokers (N=9772); the survey includes baseline measurements of time perspective, intentions, quit attempts, and self-reported quit status at follow-up over 8 years. We examined the predictive power of time perspective for smoking cessation, as mediated through strength of quit intentions and prior history of quit attempts. Findings indicated that those smokers with a stronger future orientation at baseline were more likely to have successfully quit at follow-up. This effect was partially explained by intention-mediated effects of future orientation on quit attempts. Future orientation predicts smoking cessation across four English-speaking countries; the cessation-facilitating effects of future orientation may be primarily due to future oriented individuals' motivated and sustained involvement in the quit cycle over time. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Effect of internal R&D activities to the accumulation of organizational technical knowledge with the mediation role of absorptive capacity to establish the innovation capability of electronic industries

    Directory of Open Access Journals (Sweden)

    Purwanggono Bambang

    2018-01-01

    Full Text Available Innovation is a strategy for the electronics industry to create a sustainable competitive advantage, in the midst of a rapidly changing environment with all its complexity. Seven AT program as an effort for PT. Hartono Istana Teknologi (Polytron into enterprise knowledge, will accelerate the innovation process, combined with good organizational technical knowledge management. Organizational technical knowledge will be instrumental in innovation capabilities properly if there is an internal R & D activities that support and absorptive capacity as a mediator. This study reviewed the organizational technical knowledge influence to innovation capability, the influence of R & D activities to organizational technical knowledge, as well as the role of absorptive capacity as a mediator. The study was conducted by distributing questionnaires to 130 employees of PT. Hartono Istana Teknologi. Data processing was conducted using SEM. The results showed that the absorptive capacity mediate the relationship between R & D activities and organizational technical knowledge by 51%, and organizational technical knowledge affect innovation capabilities by 64%.

  3. Comorbid psychopathology and stress mediate the relationship between autistic traits and repetitive behaviours in adults with autism.

    Science.gov (United States)

    García-Villamisar, D; Rojahn, J

    2015-02-01

    Comorbid psychopathology and stress were considered possible mediators that may explain the relationship between some autistic traits and repetitive behaviours. The current study sought to examine the mediational effects of comorbid psychopathology, executive dysfunctions and stress in the relationship between some autistic traits and repetitive behaviours. A battery of questionnaires including measures of autistic traits, repetitive behaviours, stress, executive dysfunctions and comorbid psychopathology were administered to a sample of adults with autism and intellectual disabilities (n = 43). We found that when taken as set dimensions of comorbidity, dysexecutive functioning and stress mediated or explained the effects of autistic symptoms on repetitive behaviour. The total model explained 60% of the variation in repetitive behaviours (R = 0.60; F = 13.64, P autism, while executive functioning did not contribute to that relationship. © 2013 2013 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

  4. Longitudinal pathways from early maternal depression to children's dysregulated representations: a moderated mediation analysis of harsh parenting and gender.

    Science.gov (United States)

    Martoccio, Tiffany L; Brophy-Herb, Holly E; Maupin, Angela N; Robinson, Joann L

    2016-01-01

    There is some evidence linking maternal depression, harsh parenting, and children's internal representations of attachment, yet, longitudinal examinations of these relationships and differences in the developmental pathways between boys and girls are lacking. Moderated mediation growth curves were employed to examine harsh parenting as a mechanism underlying the link between maternal depression and children's dysregulated representations using a nationally-representative, economically-vulnerable sample of mothers and their children (n = 575; 49% boys, 51% girls). Dysregulation representations were measured using the MacArthur Story Stem Battery at five years of age (M = 5.14, SD = 0.29). Harsh parenting mediated the association between early maternal depression and dysregulated representations for girls. Though initial harsh parenting was a significant mediator for boys, a stronger direct effect of maternal depression to dysregulated representations emerged over time. Results are discussed in terms of their implications for intervention efforts aimed at promoting early supportive parenting.

  5. The Application of Intentional Subjective Properties and Mediated Communication Tools to Software Agents in Online Disputes Resolution Environments

    Directory of Open Access Journals (Sweden)

    Renzo Gobbin

    2004-11-01

    Full Text Available This paper examines the use of subjective properties in modeling an architecture for cooperative agents using Agent Communication Language (ACL that is used as a mediating tool for cooperative communication activities between and within software agents. The role that subjective and objective properties have in explaining and modeling agent internalization and externalization of ACL messages is investigated and related to Vygotsky’s developmental learning theories such as Mediated Activity Theory. A novel agent architecture ALMA (Agent Language Mediated Activity based on the integration of agents’ subjective and objective properties within an agent communication activity framework will be presented. The relevance of software agents subjective properties in modeling applications such as e-Law Online Dispute Resolution for e-business contractual arrangements using natural language subject/object relation in their communication patterns will be discussed.

  6. I. DEVELOPMENTAL METHODOLOGY AS A CENTRAL SUBDISCIPLINE OF DEVELOPMENTAL SCIENCE.

    Science.gov (United States)

    Card, Noel A

    2017-06-01

    This first chapter introduces the main goals of the monograph and previews the remaining chapters. The goals of this monograph are to provide summaries of our current understanding of advanced developmental methodologies, provide information that can advance our understanding of human development, identify shortcomings in our understanding of developmental methodology, and serve as a flagpost for organizing developmental methodology as a subdiscipline within the broader field of developmental science. The remaining chapters in this monograph address issues in design (sampling and big data), longitudinal data analysis, and issues of replication and research accumulation. The final chapter describes the history of developmental methodology, considers how the previous chapters in this monograph fit within this subdiscipline, and offers recommendations for further advancement. © 2017 The Society for Research in Child Development, Inc.

  7. Constructivist developmental theory is needed in developmental neuroscience

    Science.gov (United States)

    Arsalidou, Marie; Pascual-Leone, Juan

    2016-12-01

    Neuroscience techniques provide an open window previously unavailable to the origin of thoughts and actions in children. Developmental cognitive neuroscience is booming, and knowledge from human brain mapping is finding its way into education and pediatric practice. Promises of application in developmental cognitive neuroscience rests however on better theory-guided data interpretation. Massive amounts of neuroimaging data from children are being processed, yet published studies often do not frame their work within developmental models—in detriment, we believe, to progress in this field. Here we describe some core challenges in interpreting the data from developmental cognitive neuroscience, and advocate the use of constructivist developmental theories of human cognition with a neuroscience interpretation.

  8. Focal adhesion kinase-mediated activation of glycogen synthase kinase 3β regulates IL-33 receptor internalization and IL-33 signaling.

    Science.gov (United States)

    Zhao, Jing; Wei, Jianxin; Bowser, Rachel K; Traister, Russell S; Fan, Ming-Hui; Zhao, Yutong

    2015-01-15

    IL-33, a relatively new member of the IL-1 cytokine family, plays a crucial role in allergic inflammation and acute lung injury. Long form ST2 (ST2L), the receptor for IL-33, is expressed on immune effector cells and lung epithelia and plays a critical role in triggering inflammation. We have previously shown that ST2L stability is regulated by the ubiquitin-proteasome system; however, its upstream internalization has not been studied. In this study, we demonstrate that glycogen synthase kinase 3β (GSK3β) regulates ST2L internalization and IL-33 signaling. IL-33 treatment induced ST2L internalization, and an effect was attenuated by inhibition or downregulation of GSK3β. GSK3β was found to interact with ST2L on serine residue 446 in response to IL-33 treatment. GSK3β binding site mutant (ST2L(S446A)) and phosphorylation site mutant (ST2L(S442A)) are resistant to IL-33-induced ST2L internalization. We also found that IL-33 activated focal adhesion kinase (FAK). Inhibition of FAK impaired IL-33-induced GSK3β activation and ST2L internalization. Furthermore, inhibition of ST2L internalization enhanced IL-33-induced cytokine release in lung epithelial cells. These results suggest that modulation of the ST2L internalization by FAK/GSK3β might serve as a unique strategy to lessen pulmonary inflammation. Copyright © 2015 by The American Association of Immunologists, Inc.

  9. ARF6 Activated by the LHCG Receptor through the Cytohesin Family of Guanine Nucleotide Exchange Factors Mediates the Receptor Internalization and Signaling*

    Science.gov (United States)

    Kanamarlapudi, Venkateswarlu; Thompson, Aiysha; Kelly, Eamonn; López Bernal, Andrés

    2012-01-01

    The luteinizing hormone chorionic gonadotropin receptor (LHCGR) is a Gs-coupled GPCR that is essential for the maturation and function of the ovary and testis. LHCGR is internalized following its activation, which regulates the biological responsiveness of the receptor. Previous studies indicated that ADP-ribosylation factor (ARF)6 and its GTP-exchange factor (GEF) cytohesin 2 regulate LHCGR internalization in follicular membranes. However, the mechanisms by which ARF6 and cytohesin 2 regulate LHCGR internalization remain incompletely understood. Here we investigated the role of the ARF6 signaling pathway in the internalization of heterologously expressed human LHCGR (HLHCGR) in intact cells using a combination of pharmacological inhibitors, siRNA and the expression of mutant proteins. We found that human CG (HCG)-induced HLHCGR internalization, cAMP accumulation and ARF6 activation were inhibited by Gallein (βγ inhibitor), Wortmannin (PI 3-kinase inhibitor), SecinH3 (cytohesin ARF GEF inhibitor), QS11 (an ARF GAP inhibitor), an ARF6 inhibitory peptide and ARF6 siRNA. However, Dynasore (dynamin inhibitor), the dominant negative mutants of NM23-H1 (dynamin activator) and clathrin, and PBP10 (PtdIns 4,5-P2-binding peptide) inhibited agonist-induced HLHCGR and cAMP accumulation but not ARF6 activation. These results indicate that heterotrimeric G-protein, phosphatidylinositol (PI) 3-kinase (PI3K), cytohesin ARF GEF and ARF GAP function upstream of ARF6 whereas dynamin and clathrin act downstream of ARF6 in the regulation of HCG-induced HLHCGR internalization and signaling. In conclusion, we have identified the components and molecular details of the ARF6 signaling pathway required for agonist-induced HLHCGR internalization. PMID:22523074

  10. Triphenyl phosphate-induced developmental toxicity in zebrafish: Potential role of the retinoic acid receptor

    Energy Technology Data Exchange (ETDEWEB)

    Isales, Gregory M.; Hipszer, Rachel A.; Raftery, Tara D. [Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC (United States); Chen, Albert; Stapleton, Heather M. [Division of Environmental Sciences and Policy, Nicholas School of the Environment, Duke University, Durham, NC (United States); Volz, David C., E-mail: volz@mailbox.sc.edu [Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC (United States)

    2015-04-15

    Highlights: • Triphenyl phosphate-induced toxicity in zebrafish embryos is enhanced in the presence of a retinoic acid receptor antagonist. • Triphenyl phosphate uptake or metabolism within zebrafish embryos is not altered in the presence of a retinoic acid receptor antagonist. • Triphenyl phosphate decreases expression of cytochrome P450 26a1 in zebrafish embryos. • Triphenyl phosphate inhibits retinoic acid-induced activation of human retinoic acid receptors. - Abstract: Using zebrafish as a model, we previously reported that developmental exposure to triphenyl phosphate (TPP) – a high-production volume organophosphate-based flame retardant – results in dioxin-like cardiac looping impairments that are independent of the aryl hydrocarbon receptor. Using a pharmacologic approach, the objective of this study was to investigate the potential role of retinoic acid receptor (RAR) – a nuclear receptor that regulates vertebrate heart morphogenesis – in mediating TPP-induced developmental toxicity in zebrafish. We first revealed that static exposure of zebrafish from 5–72 h post-fertilization (hpf) to TPP in the presence of non-toxic concentrations of an RAR antagonist (BMS493) significantly enhanced TPP-induced toxicity (relative to TPP alone), even though identical non-toxic BMS493 concentrations mitigated retinoic acid (RA)-induced toxicity. BMS493-mediated enhancement of TPP toxicity was not a result of differential TPP uptake or metabolism, as internal embryonic doses of TPP and diphenyl phosphate (DPP) – a primary TPP metabolite – were not different in the presence or absence of BMS493. Using real-time PCR, we then quantified the relative change in expression of cytochrome P450 26a1 (cyp26a1) – a major target gene for RA-induced RAR activation in zebrafish – and found that RA and TPP exposure resulted in a ∼5-fold increase and decrease in cyp26a1 expression, respectively, relative to vehicle-exposed embryos. To address whether TPP may

  11. An Examination of Specific Child Behavior Problems as Predictors of Parenting Stress among Families of Children with Pervasive Developmental Disorders

    Science.gov (United States)

    Davis, Allyson L.; Neece, Cameron L.

    2017-01-01

    Introduction: Studies have shown that parents of children with pervasive developmental disorders (PDD) exhibit higher levels of stress than parents of typically developing children or children with other types of developmental delays (DD). This relationship appears to be mediated by elevated levels of behavior problems observed in children with…

  12. Building clinical networks: a developmental evaluation framework.

    Science.gov (United States)

    Carswell, Peter; Manning, Benjamin; Long, Janet; Braithwaite, Jeffrey

    2014-05-01

    Clinical networks have been designed as a cross-organisational mechanism to plan and deliver health services. With recent concerns about the effectiveness of these structures, it is timely to consider an evidence-informed approach for how they can be developed and evaluated. To document an evaluation framework for clinical networks by drawing on the network evaluation literature and a 5-year study of clinical networks. We searched literature in three domains: network evaluation, factors that aid or inhibit network development, and on robust methods to measure network characteristics. This material was used to build a framework required for effective developmental evaluation. The framework's architecture identifies three stages of clinical network development; partner selection, network design and network management. Within each stage is evidence about factors that act as facilitators and barriers to network growth. These factors can be used to measure progress via appropriate methods and tools. The framework can provide for network growth and support informed decisions about progress. For the first time in one place a framework incorporating rigorous methods and tools can identify factors known to affect the development of clinical networks. The target user group is internal stakeholders who need to conduct developmental evaluation to inform key decisions along their network's developmental pathway.

  13. Developmentally Appropriate Peace Education Curricula

    Science.gov (United States)

    Lewsader, Joellen; Myers-Walls, Judith A.

    2017-01-01

    Peace education has been offered to children for decades, but those curricula have been only minimally guided by children's developmental stages and needs. In this article, the authors apply their research on children's developmental understanding of peace along with peace education principles and Vygotsky's sociocultural theory to present…

  14. Developmental Kindergarten Program Evaluation Report.

    Science.gov (United States)

    Blois, George T.; Cushing, Katherine S.

    The evaluation of the Developmental Kindergarten (DK) Program at the Harrison School District #2, Colorado Springs, Colorado, involved pre- and post-testing of student academic gains and interviewing of principals and teachers. The program aimed to provide developmentally appropriate activities for students believed to be "at risk" of…

  15. Developmental programming of happiness.

    Science.gov (United States)

    Schmidt, Louis A; Fortier, Paz; Lahat, Ayelet; Tang, Alva; Mathewson, Karen J; Saigal, Saroj; Boyle, Michael H; Van Lieshout, Ryan J

    2017-09-01

    Being born at an extremely low birth weight (ELBW; programming hypotheses. Interfacing prenatal programming and differential susceptibility hypotheses, we tested whether individuals with ELBW in different childhood rearing environments showed different attention biases to positive and negative facial emotions in adulthood. Using the oldest known, prospectively followed cohort of ELBW survivors, we found that relative to normal birth weight controls (NBW; >2,500 grams), ELBW survivors displayed the highest and lowest attention bias to happy faces at age 30-35, depending on whether their total family income at age 8 was relatively low (environmental match) or high (environmental mismatch), respectively. This bias to happy faces was associated with a reduced likelihood of emotional problems. Findings suggest that differential susceptibility to positive emotions may be prenatally programmed, with effects lasting into adulthood. We discuss implications for integrating prenatal programming and differential susceptibility hypotheses, and the developmental origins of postnatal plasticity and resilience. © 2017 Wiley Periodicals, Inc.

  16. Developmental colour agnosia.

    Science.gov (United States)

    van Zandvoort, Martine J E; Nijboer, Tanja C W; de Haan, Edward

    2007-08-01

    Colour agnosia concerns the inability to recognise colours despite intact colour perception, semantic memory for colour information, and colour naming. Patients with selective colour agnosia have been described and the deficit is associated with left hemisphere damage. Here we report a case study of a 43-year-old man who was referred to us with a stroke in his right cerebellar hemisphere. During the standard assessment it transpired that he was unable to name coloured patches. Detailed assessment of his colour processing showed that he suffers from a selective colour agnosia. As he claimed to have had this problem all his life, and the fact that the infratentorial infarct that he had incurred was in an area far away from the brain structures that are known to be involved in colour processing, we suggest that he is the first reported case of developmental colour agnosia.

  17. [Neurotransmission in developmental disorders].

    Science.gov (United States)

    Takeuchi, Yoshihiro

    2008-11-01

    Attention deficit/hyperactivity disorder (AD/HD) is a heterogeneous developmental disorder with an etiology that is not fully understood. AD/HD has been considered to occur due to a disturbance in cathecholaminergic neurotransmission, with particular emphasis on dopamine. The neurotransmission of dopamine in subcortical regions such as the basal ganglia and limbic areas is synaptic; on the other hand, dopamine neurotransmission in the frontal cortex is quite different, because there are very few dopamine transporters (DAT) in the frontal cortex that allow dopamine to diffuse away from the dopamine synapse ("volume transmission"). It is now clear that noradrenergic neurons play a key regulatory role in dopaminergic function in the frontal cortex. Furthermore, serotonergic neurons exert an inhibitory effect on midbrain dopamine cell bodies, and they have an influence on dopamine release in terminal regions. There is accumulating neurobiological evidence pointing toward a role of the serotonin system in AD/HD. The etiology of autism spectrum disorders (ASD) is still unclear, but information from genetics, neuropathology, brain imaging, and basic neuroscience has provided insights into the understanding of this developmental disorder. In addition to abnormal circuitry in specific limbic and neocortical areas of the cerebral cortex, impairments in brainstem, cerebellar, thalamic, and basal ganglia connections have been reported. Numerous studies have pointed to abnormalities in serotonin and glutamate neurotransmission. Three important aspects involved in the pathophysiology of ASD have been proposed. The first is cell migration, the second is unbalanced excitatory-inhibitory networks, and the third is synapse formation and pruning, the key factors being reelin, neurexin, and neuroligin. Serotonin is considered to play an important role in all of these aspects of the pathophysiology of ASD. Finally, I would like to emphasize that it is crucial in the field of child

  18. Eps15R is a tyrosine kinase substrate with characteristics of a docking protein possibly involved in coated pits-mediated internalization

    DEFF Research Database (Denmark)

    Coda, L; Salcini, A E; Confalonieri, S

    1998-01-01

    in NIH-3T3 cells overexpressing the receptor, even at low levels of receptor occupancy, thus behaving as physiological substrates. A role for eps15R in clathrin-mediated endocytosis is suggested by its localization in plasma membrane-coated pits and in vivo association to the coated pits' adapter protein...... AP-2. Finally, we demonstrate that a sizable fraction of eps15R exists in the cell as a complex with eps15 and that its EH domains exhibit binding specificities that are partially distinct from those of eps15. We propose that eps15 and eps15R are multifunctional binding proteins that serve...

  19. 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...

  20. Developmental pathways from child maltreatment to adolescent marijuana dependence: Examining moderation by FKBP5

    Science.gov (United States)

    Handley, Elizabeth D.; Rogosch, Fred A.; Cicchetti, Dante

    2015-01-01

    The current study examined the prospective association between child maltreatment and the development of substance use disorder (SUD) in adolescence with the aim of investigating pathways underlying this relation, as well as genetic moderation of these developmental mechanisms. Specifically, we tested whether youth who experienced maltreatment prior to age 8 were at risk for the development of marijuana dependence in adolescence by way of a childhood externalizing pathway and a childhood internalizing pathway. Moreover, we tested whether variation in FKBP5 CATT haplotype moderated these pathways. The participants were 326 children (n=179 maltreated; n=147 nonmaltreated) assessed across two waves of data collection (childhood: ages 7–9 and adolescence: ages 15–18). Results indicated that higher levels of child externalizing symptoms significantly mediated the effect of child maltreatment on adolescent marijuana dependence symptoms for individuals with 1–2 copies of the FKBP5 CATT haplotype only. We did not find support for an internalizing pathway from child maltreatment to adolescent marijuana dependence, nor did we find evidence of moderation of the internalizing pathway by FKBP5 haplotype variation. Findings extend previous research by demonstrating that whether a maltreated child will traverse an externalizing pathway toward SUD in adolescence is dependent on FKBP5 genetic variation. PMID:26535939

  1. Developmental Trends of the Defence of Superior Order: Acritical ...

    African Journals Online (AJOL)

    Developmental Trends of the Defence of Superior Order: Acritical Appraisal of the Statute of the International Criminal Court. Eni E Alobo. Abstract. No Abstract. LWATI: A Journal of Contemporary Research, 9(3), 107-125, 2012. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL ...

  2. Insomnia and Psychosocial Crisis: Two Studies of Erikson's Developmental Theory.

    Science.gov (United States)

    Wagner, Karen Dineen; And Others

    1983-01-01

    Examines the role of internal stressors in the development of sleep disturbances in two studies of 122 older adults and 66 college students. Results confirmed Erikson's (1959) developmental theory. Failure to resolve the psychosocial crises of old age and adolescence were related to insomnia. (WAS)

  3. Causal mediation analysis with multiple mediators.

    Science.gov (United States)

    Daniel, R M; De Stavola, B L; Cousens, S N; Vansteelandt, S

    2015-03-01

    In diverse fields of empirical research-including many in the biological sciences-attempts are made to decompose the effect of an exposure on an outcome into its effects via a number of different pathways. For example, we may wish to separate the effect of heavy alcohol consumption on systolic blood pressure (SBP) into effects via body mass index (BMI), via gamma-glutamyl transpeptidase (GGT), and via other pathways. Much progress has been made, mainly due to contributions from the field of causal inference, in understanding the precise nature of statistical estimands that capture such intuitive effects, the assumptions under which they can be identified, and statistical methods for doing so. These contributions have focused almost entirely on settings with a single mediator, or a set of mediators considered en bloc; in many applications, however, researchers attempt a much more ambitious decomposition into numerous path-specific effects through many mediators. In this article, we give counterfactual definitions of such path-specific estimands in settings with multiple mediators, when earlier mediators may affect later ones, showing that there are many ways in which decomposition can be done. We discuss the strong assumptions under which the effects are identified, suggesting a sensitivity analysis approach when a particular subset of the assumptions cannot be justified. These ideas are illustrated using data on alcohol consumption, SBP, BMI, and GGT from the Izhevsk Family Study. We aim to bridge the gap from "single mediator theory" to "multiple mediator practice," highlighting the ambitious nature of this endeavor and giving practical suggestions on how to proceed. © 2014 The Authors Biometrics published by Wiley Periodicals, Inc. on behalf of International Biometric Society.

  4. Where Do Epigenetics and Developmental Origins Take the Field of Developmental Psychopathology?

    Science.gov (United States)

    Nigg, Joel T

    2016-04-01

    The time is ripe for upgrading or rethinking the assumed paradigms for how we study developmental psychopathology. The classic transactional models appear robust but need specification in terms of biological and psychosocial processes. That specification is increasingly tractable due to developments in genetics, epigenetics, the measurement of psychosocial processes, and theory and data on developmental origins of health and disease. This essay offers a high-level view of where the field has been and where it may be going in regard to nosology and conceptions of etiology. Remarks seek to consider rapidly evolving contexts not only for children, but also for the science itself due to progress in our field and in neighboring fields. Illustrations are provided as to how syndromal nosology can be enriched and advanced by careful integration with biologically relevant behavioral dimensions and application of quantitative methods. It is concluded that a revised, forward-looking, transactional model of abnormal child psychology will incorporate prenatal and postnatal developmental programming, epigenetic mechanisms and their associated genotype x environment interactions, and inflammatory processes as a potential common mediator influencing numerous health and mental health conditions.

  5. Charles Darwin and the origins of plant evolutionary developmental biology.

    Science.gov (United States)

    Friedman, William E; Diggle, Pamela K

    2011-04-01

    Much has been written of the early history of comparative embryology and its influence on the emergence of an evolutionary developmental perspective. However, this literature, which dates back nearly a century, has been focused on metazoans, without acknowledgment of the contributions of comparative plant morphologists to the creation of a developmental view of biodiversity. We trace the origin of comparative plant developmental morphology from its inception in the eighteenth century works of Wolff and Goethe, through the mid nineteenth century discoveries of the general principles of leaf and floral organ morphogenesis. Much like the stimulus that von Baer provided as a nonevolutionary comparative embryologist to the creation of an evolutionary developmental view of animals, the comparative developmental studies of plant morphologists were the basis for the first articulation of the concept that plant (namely floral) evolution results from successive modifications of ontogeny. Perhaps most surprisingly, we show that the first person to carefully read and internalize the remarkable advances in the understanding of plant morphogenesis in the 1840s and 1850s is none other than Charles Darwin, whose notebooks, correspondence, and (then) unpublished manuscripts clearly demonstrate that he had discovered the developmental basis for the evolutionary transformation of plant form.

  6. Attentional networks in developmental dyscalculia

    Directory of Open Access Journals (Sweden)

    Henik Avishai

    2010-01-01

    Full Text Available Abstract Background Very little is known about attention deficits in developmental dyscalculia, hence, this study was designed to provide the missing information. We examined attention abilities of participants suffering from developmental dyscalculia using the attention networks test - interactions. This test was designed to examine three different attention networks--executive function, orienting and alerting--and the interactions between them. Methods Fourteen university students that were diagnosed as suffering from developmental dyscalculia--intelligence and reading abilities in the normal range and no indication of attention-deficit hyperactivity disorder--and 14 matched controls were tested using the attention networks test - interactions. All participants were given preliminary tests to measure mathematical abilities, reading, attention and intelligence. Results The results revealed deficits in the alerting network--a larger alerting effect--and in the executive function networks--a larger congruity effect in developmental dyscalculia participants. The interaction between the alerting and executive function networks was also modulated by group. In addition, developmental dyscalculia participants were slower to respond in the non-cued conditions. Conclusions These results imply specific attentional deficits in pure developmental dyscalculia. Namely, those with developmental dyscalculia seem to be deficient in the executive function and alertness networks. They suffer from difficulty in recruiting attention, in addition to the deficits in numerical processing.

  7. Attentional networks in developmental dyscalculia.

    Science.gov (United States)

    Askenazi, Sarit; Henik, Avishai

    2010-01-07

    Very little is known about attention deficits in developmental dyscalculia, hence, this study was designed to provide the missing information. We examined attention abilities of participants suffering from developmental dyscalculia using the attention networks test - interactions. This test was designed to examine three different attention networks--executive function, orienting and alerting--and the interactions between them. Fourteen university students that were diagnosed as suffering from developmental dyscalculia--intelligence and reading abilities in the normal range and no indication of attention-deficit hyperactivity disorder--and 14 matched controls were tested using the attention networks test-interactions. All participants were given preliminary tests to measure mathematical abilities, reading, attention and intelligence. The results revealed deficits in the alerting network--a larger alerting effect--and in the executive function networks--a larger congruity effect in developmental dyscalculia participants. The interaction between the alerting and executive function networks was also modulated by group. In addition, developmental dyscalculia participants were slower to respond in the non-cued conditions. These results imply specific attentional deficits in pure developmental dyscalculia. Namely, those with developmental dyscalculia seem to be deficient in the executive function and alertness networks. They suffer from difficulty in recruiting attention, in addition to the deficits in numerical processing.

  8. 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

  9. Factors influencing work participation of adults with developmental dyslexia : a systematic review

    NARCIS (Netherlands)

    de Beer, Joost; Engels, Josephine; Heerkens, Yvonne; van der Klink, Jac

    2014-01-01

    Background: Evidence has been synthesized to determine hindering and facilitating factors associated with the work participation of adults with developmental dyslexia (DD), classified according to the International Classification of Functioning, Disability and Health (ICF). Methods: A systematic

  10. The Impact of Direct and Indirect of internal marketing on service quality and mediating role of OCB CASE: Iran Insurance Company

    OpenAIRE

    Hassan Ghorbani; Maedeh Mostafavi

    2013-01-01

    Internal Marketing is attracting, developing, motivating, and retaining qualified employees through job-products that satisfy their needs. Organizational citizenship behavior is conceptualized as synonymous with the concept of contextual performance, defined as ‘performance that supports the social and psychological environment in which task performance takes place. Service quality is defined as how well the service meets or exceeds the customers’ expectations on a consistent basis. The conce...

  11. Maternal Obesity, Inflammation, and Developmental Programming

    Directory of Open Access Journals (Sweden)

    Stephanie A. Segovia

    2014-01-01

    Full Text Available The prevalence of obesity, especially in women of child-bearing age, is a global health concern. In addition to increasing the immediate risk of gestational complications, there is accumulating evidence that maternal obesity also has long-term consequences for the offspring. The concept of developmental programming describes the process in which an environmental stimulus, including altered nutrition, during critical periods of development can program alterations in organogenesis, tissue development, and metabolism, predisposing offspring to obesity and metabolic and cardiovascular disorders in later life. Although the mechanisms underpinning programming of metabolic disorders remain poorly defined, it has become increasingly clear that low-grade inflammation is associated with obesity and its comorbidities. This review will discuss maternal metainflammation as a mediator of programming in insulin sensitive tissues in offspring. Use of nutritional anti-inflammatories in pregnancy including omega 3 fatty acids, resveratrol, curcumin, and taurine may provide beneficial intervention strategies to ameliorate maternal obesity-induced programming.

  12. Role of developmental factors in hypothalamic function

    Directory of Open Access Journals (Sweden)

    Jakob eBiran

    2015-04-01

    Full Text Available The hypothalamus is a brain region which regulates homeostasis by mediating endocrine, autonomic and behavioral functions. It is comprised of several nuclei containing distinct neuronal populations producing neuropeptides and neurotransmitters that regulate fundamental body functions including temperature and metabolic rate, thirst and hunger, sexual behavior and reproduction, circadian rhythm, and emotional responses. The identity, number and connectivity of these neuronal populations are established during the organism’s development and are of crucial importance for normal hypothalamic function. Studies have suggested that developmental abnormalities in specific hypothalamic circuits can lead to obesity, sleep disorders, anxiety, depression and autism. At the molecular level, the development of the hypothalamus is regulated by transcription factors, secreted growth factors, neuropeptides and their receptors. Recent studies in zebrafish and mouse have demonstrated that some of these molecules maintain their expression in the adult brain and subsequently play a role in the physiological functions that are regulated by hypothalamic neurons. Here, we summarize the involvement of some of the key developmental factors in hypothalamic development and function by focusing on the mouse and zebrafish genetic model organisms.

  13. Letter and Colour Matching Tasks: Parametric Measures of Developmental Working Memory Capacity

    OpenAIRE

    Powell, Tamara L.; Arsalidou, Marie; Vogan, Vanessa M.; Taylor, Margot J.

    2014-01-01

    We investigated the mediating role of interference in developmental assessments of working memory (WM) capacity across childhood, adolescence, and young adulthood. One hundred and forty-two participants completed two versions of visuospatial (colour matching task, CMT) and verbal (letter matching task, LMT) WM tasks, which systematically varied cognitive load in a high and low interference condition. Results showed similar developmental trajectories across high interference contexts (CMT- and...

  14. International Journal of Health Research

    African Journals Online (AJOL)

    Erah

    The International Journal of Health Research is an online international ... The journal welcomes original research papers, reviews and case reports on ..... mediator generated by endothelial cells, ... Springer Science and Business Media,.

  15. Letter and Colour Matching Tasks: Parametric Measures of Developmental Working Memory Capacity

    Directory of Open Access Journals (Sweden)

    Tamara L. Powell

    2014-01-01

    Full Text Available We investigated the mediating role of interference in developmental assessments of working memory (WM capacity across childhood, adolescence, and young adulthood. One hundred and forty-two participants completed two versions of visuospatial (colour matching task, CMT and verbal (letter matching task, LMT WM tasks, which systematically varied cognitive load in a high and low interference condition. Results showed similar developmental trajectories across high interference contexts (CMT- and LMT-Complex and divergent developmental growth patterns across low interference contexts (CMT- and LMT-Simple. Performance on tasks requiring greater cognitive control was in closer agreement with developmental predictions relative to simple recall guided tasks that rely solely on the storage components of WM. These findings suggest that developmental WM capacity, as measured by the CMT and LMT paradigms, can be better quantified using high interference contexts, in both content domains, and demonstrate steady increases in WM through to mid-adolescence.

  16. Developmental transcriptome of Aplysia californica'

    KAUST Repository

    Heyland, Andreas; Vue, Zer; Voolstra, Christian R.; Medina, Mó nica; Moroz, Leonid L.

    2010-01-01

    developmental transcriptome with similar studies in the zebra fish Danio rerio, the fruit fly Drosophila melanogaster, the nematode Caenorhabditis elegans, and other studies on molluscs suggests an overall highly divergent pattern of gene regulatory mechanisms

  17. PREVALENCE AND EFFECT OF DEVELOPMENTAL ...

    African Journals Online (AJOL)

    uvp

    among children might even be higher, as medical and educational systems frequently fail to ... formally diagnosed, but rather described by their teachers as lazy or ..... Developmental Coordination Disorder Questionnaire for Brazilian children.

  18. The Management of Developmental Apraxia.

    Science.gov (United States)

    Gubbay, S. S.

    1978-01-01

    Of 39 children (5-12 years old) with developmental apraxia and agnosia, who were assessed neurologically, 19 were also given simple standarized tests of motor ability. Journal availability: see EC 112 661. (Author/SBH)

  19. Phosphorylation of the norepinephrine transporter at threonine 258 and serine 259 is linked to protein kinase C-mediated transporter internalization

    DEFF Research Database (Denmark)

    Jayanthi, Lankupalle D; Annamalai, Balasubramaniam; Samuvel, Devadoss J

    2006-01-01

    . Most interestingly, the plasma membrane insertion of the WT-hNET and hNET double mutant were not affected by beta-PMA. Although the WT-hNET showed increased endocytosis and redistribution from caveolin-rich plasma membrane domains following beta-PMA treatment, the hNET double mutant was completely......-regulation. These results suggest that Thr-258 and Ser-259 serve as a PKC-specific phospho-acceptor site and that phosphorylation of this motif is linked to PKC-induced NET internalization....

  20. Sorafenib suppresses TGF-β responses by inducing caveolae/lipid raft-mediated internalization/degradation of cell-surface type II TGF-β receptors: Implications in development of effective adjunctive therapy for hepatocellular carcinoma.

    Science.gov (United States)

    Chung, Chih-Ling; Wang, Shih-Wei; Sun, Wei-Chih; Shu, Chih-Wen; Kao, Yu-Chen; Shiao, Meng-Shin; Chen, Chun-Lin

    2018-04-18

    Sorafenib is the only FDA approved drug for the treatment of advanced hepatocellular carcinoma (HCC) and other malignancies. Studies indicate that TGF-β signalling is associated with tumour progression in HCC. Autocrine and paracrine TGF-β promotes tumour growth and malignancy by inducing epithelial-mesenchymal transition (EMT). Sorafenib is believed to antagonize tumour progression by inhibiting TGF-β-induced EMT. It improves survival of patients but HCC later develops resistance and relapses. The underlying mechanism of resistance is unknown. Understanding of the molecular mechanism of sorafenib inhibition of TGF-β-induced signalling or responses in HCC may lead to development of adjunctive effective therapy for HCC. In this study, we demonstrate that sorafenib suppresses TGF-β responsiveness in hepatoma cells, hepatocytes, and animal liver, mainly by downregulating cell-surface type II TGF-β receptors (TβRII) localized in caveolae/lipid rafts and non-lipid raft microdomains via caveolae/lipid rafts-mediated internalization and degradation. Furthermore, sorafenib-induced downregulation and degradation of cell-surface TβRII is prevented by simultaneous treatment with a caveolae disruptor or lysosomal inhibitors. On the other hand, sorafenib only downregulates cell-surface TβRII localized in caveolae/lipid rafts but not localized in non-lipid raft microdomains in hepatic stellate cells. These results suggest that sorafenib inhibits TGF-β signalling mainly by inducing caveolae/lipid raft-mediated internalization and degradation of cell-surface TβR-II in target cells. They may also imply that treatment with agents which promote formation of caveolae/lipid rafts, TGF-β receptor kinase inhibitors (e.g., LY2157299) or TGF-β peptide antagonists (by liver-targeting delivery) may be considered as effective adjunct therapy with sorafenib for HCC. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Developmental toxicity of engineered nanomaterials

    DEFF Research Database (Denmark)

    Hougaard, Karin S.; Hansen, Jitka S.; Jackson, Petra

    2016-01-01

    Study of air pollution indicates that minute particles may adversely interfere with pregnancy and fetal development. As engineering of nanoparticles have emerged, so has concern that these might interfere with reproductive and developmental functions. This is because nanotechnology may potentially...... increase the overall particle burden in air and introduce particles with novel characteristics and surface reactivity. To evaluate safety for pregnant women, we have studied developmental toxicity of engineered nanoparticles (ENPs), following exposure of pregnant mice by inhalation (ENPs of titanium...

  2. DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.

    Science.gov (United States)

    Mueller, Michael M; Castells-Roca, Laia; Babu, Vipin; Ermolaeva, Maria A; Müller, Roman-Ulrich; Frommolt, Peter; Williams, Ashley B; Greiss, Sebastian; Schneider, Jennifer I; Benzing, Thomas; Schermer, Bernhard; Schumacher, Björn

    2014-12-01

    Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature ageing. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with ageing. Here we show that the FOXO transcription factor DAF-16 is activated in response to DNA damage during development, whereas the DNA damage responsiveness of DAF-16 declines with ageing. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA-damage-induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16-mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.

  3. PrPc Does Not Mediate Internalization of PrPSc but Is Required at an Early Stage for De Novo Prion Infection of Rov Cells▿

    Science.gov (United States)

    Paquet, Sophie; Daude, Nathalie; Courageot, Marie-Pierre; Chapuis, Jérôme; Laude, Hubert; Vilette, Didier

    2007-01-01

    We have studied the interactions of exogenous prions with an epithelial cell line inducibly expressing PrPc protein and permissive to infection by a sheep scrapie agent. We demonstrate that abnormal PrP (PrPSc) and prion infectivity are efficiently internalized in Rov cells, whether or not PrPc is expressed. At odds with earlier studies implicating cellular heparan sulfates in PrPSc internalization, we failed to find any involvement of such molecules in Rov cells, indicating that prions can enter target cells by several routes. We further show that PrPSc taken up in the absence of PrPc was unable to promote efficient prion multiplication once PrPc expression was restored in the cells. This observation argues that interaction of PrPSc with PrPc has to occur early, in a specific subcellular compartment(s), and is consistent with the view that the first prion multiplication events may occur at the cell surface. PMID:17626095

  4. Developmental Science: Past, Present, and Future

    Science.gov (United States)

    Lerner, Richard M.

    2012-01-01

    The goal of developmental science is to describe, explain, and optimize intraindividual changes in adaptive developmental regulations and, as well, interindividual differences in such relations, across life. The history of developmental science is reviewed and its current foci, which are framed by relational developmental systems models that…

  5. Relations of Early Motor Skills on Age and Socialization, Communication, and Daily Living in Young Children With Developmental Disabilities.

    Science.gov (United States)

    MacDonald, Megan; Ross, Samantha; McIntyre, Laura Lee; Tepfer, Amanda

    2017-04-01

    Young children with developmental disabilities experience known deficits in salient child behaviors, such as social behaviors, communication, and aspects of daily living, behaviors that generally improve with chronological age. The purpose of this study was to examine the mediating effects of motor skills on relations of age and salient child behaviors in a group of young children with developmental disabilities, thus tapping into the potential influences of motor skills in the development of salient child behaviors. One hundred thirteen young children with developmental disabilities participated in this study. Independent mediation analysis, with gender as a moderator between the mediating and outcome variable, indicated that motor skills meditated relations between age and socialization, communication, and daily living skills in young male children with developmental disabilities, but not female participants. Findings suggest motor skill content needs to be considered in combination with other child behaviors commonly focused on in early intervention.

  6. Complex Mediation

    DEFF Research Database (Denmark)

    Bødker, Susanne; Andersen, Peter Bøgh

    2005-01-01

    This article has its starting point in a large number of empirical findings regarding computer-mediated work. These empirical findings have challenged our understanding of the role of mediation in such work; on the one hand as an aspect of communication and cooperation at work and on the other hand...... as an aspect of human engagement with instruments of work. On the basis of previous work in activity-theoretical and semiotic human—computer interaction, we propose a model to encompass both of these aspects. In a dialogue with our empirical findings we move on to propose a number of types of mediation...... that have helped to enrich our understanding of mediated work and the design of computer mediation for such work....

  7. Robust and enduring atorvastatin-mediated memory recovery following the 4-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion in middle-aged rats.

    Science.gov (United States)

    Zaghi, Gislene Gonçalves Dias; Godinho, Jacqueline; Ferreira, Emilene Dias Fiuza; Ribeiro, Matheus Henrique Dal Molin; Previdelli, Isolde Santos; de Oliveira, Rúbia Maria Weffort; Milani, Humberto

    2016-02-04

    Chronic cerebral hypoperfusion (CCH) is a common condition associated with the development and/or worsening of age-related dementia.We previously reported persistent memory loss and neurodegeneration after CCH in middle-aged rats. Statin-mediated neuroprotection has been reported after acute cerebral ischemia. Unknown, however, is whether statins can alleviate the outcome of CCH. The present study investigated whether atorvastatin attenuates the cognitive and neurohistological outcome of CCH. Rats (12–15 months old) were trained in a non-food-rewarded radial maze, and then subjected to CCH. Atorvastatin (10 mg/kg, p.o.) was administered for 42 days or 15 days, beginning 5 h after the first occlusion stage. Retrograde memory performance was assessed at 7, 14, 21, 28, and 35 days of CCH, and expressed by “latency,” “number of reference memory errors” and “number of working memory errors.” Neurodegeneration was then examined at the hippocampus and cerebral cortex. Compared to sham, CCH caused profound and persistent memory loss in the vehicle-treated groups, as indicated by increased latency (91.2% to 107.3%) and number of errors (123.5% to 2508.2%), effects from which the animals did not spontaneously recover across time. This CCH-induced retrograde amnesia was completely prevented by atorvastatin (latency: −4.3% to 3.3%; reference/working errors: −2.5% to 45.7%), regardless of the treatment duration. This effect was sustained during the entire behavioral testing period (5 weeks), even after discontinuing treatment. This robust and sustained memory-protective effect of atorvastatin occurred in the absence of neuronal rescue (39.58% to 56.45% cell loss). We suggest that atorvastatin may be promising for the treatment of cognitive sequelae associated with CCH.

  8. Childhood Maltreatment Exposure and Disruptions in Emotion Regulation: A Transdiagnostic Pathway to Adolescent Internalizing and Externalizing Psychopathology

    Science.gov (United States)

    Jenness, Jessica L.; Stoep, Ann Vander; McCauley, Elizabeth; McLaughlin, Katie A.

    2016-01-01

    Child maltreatment is a robust risk factor for internalizing and externalizing psychopathology in children and adolescents. We examined the role of disruptions in emotion regulation processes as a developmental mechanism linking child maltreatment to the onset of multiple forms of psychopathology in adolescents. Specifically, we examined whether child maltreatment was associated with emotional reactivity and maladaptive cognitive and behavioral responses to distress, including rumination and impulsive behaviors, in two separate samples. We additionally investigated whether each of these components of emotion regulation were associated with internalizing and externalizing psychopathology and mediated the association between child maltreatment and psychopathology. Study 1 included a sample of 167 adolescents recruited based on exposure to physical, sexual, or emotional abuse. Study 2 included a sample of 439 adolescents in a community-based cohort study followed prospectively for 5 years. In both samples, child maltreatment was associated with higher levels of internalizing psychopathology, elevated emotional reactivity, and greater habitual engagement in rumination and impulsive responses to distress. In Study 2, emotional reactivity and maladaptive responses to distress mediated the association between child maltreatment and both internalizing and externalizing psychopathology. These findings provide converging evidence for the role of emotion regulation deficits as a transdiagnostic developmental pathway linking child maltreatment with multiple forms of psychopathology. PMID:27695145

  9. Childhood Maltreatment Exposure and Disruptions in Emotion Regulation: A Transdiagnostic Pathway to Adolescent Internalizing and Externalizing Psychopathology.

    Science.gov (United States)

    Heleniak, Charlotte; Jenness, Jessica L; Stoep, Ann Vander; McCauley, Elizabeth; McLaughlin, Katie A

    2016-06-01

    Child maltreatment is a robust risk factor for internalizing and externalizing psychopathology in children and adolescents. We examined the role of disruptions in emotion regulation processes as a developmental mechanism linking child maltreatment to the onset of multiple forms of psychopathology in adolescents. Specifically, we examined whether child maltreatment was associated with emotional reactivity and maladaptive cognitive and behavioral responses to distress, including rumination and impulsive behaviors, in two separate samples. We additionally investigated whether each of these components of emotion regulation were associated with internalizing and externalizing psychopathology and mediated the association between child maltreatment and psychopathology. Study 1 included a sample of 167 adolescents recruited based on exposure to physical, sexual, or emotional abuse. Study 2 included a sample of 439 adolescents in a community-based cohort study followed prospectively for 5 years. In both samples, child maltreatment was associated with higher levels of internalizing psychopathology, elevated emotional reactivity, and greater habitual engagement in rumination and impulsive responses to distress. In Study 2, emotional reactivity and maladaptive responses to distress mediated the association between child maltreatment and both internalizing and externalizing psychopathology. These findings provide converging evidence for the role of emotion regulation deficits as a transdiagnostic developmental pathway linking child maltreatment with multiple forms of psychopathology.

  10. LEGAL CULTURES AND MEDIATION. INTERACTIONS AND EVOLUTIONS

    Directory of Open Access Journals (Sweden)

    Claudiu Ramon D. BUTCULESCU

    2014-05-01

    Full Text Available Mediation, as an alternative dispute resolution method, is closely connected with the system of legal cultures. Mediation is an important link between legal culture and the judicial system. Mediation also acts as an interface between internal legal culture and external legal culture. This paper addresses the issues regarding the links and interactions between mediation and legal cultures, as well as the effects that arise from these interactions.

  11. Synthesis, characterization and applications of carboxylated and polyethylene-glycolated bifunctionalized InP/ZnS quantum dots in cellular internalization mediated by cell-penetrating peptides.

    Science.gov (United States)

    Liu, Betty R; Winiarz, Jeffrey G; Moon, Jong-Sik; Lo, Shih-Yen; Huang, Yue-Wern; Aronstam, Robert S; Lee, Han-Jung

    2013-11-01

    Semiconductor nanoparticles, also known as quantum dots (QDs), are widely used in biomedical imaging studies and pharmaceutical research. Cell-penetrating peptides (CPPs) are a group of small peptides that are able to traverse cell membrane and deliver a variety of cargoes into living cells. CPPs deliver QDs into cells with minimal nonspecific absorption and toxic effect. In this study, water-soluble, monodisperse, carboxyl-functionalized indium phosphide (InP)/zinc sulfide (ZnS) QDs coated with polyethylene glycol lipids (designated QInP) were synthesized for the first time. The physicochemical properties (optical absorption, fluorescence and charging state) and cellular internalization of QInP and CPP/QInP complexes were characterized. CPPs noncovalently interact with QInP in vitro to form stable CPP/QInP complexes, which can then efficiently deliver QInP into human A549 cells. The introduction of 500nM of CPP/QInP complexes and QInP at concentrations of less than 1μM did not reduce cell viability. These results indicate that carboxylated and polyethylene-glycolylated (PEGylated) bifunctionalized QInP are biocompatible nanoparticles with potential for use in biomedical imaging studies and drug delivery applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. The Mediator complex and transcription regulation

    Science.gov (United States)

    Poss, Zachary C.; Ebmeier, Christopher C.

    2013-01-01

    The Mediator complex is a multi-subunit assembly that appears to be required for regulating expression of most RNA polymerase II (pol II) transcripts, which include protein-coding and most non-coding RNA genes. Mediator and pol II function within the pre-initiation complex (PIC), which consists of Mediator, pol II, TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH and is approximately 4.0 MDa in size. Mediator serves as a central scaffold within the PIC and helps regulate pol II activity in ways that remain poorly understood. Mediator is also generally targeted by sequence-specific, DNA-binding transcription factors (TFs) that work to control gene expression programs in response to developmental or environmental cues. At a basic level, Mediator functions by relaying signals from TFs directly to the pol II enzyme, thereby facilitating TF-dependent regulation of gene expression. Thus, Mediator is essential for converting biological inputs (communicated by TFs) to physiological responses (via changes in gene expression). In this review, we summarize an expansive body of research on the Mediator complex, with an emphasis on yeast and mammalian complexes. We focus on the basics that underlie Mediator function, such as its structure and subunit composition, and describe its broad regulatory influence on gene expression, ranging from chromatin architecture to transcription initiation and elongation, to mRNA processing. We also describe factors that influence Mediator structure and activity, including TFs, non-coding RNAs and the CDK8 module. PMID:24088064

  13. Mediation: The Wise Advocacy

    Directory of Open Access Journals (Sweden)

    Towseef Ahmad

    2016-01-01

    Full Text Available AbstractAdversarial litigation is not the only means of resolving disputes and settling of claims. There are various options. Alternative means of dispute resolution can save money and time, and can help to anchor and resolve the dispute while exploring valuable good offices, amicable approaches and facilitation. Mediation, as used in law, is a process of managing negotiation by a neutral third party in the form of Alternative Dispute Resolution (ADR, as a convenient way of resolving disputes between two or more parties with speediation processes. On the sidelines typically, a neutral third party, the mediator assists the parties to negotiate a settlement. The term “mediation” broadly refers to any instance in which a neutral third party helps others to reach an amicable and mutually acceptable agreement. More specifically, mediation has a structure, timetable and dynamic approaches that “ordinary” negotiations usually lack. The process helps the parties to flourish the healthy ideas which are different and distinct from the legal rights in a Court of law. It is well known in International Law also and disputants can submit their disputes to mediation in a variety of matters such as commercial, legal, diplomatic, workplace, community and family matters, which assumes a great significance and it is bricolaged within the framework of this article.Keywords: Adversarial, Litigation, Mediation, Negotiation and Amicable.

  14. Neurobehavioural effects of developmental toxicity

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Landrigan, Philip J

    2014-01-01

    Neurodevelopmental disabilities, including autism, attention-deficit hyperactivity disorder, dyslexia, and other cognitive impairments, affect millions of children worldwide, and some diagnoses seem to be increasing in frequency. Industrial chemicals that injure the developing brain are among...... the known causes for this rise in prevalence. In 2006, we did a systematic review and identified five industrial chemicals as developmental neurotoxicants: lead, methylmercury, polychlorinated biphenyls, arsenic, and toluene. Since 2006, epidemiological studies have documented six additional developmental...... chemicals should not be presumed to be safe to brain development, and chemicals in existing use and all new chemicals must therefore be tested for developmental neurotoxicity. To coordinate these efforts and to accelerate translation of science into prevention, we propose the urgent formation of a new...

  15. DEVELOPMENTAL TAXONOMY OF CONDUCT DISORDER

    Directory of Open Access Journals (Sweden)

    Jelena Kostić

    2015-12-01

    Full Text Available Conduct disorder is a heterogeneous disorder in terms of etiology, course and prognosis, and currently, there is no singular model that would describe the development of the disorder. The results of empirical research on males confirm this heterogeneity, as they point out to two possible developmental pathways: childhood-onset and adolescentonset type. This paper presents the basic elements of developmental taxonomic theory which argues that there are two different developmental pathways to conduct disorder which have different causes and serve as the basis for the current typology of conduct disorders in the classification systems. Such a typology of conduct disorders in the diagnostic classification allows better understanding, prognosis and choice of treatment.

  16. Developmental analytic view on narcissism

    Directory of Open Access Journals (Sweden)

    Polona Matjan Štuhec

    2009-07-01

    Full Text Available Narcissistic pathology is connected to the pathology of the self. This article makes an overview of definitions of developmental analytic theories and stops with Kohut, Kernberg, Masterson, Auerbach and Mollon. The self is understood as a separate personality structure and has its own developmental line. Narcissism is a personality disorder that has its roots in preodipal developmental phases, mostly in the practicing and rapprochement subphase and in the oedipal phase as well. Recent research shows that the oedipal phase and the relation between the mother, the child's father (or her partner in general and the child is crucial for the maintenance of the pathological narcissism. Mothers who do not believe in a satisfying relationship with a man in general, keep the child in the dyadic position and do not support the development of the child's own identity.

  17. S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization.

    Science.gov (United States)

    Lee, Mi-Hye; Appleton, Kathryn M; El-Shewy, Hesham M; Sorci-Thomas, Mary G; Thomas, Michael J; Lopes-Virella, Maria F; Luttrell, Louis M; Hammad, Samar M; Klein, Richard L

    2017-02-01

    HDL normally transports about 50-70% of plasma sphingosine 1-phosphate (S1P), and the S1P in HDL reportedly mediates several HDL-associated biological effects and signaling pathways. The HDL receptor, SR-BI, as well as the cell surface receptors for S1P (S1PRs) may be involved partially and/or completely in these HDL-induced processes. Here we investigate the nature of the HDL-stimulated interaction between the HDL receptor, SR-BI, and S1PR1 using a protein-fragment complementation assay and confocal microscopy. In both primary rat aortic vascular smooth muscle cells and HEK293 cells, the S1P content in HDL particles increased intracellular calcium concentration, which was mediated by S1PR1. Mechanistic studies performed in HEK293 cells showed that incubation of cells with HDL led to an increase in the physical interaction between the SR-BI and S1PR1 receptors that mainly occurred on the plasma membrane. Model recombinant HDL (rHDL) particles formed in vitro with S1P incorporated into the particle initiated the internalization of S1PR1, whereas rHDL without supplemented S1P did not, suggesting that S1P transported in HDL can selectively activate S1PR1. In conclusion, these data suggest that S1P in HDL stimulates the transient interaction between SR-BI and S1PRs that can activate S1PRs and induce an elevation in intracellular calcium concentration.

  18. Developmental orthopaedic diseases in foals

    International Nuclear Information System (INIS)

    Şİrİn, Özlem; Alkan, Zeki

    2010-01-01

    Developmental Orthopaedic Diseases (DOD) is seen frequently in horses which completed their maturity. Osteochondrosis, physitis, angular limb deformities, flexural deformities, juvenil arthritis, cervical vertebral anomalies, cuboidal bone abnormalities are problems investigated under Developmental Orthopaedic Diseases title. This diseases can develop single or some together in fast growing, heavy animals (especially Arabian and English Thoroughbreds). Multifactorial causes of this diseases etiopathogenesis can be listed as genetic predisposition, trauma, nutrition, vitamins/minerals and endocrine disorders. But the exact causes of these diseases are not known. In this review detailed information are given about the diseases mentioned above

  19. PERSONALITY PREDISPOSITIONS IN CHINESE ADOLESCENTS: THE RELATION BETWEEN SELF-CRITICISM, DEPENDENCY, AND PROSPECTIVE INTERNALIZING SYMPTOMS

    Science.gov (United States)

    Cohen, Joseph R.; Young, Jami F.; Hankin, Benjamin L.; Yao, Shuqiao; Zhu, Xiong Zhao; Abela, John R.Z.

    2015-01-01

    The present study examined the prospective relation between two personality predispositions, self-criticism and dependency, and internalizing symptoms. Specifically, it was examined whether self-criticism and dependency predicted symptoms of depression and social anxiety, and if a moderation (e.g. diathesis-stress) or mediation model best explained the relation between the personality predispositions and emotional distress in Chinese adolescents. Participants included 1,150 adolescents (597 females and 553 males) from mainland China. Participants completed self-report measures of self-criticism, dependency, and neuroticism at baseline, and self-report measures of negative events, depressive symptoms, and social anxiety symptoms once a month for six months. Findings showed that self-criticism predicted depressive symptoms, while dependency predicted social anxiety symptoms. In addition, support was found for a mediation model, as opposed to a moderation model, with achievement stressors mediating the relation between self-criticism and depressive symptoms. Overall, these findings highlight new developmental pathways for the development of depression and social anxiety symptoms in mainland Chinese adolescents. Implications for cross-cultural developmental psychopathology research are discussed. PMID:25798026

  20. Practical Guide to Civil Mediation

    CERN Document Server

    2006-01-01

    The Permanent Mission of Switzerland has informed CERN that the Département des Institutions of the Republic and Canton of Geneva and the Groupement suisse des Magistrats pour la médiation (GEMME) - Swiss Association of Magistrates for Mediation have published a multilingual Practical Guide to Civil Mediation (including English). In this context, the Swiss Mission has underlined the benefits of resorting to mediation, especially for the personnel of international organizations, and which the Secretary-General of the GEMME has summarised as follows: it is a private process not requiring the waiver of the parties' immunities; the confidentiality of the mediation process is guaranteed both by the mediator and the parties to it; the search for an amicable settlement does not need to be determined by reference to law (provided that public order is respected); the process is faster (2 to 3 sessions), less costly and more flexible than civil or arbitration procedures; in order to reinforce the agreeme...

  1. Practical Guide to Civil Mediation

    CERN Multimedia

    2006-01-01

    The Permanent Mission of Switzerland has informed CERN that the Département des Institutions of the Republic and Canton of Geneva and the Groupement suisse des Magistrats pour la médiation (GEMME) - Swiss Association of Magistrates for Mediation have published a multilingual Practical Guide to Civil Mediation (including English). In this context, the Swiss Mission has underlined the benefits of resorting to mediation, especially for the personnel of International Organizations, and which the Secretary-General of the GEMME has summarised as follows: it is a private process not requiring the waiver of the parties' immunities; the confidentiality of the mediation process is guaranteed both by the mediator and the parties to it; the search for an amicable settlement does not need to be determined by reference to law (provided that public order is respected); the process is faster (2 to 3 sessions), less costly and more flexible than civil or arbitration procedures; in order to reinforce the agreem...

  2. The diversification of developmental biology.

    Science.gov (United States)

    Crowe, Nathan; Dietrich, Michael R; Alomepe, Beverly S; Antrim, Amelia F; ByrneSim, Bay Lauris; He, Yi

    2015-10-01

    In the 1960s, "developmental biology" became the dominant term to describe some of the research that had previously been included under the rubrics of embryology, growth, morphology, and physiology. As scientific societies formed under this new label, a new discipline took shape. Historians, however, have a number of different perspectives on what changes led to this new field of developmental biology and how the field itself was constituted during this period. Using the General Embryological Information Service, a global index of post-World War II development-related research, we have documented and visualized significant changes in the kinds of research that occurred as this new field formed. In particular, our analysis supports the claim that the transition toward developmental biology was marked by a growth in new topics and forms of research. Although many historians privilege the role of molecular biology and/or the molecularization of biology in general during this formative period, we have found that the influence of molecular biology is not sufficient to account for the wide range of new research that constituted developmental biology at the time. Overall, our work creates a robust characterization of the changes that occurred with regard to research on growth and development in the decades following World War II and provides a context for future work on the specific drivers of those changes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Transforming Developmental Education in Texas

    Science.gov (United States)

    Journal of Developmental Education, 2014

    2014-01-01

    In recent years, with support from the Texas Legislature, the Texas Higher Education Coordinating Board has funded various developmental education initiatives, including research and evaluation efforts, to help Texas public institutions of higher education provide more effective programs and services to underprepared students. Based on evaluation…

  4. Developmental principles: fact or fiction.

    Science.gov (United States)

    Durston, A J

    2012-01-01

    While still at school, most of us are deeply impressed by the underlying principles that so beautifully explain why the chemical elements are ordered as they are in the periodic table, and may wonder, with the theoretician Brian Goodwin, "whether there might be equally powerful principles that account for the awe-inspiring diversity of body forms in the living realm". We have considered the arguments for developmental principles, conclude that they do exist and have specifically identified features that may generate principles associated with Hox patterning of the main body axis in bilaterian metazoa in general and in the vertebrates in particular. We wonder whether this exercise serves any purpose. The features we discuss were already known to us as parts of developmental mechanisms and defining developmental principles (how, and at which level?) adds no insight. We also see little profit in the proposal by Goodwin that there are principles outside the emerging genetic mechanisms that need to be taken into account. The emerging developmental genetic hierarchies already reveal a wealth of interesting phenomena, whatever we choose to call them.

  5. Developmental Principles: Fact or Fiction

    Directory of Open Access Journals (Sweden)

    A. J. Durston

    2012-01-01

    Full Text Available While still at school, most of us are deeply impressed by the underlying principles that so beautifully explain why the chemical elements are ordered as they are in the periodic table, and may wonder, with the theoretician Brian Goodwin, “whether there might be equally powerful principles that account for the awe-inspiring diversity of body forms in the living realm”. We have considered the arguments for developmental principles, conclude that they do exist and have specifically identified features that may generate principles associated with Hox patterning of the main body axis in bilaterian metazoa in general and in the vertebrates in particular. We wonder whether this exercise serves any purpose. The features we discuss were already known to us as parts of developmental mechanisms and defining developmental principles (how, and at which level? adds no insight. We also see little profit in the proposal by Goodwin that there are principles outside the emerging genetic mechanisms that need to be taken into account. The emerging developmental genetic hierarchies already reveal a wealth of interesting phenomena, whatever we choose to call them.

  6. Measuring Developmental Students' Mathematics Anxiety

    Science.gov (United States)

    Ding, Yanqing

    2016-01-01

    This study conducted an item-level analysis of mathematics anxiety and examined the dimensionality of mathematics anxiety in a sample of developmental mathematics students (N = 162) by Multi-dimensional Random Coefficients Multinominal Logit Model (MRCMLM). The results indicate a moderately correlated factor structure of mathematics anxiety (r =…

  7. Developmental dyscalculia: a dysconnection syndrome?

    Science.gov (United States)

    Kucian, Karin; Ashkenazi, Simone Schwizer; Hänggi, Jürgen; Rotzer, Stephanie; Jäncke, Lutz; Martin, Ernst; von Aster, Michael

    2014-09-01

    Numerical understanding is important for everyday life. For children with developmental dyscalculia (DD), numbers and magnitudes present profound problems which are thought to be based upon neuronal impairments of key regions for numerical understanding. The aim of the present study was to investigate possible differences in white matter fibre integrity between children with DD and controls using diffusion tensor imaging. White matter integrity and behavioural measures were evaluated in 15 children with developmental dyscalculia aged around 10 years and 15 matched controls. The main finding, obtained by a whole brain group comparison, revealed reduced fractional anisotropy in the superior longitudinal fasciculus in children with developmental dyscalculia. In addition, a region of interest analysis exhibited prominent deficits in fibres of the superior longitudinal fasciculus adjacent to the intraparietal sulcus, which is thought to be the core region for number processing. To conclude, our results outline deficient fibre projection between parietal, temporal and frontal regions in children with developmental dyscalculia, and therefore raise the question of whether dyscalculia can be seen as a dysconnection syndrome. Since the superior longitudinal fasciculus is involved in the integration and control of distributed brain processes, the present results highlight the importance of considering broader domain-general mechanisms in the diagnosis and therapy of dyscalculia.

  8. Neuropsychological Aspects of Developmental Dyscalculia.

    Science.gov (United States)

    Shalev, R. S.; Manor, O.; Gross-Tsur, V.

    1997-01-01

    Classification of arithmetic disorders is predicated on neuropsychological features and associated learning disabilities. Assesses the compatibility of these classifications on a nonreferred, population-based cohort of children (N=139) with developmental dyscalculia. Concludes that children with dyscalculia and disabilities in reading and/or…

  9. Developmental trends in adaptive memory.

    Science.gov (United States)

    Otgaar, Henry; Howe, Mark L; Smeets, Tom; Garner, Sarah R

    2014-01-01

    Recent studies have revealed that memory is enhanced when information is processed for fitness-related purposes. The main objective of the current experiments was to test developmental trends in the evolutionary foundation of memory using different types of stimuli and paradigms. In Experiment 1, 11-year-olds and adults were presented with neutral, negative, and survival-related DRM word lists. We found a memory benefit for the survival-related words and showed that false memories were more likely to be elicited for the survival-related word lists than for the other lists. Experiment 2 examined developmental trends in the survival processing paradigm using neutral, negative, and survival-related pictures. A survival processing advantage was found for survival-related pictures in adults, for negative pictures in 11/12-year-olds, and for neutral pictures in 7/8-year-olds. In Experiment 3, 11/12-year-olds and adults had to imagine the standard survival scenario or an adapted survival condition (or pleasantness condition) that was designed to reduce the possibilities for elaborative processing. We found superior memory retention for both survival scenarios in children and adults. Collectively, our results evidently show that the survival processing advantage is developmentally invariant and that certain proximate mechanisms (elaboration and distinctiveness) underlie these developmental trends.

  10. Developmental control of cell division

    NARCIS (Netherlands)

    Boxem, M. (Mike)

    2002-01-01

    During development of multicellular organisms, cell divisions need to be coordinated with the developmental program of the entire organism. Although the mechanisms that drive cells through the division cycle are well understood, very little is known about the pathways that link extracellular signals

  11. Student Development and Developmental Studies.

    Science.gov (United States)

    Champaigne, John

    1982-01-01

    Reviews the nine-stage Perry Scheme of Intellectual and Ethical Development, detailing three major student orientations--dualism, multiplicity, and commitments in relativism. Suggests techniques developmental educators can use to communicate with, support, and challenge students to promote intellectual development. Underscores the importance of…

  12. Mapping Developmental Precursors of Cyber-Aggression: Trajectories of Risk Predict Perpetration and Victimization

    Science.gov (United States)

    Modecki, Kathryn L.; Barber, Bonnie L.; Vernon, Lynnette

    2013-01-01

    Technologically mediated contexts are social arenas in which adolescents can be both perpetrators and victims of aggression. Yet, there remains little understanding of the developmental etiology of cyber aggression, itself, as experienced by either perpetrators or victims. The current study examines 3-year latent within-person trajectories of…

  13. Acceptance of Disability and Hwa-Byung among Korean Mothers of Children with Developmental Disabilities

    Science.gov (United States)

    Kim, Eunha; Hwang, Jowon; Park, Sukyoung

    2018-01-01

    This study examined how child problem behaviour could be related to maternal Hwa-Byung (HB; Korean culture syndrome, meaning "anger illness") among Korean mothers of children with developmental disabilities. Acceptance of disabilities and parenting stress were tested as mediators for the relationship between child problem behaviour and…

  14. Longitudinal associations between marital stress and externalizing behavior : Does Parental Sense of Competence Mediate Processes?

    NARCIS (Netherlands)

    van Eldik, W. M.; Prinzie, Peter; Dekovic, M.; de Haan, A.D.

    2017-01-01

    Ecological theories emphasize associations between children and elements within their family system, such as the marital relationship. Within a developmental perspective, we longitudinally examined (a) dynamic associations between marital stress and children’s externalizing behavior, (b) mediation

  15. Longitudinal associations between marital stress and externalizing behavior: Does parental sense of competence mediate processes?

    NARCIS (Netherlands)

    Eldik, W.M. van; Prinzie, P.; Dekoviç, M.; Haan, A.D. de

    2017-01-01

    Ecological theories emphasize associations between children and elements within their family system, such as the marital relationship. Within a developmental perspective, we longitudinally examined (a) dynamic associations between marital stress and children's externalizing behavior, (b) mediation

  16. Developmental pathways from child maltreatment to adolescent marijuana dependence: Examining moderation by FK506 binding protein 5 gene (FKBP5).

    Science.gov (United States)

    Handley, Elizabeth D; Rogosch, Fred A; Cicchetti, Dante

    2015-11-01

    The current study examined the prospective association between child maltreatment and the development of substance use disorder in adolescence with the aim of investigating pathways underlying this relation, as well as genetic moderation of these developmental mechanisms. Specifically, we tested whether youth who experienced maltreatment prior to age 8 were at risk for the development of marijuana dependence in adolescence by way of a childhood externalizing pathway and a childhood internalizing pathway. Moreover, we tested whether variation in FK506 binding protein 5 gene (FKBP5) CATT haplotype moderated these pathways. The participants were 326 children (n =179 maltreated; n = 147 nonmaltreated) assessed across two waves of data collection (childhood: ages 7-9 and adolescence: ages 15-18). Results indicated that higher levels of child externalizing symptoms significantly mediated the effect of child maltreatment on adolescent marijuana dependence symptoms for individuals with one or two copies of the FKBP5 CATT haplotype only. We did not find support for an internalizing pathway from child maltreatment to adolescent marijuana dependence, nor did we find evidence of moderation of the internalizing pathway by FKBP5 haplotype variation. Findings extend previous research by demonstrating that whether a maltreated child will traverse an externalizing pathway toward substance use disorder in adolescence is dependent on FKBP5 genetic variation.

  17. 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.

  18. What Is a Developmental-Behavioral Pediatrician?

    Science.gov (United States)

    ... social worker. Developmental-behavioral pediatricians work closely with parents, families, and schools. Developmental-behavioral pediatricians understand that children’s development and behavior happen first and foremost in the ...

  19. 29 CFR 1902.33 - Developmental period.

    Science.gov (United States)

    2010-07-01

    ... consideration of developmental changes by OSHA. Generally, whenever a State completes a developmental step, it must submit the resulting plan change as a supplement to its plan to OSHA for approval. OSHA's approval...

  20. Ethiopia: A Democratic Developmental State?

    Directory of Open Access Journals (Sweden)

    Fesseha Mulu Gebremariam

    2017-12-01

    Full Text Available The ruling Ethiopia People’s Revolutionary Democratic Front (EPRDF in its notable second reform appraisal held in the aftermath of the 2005 national election concluded that the utmost priority of the government should be realizing fastest and sustainable economic growth that fairly benefits its citizens’ unless the very existence of the country wouldn’t be guaranteed. Given the history of poverty reduction in developing countries, particularly in Africa, EPRDF realized that it is unthinkable to eradicate poverty from Ethiopia adopting neo-liberalism. Above all, the miraculous economic transformation of the South East Asian countries like South Korea, Taiwan, Singapore and Hong Kong has proved that there is another way to development, not just neo-liberalism. Accordingly, EPRDF, after examining South Korea’s and Taiwan’s history of economic development in particular where both countries have had a large section of rural population unlike Hong Kong and Singapore where both are urban, found ‘developmental state’ relevant to Ethiopia. However, unlike these countries which were originally under non-democratic regimes where their leaders fear the rural peasant and external aggression from their communist rivals, EPRDF has had a great support of rural and urban population with no imminent foreign threat(s, and decided to execute the ideology rather under the umbrella of democracy. Therefore, employing secondary sources, this desk study aims to analyze whether Ethiopia is a ‘democratic developmental state?’ And, concludes that given the practices of the government vis-a-vis the principles of democracy and developmental state, Ethiopia couldn’t be taken as best model for democratic developmental state, rather emerging developmental state.

  1. Parental Bonds, Attachment Anxiety, Media Susceptibility, and Body Dissatisfaction: A Mediation Model

    Science.gov (United States)

    Patton, Sarah C.; Beaujean, A. Alexander; Benedict, Helen E.

    2014-01-01

    The developmental trajectory of body image dissatisfaction is unclear. Researchers have investigated sociocultural and developmental risk factors; however, the literature needs an integrative etiological model. In 2009, Cheng and Mallinckrodt proposed a dual mediation model, positing that poor-quality parental bonds, via the mechanisms of…

  2. Mediatized play

    DEFF Research Database (Denmark)

    Johansen, Stine Liv

    Children’s play must nowadays be understood as a mediatized field in society and culture. Media – understood in a very broad sense - holds severe explanatory power in describing and understanding the practice of play, since play happens both with, through and inspired by media of different sorts........ In this presentation the case of ‘playing soccer’ will be outlined through its different mediated manifestations, including soccer games and programs on TV, computer games, magazines, books, YouTube videos and soccer trading cards....

  3. Mediating Business

    DEFF Research Database (Denmark)

    "Mediating Business" is a study of the expansion of business journalism. Building on evidence from Denmark, Finland, Norway and Sweden, "Mediating Business" is a comparative and multidisciplinary study of one of the major transformations of the mass media and the realm of business - nationally...... and globally. The book explores the history of key innovations and innovators in the business press. It analyzes changes in the discourse of business journalism associated with the growth in business news and the development of new ways of framing business issues and events. Finally, it examines...... the organizational implications of the increased media visibility of business and, in particular, the development of corporate governance and media relations....

  4. Motor imagery training for children with developmental coordination disorder - study protocol for a randomized controlled trial

    NARCIS (Netherlands)

    Adams, I.L.; Steenbergen, B.; Lust, J.M.; Smits-Engelsman, B.C.

    2016-01-01

    BACKGROUND: Previous studies have shown that the predictive control of movements is impaired in children with Developmental Coordination Disorder (DCD), most likely due to a deficit in the internal modeling of movements. Motor imagery paradigms have been used to test this internal modeling deficit.

  5. Motor imagery training for children with developmental coordination disorder: Study protocol for a randomized controlled trial

    NARCIS (Netherlands)

    Adams, I.L.J.; Steenbergen, B.; Lust, J.M.; Smits-Engelsman, B.C.M.

    2016-01-01

    Background: Previous studies have shown that the predictive control of movements is impaired in children with Developmental Coordination Disorder (DCD), most likely due to a deficit in the internal modeling of movements. Motor imagery paradigms have been used to test this internal modeling deficit.

  6. Rational Choice and Developmental Influences on Recidivism Among Adolescent Felony Offenders

    OpenAIRE

    Fagan, Jeffrey; Piquero, Alex R.

    2007-01-01

    Recent case law and social science both have claimed that the developmental limitations of adolescents affect their capacity for control and decision making with respect to crime, diminishing their culpability and reducing their exposure to punishment. Social science has focused on two concurrent adolescent developmental influences: the internalization of legal rules and norms that regulate social and antisocial behaviors, and the development of rationality to frame behavioral choices and dec...

  7. The developmental state in Brazil: comparative and historical perspectives

    Directory of Open Access Journals (Sweden)

    BEN ROSS SCHNEIDER

    2015-03-01

    Full Text Available The record of successful developmental states in East Asia and the partial successes of developmental states in Latin America suggest several common preconditions for effective state intervention including a Weberian bureaucracy, monitoring of implementation, reciprocity (subsidies in exchange for performance, and collaborative relations between government and business. Although Brazil failed to develop the high technology manufacturing industry and exports that have fueled sustained growth in East Asia, its developmental state had a number of important, and often neglected, successes, especially in steel, automobiles, mining, ethanol, and aircraft manufacturing. Where Brazil's developmental state was less successful was in promoting sectors like information technology and nuclear energy, as well as overall social and regional equality. In addition, some isolated initiatives by state governments were also effective in promoting particular local segments of industry and agriculture. Comparisons with East Asia, highlight the central role of state enterprises in Brazil that in effect internalized monitoring and reciprocity and bypassed collaboration between business and government (that was overall rarer in Brazil.

  8. MEDIATOR18 and MEDIATOR20 confer susceptibility to Fusarium oxysporum in Arabidopsis thaliana

    Science.gov (United States)

    Stiller, Jiri; Davoine, Celine; Björklund, Stefan; Manners, John M.; Kazan, Kemal; Schenk, Peer M.

    2017-01-01

    The conserved protein complex known as Mediator conveys transcriptional signals by acting as an intermediary between transcription factors and RNA polymerase II. As a result, Mediator subunits play multiple roles in regulating developmental as well as abiotic and biotic stress pathways. In this report we identify the head domain subunits MEDIATOR18 and MEDIATOR20 as important susceptibility factors for Fusarium oxysporum infection in Arabidopsis thaliana. Mutants of MED18 and MED20 display down-regulation of genes associated with jasmonate signaling and biosynthesis while up-regulation of salicylic acid associated pathogenesis related genes and reactive oxygen producing and scavenging genes. We propose that MED18 and MED20 form a sub-domain within Mediator that controls the balance of salicylic acid and jasmonate associated defense pathways. PMID:28441405

  9. Dissociation in mediation

    Directory of Open Access Journals (Sweden)

    Daniela Muraru

    2008-01-01

    Full Text Available This paper approaches several texts that are part of the so-called discourse of mediation, adopting a pragma-dialectical perspective of the theory of dissociation. It is an attempt to identify the uses of dissociative patterns, with special emphasis on the indicators of dissociation. The paper investigates the various uses of the concept of dissociation as a discursive technique in the argumentation on the different aspects that are involved in international conflict, such as the discussion of the notion of peace. The purpose is to identify the role of dissociation, as a device strategically used by the mediator to help the parties minimize the disagreement space, and come to a conflict resolution.

  10. Developmental insights into mature cognition.

    Science.gov (United States)

    Keil, Frank C

    2015-02-01

    Three cases are described that illustrate new ways in which developmental research is informing the study of cognition in adults: statistical learning, neural substrates of cognition, and extended concepts. Developmental research has made clear the ubiquity of statistical learning while also revealing is limitations as a stand-alone way to acquire knowledge. With respect to neural substrates, development has uncovered links between executive processing and fronto-striatal circuits while also pointing to many aspects of high-level cognition that may not be neatly reducible to coherent neural descriptions. For extended concepts, children have made especially clear the weaknesses of intuitive theories in both children and adults while also illustrating other cognitive capacities that are used at all ages to navigate the socially distributed aspects of knowledge. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Developmental language and speech disability.

    Science.gov (United States)

    Spiel, G; Brunner, E; Allmayer, B; Pletz, A

    2001-09-01

    Speech disabilities (articulation deficits) and language disorders--expressive (vocabulary) receptive (language comprehension) are not uncommon in children. An overview of these along with a global description of the impairment of communication as well as clinical characteristics of language developmental disorders are presented in this article. The diagnostic tables, which are applied in the European and Anglo-American speech areas, ICD-10 and DSM-IV, have been explained and compared. Because of their strengths and weaknesses an alternative classification of language and speech developmental disorders is proposed, which allows a differentiation between expressive and receptive language capabilities with regard to the semantic and the morphological/syntax domains. Prevalence and comorbidity rates, psychosocial influences, biological factors and the biological social interaction have been discussed. The necessity of the use of standardized examinations is emphasised. General logopaedic treatment paradigms, specific therapy concepts and an overview of prognosis have been described.

  12. International Trade. International Business

    OpenAIRE

    Мохнюк, А. М.; Mokhniuk, A. M.

    2015-01-01

    Work programme of the study course “International Trade. International Business” was prepared in accordance with educational and vocational training program for bachelors of training direction 6.030601 “Management”.

  13. Ecdysone Control of Developmental Transitions

    DEFF Research Database (Denmark)

    Rewitz, Kim; Yamanaka, Naoki; O'Connor, Michael B.

    2013-01-01

    The steroid hormone ecdysone is the central regulator of insect developmental transitions. Recent new advances in our understanding of ecdysone action have relied heavily on the application of Drosophila melanogaster molecular genetic tools to study insect metamorphosis. In this review, we focus...... on three major aspects of Drosophila ecdysone biology: (a) factors that regulate the timing of ecdysone release, (b) molecular basis of stage- and tissue-specific responses to ecdysone, and (c) feedback regulation and coordination of ecdysone signaling....

  14. Gestational Hyperandrogenism in Developmental Programming

    Science.gov (United States)

    Hakim, Christopher; Padmanabhan, Vasantha

    2017-01-01

    Androgen excess (hyperandrogenism) is a common endocrine disorder affecting women of reproductive age. The potential causes of androgen excess in women include polycystic ovary syndrome, congenital adrenal hyperplasia (CAH), adrenal tumors, and racial disparity among many others. During pregnancy, luteoma, placental aromatase deficiency, and fetal CAH are additional causes of gestational hyperandrogenism. The present report reviews the various phenotypes of hyperandrogenism during pregnancy and its origin, pathophysiology, and the effect of hyperandrogenism on the fetal developmental trajectory and offspring consequences. PMID:27967205

  15. 20170312 - Computer Simulation of Developmental ...

    Science.gov (United States)

    Rationale: Recent progress in systems toxicology and synthetic biology have paved the way to new thinking about in vitro/in silico modeling of developmental processes and toxicities, both for embryological and reproductive impacts. Novel in vitro platforms such as 3D organotypic culture models, engineered microscale tissues and complex microphysiological systems (MPS), together with computational models and computer simulation of tissue dynamics, lend themselves to a integrated testing strategies for predictive toxicology. As these emergent methodologies continue to evolve, they must be integrally tied to maternal/fetal physiology and toxicity of the developing individual across early lifestage transitions, from fertilization to birth, through puberty and beyond. Scope: This symposium will focus on how the novel technology platforms can help now and in the future, with in vitro/in silico modeling of complex biological systems for developmental and reproductive toxicity issues, and translating systems models into integrative testing strategies. The symposium is based on three main organizing principles: (1) that novel in vitro platforms with human cells configured in nascent tissue architectures with a native microphysiological environments yield mechanistic understanding of developmental and reproductive impacts of drug/chemical exposures; (2) that novel in silico platforms with high-throughput screening (HTS) data, biologically-inspired computational models of

  16. Developmental transcriptome of Aplysia californica'

    KAUST Repository

    Heyland, Andreas

    2010-12-06

    Genome-wide transcriptional changes in development provide important insight into mechanisms underlying growth, differentiation, and patterning. However, such large-scale developmental studies have been limited to a few representatives of Ecdysozoans and Chordates. Here, we characterize transcriptomes of embryonic, larval, and metamorphic development in the marine mollusc Aplysia californica and reveal novel molecular components associated with life history transitions. Specifically, we identify more than 20 signal peptides, putative hormones, and transcription factors in association with early development and metamorphic stages-many of which seem to be evolutionarily conserved elements of signal transduction pathways. We also characterize genes related to biomineralization-a critical process of molluscan development. In summary, our experiment provides the first large-scale survey of gene expression in mollusc development, and complements previous studies on the regulatory mechanisms underlying body plan patterning and the formation of larval and juvenile structures. This study serves as a resource for further functional annotation of transcripts and genes in Aplysia, specifically and molluscs in general. A comparison of the Aplysia developmental transcriptome with similar studies in the zebra fish Danio rerio, the fruit fly Drosophila melanogaster, the nematode Caenorhabditis elegans, and other studies on molluscs suggests an overall highly divergent pattern of gene regulatory mechanisms that are likely a consequence of the different developmental modes of these organisms. © 2010 Wiley-Liss, Inc., A Wiley Company.

  17. Psychotherapy with people with developmental disabilities

    Directory of Open Access Journals (Sweden)

    Barbara Zafošnik

    2011-08-01

    Full Text Available People with developmental disabilities can experience any psychological abnormalitiy and psychiatric illness as do people without developmental disabilities. Due to different diagnostic criteria, assessment procedures and instruments, we lack definite prevalence rates for people with developmental disabilities, also suffering from mental health problems, eventhough most studies place the rate at 20 to 40%. One of the possible treatment alternatives for augmenting psychological well-being is psychotherapy, but is extremely rarely used for people with severe and profound disabilities, where speech cannot be the main therapeutic medium. So, those that are included in the psychotherapuetic process are predominantly clients with mild developmental disabilities, and they are mostly in cognitive-behavioral therapy. Recently, two models of (psychotherapy for persons with severe and profound developmental disabilities were developed: developmental-dynamic relationship therapy and attachment-based behaviour therapy for children. Conceptually, they both originate form developmental psychoanalytic theories.

  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. Altered morphology of the nucleus accumbens in persistent developmental stuttering.

    Science.gov (United States)

    Neef, Nicole E; Bütfering, Christoph; Auer, Tibor; Metzger, F Luise; Euler, Harald A; Frahm, Jens; Paulus, Walter; Sommer, Martin

    2018-03-01

    Neuroimaging studies in persistent developmental stuttering repeatedly report altered basal ganglia functions. Together with thalamus and cerebellum, these structures mediate sensorimotor functions and thus represent a plausible link between stuttering and neuroanatomy. However, stuttering is a complex, multifactorial disorder. Besides sensorimotor functions, emotional and social-motivational factors constitute major aspects of the disorder. Here, we investigated cortical and subcortical gray matter regions to study whether persistent developmental stuttering is also linked to alterations of limbic structures. The study included 33 right-handed participants who stutter and 34 right-handed control participants matched for sex, age, and education. Structural images were acquired using magnetic resonance imaging to estimate volumetric characteristics of the nucleus accumbens, hippocampus, amygdala, pallidum, putamen, caudate nucleus, and thalamus. Volumetric comparisons and vertex-based shape comparisons revealed structural differences. The right nucleus accumbens was larger in participants who stutter compared to controls. Recent theories of basal ganglia functions suggest that the nucleus accumbens is a motivation-to-movement interface. A speaker intends to reach communicative goals, but stuttering can derail these efforts. It is therefore highly plausible to find alterations in the motivation-to-movement interface in stuttering. While behavioral studies of stuttering sought to find links between the limbic and sensorimotor system, we provide the first neuroimaging evidence of alterations in the limbic system. Thus, our findings might initialize a unified neurobiological framework of persistent developmental stuttering that integrates sensorimotor and social-motivational neuroanatomical circuitries. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Feedforward motor control in developmental dyslexia and developmental coordination disorder: Does comorbidity matter?

    Science.gov (United States)

    Cignetti, Fabien; Vaugoyeau, Marianne; Fontan, Aurelie; Jover, Marianne; Livet, Marie-Odile; Hugonenq, Catherine; Audic, Frédérique; Chabrol, Brigitte; Assaiante, Christine

    2018-05-01

    Feedforward and online controls are two facets of predictive motor control from internal models, which is suspected to be impaired in learning disorders. We examined whether the feedforward component is affected in children (8-12 years) with developmental dyslexia (DD) and/or with developmental coordination disorder (DCD) compared to typically developing (TD) children. Children underwent a bimanual unloading paradigm during which a load supported to one arm, the postural arm, was either unexpectedly unloaded by a computer or voluntary unloaded by the subject with the other arm. All children showed a better stabilization (lower flexion) of the postural arm and an earlier inhibition of the arm flexors during voluntary unloading, indicating anticipation of unloading. Between-group comparisons of kinematics and electromyographic activity of the postural arm revealed that the difference during voluntary unloading was between DD-DCD children and the other groups, with the former showing a delayed inhibition of the flexor muscles. Deficit of the feedforward component of motor control may particularly apply to comorbid subtypes, here the DD-DCD subtype. The development of a comprehensive framework for motor performance deficits in children with learning disorders will be achieved only by dissociating key components of motor prediction and focusing on subtypes and comorbidities. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. A small great history of the sister Societies of Developmental Biology in Spain and Portugal.

    Science.gov (United States)

    Palmeirim, Isabel; Aréchaga, Juan

    2009-01-01

    We revise the historical evolution of the societies devoted to Developmental Biology from the early activities of the Institut International dEmbryologie (IIE), founded in 1911, with particular emphasis on the more recent constitution of the Spanish Sociedad Española de Biología del Desarrollo (SEBD), founded in 1994, and the Portuguese Sociedade Portuguesa de Biologia do Desenvolvimento (SPBD), founded in 2006. We also describe the role played by The International Journal of Developmental Biology (IJDB) in the constitution of the SEBD and its projection and support to international Developmental Biology societies and individual researchers in the world, according to its mission to be a non-for-profit publication for scientists, by scientists.

  2. Atrial natriuretic peptide regulates Ca channel in early developmental cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Lin Miao

    Full Text Available BACKGROUND: Cardiomyocytes derived from murine embryonic stem (ES cells possess various membrane currents and signaling cascades link to that of embryonic hearts. The role of atrial natriuretic peptide (ANP in regulation of membrane potentials and Ca(2+ currents has not been investigated in developmental cardiomyocytes. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the role of ANP in regulating L-type Ca(2+ channel current (I(CaL in different developmental stages of cardiomyocytes derived from ES cells. ANP decreased the frequency of action potentials (APs in early developmental stage (EDS cardiomyocytes, embryonic bodies (EB as well as whole embryo hearts. ANP exerted an inhibitory effect on basal I(CaL in about 70% EDS cardiomyocytes tested but only in about 30% late developmental stage (LDS cells. However, after stimulation of I(CaL by isoproterenol (ISO in LDS cells, ANP inhibited the response in about 70% cells. The depression of I(CaL induced by ANP was not affected by either Nomega, Nitro-L-Arginine methyl ester (L-NAME, a nitric oxide synthetase (NOS inhibitor, or KT5823, a cGMP-dependent protein kinase (PKG selective inhibitor, in either EDS and LDS cells; whereas depression of I(CaL by ANP was entirely abolished by erythro-9-(2-Hydroxy-3-nonyl adenine (EHNA, a selective inhibitor of type 2 phosphodiesterase(PDE2 in most cells tested. CONCLUSION/SIGNIFICANCES: Taken together, these results indicate that ANP induced depression of action potentials and I(CaL is due to activation of particulate guanylyl cyclase (GC, cGMP production and cGMP-activation of PDE2 mediated depression of adenosine 3', 5'-cyclic monophophate (cAMP-cAMP-dependent protein kinase (PKA in early cardiomyogenesis.

  3. Bilateral duplication of the internal auditory canal

    International Nuclear Information System (INIS)

    Weon, Young Cheol; Kim, Jae Hyoung; Choi, Sung Kyu; Koo, Ja-Won

    2007-01-01

    Duplication of the internal auditory canal is an extremely rare temporal bone anomaly that is believed to result from aplasia or hypoplasia of the vestibulocochlear nerve. We report bilateral duplication of the internal auditory canal in a 28-month-old boy with developmental delay and sensorineural hearing loss. (orig.)

  4. Developmental stage-dependent influence of environmental factors on growth of rural Sundanese children in West Java, Indonesia.

    Science.gov (United States)

    Sekiyama, Makiko; Roosita, Katrin; Ohtsuka, Ryutaro

    2015-05-01

    This study investigated the growth trajectories and the relative relevance levels of nutrition, disease, and hormonal status at various developmental stages among children in adverse environments to provide population-based empirical evidence for the life history theory. Three years of longitudinal anthropometric data in 1-year intervals were obtained from 418 boys and girls aged 0 to 12 years at recruitment. Following the final measurement, the main survey, which included blood and feces sampling, 3-h interval food consumption recall surveys for energy and nutrient intakes and anthropometry, was performed. Blood and feces were used for detecting, respectively, anemia and hormonal (IGF-I and IGFBP-3) levels as well as intestinal helminthiasis (Ascaris, Trichuris, and hookworm). The major findings of this study are summarized as follows: 1) the growth velocity of the subject children lagged behind international standards during childhood and juvenility but caught up during early adolescence; 2) diseases, both intestinal helminths and anemia, had significant effects on growth in childhood but not at older ages; and 3) hormonal status significantly affected growth in the children, with its highest significance in early adolescence. A larger growth than international standards in early adolescence likely follows programmed hormonal mechanisms after the onset of puberty. The onset of puberty might be associated with adequate amounts of nutrient intake and be mediated by hormonal function, because the IGF-IZ score was significantly correlated with energy and protein intakes at the transitional period from juvenility to adolescence, when puberty occurs. © 2015 Wiley Periodicals, Inc.

  5. Music cognition: a developmental perspective.

    Science.gov (United States)

    Stalinski, Stephanie M; Schellenberg, E Glenn

    2012-10-01

    Although music is universal, there is a great deal of cultural variability in music structures. Nevertheless, some aspects of music processing generalize across cultures, whereas others rely heavily on the listening environment. Here, we discuss the development of musical knowledge, focusing on four themes: (a) capabilities that are present early in development; (b) culture-general and culture-specific aspects of pitch and rhythm processing; (c) age-related changes in pitch perception; and (d) developmental changes in how listeners perceive emotion in music. Copyright © 2012 Cognitive Science Society, Inc.

  6. Promoting positive human development and social justice: Integrating theory, research and application in contemporary developmental science.

    Science.gov (United States)

    Lerner, Richard M

    2015-06-01

    The bold claim that developmental science can contribute to both enhancing positive development among diverse individuals across the life span and promoting social justice in their communities, nations and regions is supported by decades of theoretical, methodological and research contributions. To explain the basis of this claim, I describe the relational developmental systems (RDS) metamodel that frames contemporary developmental science, and I present an example of a programme of research within the adolescent portion of the life span that is associated with this metamodel and is pertinent to promoting positive human development. I then discuss methodological issues associated with using RDS-based models as frames for research and application. Finally, I explain how the theoretical and methodological ideas associated with RDS thinking may provide the scholarly tools needed by developmental scientists seeking to contribute to human thriving and to advance social justice in the Global South. © 2015 International Union of Psychological Science.

  7. Report on the results of the FY 1998 hydrogen utilization international clean energy system technology (WE-NET). Subtask 1. Survey/research for the comprehensive evaluation and developmental plan; 1998 nendo suiso riyo kokusai clean energy system gijutsu (WE-NET). 1. Sogo hyoka to kaihatsu keikaku no tame no chosa kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-03-01

    The paper described the results of the FY 1998 WE-NET project survey. WE-NET is composed of various element technologies such as hydrogen production, hydrogen transportation, storage technology, low-temperature materials, hydrogen utilization, and hydrogen combustion turbine technology. Therefore, considering the effectiveness as a total system, it is extremely important to traversally evaluate the situation of the R and D of each technology and developmental achievements and to work out developmental plans with integration, considering the effectiveness as a total system. From viewpoints of making effective promotion of the project and attempting optimization as a total system, it is necessary to make organic/comprehensive connection and adjustment among individual subtasks all the time. In this survey/research, in the case of proceeding with the above-mentioned studies, a committee having knowledgeable persons and learned persons as members was established. There, an investigational study was conducted over the whole WE-NET structural technology, and at the same time the following were attempted: the constant/mobile comprehensive adjustment of the whole project, evaluation of the developmental results, and optimization of the developmental plans. The results obtained in 6 years of Period I were evaluated traversally and comprehensively, and how to proceed with the development in Period II was proposed, which showed the developmental continuity. (NEDO)

  8. Sexual dysfunction within an adult developmental perspective.

    Science.gov (United States)

    Fagan, P J; Meyer, J K; Schmidt, C W

    1986-01-01

    The focus of this paper is on the adult who has adequately mastered the oedipal stage of psychosexual development and who presents with a sexual dysfunction. Drawing on the developmental sequence of Erik Erikson, the authors suggest that failure to address adequately an adult psychosocial crisis may result in sexual dysfunction. There may be both adult developmental deficits and regression to adolescent and adult stages previously negotiated. Both may be symptomatically represented by sexual dysfunction. The authors urge that the sexual and marital problems be evaluated within an adult developmental framework and that the therapy address the psychosocial issues which are appropriate to the developmental stage of the patient.

  9. Eco-Evo-Devo: developmental symbiosis and developmental plasticity as evolutionary agents.

    Science.gov (United States)

    Gilbert, Scott F; Bosch, Thomas C G; Ledón-Rettig, Cristina

    2015-10-01

    The integration of research from developmental biology and ecology into evolutionary theory has given rise to a relatively new field, ecological evolutionary developmental biology (Eco-Evo-Devo). This field integrates and organizes concepts such as developmental symbiosis, developmental plasticity, genetic accommodation, extragenic inheritance and niche construction. This Review highlights the roles that developmental symbiosis and developmental plasticity have in evolution. Developmental symbiosis can generate particular organs, can produce selectable genetic variation for the entire animal, can provide mechanisms for reproductive isolation, and may have facilitated evolutionary transitions. Developmental plasticity is crucial for generating novel phenotypes, facilitating evolutionary transitions and altered ecosystem dynamics, and promoting adaptive variation through genetic accommodation and niche construction. In emphasizing such non-genomic mechanisms of selectable and heritable variation, Eco-Evo-Devo presents a new layer of evolutionary synthesis.

  10. Developmental constraints on behavioural flexibility.

    Science.gov (United States)

    Holekamp, Kay E; Swanson, Eli M; Van Meter, Page E

    2013-05-19

    We suggest that variation in mammalian behavioural flexibility not accounted for by current socioecological models may be explained in part by developmental constraints. From our own work, we provide examples of constraints affecting variation in behavioural flexibility, not only among individuals, but also among species and higher taxonomic units. We first implicate organizational maternal effects of androgens in shaping individual differences in aggressive behaviour emitted by female spotted hyaenas throughout the lifespan. We then compare carnivores and primates with respect to their locomotor and craniofacial adaptations. We inquire whether antagonistic selection pressures on the skull might impose differential functional constraints on evolvability of skulls and brains in these two orders, thus ultimately affecting behavioural flexibility in each group. We suggest that, even when carnivores and primates would theoretically benefit from the same adaptations with respect to behavioural flexibility, carnivores may nevertheless exhibit less behavioural flexibility than primates because of constraints imposed by past adaptations in the morphology of the limbs and skull. Phylogenetic analysis consistent with this idea suggests greater evolutionary lability in relative brain size within families of primates than carnivores. Thus, consideration of developmental constraints may help elucidate variation in mammalian behavioural flexibility.

  11. A developmental metatheory of psychopathology.

    Science.gov (United States)

    Karasu, T B

    1994-01-01

    The author proposes an integrative model of psychopathology in light of the contemporary need to bridge diverse ideological frameworks. This model has its major foundations in drive, ego, object relations, and self psychoanalytic perspectives as they impact upon interactional patterns of infancy. The chronology of these theoretical orientations is presented as parallel to a changing focus upon different successive stages in the course of individual development. The longstanding controversy between conflict and deficit theories, which undergirds the various schools of thought, is addressed: a developmental orientation is offered as the overriding conceptual connection between them. Conflict and deficit phenomena are regarded as intertwined and not incompatible: Unconscious drives, desires and wishes, ego defenses, and compromise formations as well as object relationship deficiencies and structural voids and defects in the self are combined to encompass a broad spectrum of psychopathology and its sources: the above intrapsychic and interpersonal factors are interfaced with significant reciprocal dyadic (mother/child) and triadic (father/mother/child) influences upon ongoing maturational processes. For heuristic purposes, a fourfold matrix--dyadic deficit, dyadic conflict, triadic deficit, and triadic conflict--is delineated. Clinical characteristics and developmental precursors of each of the four prototypes, especially with regard to early relational events, are examined.

  12. Developmental constraint of insect audition

    Directory of Open Access Journals (Sweden)

    Strauß Johannes

    2006-12-01

    Full Text Available Abstract Background Insect ears contain very different numbers of sensory cells, from only one sensory cell in some moths to thousands of sensory cells, e.g. in cicadas. These differences still await functional explanation and especially the large numbers in cicadas remain puzzling. Insects of the different orders have distinct developmental sequences for the generation of auditory organs. These sensory cells might have different functions depending on the developmental stages. Here we propose that constraints arising during development are also important for the design of insect ears and might influence cell numbers of the adults. Presentation of the hypothesis We propose that the functional requirements of the subadult stages determine the adult complement of sensory units in the auditory system of cicadas. The hypothetical larval sensory organ should function as a vibration receiver, representing a functional caenogenesis. Testing the hypothesis Experiments at different levels have to be designed to test the hypothesis. Firstly, the neuroanatomy of the larval sense organ should be analyzed to detail. Secondly, the function should be unraveled neurophysiologically and behaviorally. Thirdly, the persistence of the sensory cells and the rebuilding of the sensory organ to the adult should be investigated. Implications of the hypothesis Usually, the evolution of insect ears is viewed with respect to physiological and neuronal mechanisms of sound perception. This view should be extended to the development of sense organs. Functional requirements during postembryonic development may act as constraints for the evolution of adult organs, as exemplified with the auditory system of cicadas.

  13. Ga-66 labeled somatostatin analogue DOTA-DPhe1-Tyr3-octreotide as a potential agent for positron emission tomography imaging and receptor mediated internal radiotherapy of somatostatin receptor positive tumors

    International Nuclear Information System (INIS)

    Ugur, Oemer; Kothari, Paresh J.; Finn, Ronald D.; Zanzonico, Pat; Ruan, Shutian; Guenther, Ilonka; Maecke, Helmut R.; Larson, Steven M.

    2002-01-01

    Radionuclide labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these tumors. Recently, a DOTA-functionalized somatostatin analogue, DOTATOC (DOTA-DPhe 1 -Tyr 3 -octreotide) has been developed. This compound has been shown to be superior to the other somatostatin analogues as indicated by its uniquely high tumor-to-non-target tissue ratio. DOTATOC can be labeled with a variety of radiometals including gallium radioisotopes. Gallium-66 is a positron emitting radionuclide (T 1/2 =9.5 hr; β + =56%), that can be produced in carrier free form by a low-beam energy cyclotron. In this study we investigated SSTR targeting characteristics of 66 Ga-DOTATOC in AR42J rat pancreas tumor implanted nude mice as a potential agent for diagnosis and receptor-mediated internal radiotherapy of SSTR-expressing tumors. We compared our results with 67 Ga- and 68 Ga- labeled DOTATOC. The radiolabeling procedure gave labeling yield ranged from 85-95% and radiochemical and chemical purity was >95%. In-vitro competitive binding curves and in-vivo competitive displacement studies with an excess of unlabeled peptide indicates that there is specific binding of the radioligand to SSTR. Animal biodistribution data and serial microPET TM images demonstrated rapid tumor uptake and rapid clearance from the blood and all tissues except kidney. Maximum % ID/g values for tumor were 10.0±0.7, 13.2±2.1 and 9.8±1.5 for 66 Ga-, 67 Ga-, and 68 Ga-DOTATOC, respectively. Calculated tumor, kidney and bone marrow doses for 66 Ga-DOTATOC based on biodistribution data were 178, 109 and 1.2 cGy/MBq, respectively. We conclude that 66 Ga labeled DOTATOC can be used for PET diagnosis and quantitative imaging-based dosimetry of SSTR positive tumors. 66 Ga-DOTATOC may also be used in higher doses for ablation of these tumors. However, kidney is the critical organ for toxicity (tumor/kidney ratio 1.64), and high kidney uptake must

  14. Ga-66 labeled somatostatin analogue DOTA-DPhe{sup 1}-Tyr{sup 3}-octreotide as a potential agent for positron emission tomography imaging and receptor mediated internal radiotherapy of somatostatin receptor positive tumors

    Energy Technology Data Exchange (ETDEWEB)

    Ugur, Oemer E-mail: ougur@hacettepe.edu.tr; Kothari, Paresh J.; Finn, Ronald D.; Zanzonico, Pat; Ruan, Shutian; Guenther, Ilonka; Maecke, Helmut R.; Larson, Steven M

    2002-02-01

    Radionuclide labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these tumors. Recently, a DOTA-functionalized somatostatin analogue, DOTATOC (DOTA-DPhe{sup 1}-Tyr{sup 3}-octreotide) has been developed. This compound has been shown to be superior to the other somatostatin analogues as indicated by its uniquely high tumor-to-non-target tissue ratio. DOTATOC can be labeled with a variety of radiometals including gallium radioisotopes. Gallium-66 is a positron emitting radionuclide (T{sub 1/2} =9.5 hr; {beta}{sup +}=56%), that can be produced in carrier free form by a low-beam energy cyclotron. In this study we investigated SSTR targeting characteristics of {sup 66}Ga-DOTATOC in AR42J rat pancreas tumor implanted nude mice as a potential agent for diagnosis and receptor-mediated internal radiotherapy of SSTR-expressing tumors. We compared our results with {sup 67}Ga- and {sup 68}Ga- labeled DOTATOC. The radiolabeling procedure gave labeling yield ranged from 85-95% and radiochemical and chemical purity was >95%. In-vitro competitive binding curves and in-vivo competitive displacement studies with an excess of unlabeled peptide indicates that there is specific binding of the radioligand to SSTR. Animal biodistribution data and serial microPET{sup TM} images demonstrated rapid tumor uptake and rapid clearance from the blood and all tissues except kidney. Maximum % ID/g values for tumor were 10.0{+-}0.7, 13.2{+-}2.1 and 9.8{+-}1.5 for {sup 66}Ga-, {sup 67}Ga-, and {sup 68}Ga-DOTATOC, respectively. Calculated tumor, kidney and bone marrow doses for {sup 66}Ga-DOTATOC based on biodistribution data were 178, 109 and 1.2 cGy/MBq, respectively. We conclude that {sup 66}Ga labeled DOTATOC can be used for PET diagnosis and quantitative imaging-based dosimetry of SSTR positive tumors. {sup 66}Ga-DOTATOC may also be used in higher doses for ablation of these tumors. However, kidney is the

  15. An Interpretation of Part of Gilbert Gottlieb's Legacy: Developmental Systems Theory Contra Developmental Behavior Genetics

    Science.gov (United States)

    Molenaar, Peter C. M.

    2015-01-01

    The main theme of this paper concerns the persistent critique of Gilbert Gottlieb on developmental behavior genetics and my reactions to this critique, the latter changing from rejection to complete acceptation. Concise characterizations of developmental behavior genetics, developmental systems theory (to which Gottlieb made essential…

  16. Developmental toxicity of engineered nanomaterials in rodents

    Energy Technology Data Exchange (ETDEWEB)

    Ema, Makoto, E-mail: ema-makoto@aist.go.jp; Gamo, Masashi; Honda, Kazumasa

    2016-05-15

    We summarized significant effects reported in the literature on the developmental toxicity of engineered nanomaterials (ENMs) in rodents. The developmental toxicity of ENMs included not only structural abnormalities, but also death, growth retardation, and behavioral and functional abnormalities. Most studies were performed on mice using an injection route of exposure. Teratogenic effects were indicated when multi-walled carbon nanotubes (MWCNTs), single-walled carbon nanotubes (SWCNTs), and TiO{sub 2}-nanoparticles were administered to mice during early gestation. Reactive oxygen species levels were increased in placentas and malformed fetuses and their placentas after prenatal exposure to MWCNTs and SWCNTs, respectively. The pre- and postnatal mortalities and growth retardation in offspring increased after prenatal exposure to ENMs. Histopathological and functional abnormalities were also induced in placentas after prenatal exposure to ENMs. Maternal exposure to ENMs induced behavioral alterations, histopathological and biochemical changes in the central nervous system, increased susceptibility to allergy, transplacental genotoxicity, and vascular, immunological, and reproductive effects in offspring. The size- and developmental stage-dependent placental transfer of ENMs was noted after maternal exposure. Silver accumulated in the visceral yolk sac after being injected with Ag-NPs during early gestation. Although currently available data has provided initial information on the potential developmental toxicity of ENMs, that on the developmental toxicity of ENMs is still very limited. Further studies using well-characterized ENMs, state-of the-art study protocols, and appropriate routes of exposure are required in order to clarify these developmental effects and provide information suitable for risk assessments of ENMs. - Highlights: • We review the developmental toxicity studies of engineered nanomaterials (ENMs). • Various developmental endpoints have been

  17. Predicting Developmental Disorder in Infants Using an Artificial Neural Network

    Directory of Open Access Journals (Sweden)

    Farin Soleimani

    2013-06-01

    Full Text Available Early recognition of developmental disorders is an important goal, and equally important is avoiding misdiagnosing a disorder in a healthy child without pathology. The aim of the present study was to develop an artificial neural network using perinatal information to predict developmental disorder at infancy. A total of 1,232 mother–child dyads were recruited from 6,150 in the original data of Karaj, Alborz Province, Iran. Thousands of variables are examined in this data including basic characteristics, medical history, and variables related to infants. The validated Infant Neurological International Battery test was employed to assess the infant’s development. The concordance indexes showed that true prediction of developmental disorder in the artificial neural network model, compared to the logistic regression model, was 83.1% vs. 79.5% and the area under ROC curves, calculated from testing data, were 0.79 and 0.68, respectively. In addition, specificity and sensitivity of the ANN model vs. LR model was calculated 93.2% vs. 92.7% and 39.1% vs. 21.7%. An artificial neural network performed significantly better than a logistic regression model.

  18. Developmental tumors and adjacent cortical dysplasia: single or dual pathology?

    Science.gov (United States)

    Palmini, André; Paglioli, Eliseu; Silva, Vinicius Duval

    2013-12-01

    Developmental tumors often lead to refractory partial seizures and constitute a well-defined, surgically remediable epilepsy syndrome. Dysplastic features are often associated with these tumors, and their significance carries both practical and conceptual relevance. If associated focal cortical dysplasia (FCD) relates to the extent of the epileptogenic tissue, then presurgical evaluation and surgical strategies should target both the tumor and the surrounding dyslaminated cortex. Furthermore, the association has been included in the recently revised classification of FCD and the epileptogenicity of this associated dysplastic tissue is crucial to validate such revision. In addition to the possibility of representing dual pathology, the association of developmental tumors and adjacent dysplasia may instead represent a single developmental lesion with distinct parts distributed along a histopathologic continuum. Moreover, the possibility that this adjacent dyslamination is of minor epileptogenic relevance should also be entertained. Surgical data show that complete resection of the solid tumors and immediately adjacent tissue harboring satellites may disrupt epileptogenic networks and lead to high rates of seizure freedom, challenging the epileptogenic relevance of more extensive adjacent dyslaminated cortex. Whether the latter is a primary or secondary abnormality and whether dyslaminated cortex in the context of a second lesion may produce seizures after complete resection of the main lesion is still to be proven. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  19. Social Influence on Positive Youth Development: A Developmental Neuroscience Perspective.

    Science.gov (United States)

    Telzer, Eva H; van Hoorn, Jorien; Rogers, Christina R; Do, Kathy T

    2018-01-01

    Susceptibility to social influence is associated with a host of negative outcomes during adolescence. However, emerging evidence implicates the role of peers and parents in adolescents' positive and adaptive adjustment. Hence, in this chapter we highlight social influence as an opportunity for promoting social adjustment, which can redirect negative trajectories and help adolescents thrive. We discuss influential models about the processes underlying social influence, with a particular emphasis on internalizing social norms, embedded in social learning and social identity theory. We link this behavioral work to developmental social neuroscience research, rooted in neurobiological models of decision making and social cognition. Work from this perspective suggests that the adolescent brain is highly malleable and particularly oriented toward the social world, which may account for heightened susceptibility to social influences during this developmental period. This chapter underscores the need to leverage social influences during adolescence, even beyond the family and peer context, to promote positive developmental outcomes. By further probing the underlying neural mechanisms as an additional layer to examining social influence on positive youth development, we will be able to gain traction on our understanding of this complex phenomenon. © 2018 Elsevier Inc. All rights reserved.

  20. Rethinking developmental toxicity testing: Evolution or revolution?

    NARCIS (Netherlands)

    Scialli, Anthony R; Daston, George; Chen, Connie; Coder, Prägati S; Euling, Susan Y; Foreman, Jennifer; Hoberman, Alan M; Hui, Julia; Knudsen, Thomas; Makris, Susan L; Morford, LaRonda; Piersma, Aldert H; Stanislaus, Dinesh; Thompson, Kary E

    2018-01-01

    Current developmental toxicity testing adheres largely to protocols suggested in 1966 involving the administration of test compound to pregnant laboratory animals. After more than 50 years of embryo-fetal development testing, are we ready to consider a different approach to human developmental

  1. Developmental neurotoxicity of Propylthiouracil in rats

    DEFF Research Database (Denmark)

    Petersen, Marta Axelstad; Hansen, P.; Christiansen, S.

    2007-01-01

    early in pregnancy may cause adverse effects on the offspring. This has led to increased concern about thyroid hormone disrupting chemicals (TDCs) in our environment. We have studied how developmental exposure to the known antithyroid agent propylthiouracil (PTU) affects the development of rat pups...... behaviour and hearing function. This supports that exposure to TDC's in general may cause long-lasting developmental neurotoxicity....

  2. Are Students with Developmental Dyslexia Neurologically Different?

    Science.gov (United States)

    Goldsmith-Phillips, Josephine

    1994-01-01

    Reviews the controversy over a biological basis for developmental dyslexia and illustrates it with two case studies of junior high school students. Reviews neurological evidence for developmental dyslexia, and proposes seven signs characteristic of reading disability that may qualify as dyslexia. (SR)

  3. Essential Role of Culture in Developmental Psychology

    Science.gov (United States)

    Miller, Joan G.

    2005-01-01

    This chapter argues for the essential role of culture in forming the basic constructs and theories of developmental psychology. The case is made for the need to overcome the cultural insularity of core developmental concepts and methods in order to create a psychology that is more truly universal.

  4. Delaying Developmental Mathematics: The Characteristics and Costs

    Science.gov (United States)

    Johnson, Marianne; Kuennen, Eric

    2004-01-01

    This paper investigates which students delay taking a required developmental mathematics course and the impact of delay on student performance in introductory microeconomics. Analysis of a sample of 1462 students at a large Midwestern university revealed that, although developmental-level mathematics students did not reach the same level of…

  5. Unpacking developmental local government using Soft Systems ...

    African Journals Online (AJOL)

    Unpacking developmental local government using Soft Systems Methodology and MCDA tools. L Scott. Abstract. This paper presents two different analytical approaches that may be useful in developing an understanding of developmental local government (DLG). DLG implies a significant commitment with respect to ...

  6. Desiccation stress induces developmental heterochrony in ...

    Indian Academy of Sciences (India)

    Stressful environments are known to perturb developmental patterns in insects. In the purview of desiccation as astressor, relatively little is known about the developmental consequences linked with desiccation tolerance. In thisstudy, we have particularly focused on the exploration of the temporal profile of postembryonic ...

  7. Psychological Resources of Adults with Developmental Dyslexia

    Science.gov (United States)

    Lockiewicz, Marta; Bogdanowicz, Katarzyna M.; Bogdanowicz, Marta

    2014-01-01

    The aim of our study was to describe specific psychological resources of adults with developmental dyslexia and compare them with psychological resources of adults without developmental dyslexia. Potential differences were analyzed in visual-spatial, creative, and motivational abilities. No evidence was found for either creative, or visuospatial…

  8. Prevalence and sociodemographic determinants of developmental ...

    African Journals Online (AJOL)

    Birth order and household size also had significant association with delay in various domains. There was no significant association between socioeconomic class and developmental delay in any of the domains. Conclusion: The study showed that developmental delay was relatively common among under-five children in ...

  9. Introducing Newspapers in Developmental Reading Classes

    Science.gov (United States)

    Karstadt, Roberta; Rey, Victoria M.

    2009-01-01

    Newspapers are an effective educational and motivational tool in developmental reading classes. However, many students are unfamiliar with newspapers and read them infrequently. In order to foster newspaper reading and familiarize the college freshmen enrolled in their developmental reading classes with newspapers, the writers of this article…

  10. Developmental hip dysplasia in adolescence

    Directory of Open Access Journals (Sweden)

    Vukašinović Zoran

    2009-01-01

    Full Text Available The authors define adolescence and developmental dysplasia of the hip (DDH. Special attention is paid to pathological findings characteristic of DDH in adolescence (unrecognized and untreated DDH; treated DDH, but non-terminated treatment; DDH diagnosed with delay, inadequately treated, with complications. The authors emphasise that DDH treatment has to be successfully terminated well before the adolescence; possibilities are explained on management modes at the time of adolescence, and possible persons guilty for the persistence of later hip problems are indicated. Based on the authors' experience and having in mind all surgical possibilities for the treatment (pelvic osteotomies, femoral osteotomies, trochanteroplasties, leg length equalization procedures the authors propose treatment protocols. The intention is to provide better treatment results and to prevent secondary hip arthrosis. Furthermore, how to improve the struggle against DDH is suggested.

  11. Legal and Psychological Aspects of Mediation

    Directory of Open Access Journals (Sweden)

    Dobrokhotova E. N.

    2016-01-01

    Full Text Available The article focuses on gradual innovation of mediation into the practice of social conflict resolution in the light of legal and psychological means of mediation. While mediation is perceived as a conflictological concept and is more widely used in dispute settlement and resolution, a new interdisciplinary field of theoretical knowledge with its own conceptual framework as well as a new professional and practical field are beginning to form both in Russia and in other countries. As theoretical and practical aspects of innovation in mediation require consolidation not only for its national development but also for the guaranteed international cooperation, the article touches upon some of the particular theoretical issues of the topic in question: terminological consistency, consolidation of the system of mediation principles, the phenomenon of juridisation of mediation and its limits.

  12. Future Directions in Sleep and Developmental Psychopathology.

    Science.gov (United States)

    Meltzer, Lisa J

    2017-01-01

    It is critical for psychologists to gain a better understanding about the intersection between sleep and developmental psychopathology. However, while many strive to answer the question of whether sleep causes developmental psychopathology, or vice versa, ultimately the relationship between sleep and developmental psychopathology is complex and dynamic. This article considers future directions in the field of clinical child and adolescent psychology that go beyond this mechanistic question, highlighting areas important to address for clinicians and researchers who strive to better understand how best to serve children and adolescents with developmental psychopathology. Questions are presented about what is normal in terms of sleep across development, the role of individual variability in terms of sleep needs and vulnerability to sleep loss, and how sleep may serve as a risk or resilience factor for developmental psychopathology, concluding with considerations for interventions.

  13. Early Intervention in Children with Developmental Disabilities

    Directory of Open Access Journals (Sweden)

    Beena Johnson

    2016-01-01

    Full Text Available Developmental disabilities consist of conditions that delay or impair the physical, cognitive, and/or psychological development of children. If not intervened at the earliest, these disabilities will cause significant negative impact on multiple domains of functioning such as learning, language, self-care and capacity for independent living. Common developmental disabilities include autism spectrum disorders, intellectual disabilities, developmental delay and cerebral palsy. About one fourth of young children in developing countries are at risk for or have developmental delay or disabilities. Inadequate stimulation has significant negative impact on physical, socioemotional and cognitive development of children. Hence early scientific intervention programs are necessary in the management of children at risk for developmental delay.

  14. Gender and developmental differences in exercise beliefs among youth and prediction of their exercise behavior.

    Science.gov (United States)

    Garcia, A W; Broda, M A; Frenn, M; Coviak, C; Pender, N J; Ronis, D L

    1995-08-01

    This study examined gender and developmental differences in exercise-related beliefs and exercise behaviors of 286 racially diverse youth and explored factors predictive of exercise. Compared to males, females reported less prior and current exercise, lower self-esteem, poorer health status, and lower exercise self-schema. Adolescents, in contrast to pre-adolescents, reported less social support for exercise and fewer exercise role models. In a path model, gender, the benefits/barriers differential, and access to exercise facilities and programs directly predicted exercise. Effects of grade, perceived health status, exercise self-efficacy, social support for exercise, and social norms for exercise on exercise behavior, were mediated through the benefits/barriers differential. Effect of race on exercise was mediated by access to exercise facilities and programs. Continued exploration of gender and developmental differences in variables influencing physical activity can yield valuable information for tailoring exercise promotion interventions to the unique needs of youth.

  15. Early developmental responses to seedling environment modulate later plasticity to light spectral quality.

    Directory of Open Access Journals (Sweden)

    Eric J B von Wettberg

    Full Text Available Correlations between developmentally plastic traits may constrain the joint evolution of traits. In plants, both seedling de-etiolation and shade avoidance elongation responses to crowding and foliage shade are mediated by partially overlapping developmental pathways, suggesting the possibility of pleiotropic constraints. To test for such constraints, we exposed inbred lines of Impatiens capensis to factorial combinations of leaf litter (which affects de-etiolation and simulated foliage shade (which affects phytochrome-mediated shade avoidance. Increased elongation of hypocotyls caused by leaf litter phenotypically enhanced subsequent elongation of the first internode in response to low red:far red (R:FR. Trait expression was correlated across litter and shade conditions, suggesting that phenotypic effects of early plasticity on later plasticity may affect variation in elongation traits available to selection in different light environments.

  16. Developmental Pathways to Depressive Symptoms in Adolescence: A Multi-Wave Prospective Study of Negative Emotionality, Stressors, and Anxiety

    Science.gov (United States)

    Barrocas, Andrea L.; Hankin, Benjamin L.

    2011-01-01

    This study examined two potential developmental pathways through which the temperament risk factor of negative emotionality (NE) leads to prospective increases in depressive symptoms through the mediating role of stressors and anxious symptoms in a sample of early to middle adolescents (N = 350, 6th-10th graders). The primary hypothesized model…

  17. The contribution of mediator-based deficiencies to age differences in associative learning.

    Science.gov (United States)

    Dunlosky, John; Hertzog, Christopher; Powell-Moman, Amy

    2005-03-01

    Production, mediational, and utilization deficiencies, which describe how strategy use may contribute to developmental trends in episodic memory, have been intensively investigated. Using a mediator report-and-retrieval method, the authors present evidence concerning the degree to which 2 previously unexplored mediator-based deficits--retrieval and decoding deficiencies--account for age deficits in learning. During study, older and younger adults were instructed to use a strategy (imagery or sentence generation) to associate words within paired associates. They also reported each mediator and later attempted to retrieve each response and the mediator produced at study. Substantial deficits occurred in mediator recall, and small differences were observed in decoding mediators. Mediator recall also accounted for a substantial proportion of the age deficits in criterion recall independently of fluid or crystallized intelligence. Discussion focuses on mediator-based deficiencies and their implications for theories of age deficits in episodic memory. Copyright 2005 APA, all rights reserved.

  18. The Role of Early Childhood Personality in the Developmental Course of Social Adjustment

    Science.gov (United States)

    Kavcic, Tina; Podlesek, Anja; Zupancic, Maja

    2012-01-01

    This study explored children, preschool, and family characteristics that contribute to individual differences in the developmental trajectories of social competence and internalizing and externalizing behavior. Teachers reported on personality and social adjustment of 304 children at ages 3, 4, 5, and 6 years. Predictors of social adjustment…

  19. The Interplay of Spatial Attentional Biases and Mental Codes in VSTM: Developmentally Informed Hypotheses

    Science.gov (United States)

    Shimi, Andria; Scerif, Gaia

    2015-01-01

    What cognitive processes influence how well we maintain information in visual short-term memory (VSTM)? We used a developmentally informed design to delve into the interplay of top-down spatial biases with the nature of the internal memory codes, motivated by documented changes for both factors over childhood. Seven-year-olds, 11-year-olds, and…

  20. Homicides of People with Developmental Disabilities: An Analysis of News Stories

    Science.gov (United States)

    Lucardie, Richard; Sobsey, Dick

    2005-01-01

    Over the past decade, there has been increased interest in crimes against people with developmental disabilities (PWDD). While national and international information has been available on homicides of people in general, little attention has been given to homicides of PWDD specifically. This paper provides a preliminary description of homicides as…

  1. Graphic Representation of Organs and Organ Systems: Psychological View and Developmental Patterns

    Science.gov (United States)

    Bartoszeck, Amauri Betini; Machado, Danielle Zagonel; Amann-Gainotti, Merete

    2011-01-01

    The objective of this exploratory study is to characterize by means of drawings if the developmental patterns in the graphic representation of organ and organ systems progresses related to age of participants. Secondly, whether there is an integration of sex organs into the internal body image. The drawings representing the inside of the body in…

  2. Impairment of recollection but not familiarity in a case of developmental amnesia

    Science.gov (United States)

    Brandt, Karen R.; Gardiner, John M.; Vargha-Khadem, Faraneh; Baddeley, Alan D.; Mishkin, Mortimer

    2010-01-01

    In a re-examination of the recognition memory of Jon, a young adult with developmental amnesia due to perinatal hippocampal damage, we used a test procedure that provides estimates of the separate contributions to recognition of recollection and familiarity. Comparison between Jon and his controls revealed that, whereas he was unimpaired in the familiarity process, he showed abnormally low levels of recollection, supporting the view that the hippocampus mediates the latter process selectively. PMID:19090415

  3. Impairment of recollection but not familiarity in a case of developmental amnesia.

    Science.gov (United States)

    Brandt, Karen R; Gardiner, John M; Vargha-Khadem, Faraneh; Baddeley, Alan D; Mishkin, Mortimer

    2008-01-01

    In a re-examination of the recognition memory of Jon, a young adult with developmental amnesia due to perinatal hippocampal damage, we used a test procedure that provides estimates of the separate contributions to recognition of recollection and familiarity. Comparison between Jon and his controls revealed that, whereas he was unimpaired in the familiarity process, he showed abnormally low levels of recollection, supporting the view that the hippocampus mediates the latter process selectively.

  4. 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...

  5. Micro dynamics in mediation

    OpenAIRE

    Boserup, Hans

    2014-01-01

    The author has identified a number of styles in mediation, which lead to different processes and different outcomes. Through discourse and conversation analysis he examines the micro dynamics in three of these, the postmodern styles: systemic, transformative and narrative mediation. The differences between the three mediation ideologies and practice is illustrated through role play scripts enacted in each style. Mediator and providers of mediation and trainers in mediation are encouraged to a...

  6. A Longitudinal Study of Maternal and Child Internalizing Symptoms Predicting Early Adolescent Emotional Eating.

    Science.gov (United States)

    Kidwell, Katherine M; Nelson, Timothy D; Nelson, Jennifer Mize; Espy, Kimberly Andrews

    2017-05-01

    To examine maternal and child internalizing symptoms as predictors of early adolescent emotional eating in a longitudinal framework spanning three critical developmental periods (preschool, elementary school, and early adolescence). Participants were 170 children recruited at preschool age for a longitudinal study. When children were 5.25 years, their mothers completed ratings of their own internalizing symptoms. During the spring of 4th grade, children completed measures of internalizing symptoms. In early adolescence, youth completed a measure of emotional eating. Maternal and child internalizing symptoms predicted adolescent emotional eating. The results indicated that child psychopathology moderated the association between maternal psychopathology (except for maternal anxiety) and early adolescent emotional eating. There was no evidence of mediation. Pediatric psychologists are encouraged to provide early screening of, and interventions for, maternal and child internalizing symptoms to prevent children's emotional eating. © The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  7. Mediating environmental disputes

    Energy Technology Data Exchange (ETDEWEB)

    Lake, L.M.

    1977-09-01

    Environmental disputes and lawsuits are examined. Site-specific disputes focus on visible physical phenomena, such as a power plant or local river, and have an immediacy and intensity about them that make it politically hazardous for public officials to assume responsibility for resolving them. As new precedents in environmental case law become less frequent and the number of disputes increases, alternative processes for environmental conflict resolution, such as third-party intervention, become appropriate. Third-party intervention techniques of fact finding, conflict avoidance, conciliation and mediation have been applied to international, labor, prison, school, racial, and hospital disputes. Underlying concepts are described. Two case studies, the Snoqualmie Dam dispute in Washington and the West Side Highway dispute in New York City, illustrate the basic elements associated with third-party intervention. 1 map, 17 references.

  8. Developmental origins of brain disorders: roles for dopamine

    Directory of Open Access Journals (Sweden)

    Kelli M Money

    2013-12-01

    Full Text Available Neurotransmitters and neuromodulators, such as dopamine, participate in a wide range of behavioral and cognitive functions in the adult brain, including movement, cognition, and reward. Dopamine-mediated signaling plays a fundamental neurodevelopmental role in forebrain differentiation and circuit formation. These developmental effects, such as modulation of neuronal migration and dendritic growth, occur before synaptogenesis and demonstrate novel roles for dopaminergic signaling beyond neuromodulation at the synapse. Pharmacologic and genetic disruptions demonstrate that these effects are brain region- and receptor subtype-specific. For example, the striatum and frontal cortex exhibit abnormal neuronal structure and function following prenatal disruption of dopamine receptor signaling. Alterations in these processes are implicated in the pathophysiology of neuropsychiatric disorders, and emerging studies of neurodevelopmental disruptions may shed light on the pathophysiology of abnormal neuronal circuitry in neuropsychiatric disorders.

  9. Developmental psychopathology: a paradigm shift or just a relabeling?

    Science.gov (United States)

    Rutter, Michael

    2013-11-01

    Developmental psychopathology is described as a conceptual approach that involves a set of research methods that capitalize on developmental and psychopathological variations to ask questions about mechanisms and processes. Achievements are described in relation to attachment and attachment disorders, autism, schizophrenia, childhood antecedents of adult psychopathology, testing for environmental mediation of risk effects, gene-environment interplay, intellectual and language functioning, effects of mentally ill parents on the children, stress and vulnerability to depression, ethnicity and schizophrenia, and drug response. Continuities and discontinuities over the course of development are discussed in relation to attention-deficit/hyperactivity disorder, antisocial behavior, eating disorders, substance abuse and dependency, pharmacological and behavioral addictions, and a range of other disorders. Research challenges are considered in relation to spectrum concepts, the adolescent development of a female preponderance for depression, the mechanisms involved in age differences in response to drugs and to lateralized brain injury, the processing of experiences, the biological embedding of experiences, individual differences in response to environmental hazards, nature-nurture integration, and brain plasticity.

  10. Mental health outcomes of developmental coordination disorder in late adolescence.

    Science.gov (United States)

    Harrowell, Ian; Hollén, Linda; Lingam, Raghu; Emond, Alan

    2017-09-01

    To assess the relationship between developmental coordination disorder (DCD) and mental health outcomes in late adolescence. Data were analyzed from the Avon Longitudinal Study of Parents and Children. Moderate-to-severe DCD was defined at 7 to 8 years according to the DSM-IV-TR criteria. Mental health was assessed at 16 to 18 years using self-reported questionnaires: Strengths and Difficulties Questionnaire, Short Moods and Feelings Questionnaire, and the Warwick-Edinburgh Mental Well-being Scale. Logistic and linear regressions assessed the associations between DCD and mental health, using multiple imputation to account for missing data. Adjustments were made for socio-economic status, IQ, and social communication difficulties. Adolescents with DCD (n=168) had an increased risk of mental health difficulties (total Strengths and Difficulties Questionnaire score) than their peers (n=3750) (odds ratio 1.78, 95% confidence interval 1.12-2.83, adjusted for socio-economic status and IQ). This was, in part, mediated through poor social communication skills. Adolescent females with DCD (n=59) were more prone to mental health difficulties than males. Greater mental well-being was associated with better self-esteem (β 0.82, pcommunication skills and self-esteem. © 2017 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.

  11. Developmental programming of auditory learning

    Directory of Open Access Journals (Sweden)

    Melania Puddu

    2012-10-01

    Full Text Available The basic structures involved in the development of auditory function and consequently in language acquisition are directed by genetic code, but the expression of individual genes may be altered by exposure to environmental factors, which if favorable, orient it in the proper direction, leading its development towards normality, if unfavorable, they deviate it from its physiological course. Early sensorial experience during the foetal period (i.e. intrauterine noise floor, sounds coming from the outside and attenuated by the uterine filter, particularly mother’s voice and modifications induced by it at the cochlear level represent the first example of programming in one of the earliest critical periods in development of the auditory system. This review will examine the factors that influence the developmental programming of auditory learning from the womb to the infancy. In particular it focuses on the following points: the prenatal auditory experience and the plastic phenomena presumably induced by it in the auditory system from the basilar membrane to the cortex;the involvement of these phenomena on language acquisition and on the perception of language communicative intention after birth;the consequences of auditory deprivation in critical periods of auditory development (i.e. premature interruption of foetal life.

  12. Executive Functions in Developmental Dyslexia

    Directory of Open Access Journals (Sweden)

    Pamela eVarvara

    2014-03-01

    Full Text Available The present study was aimed at investigating different aspects of Executive Functions (EF in children with Developmental Dyslexia (DD.A neuropsychological battery tapping verbal fluency, spoonerism, attention, verbal shifting, short-term and working memory was used to assess 60 children with DD and 65 with typical reading abilities.Compared to their controls, children with DD showed deficits in several EF domains such as verbal categorical and phonological fluency, visual-spatial and auditory attention, spoonerism, verbal and visual short-term memory, and verbal working memory. Moreover, exploring predictive relationships between EF measures and reading, we found that spoonerism abilities better explained word and non-word reading deficits. Although to a lesser extent, auditory and visual-spatial attention also explained the increased percentage of variance related to reading deficit.EF deficits found in DD are interpreted as an expression of a deficient functioning of the Central Executive System and are discussed in the context of the recent temporal sampling theory.

  13. Pervasive Developmental Disorder with Age?

    Directory of Open Access Journals (Sweden)

    M. Balfe

    2011-01-01

    Full Text Available A survey was undertaken to investigate the prevalence of high-functioning pervasive developmental disorder (HFPDD in a community sample of teenagers and adults aged 13 and above in the city of Sheffield, UK. 112 possible and definite cases were found, of whom 65 (57% had a previous diagnosis. The detected prevalence of possible or definite HFPDD was found to be 0.24 per 1000 of the population of Sheffield city aged 13 or over, but the prevalence by year of age fell from a maximum of 1.1 per 1000 in the group aged 13 to 14 years old (1 young adult in every 900 in this age group to 0.03 per 1000 in the over 60s (1 person in every 38500 in this age group. The results of this study are preliminary and need follow-up investigation in larger studies. We suggest several explanations for the findings, including reduced willingness to participate in a study as people get older, increased ascertainment in younger people, and increased mortality. Another contributory factor might be that the prevalence of high-functioning pervasive development disorder may decline with age. This raises the possibility that AS symptoms might become subclinical in adulthood in a proportion of people with HFPDD.

  14. From Parent-Child Mutuality to Security to Socialization Outcomes: Developmental Cascade toward Positive Adaptation in Preadolescence

    Science.gov (United States)

    Kim, Sanghag; Boldt, Lea J.; Kochanska, Grazyna

    2016-01-01

    A developmental cascade from positive early parent-child relationship to child security with the parent to adaptive socialization outcomes, proposed in attachment theory and often implicitly accepted but rarely formally tested, was examined in 100 mothers, fathers, and children followed from toddler age to preadolescence. Parent-child Mutually Responsive Orientation (MRO) was observed in lengthy interactions at 38, 52, 67, and 80 months; children reported their security with parents at age 8. Socialization outcomes (parent- and child-reported cooperation with parental monitoring and teacher-reported school competence) were assessed at age 10. Mediation was tested with PROCESS (Hayes, 2013). The parent-child history of MRO significantly predicted both mother-child and father-child security. For mother-child dyads, security mediated links between history of MRO and cooperation with maternal monitoring and school competence, controlling for developmental continuity of the studied constructs. For father-child dyads, the mediation effect was not evident. PMID:26258443

  15. Developmental toxicity and molecular responses of marine medaka (Oryzias melastigma) embryos to ciguatoxin P-CTX-1 exposure.

    Science.gov (United States)

    Yan, Meng; Leung, Priscilla T Y; Ip, Jack C H; Cheng, Jin-Ping; Wu, Jia-Jun; Gu, Jia-Rui; Lam, Paul K S

    2017-04-01

    Ciguatoxins are produced by toxic benthic dinoflagellates and cause ciguatera fish poisoning worldwide, but the toxic effects on developing marine fish have not been well investigated. The Pacific ciguatoxin (P-CTX-1), is a potent sodium channel agonist, which is one of the most toxic members among all CTXs. This study evaluated the toxic effects of microinjecting purified Pacific ciguatoxin-1 (P-CTX-1) on embryonic development of marine medaka Oryzias melastigma. A lower 96h-LD 50 value was estimated for eleuthero-embryos (1.32ngg -1 ) than that for embryos (1.71ngg -1 ), indicating that P-CTX-1 is more lethal to newly hatched medaka larvae. P-CTX-1 induced detrimental effects during embryonic development, including hatching failure, abnormalities in physical development (caudal fin malformation and spinal deformities), internal damage (green coloration of the gall bladder and hemorrhaging), immune dysfunction, and altered muscle physiology (bradycardia and hyperkinetic twitching). The results of a transcriptional expression analysis of genes related to the stress/immune responses, cardiac and bone development, and apoptosis supported the observed developmental abnormalities. This study advanced the understanding of P-CTX-1 mediated toxic mechanisms in the development of early life stages of a fish, and thus contributed to the toxicity assessment of CTXs in marine ecosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Topsy-Turvy Neo-Developmentalism: An Analysis of the Current Brazilian Model of Development

    Directory of Open Access Journals (Sweden)

    Bruno Milanez

    2015-09-01

    Full Text Available The paper discusses the similarities and differences between neo-developmentalism and neo-extractivism. The evaluation compares Brazil with nine other Latin American countries and is based on a framework that considers both economic policies and their outcomes. On the policy side, it looks at income, monetary, international trade, industrial and mineral resource policies; on the outcome side, it observes the composition of both exports and the Gross Domestic Product. In the end, we argue that neo-developmentalism and neo-extractivism are actually variations of the same development route and may face similar challenges in the long term.

  17. A Clinical Case Presentation: Understanding and Interpreting Dreams while Working Through Developmental Trauma.

    Science.gov (United States)

    Levy, Joshua; Finnegan, Paul

    2016-02-01

    The purpose of this paper is to demonstrate the unique place of understanding and interpreting dreams in the psychoanalytic process while working through developmental trauma. This psychoanalytic process extended over six years and is presented in four phases: establishing the therapeutic alliance, a crisis, working through, and termination. Dreams from each of these four phases of the analysis are presented, and the collaborative work of understanding and interpreting these dreams is highlighted. Evidence is presented that from this analytic work there ensued an amelioration of the impact of developmental trauma and a furtherance of the development of internal psychic structure. © 2016 by the American Psychoanalytic Association.

  18. Etiology and Treatment of Developmental Stammering

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2008-01-01

    Full Text Available The etiology and treatment of developmental stammering in childhood (DS, also called idiopathic stammering or stuttering are reviewed by a speech pathologist and psychologist at the University of Reading, UK.

  19. Unpacking developmental local government using Soft Systems ...

    African Journals Online (AJOL)

    Developmental local government, soft systems methodology, multiple criteria ..... land and property), 26 (adequate housing), 27 (access to health care, food, water .... It is important to articulate that any decision making or resource allocation.

  20. Wanted: A Developmentally Oriented Alcohol Prevention Program.

    Science.gov (United States)

    Spoth, Richard; Rosenthal, David

    1980-01-01

    Describes an alcohol prevention program with a comprehensive developmental skills orientation. The program includes values clarification, decision making, career planning and communication skills, assertiveness and relaxation training, and relationship with parents and peers. (Author/JAC)

  1. Developmental and Reproductive Toxicology Database (DART)

    Data.gov (United States)

    U.S. Department of Health & Human Services — A bibliographic database on the National Library of Medicine's (NLM) Toxicology Data Network (TOXNET) with references to developmental and reproductive toxicology...

  2. Characteristics of children with pervasive developmental disorders ...

    African Journals Online (AJOL)

    of children presenting with features of ASD to a developmental clinic in Johannesburg over ... social interaction deficits without meeting the full criteria for PDD were excluded, as were those ..... Recurrent otitis media. 7 (12.1). Myringotomies.

  3. Current status of developmental neurotoxicity: regulatory view

    DEFF Research Database (Denmark)

    Hass, Ulla

    2003-01-01

    in the testing strategy for new and existing substances, and biocides. Hopefully, this will lead to an improved database for risk assessment of potential developmental neurotoxicants. However, the regulatory authorities and toxicologists will also be faced with the challenge that decisions have to be made......The need for developmental neurotoxicity testing has been recognized for decades and guidelines are available, as the USEPA guideline and the OECD draft TG 426. Regulatory testing of industrial chemicals for developmental neurotoxicity is required to some extent, especially for pesticides in the US....... Until recently, however, developmental neurotoxicity testing of industrial chemicals has not been a clear regulatory requirement in EU, probably due to the lack of an accepted OECD TG. The revised EU Technical Guidance Document for Risk Assessment (EU-TGD) has now included the OECD draft TG 426...

  4. Highly precise and developmentally programmed genome assembly in Paramecium requires ligase IV-dependent end joining.

    Directory of Open Access Journals (Sweden)

    Aurélie Kapusta

    2011-04-01

    Full Text Available During the sexual cycle of the ciliate Paramecium, assembly of the somatic genome includes the precise excision of tens of thousands of short, non-coding germline sequences (Internal Eliminated Sequences or IESs, each one flanked by two TA dinucleotides. It has been reported previously that these genome rearrangements are initiated by the introduction of developmentally programmed DNA double-strand breaks (DSBs, which depend on the domesticated transposase PiggyMac. These DSBs all exhibit a characteristic geometry, with 4-base 5' overhangs centered on the conserved TA, and may readily align and undergo ligation with minimal processing. However, the molecular steps and actors involved in the final and precise assembly of somatic genes have remained unknown. We demonstrate here that Ligase IV and Xrcc4p, core components of the non-homologous end-joining pathway (NHEJ, are required both for the repair of IES excision sites and for the circularization of excised IESs. The transcription of LIG4 and XRCC4 is induced early during the sexual cycle and a Lig4p-GFP fusion protein accumulates in the developing somatic nucleus by the time IES excision takes place. RNAi-mediated silencing of either gene results in the persistence of free broken DNA ends, apparently protected against extensive resection. At the nucleotide level, controlled removal of the 5'-terminal nucleotide occurs normally in LIG4-silenced cells, while nucleotide addition to the 3' ends of the breaks is blocked, together with the final joining step, indicative of a coupling between NHEJ polymerase and ligase activities. Taken together, our data indicate that IES excision is a "cut-and-close" mechanism, which involves the introduction of initiating double-strand cleavages at both ends of each IES, followed by DSB repair via highly precise end joining. This work broadens our current view on how the cellular NHEJ pathway has cooperated with domesticated transposases for the emergence of new

  5. Highly precise and developmentally programmed genome assembly in Paramecium requires ligase IV-dependent end joining.

    Science.gov (United States)

    Kapusta, Aurélie; Matsuda, Atsushi; Marmignon, Antoine; Ku, Michael; Silve, Aude; Meyer, Eric; Forney, James D; Malinsky, Sophie; Bétermier, Mireille

    2011-04-01

    During the sexual cycle of the ciliate Paramecium, assembly of the somatic genome includes the precise excision of tens of thousands of short, non-coding germline sequences (Internal Eliminated Sequences or IESs), each one flanked by two TA dinucleotides. It has been reported previously that these genome rearrangements are initiated by the introduction of developmentally programmed DNA double-strand breaks (DSBs), which depend on the domesticated transposase PiggyMac. These DSBs all exhibit a characteristic geometry, with 4-base 5' overhangs centered on the conserved TA, and may readily align and undergo ligation with minimal processing. However, the molecular steps and actors involved in the final and precise assembly of somatic genes have remained unknown. We demonstrate here that Ligase IV and Xrcc4p, core components of the non-homologous end-joining pathway (NHEJ), are required both for the repair of IES excision sites and for the circularization of excised IESs. The transcription of LIG4 and XRCC4 is induced early during the sexual cycle and a Lig4p-GFP fusion protein accumulates in the developing somatic nucleus by the time IES excision takes place. RNAi-mediated silencing of either gene results in the persistence of free broken DNA ends, apparently protected against extensive resection. At the nucleotide level, controlled removal of the 5'-terminal nucleotide occurs normally in LIG4-silenced cells, while nucleotide addition to the 3' ends of the breaks is blocked, together with the final joining step, indicative of a coupling between NHEJ polymerase and ligase activities. Taken together, our data indicate that IES excision is a "cut-and-close" mechanism, which involves the introduction of initiating double-strand cleavages at both ends of each IES, followed by DSB repair via highly precise end joining. This work broadens our current view on how the cellular NHEJ pathway has cooperated with domesticated transposases for the emergence of new mechanisms

  6. Phonemic restoration in developmental dyslexia

    Directory of Open Access Journals (Sweden)

    Stephanie N. Del Tufo

    2014-06-01

    Full Text Available The comprehension of fluent speech in one’s native language requires that listeners integrate the detailed acoustic-phonetic information available in the sound signal with linguistic knowledge. This interplay is especially apparent in the phoneme restoration effect, a phenomenon in which a missing phoneme is ‘restored’ via the influence of top-down information from the lexicon and through bottom-up acoustic processing. Developmental dyslexia is a disorder characterized by an inability to read at the level of one’s peers without any clear failure due to environmental influences. In the current study we utilized the phonemic restoration illusion paradigm, to examine individual differences in phonemic restoration across a range of reading ability, from very good to dyslexic readers. Results demonstrate that restoration occurs less in those who have high scores on measures of phonological processing. Based on these results, we suggest that the processing or representation of acoustic detail may not be as reliable in poor and dyslexic readers, with the result that lexical information is more likely to override acoustic properties of the stimuli. This pattern of increased restoration could result from a failure of perceptual tuning, in which unstable representations of speech sounds result in the acceptance of non-speech sounds as speech. An additional or alternative theory is that degraded or impaired phonological processing at the speech sound level may reflect architecture that is overly plastic and consequently fails to stabilize appropriately for speech sound representations. Therefore the inability to separate speech and noise may result as a deficit in separating noise from the acoustic signal.

  7. Developmental plasticity: re-conceiving the genotype.

    Science.gov (United States)

    Sultan, Sonia E

    2017-10-06

    In recent decades, the phenotype of an organism (i.e. its traits and behaviour) has been studied as the outcome of a developmental 'programme' coded in its genotype. This deterministic view is implicit in the Modern Synthesis approach to adaptive evolution as a sorting process among genetic variants. Studies of developmental pathways have revealed that genotypes are in fact differently expressed depending on environmental conditions. Accordingly, the genotype can be understood as a repertoire of potential developmental outcomes or norm of reaction. Reconceiving the genotype as an environmental response repertoire rather than a fixed developmental programme leads to three critical evolutionary insights. First, plastic responses to specific conditions often comprise functionally appropriate trait adjustments, resulting in an individual-level, developmental mode of adaptive variation. Second, because genotypes are differently expressed depending on the environment, the genetic diversity available to natural selection is itself environmentally contingent. Finally, environmental influences on development can extend across multiple generations via cytoplasmic and epigenetic factors transmitted to progeny individuals, altering their responses to their own, immediate environmental conditions and, in some cases, leading to inherited but non-genetic adaptations. Together, these insights suggest a more nuanced understanding of the genotype and its evolutionary role, as well as a shift in research focus to investigating the complex developmental interactions among genotypes, environments and previous environments.

  8. [Contemporary cognitive theories about developmental dyscalculia].

    Science.gov (United States)

    Castro-Cañizares, D; Estévez-Pérez, N; Reigosa-Crespo, V

    To analyze the current theories describing the cognitive mechanisms underlying developmental dyscalculia. The four most researched hypotheses concerning the cognitive deficits related to developmental dyscalculia, as well as experimental evidences supporting or refusing them are presented. The first hypothesis states that developmental dyscalculia is consequence of domain general cognitive deficits. The second hypothesis suggests that it is due to a failure in the development of specialized brain systems dedicated to numerosity processing. The third hypothesis asserts the disorder is caused by a deficit in accessing quantity representation through numerical symbols. The last hypothesis states developmental dyscalculia appears as a consequence of impairments in a generalized magnitude system dedicated to the processing of continuous and discrete magnitudes. None of the hypotheses has been proven more plausible than the rest. Relevant issues rose by them need to be revisited and answered in the light of new experimental designs. In the last years the understanding of cognitive disorders involved in developmental dyscalculia has remarkably increased, but it is nonetheless insufficient. Additional research is required in order to achieve a comprehensive cognitive model of numerical processing development and its disorders. This will improve the diagnostic precision and the effectiveness of developmental dyscalculia intervention strategies.

  9. Teen Dating Violence, Sexual Harassment, and Bullying Among Middle School Students: Examining Mediation and Moderated Mediation by Gender.

    Science.gov (United States)

    Cutbush, Stacey; Williams, Jason; Miller, Shari

    2016-11-01

    This longitudinal study tested whether sexual harassment perpetration mediates the relationship between bullying perpetration and teen dating violence (TDV) perpetration and tested moderated mediation by assessing whether the developmental pathway varies by gender among middle school-aged youth. Although TDV has been associated with bullying and sexual harassment, the developmental relationship among all three behaviors has rarely been examined, especially by gender. The data were collected from one cohort of seventh grade middle school students (N = 612) from four schools. Students were surveyed every 6 months during seventh and eighth grades for a total of four waves of data collection. Structural equation modeling (SEM) was conducted to address the study aims, consisting of three stages: measurement models, mediation, and moderated mediation (otherwise known as Contrast of Mediated Effects). Results indicate no evidence of mediation. However, in the overall model, bullying and sexual harassment both emerged as significant predictors of TDV at a later time point. Among girls, only bullying significantly predicted TDV at a later time point, and, among boys, only sexual harassment significantly predicted TDV at a later time point. Prevention programs that target bullying and sexual harassment perpetration may reduce later perpetration of TDV. Further research is needed to disentangle the temporal relationships between these aggressive behaviors among youth.

  10. Exposure of children with developmental delay to social determinants of poor health: cross-sectional case record review study.

    Science.gov (United States)

    Emerson, E; Brigham, P

    2015-03-01

    Research on child development in general has highlighted the importance that the family environment plays in mediating the pathway between exposure to low socio-economic position (SEP) and child well-being. While child developmental models in intellectual disability have highlighted the interplay between social context, family environment and child development, little empirical work has attempted to formally evaluate the evidence in support of specific mediating pathways between low SEP and child outcomes. Secondary analysis of cross-sectional confidentialized needs analysis data collected in three Primary Care Trusts in England covering a total population of 1.25 million people. Case record reviews were undertaken for 46 023 households, 2236 (4.9%) of which contained a child in the target age range with developmental delay. Children with developmental delay, when compared with their non-disabled peers, were at significantly increased risk of poorer health outcomes and of being exposed to a wide range of social determinants of poor health. Controlling for between-group differences in exposure to social determinants of poor health reduced the risk of developmental delay being associated with poorer health outcomes by 45% for behaviour problems and 89% for risk of significant harm. For children with developmental delay, parenting difficulties appears to play a particularly significant role in partially mediating the effects of low SEP. The findings of the present study point to the potential effectiveness of family-focused early intervention to prevent the emergence and escalation of behavioural difficulties and health problems in children with developmental delay. © 2014 John Wiley & Sons Ltd.

  11. The Role of Stress Exposure and Family Functioning in Internalizing Outcomes of Urban Families.

    Science.gov (United States)

    Sheidow, Ashli J; Henry, David B; Tolan, Patrick H; Strachan, Martha K

    2014-11-01

    Although research suggests that stress exposure and family functioning are associated with internalizing problems in adolescents and caregivers, surprisingly few studies have investigated the mechanisms that underlie this association. To determine whether family functioning buffers the development of internalizing problems in stress-exposed families, we assessed the relation between stress exposure, family functioning, and internalizing symptoms among a large sample of inner-city male youth and their caregivers living in poverty across five waves of data collection. We hypothesized that stress exposure and family functioning would predict development of subsequent youth and caregiver internalizing problems and that family functioning would moderate this relation, with higher functioning families demonstrating greater resiliency to stress exposure. We used a longitudinal, prospective design to evaluate whether family functioning (assessed at waves one through four) activated or buffered the effects of stress exposure (assessed at wave one) on subsequent internalizing symptoms (assessed at waves four and five). Stress from Developmental Transitions and family functioning were significant predictors of depressive symptoms and anxiety in youth; however, family functioning did not moderate the relation. Family functioning mediated the relation between stress from Daily Hassles and internalizing outcomes suggesting that poor parenting practices, low structure, and low emotional cohesion activate depression and anxiety in youth exposed to chronic and frequent everyday stressors. Surprisingly, only family functioning predicted depressive symptoms in caregivers. Results validate the use of a comprehensive, multi-informant assessment of stress when investigating internalizing outcomes in youth and support using family-based interventions in the treatment and prevention of internalizing.

  12. The South African developmental landscape: restricted potentials or expansive, complex adaptive opportunities?

    Directory of Open Access Journals (Sweden)

    C J Burman

    2013-07-01

    Full Text Available This article argues that the South African developmental landscape is currently locked into an overly technical, path dependent paradigm that is unlikely to be capable of embracing the complex challenges identified by the recent National Development Plan. The article explores the internal logic of the existing path dependent, technical condition from the perspective of complexity, in the context of the Department of Science and Technology’s Fifth Grand Challenge and “continuous change”. It is argued that drawing ideas from complexity into future developmental trajectories can add value to the National Development Plan: Vision 2030, but to do so will require dynamic mind-set shifts across multiple developmental scales and interfaces if new approaches to managing development that embraces complexity, rather than denies it, is to emerge. Keywords: development; complexity; path dependency; epistemological vigilance; sense-making; National Development Plan Disciplines: Complexity Studies; Transdisciplinary studies; Management studies; Public management; Political studies; Economics; Development Studies

  13. Developmental Vitamin D Availability Impacts Hematopoietic Stem Cell Production

    Directory of Open Access Journals (Sweden)

    Mauricio Cortes

    2016-10-01

    Full Text Available Vitamin D insufficiency is a worldwide epidemic affecting billions of individuals, including pregnant women and children. Despite its high incidence, the impact of active vitamin D3 (1,25(OHD3 on embryonic development beyond osteo-regulation remains largely undefined. Here, we demonstrate that 1,25(OHD3 availability modulates zebrafish hematopoietic stem and progenitor cell (HSPC production. Loss of Cyp27b1-mediated biosynthesis or vitamin D receptor (VDR function by gene knockdown resulted in significantly reduced runx1 expression and Flk1+cMyb+ HSPC numbers. Selective modulation in vivo and in vitro in zebrafish indicated that vitamin D3 acts directly on HSPCs, independent of calcium regulation, to increase proliferation. Notably, ex vivo treatment of human HSPCs with 1,25(OHD3 also enhanced hematopoietic colony numbers, illustrating conservation across species. Finally, gene expression and epistasis analysis indicated that CXCL8 (IL-8 was a functional target of vitamin D3-mediated HSPC regulation. Together, these findings highlight the relevance of developmental 1,25(OHD3 availability for definitive hematopoiesis and suggest potential therapeutic utility in HSPC expansion.

  14. The p38 mitogen-activated protein kinase signaling pathway is involved in regulating low-density lipoprotein receptor-related protein 1-mediated β-amyloid protein internalization in mouse brain.

    Science.gov (United States)

    Ma, Kai-Ge; Lv, Jia; Hu, Xiao-Dan; Shi, Li-Li; Chang, Ke-Wei; Chen, Xin-Lin; Qian, Yi-Hua; Yang, Wei-Na; Qu, Qiu-Min

    2016-07-01

    Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Recently, increasing evidence suggests that intracellular β-amyloid protein (Aβ) alone plays a pivotal role in the progression of AD. Therefore, understanding the signaling pathway and proteins that control Aβ internalization may provide new insight for regulating Aβ levels. In the present study, the regulation of Aβ internalization by p38 mitogen-activated protein kinases (MAPK) through low-density lipoprotein receptor-related protein 1 (LRP1) was analyzed in vivo. The data derived from this investigation revealed that Aβ1-42 were internalized by neurons and astrocytes in mouse brain, and were largely deposited in mitochondria and lysosomes, with some also being found in the endoplasmic reticulum. Aβ1-42-LRP1 complex was formed during Aβ1-42 internalization, and the p38 MAPK signaling pathway was activated by Aβ1-42 via LRP1. Aβ1-42 and LRP1 were co- localized in the cells of parietal cortex and hippocampus. Furthermore, the level of LRP1-mRNA and LRP1 protein involved in Aβ1-42 internalization in mouse brain. The results of this investigation demonstrated that Aβ1-42 induced an LRP1-dependent pathway that related to the activation of p38 MAPK resulting in internalization of Aβ1-42. These results provide evidence supporting a key role for the p38 MAPK signaling pathway which is involved in the regulation of Aβ1-42 internalization in the parietal cortex and hippocampus of mouse through LRP1 in vivo. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Trisomy 21 and facial developmental instability.

    Science.gov (United States)

    Starbuck, John M; Cole, Theodore M; Reeves, Roger H; Richtsmeier, Joan T

    2013-05-01

    The most common live-born human aneuploidy is trisomy 21, which causes Down syndrome (DS). Dosage imbalance of genes on chromosome 21 (Hsa21) affects complex gene-regulatory interactions and alters development to produce a wide range of phenotypes, including characteristic facial dysmorphology. Little is known about how trisomy 21 alters craniofacial morphogenesis to create this characteristic appearance. Proponents of the "amplified developmental instability" hypothesis argue that trisomy 21 causes a generalized genetic imbalance that disrupts evolutionarily conserved developmental pathways by decreasing developmental homeostasis and precision throughout development. Based on this model, we test the hypothesis that DS faces exhibit increased developmental instability relative to euploid individuals. Developmental instability was assessed by a statistical analysis of fluctuating asymmetry. We compared the magnitude and patterns of fluctuating asymmetry among siblings using three-dimensional coordinate locations of 20 anatomic landmarks collected from facial surface reconstructions in four age-matched samples ranging from 4 to 12 years: (1) DS individuals (n = 55); (2) biological siblings of DS individuals (n = 55); 3) and 4) two samples of typically developing individuals (n = 55 for each sample), who are euploid siblings and age-matched to the DS individuals and their euploid siblings (samples 1 and 2). Identification in the DS sample of facial prominences exhibiting increased fluctuating asymmetry during facial morphogenesis provides evidence for increased developmental instability in DS faces. We found the highest developmental instability in facial structures derived from the mandibular prominence and lowest in facial regions derived from the frontal prominence. Copyright © 2013 Wiley Periodicals, Inc.

  16. Preliminary Development of the Food Allergy Coping and Emotions Questionnaires for Children, Adolescents, and Young People: Qualitative Analysis of Data on IgE-Mediated Food Allergy from Five Countries.

    Science.gov (United States)

    DunnGalvin, Audrey; Polloni, Laura; Le Bovidge, Jennifer; Muraro, Antonella; Greenhawt, Matthew; Taylor, Steve; Baumert, Joseph; Burks, Wesley; Trace, Anna; DunnGalvin, Gillian; Forristal, Lisa; McGrath, Laura; White, Jennifer; Vasquez, Marta; Allen, Katrina; Sheikh, Aziz; Hourihane, Jonathan; Tang, Mimi L K

    We have previously developed a food allergy-specific developmental model, that explained emotions and coping styles, among children aged 6 to 15years in Ireland. The objective of this study was to investigate the usefulness of the developmental model in a large multicountry data set, including any mediators of coping style, and to use the findings to generate an item pool that will form the basis for 3 age-appropriate self-report questionnaires to measure coping and emotions. We conducted deductive thematic analysis on secondary data from interviews with 274 participants aged 6 to 23 years, and 119 parents from Australia, Ireland, Italy, the UK, and the USA. Analysis was undertaken across the entire data set. The Food Allergy Coping and Emotions (FACE) model has 5 major themes: (1) experiences and emotions, (2) search for normality, (3) management and coping, (4) "external mediators," and (5) "internal mediators" (between emotions and coping). These themes were present across countries, but differed according to age. Early-life experiences provide the foundation for later cognitions and behaviors. The expanded FACE developmental model is useful in explaining emotions and coping styles across different age groups and countries. These data will also be used to generate an age-specific bank of items for the development of 3 (age-specific self-report, and parent proxy) questionnaires to assess emotions and coping in food allergy. Findings provide insight into how particular styles of coping develop and vary from patient to patient and may also guide clinician-patient communication and the development of individualized management strategies. Copyright © 2018. Published by Elsevier Inc.

  17. Communication-Based Assessment of Developmental Age for Young Children with Developmental Disabilities

    Science.gov (United States)

    DeVeney, Shari L.; Hoffman, Lesa; Cress, Cynthia J.

    2012-01-01

    Purpose: In this study, the authors compared a multiple-domain strategy for assessing developmental age of young children with developmental disabilities who were at risk for long-term reliance on augmentative and alternative communication (AAC) with a communication-based strategy composed of receptive language and communication indices that may…

  18. Developmental patterns of adolescent spiritual health in six countries

    Directory of Open Access Journals (Sweden)

    Valerie Michaelson

    2016-12-01

    Full Text Available The spiritual health of adolescents is a topic of emerging contemporary importance. Limited numbers of international studies provide evidence about developmental patterns of this aspect of health during the adolescent years. Using multidimensional indicators of spiritual health that have been adapted for use within younger adolescent populations, we therefore: (1 describe aspects of the perceptions of the importance of spiritual health of adolescents by developmental stage and within genders; (2 conduct similar analyses across measures related to specific domains of adolescent spiritual health; (3 relate perceptions of spiritual health to self-perceived personal health status. Cross-sectional surveys were administered to adolescent populations in school settings during 2013–2014. Participants (n=45,967 included eligible and consenting students aged 11–15 years in sampled schools from six European and North American countries. Our primary measures of spiritual health consisted of eight questions in four domains (perceived importance of connections to: self, others, nature, and the transcendent. Socio-demographic factors included age, gender, and country of origin. Self-perceived personal health status was assessed using a simple composite measure. Self-rated importance of spiritual health, both overall and within most questions and domains, declined as young people aged. This declining pattern persisted for both genders and in all countries, and was most notable for the domains of “connections with nature” and “connections with the transcendent”. Girls consistently rated their perceptions of the importance of spiritual health higher than boys. Spiritual health and its domains related strongly and consistently with self-perceived personal health status. While limited by the 8-item measure of perceived spiritual health employed, study findings confirm developmental theories proposed from qualitative observation, provide foundational

  19. Rational Choice and Developmental Influences on Recidivism Among Adolescent Felony Offenders.

    Science.gov (United States)

    Fagan, Jeffrey; Piquero, Alex R

    2007-12-01

    Recent case law and social science both have claimed that the developmental limitations of adolescents affect their capacity for control and decision making with respect to crime, diminishing their culpability and reducing their exposure to punishment. Social science has focused on two concurrent adolescent developmental influences: the internalization of legal rules and norms that regulate social and antisocial behaviors, and the development of rationality to frame behavioral choices and decisions. The interaction of these two developmental processes, and the identification of one domain of socialization and development as the primary source of motivation or restraint in adolescence, is the focus of this article. Accordingly, we combine rational choice and legal socialization frameworks into an integrated, developmental model of criminality. We test this framework in a large sample of adolescent felony offenders who have been interviewed at six-month intervals for two years. Using hierarchical and growth curve models, we show that both legal socialization and rational choice factors influence patterns of criminal offending over time. When punishment risks and costs are salient, crime rates are lower over time. We show that procedural justice is a significant antecedent of legal socialization, but not of rational choice. We also show that both mental health and developmental maturity moderate the effects of perceived crime risks and costs on criminal offending.

  20. Rational Choice and Developmental Influences on Recidivism Among Adolescent Felony Offenders

    Science.gov (United States)

    Fagan, Jeffrey; Piquero, Alex R.

    2009-01-01

    Recent case law and social science both have claimed that the developmental limitations of adolescents affect their capacity for control and decision making with respect to crime, diminishing their culpability and reducing their exposure to punishment. Social science has focused on two concurrent adolescent developmental influences: the internalization of legal rules and norms that regulate social and antisocial behaviors, and the development of rationality to frame behavioral choices and decisions. The interaction of these two developmental processes, and the identification of one domain of socialization and development as the primary source of motivation or restraint in adolescence, is the focus of this article. Accordingly, we combine rational choice and legal socialization frameworks into an integrated, developmental model of criminality. We test this framework in a large sample of adolescent felony offenders who have been interviewed at six-month intervals for two years. Using hierarchical and growth curve models, we show that both legal socialization and rational choice factors influence patterns of criminal offending over time. When punishment risks and costs are salient, crime rates are lower over time. We show that procedural justice is a significant antecedent of legal socialization, but not of rational choice. We also show that both mental health and developmental maturity moderate the effects of perceived crime risks and costs on criminal offending. PMID:20148123

  1. Developmental toxicology: adequacy of current methods.

    Science.gov (United States)

    Peters, P W

    1998-01-01

    Toxicology embraces several disciplines such as carcinogenicity, mutagenicity and reproductive toxicity. Reproductive toxicology is concerned with possible effects of substances on the reproductive process, i.e. on sexual organs and their functions, endocrine regulation, fertilization, transport of the fertilized ovum, implantation, and embryonic, fetal and postnatal development, until the end-differentiation of the organs is achieved. Reproductive toxicology is divided into areas related to male and female fertility, and developmental toxicology. Developmental toxicology can be further broken down into prenatal and postnatal toxicology. Today, much new information is available about the origins of developmental disorders resulting from chemical exposure. While these findings seem to promise important new developments in methodology and research, there is a danger of losing sight of the precepts and principles established in the light of existing knowledge. There is also a danger that we may fail to correct shortcomings in our existing procedures and practice. The aim of this presentation is to emphasize the importance of testing substances for their impact in advance of their use and to underline that we must use the best existing tools for carrying out risk assessments. Moreover, it needs to be stressed that there are many substances that are never assessed with respect to reproductive and developmental toxicity. Similarly, our programmes for post-marketing surveillance with respect to developmental toxicology are grossly inadequate. Our ability to identify risks to normal development and reproduction would be much improved, first if a number of straightforward precepts were always followed and second, if we had a clearer understanding of what we mean by risk and acceptable levels of risk in the context of development. Other aims of this paper are: to stress the complexity of the different stages of normal prenatal development; to note the principles that are

  2. Developmentalism: An Obscure but Pervasive Restriction

    Directory of Open Access Journals (Sweden)

    J. E. Stone

    1996-04-01

    Full Text Available Despite continuing criticism of public education, experimentally demonstrated and field tested teaching methods have been ignored, rejected, and abandoned. Instead of a stable consensus regarding best teaching practices, there seems only an unending succession of innovations. A longstanding educational doctrine appears to underlie this anomalous state of affairs. Termed developmentalism, it presumes "natural" ontogenesis to be optimal and it requires experimentally demonstrated teaching practices to overcome a presumption that they interfere with an optimal developmental trajectory. It also discourages teachers and parents from asserting themselves with children. Instead of effective interventions, it seeks the preservation of a postulated natural perfection. Developmentalism's rich history is expressed in a literature extending over 400 years. Its notable exponents include Jean Jacques Rousseau, John Dewey, and Jean Piaget; and its most recent expressions include "developmentally appropriate practice" and "constructivism." In the years during which it gained ascendance, developmentalism served as a basis for rejecting harsh and inhumane teaching methods. Today it impedes efforts to hold schools accountable for student academic achievement.

  3. Assessing the Developmental Neurotoxicity of 27 ...

    Science.gov (United States)

    Assessing the Developmental Neurotoxicity of 27 Organophosphorus Pesticides Using a Zebrafish Behavioral Assay, Waalkes, M., Hunter, D.L., Jarema, K., Mundy, W., and S. Padilla. The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize organophosphorus pesticides for developmental neurotoxicity. As such, we are exploring a behavioral testing paradigm that can assess the effects of sublethal and subteratogenic concentrations of developmental neurotoxicants on zebrafish (Danio rerio). This in vivo assay quantifies the locomotor response to light stimuli under tandem light and dark conditions in a 96-well plate using a video tracking system on 6 day post fertilization zebrafish larvae. Each of twenty-seven organophosphorus pesticides was tested for their developmental neurotoxic potential by exposing zebrafish embryos/larvae to the pesticide at several concentrations (≤ 100 μM nominal concentration) during the first five days of development, followed by 24 hours of depuration and then behavioral testing. Approximately 22% of the chemicals (Acephate, Dichlorvos, Diazoxon, Bensulide,Tribufos, Tebupirimfos) did not produce any behavioral changes after developmental exposure, while many (Malaoxon Fosthiazate, Dimethoate, Dicrotophos, Ethoprop, Malathion, Naled, Diazinon, Methamidophos, Terbufos, Trichlorfon, Phorate, Pirimiphos-methyl, Profenofos, Z-Tetrachlorvinphos, Chlorpyrifos, Coumaphos, Phosmet, Omethoate) produced changes in swi

  4. Replication and robustness in developmental research.

    Science.gov (United States)

    Duncan, Greg J; Engel, Mimi; Claessens, Amy; Dowsett, Chantelle J

    2014-11-01

    Replications and robustness checks are key elements of the scientific method and a staple in many disciplines. However, leading journals in developmental psychology rarely include explicit replications of prior research conducted by different investigators, and few require authors to establish in their articles or online appendices that their key results are robust across estimation methods, data sets, and demographic subgroups. This article makes the case for prioritizing both explicit replications and, especially, within-study robustness checks in developmental psychology. It provides evidence on variation in effect sizes in developmental studies and documents strikingly different replication and robustness-checking practices in a sample of journals in developmental psychology and a sister behavioral science-applied economics. Our goal is not to show that any one behavioral science has a monopoly on best practices, but rather to show how journals from a related discipline address vital concerns of replication and generalizability shared by all social and behavioral sciences. We provide recommendations for promoting graduate training in replication and robustness-checking methods and for editorial policies that encourage these practices. Although some of our recommendations may shift the form and substance of developmental research articles, we argue that they would generate considerable scientific benefits for the field. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  5. The Comet Cometh: Evolving Developmental Systems.

    Science.gov (United States)

    Jaeger, Johannes; Laubichler, Manfred; Callebaut, Werner

    In a recent opinion piece, Denis Duboule has claimed that the increasing shift towards systems biology is driving evolutionary and developmental biology apart, and that a true reunification of these two disciplines within the framework of evolutionary developmental biology (EvoDevo) may easily take another 100 years. He identifies methodological, epistemological, and social differences as causes for this supposed separation. Our article provides a contrasting view. We argue that Duboule's prediction is based on a one-sided understanding of systems biology as a science that is only interested in functional, not evolutionary, aspects of biological processes. Instead, we propose a research program for an evolutionary systems biology, which is based on local exploration of the configuration space in evolving developmental systems. We call this approach-which is based on reverse engineering, simulation, and mathematical analysis-the natural history of configuration space. We discuss a number of illustrative examples that demonstrate the past success of local exploration, as opposed to global mapping, in different biological contexts. We argue that this pragmatic mode of inquiry can be extended and applied to the mathematical analysis of the developmental repertoire and evolutionary potential of evolving developmental mechanisms and that evolutionary systems biology so conceived provides a pragmatic epistemological framework for the EvoDevo synthesis.

  6. Evolution and developmental genetics of floral display-A review of progress

    Institute of Scientific and Technical Information of China (English)

    Qing Ma; Wenheng Zhang; Qiu-Yun (Jenny) Xiang

    2017-01-01

    Angiosperms evolved a great diversity of ways to display their flowers for reproductive success by variation in floral color,size,shape,scent,arrangements,and flowering time.The various innovations in floral forms and the aggregation of flowers into different kinds of inflorescences can drive new ecological adaptations,speciation,and angiosperm diversification.Evolutionary developmental biology (evo-devo) seeks to uncover the developmental and genetic basis underlying morphological diversification.Advances in the developmental genetics of floral display have provided a foundation for insights into the genetic basis of floral and inflorescence evolution.A number of regulatory genes controlling floral and inflorescence development have been identified in model plants (e.g.,Arabidopsis thaliana,Antirrhinum majus) using forward genetics and conserved functions of many of these genes across diverse non-model species have been revealed by reverse genetics.Gene-regulatory networks that mediated the developmental progresses of floral and inflorescence development have also been established in some plant species.Meanwhile,phylogeny-based comparative analysis of morphological and genetic character has enabled the identification of key evolutionary events that lead to morphological complexity and diversification.Here we review the recent progress on evo-devo studies of floral display including floral symmetry,petal fusion,floral color,floral scent,and inflorescences.We also review the molecular genetic approaches applied to plant evo-devo studies and highlight the future directions of evo-devo.

  7. Factors associated with bruxism in children with developmental disabilities

    Directory of Open Access Journals (Sweden)

    Valeska Aparecida Fernandes SOUZA

    2015-01-01

    Full Text Available The aim of the present study was to investigate factors associated with bruxism in children aged from 1 to 13 years with developmental disabilities. A total of 389 dental records were examined. The bruxism analyzed was determined based on parental reports. The following variables were also analyzed: gender, age, International Code of Diseases (ICD, mouth breathing, history of gastroesophageal reflux, use of psychotropic drugs, gingival status, reports of xerostomia, hyperkinesis, pacifier use, thumb sucking and involuntary movements. For the purposes of analysis, the individuals were categorized as being with and without bruxism. Variables with a p-value < 0.25 in the bivariate analysis were incorporated into the logistic regression models. Females had a 0.44-fold (95%CI: 0.25 to 0.78 greater chance of exhibiting bruxism than males. Individuals with gastroesophageal reflux had a 2.28-fold (95%CI: 1.03 to 5.02 greater chance of exhibiting bruxism. Individuals with reported involuntary movements had a 2.24-fold (95%CI: 1.19 to 4.24 greater chance of exhibiting bruxism than those without such movements. Exhibiting involuntary movements, the male gender and gastroesophageal reflux are factors associated with bruxism in children with developmental disabilities.

  8. Global Prevalence of Autism and Other Pervasive Developmental Disorders

    Science.gov (United States)

    Elsabbagh, Mayada; Divan, Gauri; Koh, Yun-Joo; Kim, Young Shin; Kauchali, Shuaib; Marcín, Carlos; Montiel-Nava, Cecilia; Patel, Vikram; Paula, Cristiane S; Wang, Chongying; Yasamy, Mohammad Taghi; Fombonne, Eric

    2012-01-01

    We provide a systematic review of epidemiological surveys of autistic disorder and pervasive developmental disorders (PDDs) worldwide. A secondary aim was to consider the possible impact of geographic, cultural/ethnic, and socioeconomic factors on prevalence estimates and on clinical presentation of PDD. Based on the evidence reviewed, the median of prevalence estimates of autism spectrum disorders was 62/10 000. While existing estimates are variable, the evidence reviewed does not support differences in PDD prevalence by geographic region nor of a strong impact of ethnic/cultural or socioeconomic factors. However, power to detect such effects is seriously limited in existing data sets, particularly in low-income countries. While it is clear that prevalence estimates have increased over time and these vary in different neighboring and distant regions, these findings most likely represent broadening of the diagnostic concets, diagnostic switching from other developmental disabilities to PDD, service availability, and awareness of autistic spectrum disorders in both the lay and professional public. The lack of evidence from the majority of the world's population suggests a critical need for further research and capacity building in low- and middle-income countries. Autism Res 2012, 5: 160–179. © 2012 International Society for Autism Research, Wiley Periodicals, Inc. PMID:22495912

  9. Factors associated with bruxism in children with developmental disabilities.

    Science.gov (United States)

    Souza, Valeska Aparecida Fernandes; Abreu, Mauro Henrique Nogueira Guimarães; Resende, Vera Lúcia Silva; Castilho, Lia Silva

    2015-01-01

    The aim of the present study was to investigate factors associated with bruxism in children aged from 1 to 13 years with developmental disabilities. A total of 389 dental records were examined. The bruxism analyzed was determined based on parental reports. The following variables were also analyzed: gender, age, International Code of Diseases (ICD), mouth breathing, history of gastroesophageal reflux, use of psychotropic drugs, gingival status, reports of xerostomia, hyperkinesis, pacifier use, thumb sucking and involuntary movements. For the purposes of analysis, the individuals were categorized as being with and without bruxism. Variables with a p-value bruxism than males. Individuals with gastroesophageal reflux had a 2.28-fold (95%CI: 1.03 to 5.02) greater chance of exhibiting bruxism. Individuals with reported involuntary movements had a 2.24-fold (95%CI: 1.19 to 4.24) greater chance of exhibiting bruxism than those without such movements. Exhibiting involuntary movements, the male gender and gastroesophageal reflux are factors associated with bruxism in children with developmental disabilities.

  10. Nordic Mediation Reseach

    DEFF Research Database (Denmark)

    A presentation of 12 studies on mediation from researchers from Denmark, Finland, Norway and Sweden.......A presentation of 12 studies on mediation from researchers from Denmark, Finland, Norway and Sweden....

  11. Intracranial developmental venous anomaly: is it asymptomatic?

    Science.gov (United States)

    Puente, A Bolívar; de Asís Bravo Rodríguez, F; Bravo Rey, I; Romero, E Roldán

    2018-03-16

    Intracranial developmental venous anomalies are the most common vascular malformation. In the immense majority of cases, these anomalies are asymptomatic and discovered incidentally, and they are considered benign. Very exceptionally, however, they can cause neurological symptoms. In this article, we present three cases of patients with developmental venous anomalies that presented with different symptoms owing to complications derived from altered venous drainage. These anomalies were located in the left insula, right temporal lobe, and cerebellum. The exceptionality of the cases presented as well as of the images associated, which show the mechanism through which the symptoms developed, lies in the low incidence of symptomatic developmental venous anomalies reported in the literature. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Infant developmental milestones and adult intelligence

    DEFF Research Database (Denmark)

    Flensborg-Madsen, Trine; Mortensen, Erik Lykke

    2015-01-01

    Intelligence Scale (WAIS). Associations between motor developmental milestones and IQwere analysed bymultiple linear regression adjusting for potential confounding factors. Results: Later acquisition of infant developmental milestones was associated with lower subsequent IQ, and the majority of significant......Background: A number of studies suggest a positive association between faster infant motor development and intellectual function in childhood and adolescence. However, studies investigating the relationship between infant motor development and intelligence in adulthood are lacking. Aims......: To investigate whether age at achievement of 12 motor developmental milestones was associated with adult intelligence and to evaluate the influence of sex, parental social status, parity,mother's cigarette consumption in the last trimester, gestational age, birthweight, and birth length on this association...

  13. Bayesian Mediation Analysis

    OpenAIRE

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    This article proposes Bayesian analysis of mediation effects. Compared to conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian mediation analysis, inference is straightforward and exact, which makes it appealing for studies with small samples. Third, the Bayesian approach is conceptua...

  14. Characterization of Mediator Complex and its Associated Proteins from Rice.

    Science.gov (United States)

    Samanta, Subhasis; Thakur, Jitendra Kumar

    2017-01-01

    The Mediator complex is a multi-protein complex that acts as a molecular bridge conveying transcriptional messages from the cis element-bound transcription factor to the RNA Polymerase II machinery. It is found in all eukaryotes including members of the plant kingdom. Increasing number of reports from plants regarding different Mediator subunits involved in a multitude of processes spanning from plant development to environmental interactions have firmly established it as a central hub of plant regulatory networks. Routine isolation of Mediator complex in a particular species is a necessity because of many reasons. First, composition of the Mediator complex varies from species to species. Second, the composition of the Mediator complex in a particular species is not static under all developmental and environmental conditions. Besides this, at times, Mediator complex is used in in vitro transcription systems. Rice, a staple food crop of the world, is used as a model monocot crop. Realizing the need of a reliable protocol for the isolation of Mediator complex from plants, we describe here the isolation of Mediator complex from rice.

  15. Developmental programming and transgenerational transmission of obesity.

    Science.gov (United States)

    Vickers, M H

    2014-01-01

    The global obesity pandemic is often causally linked to marked changes in diet and lifestyle, namely marked increases in dietary intakes of high-energy diets and concomitant reductions in physical activity levels. However, far less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from environmental perturbations during the early-life period. Human and animal studies have highlighted the link between alterations in the early-life environment and increased susceptibility to obesity and related metabolic disorders in later life. In particular, altered maternal nutrition, including both undernutrition and maternal obesity, has been shown to lead to transgenerational transmission of metabolic disorders. This association has been conceptualised as the developmental programming hypothesis whereby the impact of environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the physiology of the offspring. Further, evidence to date suggests that this developmental programming is a transgenerational phenomenon, with a number of studies showing transmission of programming effects to subsequent generations, even in the absence of continued environmental stressors, thus perpetuating a cycle of obesity and metabolic disorders. The mechanisms responsible for these transgenerational effects remain poorly understood; evidence to date suggests a number of potential mechanisms underpinning the transgenerational transmission of the developmentally programmed phenotype through both the maternal and paternal lineage. Transgenerational phenotype transmission is often seen as a form of epigenetic inheritance with evidence showing both germline and somatic inheritance of epigenetic modifications leading to phenotype changes across generations. However, there is also evidence for non-genomic components as well as an interaction between the developing fetus with the in utero

  16. Normal composite face effects in developmental prosopagnosia.

    Science.gov (United States)

    Biotti, Federica; Wu, Esther; Yang, Hua; Jiahui, Guo; Duchaine, Bradley; Cook, Richard

    2017-10-01

    Upright face perception is thought to involve holistic processing, whereby local features are integrated into a unified whole. Consistent with this view, the top half of one face appears to fuse perceptually with the bottom half of another, when aligned spatially and presented upright. This 'composite face effect' reveals a tendency to integrate information from disparate regions when faces are presented canonically. In recent years, the relationship between susceptibility to the composite effect and face recognition ability has received extensive attention both in participants with normal face recognition and participants with developmental prosopagnosia. Previous results suggest that individuals with developmental prosopagnosia may show reduced susceptibility to the effect suggestive of diminished holistic face processing. Here we describe two studies that examine whether developmental prosopagnosia is associated with reduced composite face effects. Despite using independent samples of developmental prosopagnosics and different composite procedures, we find no evidence for reduced composite face effects. The experiments yielded similar results; highly significant composite effects in both prosopagnosic groups that were similar in magnitude to the effects found in participants with normal face processing. The composite face effects exhibited by both samples and the controls were greatly diminished when stimulus arrangements were inverted. Our finding that the whole-face binding process indexed by the composite effect is intact in developmental prosopagnosia indicates that other factors are responsible for developmental prosopagnosia. These results are also inconsistent with suggestions that susceptibility to the composite face effect and face recognition ability are tightly linked. While the holistic process revealed by the composite face effect may be necessary for typical face perception, it is not sufficient; individual differences in face recognition ability

  17. 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.

  18. Bayesian Mediation Analysis

    Science.gov (United States)

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    In this article, we propose Bayesian analysis of mediation effects. Compared with conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian…

  19. 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.

  20. Shame and the Internalized Other

    OpenAIRE

    Montes Sánchez, Alba

    2016-01-01

    In Shame and Necessity, Bernard Williams engages in a forceful vindication of the ethical significance of shame. In his view, shame is an extremely productive moral emotion because of the distinctive connection that it establishes between self, others and world, through a self-evaluation that is mediated by an internalized other. In this paper, I examine Williams’ conception of the internalized other and contrast it with other ways of conceiving the role of others in shame. I argue that, alth...

  1. Tibial and fibular developmental fields defects

    International Nuclear Information System (INIS)

    Khoury, N.J.; Haddad, M.C.; Hourani, M.H.

    1999-01-01

    Malformations of the lower limbs are rare and heterogeneous anomalies. To explain the diversity and complexity of these abnormalities, authors introduced the concept of tibial and fibular developmental fields. Defects in these fields are responsible for different malformations, which have been described, to our knowledge, in only one report in the radiology literature. We present a case of a newborn with femoral bifurcation, absent fibulae and talar bones, ankle and foot malformations, and associated atrial septal defect. Our case is an example of defects in both fibular and tibial developmental fields. (orig.)

  2. Developmental programming: the role of growth hormone.

    Science.gov (United States)

    Oberbauer, Anita M

    2015-01-01

    Developmental programming of the fetus has consequences for physiologic responses in the offspring as an adult and, more recently, is implicated in the expression of altered phenotypes of future generations. Some phenotypes, such as fertility, bone strength, and adiposity are highly relevant to food animal production and in utero factors that impinge on those traits are vital to understand. A key systemic regulatory hormone is growth hormone (GH), which has a developmental role in virtually all tissues and organs. This review catalogs the impact of GH on tissue programming and how perturbations early in development influence GH function.

  3. Developmental biology in marine invertebrate symbioses.

    Science.gov (United States)

    McFall-Ngai, M J; Ruby, E G

    2000-12-01

    Associations between marine invertebrates and their cooperative bacterial symbionts offer access to an understanding of the roots of host-microbe interaction; for example, several symbioses like the squid-vibrio light organ association serve as models for investigating how each partner affects the developmental biology of the other. Previous results have identified a program of specific developmental events that unfolds as the association is initiated. In the past year, published studies have focused primarily on describing the mechanisms underlying the signaling processes that occur between the juvenile squid and the luminous bacteria that colonize it.

  4. International collaborative study on the occurrence of plasmid-mediated quinolone resistance in Salmonella enterica and Escherichia coli isolated from animals, humans, food and the environment in 13 European countries

    DEFF Research Database (Denmark)

    Veldman, Kees; Cavaco, Lina; Mevius, Dik

    2011-01-01

    OBJECTIVES: This study was initiated to collect retrospective information on the occurrence of plasmid-mediated quinolone resistance (PMQR) in Salmonella enterica and Escherichia coli isolates in Europe and to identify the responsible genes. METHODS: Databases of national reference laboratories...... containing MIC values for Salmonella and E. coli isolated between 1994 and 2009 in animals, humans, food and the environment from 13 European countries were screened for isolates exhibiting a defined quinolone resistance phenotype, i.e. reduced susceptibility to fluoroquinolones and nalidixic acid. PCR...... isolate. No qnrC or qepA genes were detected in either Salmonella or E. coli. CONCLUSIONS: This study shows the occurrence and dissemination of PMQR genes in Salmonella and E. coli in Europe with a defined quinolone resistance phenotype. We also report the first detection of qnrD in Salmonella collected...

  5. Neuromodulation and developmental contextual influences on neural and cognitive plasticity across the lifespan.

    Science.gov (United States)

    Li, Shu-Chen

    2013-11-01

    Behavioral, cognitive, and motivational development entails co-constructive interactions between the environmental and social influences from the developmental context, on the one hand, and the individual's neurobiological inheritance, on the other hand. Key brain networks underlying cognition, emotion, and motivation are innervated by major transmitter systems (e.g., the catecholamines and acetylcholine). Thus, the maturation and senescence of neurotransmitter systems have direct implications for lifespan development. In addition to reviewing evidence on life age differences in dopaminergic modulation and cognitive development, this brief review selectively highlights recent findings on how important influences from the developmental context, such as reward-mediated motivational processes, transgenerational stress transmission, psychosocial stress, and cognitive interventions, may, in part, exert their effects on brain and behavioral development through their effects on neuromodulatory mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. The sex ratio of siblings of individuals with a history of developmental language disorder

    DEFF Research Database (Denmark)

    Mouridsen, Svend Erik; Hauschild, Karen-Marie

    2010-01-01

    There is a well documented predominance of males diagnosed with neurodevelopmental disorders. The influence of sex steroids upon brain development has been suggested to mediate sex differences in developmental psychopathology, and has been epitomized in the 'extreme male brain theory......'. The objective of this study was to extend previous studies dealing with the extreme male brain theory and to study the sex ratio (proportion of males) in the siblings of 469 individuals with a developmental language disorder (DLD) who were consecutively assessed in the same clinic during a period of 10 years....... Among their 908 live-born siblings, 503 were males and 405 females. This yields a sex ratio of 0.554, which is significantly higher than the Danish live birth sex ratio of 0.514 over the same period (P = 0.02). Our findings are consistent with the hypothesis that male sex hormones may be implicated...

  7. U(1) mediation of flux supersymmetry breaking

    Science.gov (United States)

    Grimm, Thomas W.; Klemm, Albrecht

    2008-10-01

    We study the mediation of supersymmetry breaking triggered by background fluxes in Type II string compactifications with Script N = 1 supersymmetry. The mediation arises due to an U(1) vector multiplet coupling to both a hidden supersymmetry breaking flux sector and a visible D-brane sector. The required internal manifolds can be constructed by non-Kähler resolutions of singular Calabi-Yau manifolds. The effective action encoding the U(1) coupling is then determined in terms of the global topological properties of the internal space. We investigate suitable local geometries for the hidden and visible sector in detail. This includes a systematic study of orientifold symmetries of del Pezzo surfaces realized in compact geometries after geometric transition. We construct compact examples admitting the key properties to realize flux supersymmetry breaking and U(1) mediation. Their toric realization allows us to analyze the geometry of curve classes and confirm the topological connection between the hidden and visible sector.

  8. U(1) mediation of flux supersymmetry breaking

    International Nuclear Information System (INIS)

    Grimm, Thomas W.; Klemm, Albrecht

    2008-01-01

    We study the mediation of supersymmetry breaking triggered by background fluxes in Type II string compactifications with N = 1 supersymmetry. The mediation arises due to an U(1) vector multiplet coupling to both a hidden supersymmetry breaking flux sector and a visible D-brane sector. The required internal manifolds can be constructed by non-Kaehler resolutions of singular Calabi-Yau manifolds. The effective action encoding the U(1) coupling is then determined in terms of the global topological properties of the internal space. We investigate suitable local geometries for the hidden and visible sector in detail. This includes a systematic study of orientifold symmetries of del Pezzo surfaces realized in compact geometries after geometric transition. We construct compact examples admitting the key properties to realize flux supersymmetry breaking and U(1) mediation. Their toric realization allows us to analyze the geometry of curve classes and confirm the topological connection between the hidden and visible sector.

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

    Directory of Open Access Journals (Sweden)

    Zhengui Zheng

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

  10. General gauge mediation

    International Nuclear Information System (INIS)

    Meade, Patrick; Seiberg, Nathan; Shih, David

    2009-01-01

    We give a general definition of gauge mediated supersymmetry breaking which encompasses all the known gauge mediation models. In particular, it includes both models with messengers as well as direct mediation models. A formalism for computing the soft terms in the generic model is presented. Such a formalism is necessary in strongly-coupled direct mediation models where perturbation theory cannot be used. It allows us to identify features of the entire class of gauge mediation models and to distinguish them from specific signatures of various subclasses. (author)

  11. Developmental Scientist | Center for Cancer Research

    Science.gov (United States)

    blood diseases and conditions; parasitic infections; rheumatic and inflammatory diseases; and rare and neglected diseases. CMRP’s collaborative approach to clinical research and the expertise and dedication of staff to the continuation and success of the program’s mission has contributed to improving the overall standards of public health on a global scale. The Clinical Monitoring Research Program (CMRP) provides quality assurance and regulatory compliance support to the National Cancer Institute’s (NCI’s), Center for Cancer Research (CCR), Surgery Branch (SB). KEY ROLES/RESPONSIBILITIES - THIS POSITION IS CONTINGENT UPON FUNDING APPROVAL The Developmental Scientist will: Provide support and advisement to the development of the T Cell receptor gene therapy protocols. Establishes, implements and maintains standardized processes and assesses performance to make recommendations for improvement. Provides support and guidance to the cellular therapy or vector production facilities at the NIH Clinical Center engaged in the manufacture of patient-specific therapies. Manufactures cellular therapy products for human use. Develops and manufactures lentiviral and/or retroviral vectors. Prepares technical reports, abstracts, presentations and program correspondence concerning assigned projects through research and analysis of information relevant to government policy, regulations and other relevant data and monitor all assigned programs for compliance. Provides project management support with planning and development of project schedules and deliverables, tracking project milestones, managing timelines, preparing status reports and monitoring progress ensuring adherence to deadlines. Facilitates communication through all levels of staff by functioning as a liaison between internal departments, senior management, and the customer. Serves as a leader/mentor to administrative staff and prepares employee performance evaluations. Develops and implements procedures/programs to

  12. From Clinical-Developmental Theory to Assessment: The Holistic Student Assessment Tool

    Directory of Open Access Journals (Sweden)

    Gil Noam

    2012-12-01

    Full Text Available A description and test of the Holistic Student Assessment Tool (HSA, an assessment tool to measure children’s and adolescents’ resiliencies in relation to externalizing and internalizing problem behaviors. The HSA is based on the authors’ research-based clinical-developmental Clover Leaf Model of resilience and psychopathology, and is one of the first attempts at closing the gap between risk and resilience approaches in developmental assessment. The HSA was tested in a cross-sectional sample of 423 children and adolescents.The results lend support to the HSA as a valid measure of children’s and adolescents’ resiliencies. Furthermore, the resilience scales mostly exhibited the theoretically expected convergent and divergent relationships with the psychopathology scales. In addition, we show how the resilience scales predict adolescents’ externalizing and internalizing symptoms. We contend that evidence-based intervention to address youth aggression needs to be based on sounddevelopmental assessment.

  13. Activity-dependent ubiquitination of GluA1 mediates a distinct AMPA receptor endocytosis and sorting pathway.

    Science.gov (United States)

    Schwarz, Lindsay A; Hall, Benjamin J; Patrick, Gentry N

    2010-12-08

    The accurate trafficking of AMPA receptors (AMPARs) to and from the synapse is a critical component of learning and memory in the brain, whereas dysfunction of AMPAR trafficking is hypothesized to be an underlying mechanism of Alzheimer's disease. Previous work has shown that ubiquitination of integral membrane proteins is a common posttranslational modification used to mediate endocytosis and endocytic sorting of surface proteins in eukaryotic cells. Here we report that mammalian AMPARs become ubiquitinated in response to their activation. Using a mutant of GluA1 that is unable to be ubiquitinated at lysines on its C-terminus, we demonstrate that ubiquitination is required for internalization of surface AMPARs and their trafficking to the lysosome in response to the AMPAR agonist AMPA but not for internalization of AMPARs in response to the NMDA receptor agonist NMDA. Through overexpression or RNA interference-mediated knockdown, we identify that a specific E3 ligase, Nedd4-1 (neural-precursor cell-expressed developmentally downregulated gene 4-1), is necessary for this process. Finally, we show that ubiquitination of GluA1 by Nedd4-1 becomes more prevalent as neurons mature. Together, these data show that ubiquitination of GluA1-containing AMPARs by Nedd4-1 mediates their endocytosis and trafficking to the lysosome. Furthermore, these results provide insight into how hippocampal neurons regulate AMPAR trafficking and degradation with high specificity in response to differing neuronal signaling cues and suggest that changes to this pathway may occur as neurons mature.

  14. Internal Bleeding

    Science.gov (United States)

    ... Fractures (Part II) Additional Content Medical News Internal Bleeding By Amy H. Kaji, MD, PhD, Associate Professor, ... Emergency First Aid Priorities Cardiac Arrest Choking Internal Bleeding Severed or Constricted Limbs or Digits Soft-Tissue ...

  15. Bayesian dynamic mediation analysis.

    Science.gov (United States)

    Huang, Jing; Yuan, Ying

    2017-12-01

    Most existing methods for mediation analysis assume that mediation is a stationary, time-invariant process, which overlooks the inherently dynamic nature of many human psychological processes and behavioral activities. In this article, we consider mediation as a dynamic process that continuously changes over time. We propose Bayesian multilevel time-varying coefficient models to describe and estimate such dynamic mediation effects. By taking the nonparametric penalized spline approach, the proposed method is flexible and able to accommodate any shape of the relationship between time and mediation effects. Simulation studies show that the proposed method works well and faithfully reflects the true nature of the mediation process. By modeling mediation effect nonparametrically as a continuous function of time, our method provides a valuable tool to help researchers obtain a more complete understanding of the dynamic nature of the mediation process underlying psychological and behavioral phenomena. We also briefly discuss an alternative approach of using dynamic autoregressive mediation model to estimate the dynamic mediation effect. The computer code is provided to implement the proposed Bayesian dynamic mediation analysis. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  16. Time-based prospective memory in young children-Exploring executive functions as a developmental mechanism.

    Science.gov (United States)

    Kretschmer, Anett; Voigt, Babett; Friedrich, Sylva; Pfeiffer, Kathrin; Kliegel, Matthias

    2014-01-01

    The present study investigated time-based prospective memory (PM) during the transition from kindergarten/preschool to school age and applied mediation models to test the impact of executive functions (working memory, inhibitory control) and time monitoring on time-based PM development. Twenty-five preschool (age: M = 5.75, SD = 0.28) and 22 primary school children (age: M = 7.83, SD = 0.39) participated. To examine time-based PM, children had to play a computer-based driving game requiring them to drive a car on a road without hitting others cars (ongoing task) and to refill the car regularly according to a fuel gauge, which serves as clock equivalent (PM task). The level of gas that was still left in the fuel gauge was not displayed on the screen and children had to monitor it via a button press (time monitoring). Results revealed a developmental increase in time-based PM performance from preschool to school age. Applying the mediation models, only working memory was revealed to influence PM development. Neither inhibitory control alone nor the mediation paths leading from both executive functions to time monitoring could explain the link between age and time-based PM. Thus, results of the present study suggest that working memory may be one key cognitive process driving the developmental growth of time-based PM during the transition from preschool to school age.

  17. International Relations

    OpenAIRE

    McGlinchey, S.

    2017-01-01

    A ‘Day 0’ introduction to International Relations for beginners. Written by a range of emerging and established experts, the chapters offer a broad sweep of the basic components of International Relations and the key contemporary issues that concern the discipline. The narrative arc forms a complete circle, taking readers from no knowledge to competency. The journey starts by examining how the international system was formed and ends by reflecting that International Relations is always adapti...

  18. Working Memory and Developmental Language Impairments

    Science.gov (United States)

    Henry, Lucy A.; Botting, Nicola

    2017-01-01

    Children with developmental language impairments (DLI) are often reported to show difficulties with working memory. This review describes the four components of the well-established working memory model, and considers whether there is convincing evidence for difficulties within each component in children with DLI. The emphasis is on the most…

  19. Developmental Predictors of Fraction Concepts and Procedures

    Science.gov (United States)

    Jordan, Nancy C.; Hansen, Nicole; Fuchs, Lynn S.; Siegler, Robert S.; Gersten, Russell; Micklos, Deborah

    2013-01-01

    Developmental predictors of children's fraction concepts and procedures at the end of fourth grade were investigated in a 2-year longitudinal study. Participants were 357 children who started the study in third grade. Attentive behavior, language, nonverbal reasoning, number line estimation, calculation fluency, and reading fluency each…

  20. Common Developmental Tasks in Forming Reconstituted Families.

    Science.gov (United States)

    Kleinman, Judith

    1979-01-01

    Developmental tasks common to the formation of a reconstituted family are described, particularly the continued mourning of the old family; the formation of a solid marital relationship despite the difficulties presented by past failures and the presence of children; and the formation of sibling alliances across family lines. (Author)